PT J
AU Elyada, E
   Pribluda, A
   Goldstein, RE
   Morgenstern, Y
   Brachya, G
   Cojocaru, G
   Snir-Alkalay, I
   Burstain, I
   Haffner-Krausz, R
   Jung, S
   Wiener, Z
   Alitalo, K
   Oren, M
   Pikarsky, E
   Ben-Neriah, Y
AF Elyada, Ela
   Pribluda, Ariel
   Goldstein, Robert E.
   Morgenstern, Yael
   Brachya, Guy
   Cojocaru, Gady
   Snir-Alkalay, Irit
   Burstain, Ido
   Haffner-Krausz, Rebecca
   Jung, Steffen
   Wiener, Zoltan
   Alitalo, Kari
   Oren, Moshe
   Pikarsky, Eli
   Ben-Neriah, Yinon
TI CKIα ablation highlights a critical role for p53 in invasiveness control
SO NATURE
LA English
DT Article
ID oncogene-induced senescence; intestinal epithelium; mouse model; expression; invasion; tumorigenesis; transgene; mutations; apoptosis; biology
AB The mature gut renews continuously and rapidly throughout adult life, often in a damage-inflicting micro-environment. The major driving force for self-renewal of the intestinal epithelium is the Wnt-mediated signalling pathway, and Wnt signalling is frequently hyperactivated in colorectal cancer(1). Here we show that casein kinase I alpha (CKI alpha), a component of the beta-catenin-destruction complex(1), is a critical regulator of the Wnt signalling pathway. Inducing the ablation of Csnk1a1 (the gene encoding CKI alpha) in the gut triggers massive Wnt activation, surprisingly without causing tumorigenesis. CKI alpha-deficient epithelium shows many of the features of human colorectal tumours in addition to Wnt activation, in particular the induction of the DNA damage response and cellular senescence, both of which are thought to provide a barrier against malignant transformation(2). The epithelial DNA damage response in mice is accompanied by substantial activation of p53, suggesting that the p53 pathway may counteract the pro-tumorigenic effects of Wnt hyperactivation. Notably, the transition from benign adenomas to invasive colorectal cancer in humans is typically linked to p53 inactivation, underscoring the importance of p53 as a safeguard against malignant progression(3); however, the mechanism of p53-mediated tumour suppression is unknown. We show that the maintenance of intestinal homeostasis inCKI alpha-deficient gut requires p53-mediated growth control, because the combined ablation of Csnk1a1 and either p53 or its target gene p21 (also known as Waf1, Cip1, Sdi1 and Cdkn1a) triggered high-grade dysplasia with extensive proliferation. Unexpectedly, these ablations also induced non-proliferating cells to invade the villous lamina propria rapidly, producing invasive carcinomas throughout the small bowel. Furthermore, in p53-deficient gut, loss of heterozygosity of the gene encoding CKI alpha caused a highly invasive carcinoma, indicating that CKI alpha functions as a tumour suppressor when p53 is inactivated. We identified a set of genes (the p53-suppressed invasiveness signature, PSIS) that is activated by the loss of both p53 and CKI alpha and which probably accounts for the brisk induction of invasiveness. PSIS transcription and tumour invasion were suppressed by p21, independently of cell cycle control. Restraining tissue invasion through suppressing PSIS expression is thus a novel tumour-suppressor function of wild-type p53.
C1 [Elyada, Ela; Pribluda, Ariel; Goldstein, Robert E.; Morgenstern, Yael; Brachya, Guy; Cojocaru, Gady; Snir-Alkalay, Irit; Burstain, Ido; Pikarsky, Eli; Ben-Neriah, Yinon] Hebrew Univ Jerusalem, Hadassah Med Sch, IMRIC, Lautenberg Ctr Immunol, IL-91120 Jerusalem, Israel.
   [Haffner-Krausz, Rebecca] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel.
   [Jung, Steffen] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Wiener, Zoltan; Alitalo, Kari] Univ Helsinki, Biomedicum Helsinki, Mol Canc Biol Program, FIN-00014 Helsinki, Finland.
   [Wiener, Zoltan; Alitalo, Kari] Univ Helsinki, Biomedicum Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland.
   [Oren, Moshe] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Pikarsky, Eli] Hebrew Univ Jerusalem, Hadassah Med Sch, IMRIC, Dept Pathol, IL-91120 Jerusalem, Israel.
C3 Hebrew University of Jerusalem; Weizmann Institute of Science; Weizmann Institute of Science; University of Helsinki; University of Helsinki; Weizmann Institute of Science; Hebrew University of Jerusalem
RP Ben-Neriah, Y (corresponding author), Hebrew Univ Jerusalem, Hadassah Med Sch, IMRIC, Lautenberg Ctr Immunol, IL-91120 Jerusalem, Israel.
EM peli@hadassah.org.il; yinon@cc.huji.ac.il
FU Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Israel Science Foundation; RUBICON EC Network of Excellence; Israel Cancer Research Fund; Deutsches Krebsforschungszentrum-Ministry of Science and Technology (DKFZ-MOST); Marie-Curie Intra-European Fellowship
NR 42
TC 170
Z9 208
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 FEB 17
PY 2011
VL 470
IS 7334
BP 409
EP U208
DI 10.1038/nature09673
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100045
PM 21331045
DA 2026-03-09
ER

PT J
AU Ramsden, S
   Richardson, FM
   Josse, G
   Thomas, MSC
   Ellis, C
   Shakeshaft, C
   Seghier, ML
   Price, CJ
AF Ramsden, Sue
   Richardson, Fiona M.
   Josse, Goulven
   Thomas, Michael S. C.
   Ellis, Caroline
   Shakeshaft, Clare
   Seghier, Mohamed L.
   Price, Cathy J.
TI Verbal and non-verbal intelligence changes in the teenage brain
SO NATURE
LA English
DT Article
ID prefrontal cortex; cerebellum; children; acquisition; childhood; ability; fmri
AB Intelligence quotient (IQ) is a standardized measure of human intellectual capacity that takes into account a wide range of cognitive skills(1). IQ is generally considered to be stable across the lifespan, with scores at one time point used to predict educational achievement and employment prospects in later years(1). Neuroimaging allows us to test whether unexpected longitudinal fluctuations in measured IQ are related to brain development. Here we show that verbal and non-verbal IQ can rise or fall in the teenage years, with these changes in performance validated by their close correlation with changes in local brain structure. A combination of structural and functional imaging showed that verbal IQ changed with grey matter in a region that was activated by speech, whereas non-verbal IQ changed with grey matter in a region that was activated by finger movements. By using longitudinal assessments of the same individuals, we obviated the many sources of variation in brain structure that confound cross-sectional studies. This allowed us to dissociate neural markers for the two types of IQ and to show that general verbal and non-verbal abilities are closely linked to the sensorimotor skills involved in learning. More generally, our results emphasize the possibility that an individual's intellectual capacity relative to their peers can decrease or increase in the teenage years. This would be encouraging to those whose intellectual potential may improve, and would be a warning that early achievers may not maintain their potential.
C1 [Ramsden, Sue; Richardson, Fiona M.; Josse, Goulven; Ellis, Caroline; Shakeshaft, Clare; Seghier, Mohamed L.; Price, Cathy J.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
   [Thomas, Michael S. C.] Univ London, Birkbeck Coll, Dept Psychol Sci, Dev Neurocognit Lab, London WC1E 7HX, England.
C3 University of London; University College London; University of London; Birkbeck University London
RP Price, CJ (corresponding author), UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
EM c.price@fil.ion.ucl.ac.uk
FU Wellcome Trust; MRC [G0300188] Funding Source: UKRI; Medical Research Council [G0300188] Funding Source: researchfish
NR 25
TC 154
Z9 188
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 113
EP 116
DI 10.1038/nature10514
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600042
PM 22012265
DA 2026-03-09
ER

PT J
AU Sun, F
   Park, KK
   Belin, S
   Wang, DQ
   Lu, T
   Chen, G
   Zhang, K
   Yeung, CC
   Feng, GP
   Yankner, BA
   He, ZG
AF Sun, Fang
   Park, Kevin K.
   Belin, Stephane
   Wang, Dongqing
   Lu, Tao
   Chen, Gang
   Zhang, Kang
   Yeung, Cecil
   Feng, Guoping
   Yankner, Bruce A.
   He, Zhigang
TI Sustained axon regeneration induced by co-deletion of PTEN and SOCS3
SO NATURE
LA English
DT Article
ID myelin-associated inhibitor; ciliary neurotrophic factor; signal transducer; growth; requires; cns; transcription-3; activation; suppressor; expression
AB A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury(1,2). Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth-related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery.
C1 [Sun, Fang; Belin, Stephane; Chen, Gang; Yeung, Cecil; He, Zhigang] Harvard Univ, Childrens Hosp, FM Kirby Neurobiol Ctr, Sch Med, Boston, MA 02115 USA.
   [Sun, Fang; Belin, Stephane; Chen, Gang; Yeung, Cecil; He, Zhigang] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
   [Park, Kevin K.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL 33136 USA.
   [Wang, Dongqing; Feng, Guoping] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Lu, Tao; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; University of Miami; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; University of California System; University of California San Diego
RP He, ZG (corresponding author), Harvard Univ, Childrens Hosp, FM Kirby Neurobiol Ctr, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM Zhigang.he@childrens.harvard.edu
FU Wings for Life; Miami Project to Cure Paralysis; NEI
NR 30
TC 609
Z9 748
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 DEC 15
PY 2011
VL 480
IS 7377
BP 372
EP U125
DI 10.1038/nature10594
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000052
PM 22056987
DA 2026-03-09
ER

PT J
AU Kamat, SS
   Williams, HJ
   Raushel, FM
AF Kamat, Siddhesh S.
   Williams, Howard J.
   Raushel, Frank M.
TI Intermediates in the transformation of phosphonates to phosphate by bacteria
SO NATURE
LA English
DT Article
ID pyruvate formate-lyase; 3-dimensional structure; catalytic mechanism; degradation; identification; metabolism; cleavage; 14-gene; operon
AB Phosphorus is an essential element for all known forms of life. In living systems, phosphorus is an integral component of nucleic acids, carbohydrates and phospholipids, where it is incorporated as a derivative of phosphate. However, most Gram-negative bacteria have the capability to use phosphonates as a nutritional source of phosphorus under conditions of phosphate starvation(1). In these organisms, methylphosphonate is converted to phosphate and methane. In a formal sense, this transformation is a hydrolytic cleavage of a carbon-phosphorus (C-P) bond, but a general enzymatic mechanism for the activation and conversion of alkylphosphonates to phosphate and an alkane has not been elucidated despite much effort for more than two decades. The actual mechanism for C-P bond cleavage is likely to be a radical-based transformation(2). In Escherichia coli, the catalytic machinery for the C-P lyase reaction has been localized to the phn gene cluster(1). This operon consists of the 14 genes phnC, phnD, ... , phnP. Genetic and biochemical experiments have demonstrated that the genes phnG, phnH, ... , phnM encode proteins that are essential for the conversion of phosphonates to phosphate and that the proteins encoded by the other genes in the operon have auxiliary functions(1,3-6). There are no functional annotations for any of the seven proteins considered essential for C-P bond cleavage. Here we show that methylphosphonate reacts with MgATP to form alpha-D-ribose-1-methylphosphonate-5-triphosphate (RPnTP) and adenine. The triphosphate moiety of RPnTP is hydrolysed to pyrophosphate and alpha-D-ribose-1-methylphosphonate-5-phosphate (PRPn). The C-P bond of PRPn is subsequently cleaved in a radical-based reaction producing alpha-D-ribose-1,2-cyclic-phosphate-5-phosphate and methane in the presence of S-adenosyl-L-methionine. Substantial quantities of phosphonates are produced worldwide for industrial processes, detergents, herbicides and pharmaceuticals(7-9). Our elucidation of the chemical steps for the biodegradation of alkylphosphonates shows how these compounds can be metabolized and recycled to phosphate.
C1 [Kamat, Siddhesh S.; Williams, Howard J.; Raushel, Frank M.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
C3 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 National Institutes of Health [GM93342, GM71790]; Robert A. Welch Foundation [A-840]; National Science Foundation [0840464]; Division Of Chemistry; Direct For Mathematical & Physical Scien [0840464] Funding Source: National Science Foundation
NR 26
TC 120
Z9 153
U1 1
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 570
EP 573
DI 10.1038/nature10622
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000071
PM 22089136
DA 2026-03-09
ER

PT J
AU Lapkiewicz, R
   Li, PZ
   Schaeff, C
   Langford, NK
   Ramelow, S
   Wiesniak, M
   Zeilinger, A
AF Lapkiewicz, Radek
   Li, Peizhe
   Schaeff, Christoph
   Langford, Nathan K.
   Ramelow, Sven
   Wiesniak, Marcin
   Zeilinger, Anton
TI Experimental non-classicality of an indivisible quantum system
SO NATURE
LA English
DT Article
ID kochen-specker theorem; hidden-variables; mechanics
AB In contrast to classical physics, quantum theory demands that not all properties can be simultaneously well defined; the Heisenberg uncertainty principle is a manifestation of this fact(1). Alternatives have been explored-notably theories relying on joint probability distributions or non-contextual hidden-variable models, in which the properties of a system are defined independently of their own measurement and any other measurements that are made. Various deep theoretical results(2-5) imply that such theories are in conflict with quantum mechanics. Simpler cases demonstrating this conflict have been found(6-10) and tested experimentally(11,12) with pairs of quantum bits (qubits). Recently, an inequality satisfied by non-contextual hidden-variable models and violated by quantum mechanics for all states of two qubits was introduced(13) and tested experimentally(14-16). A single three-state system (a qutrit) is the simplest system in which such a contradiction is possible; moreover, the contradiction cannot result from entanglement between subsystems, because such a three-state system is indivisible. Here we report an experiment with single photonic qutrits(17,18) which provides evidence that no joint probability distribution describing the outcomes of all possible measurements-and, therefore, no non-contextual theory-can exist. Specifically, we observe a violation of the Bell-type inequality found by Klyachko, Can, Binicioglu and Shumovsky(19). Our results illustrate a deep incompatibility between quantum mechanics and classical physics that cannot in any way result from entanglement.
C1 [Lapkiewicz, Radek; Li, Peizhe; Schaeff, Christoph; Langford, Nathan K.; Ramelow, Sven; Wiesniak, Marcin; Zeilinger, Anton] Univ Vienna, Vienna Ctr Quantum Sci & Technol, Fac Phys, A-1090 Vienna, Austria.
   [Lapkiewicz, Radek; Schaeff, Christoph; Langford, Nathan K.; Ramelow, Sven; Zeilinger, Anton] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-1090 Vienna, Austria.
C3 University of Vienna; Austrian Academy of Sciences
RP Zeilinger, A (corresponding author), Univ Vienna, Vienna Ctr Quantum Sci & Technol, Fac Phys, Boltzmanngasse 5, A-1090 Vienna, Austria.
EM anton.zeilinger@univie.ac.at
FU ERC [QIT4QAD]; Austrian Science Fund [F4007]; EC (Marie Curie Research Training Network EMALI); Vienna Doctoral Program on Complex Quantum Systems; John Templeton Foundation; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 20
TC 216
Z9 223
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 JUN 23
PY 2011
VL 474
IS 7352
BP 490
EP 493
DI 10.1038/nature10119
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700044
PM 21697945
DA 2026-03-09
ER

PT J
AU Lin, DY
   Boyle, MP
   Dollar, P
   Lee, H
   Lein, ES
   Perona, P
   Anderson, DJ
AF Lin, Dayu
   Boyle, Maureen P.
   Dollar, Piotr
   Lee, Hyosang
   Lein, E. S.
   Perona, Pietro
   Anderson, David J.
TI Functional identification of an aggression locus in the mouse hypothalamus
SO NATURE
LA English
DT Article
ID brain-stimulation; female rats; anterior hypothalamus; ventromedial nucleus; violent aggression; agonistic behavior; receptor blockade; lordosis reflex; neural activity; c-fos
AB Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.
C1 [Lin, Dayu; Lee, Hyosang; Anderson, David J.] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
   [Lin, Dayu; Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Boyle, Maureen P.; Lein, E. S.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
C3 California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; Allen Institute for Brain Science
RP Lin, DY (corresponding author), CALTECH, Div Biol 216 76, 1201 E Calif Blvd, Pasadena, CA 91125 USA.
EM dayu.lin@nyumc.org; wuwei@caltech.edu
FU Weston-Havens Foundation; Jane Coffin Childs Foundation
NR 47
TC 681
Z9 836
U1 3
U2 166
PU 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 10
PY 2011
VL 470
IS 7333
BP 221
EP +
DI 10.1038/nature09736
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200036
PM 21307935
DA 2026-03-09
ER

PT J
AU David, LA
   Alm, EJ
AF David, Lawrence A.
   Alm, Eric J.
TI Rapid evolutionary innovation during an Archaean genetic expansion
SO NATURE
LA English
DT Article
ID molecular fossils; genm; ocean; model; site
AB The natural history of Precambrian life is still unknown because of the rarity of microbial fossils and biomarkers(1,2). However, the composition of modern-day genomes may bear imprints of ancient biogeochemical events(3-6). Here we use an explicit model of macroevolution including gene birth, transfer, duplication and loss events to map the evolutionary history of 3,983 gene families across the three domains of life onto a geological timeline. Surprisingly, we find that a brief period of genetic innovation during the Archaean eon, which coincides with a rapid diversification of bacterial lineages, gave rise to 27% of major modern gene families. A functional analysis of genes born during this Archaean expansion reveals that they are likely to be involved in electron-transport and respiratory pathways. Genes arising after this expansion show increasing use of molecular oxygen (P = 3.4 x 10(-8)) and redox-sensitive transition metals and compounds, which is consistent with an increasingly oxygenating biosphere.
C1 [David, Lawrence A.; Alm, Eric J.] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA.
   [Alm, Eric J.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA.
   [Alm, Eric J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Alm, Eric J.] Broad Inst, Cambridge, MA 02140 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Alm, EJ (corresponding author), MIT, Computat & Syst Biol Initiat, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ejalm@mit.edu
FU US Department of Energy [DE-AC02-05CH11231]; National Science Foundation; National Defense Science and Engineering Graduate Fellowship; Direct For Biological Sciences; Division Of Environmental Biology [0936234] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0821391] Funding Source: National Science Foundation
NR 28
TC 314
Z9 358
U1 0
U2 129
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 93
EP 96
DI 10.1038/nature09649
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600038
PM 21170026
DA 2026-03-09
ER

PT J
AU Peter, IS
   Davidson, EH
AF Peter, Isabelle S.
   Davidson, Eric H.
TI A gene regulatory network controlling the embryonic specification of endoderm
SO NATURE
LA English
DT Article
ID sea-urchin embryo; nuclear beta-catenin; strongylocentrotus-purpuratus; cell fates; expression; identification; blastomeres; lineages; family
AB Specification of endoderm is the prerequisite for gut formation in the embryogenesis of bilaterian organisms. Modern lineage labelling studies(1-3) have shown that in the sea urchin embryo model system, descendants of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2 lineage also gives rise to mesodermal cell types. It is known that Wnt/beta-catenin signalling is required for endoderm specification(4-6) and Delta/Notch signalling is required for mesoderm specification(7-9). Some directcis-regulatory targets of these signals have been found(10,11) and various phenomenological patterns of gene expression have been observed in the pre-gastrular endomesoderm. However, no comprehensive, causal explanation of endoderm specification has been conceived for sea urchins, nor for any other deuterostome. Here we propose a model, on the basis of the underlying genomic control system, that provides such an explanation, built at several levels of biological organization. The hardwired core of the control system consists of the cis-regulatory apparatus of endodermal regulatory genes, which determine the relationship between the inputs to which these genes are exposed and their outputs. The architecture of the network circuitry controlling the dynamic process of endoderm specification then explains, at the system level, a sequence of developmental logic operations, which generate the biological process. The control system initiates non-interacting endodermal and mesodermal gene regulatory networks in veg2-derived cells and extinguishes the endodermal gene regulatory network in mesodermal precursors. It also generates a cross-regulatory network that specifies future anterior endoderm in veg2 descendants and institutes a distinct network specifying posterior endoderm in veg1-derived cells. The network model provides an explanatory framework that relates endoderm specification to the genomic regulatory code.
C1 [Peter, Isabelle S.; Davidson, Eric H.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Davidson, EH (corresponding author), CALTECH, Div Biol, Pasadena, CA 91125 USA.
EM ipeter@caltech.edu; davidson@caltech.edu
FU Swiss National Science Foundation; National Institutes of Health [HD37105]
NR 30
TC 182
Z9 223
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 JUN 30
PY 2011
VL 474
IS 7353
BP 635
EP U110
DI 10.1038/nature10100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300038
PM 21623371
DA 2026-03-09
ER

PT J
AU Asaadi, N
   Ribe, NM
   Sobouti, F
AF Asaadi, N.
   Ribe, N. M.
   Sobouti, F.
TI Inferring nonlinear mantle rheology from the shape of the Hawaiian swell
SO NATURE
LA English
DT Article
ID glacial-isostatic-adjustment; geoid height; plume; lithosphere; topography; convection; creep; tomography; anisotropy; anomaly
AB The convective circulation generated within the Earth's mantle by buoyancy forces of thermal and compositional origin is intimately controlled by the rheology of the rocks that compose it. These can deform either by the diffusion of point defects (diffusion creep, with a linear relationship between strain rate and stress) or by the movement of intracrystalline dislocations (nonlinear dislocation creep)(1,2). However, there is still no reliable map showing where in the mantle each of these mechanisms is dominant, and so it is important to identify regions where the operative mechanism can be inferred directly from surface geophysical observations. Here we identify a new observable quantity-the rate of downstream decay of the anomalous seafloor topography (swell) produced by a mantle plume-which depends only on the value of the exponent in the strain rate versus stress relationship that defines the difference between diffusion and dislocation creep. Comparison of the Hawaiian swell topography with the predictions of a simple fluid mechanical model shows that the swell shape is poorly explained by diffusion creep, and requires a dislocation creep rheology. The rheology predicted by the model is reasonably consistent with laboratory deformation data for both olivine(3) and clinopyroxene(4), suggesting that the source of Hawaiian lavas could contain either or both of these components.
C1 [Asaadi, N.; Sobouti, F.] IASBS, Zanjan 4513766731, Iran.
   [Ribe, N. M.] Univ Paris 11, CNRS, Lab FAST, F-91405 Orsay, France.
C3 Institute for Advanced Studies in Basic Sciences (IASBS); Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay
RP Asaadi, N (corresponding author), IASBS, Zanjan 4513766731, Iran.
EM n_asaadi@iasbs.ac.ir; ribe@fast.u-psud.fr
FU French embassy in Tehran; INSU; ANR in France
NR 32
TC 21
Z9 23
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 MAY 26
PY 2011
VL 473
IS 7348
BP 501
EP U243
DI 10.1038/nature09993
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300038
PM 21562491
DA 2026-03-09
ER

PT J
AU Bohlen, CJ
   Chesler, AT
   Sharif-Naeini, R
   Medzihradszky, KF
   Zhou, S
   King, D
   Sánchez, EE
   Burlingame, AL
   Basbaum, AI
   Julius, D
AF Bohlen, Christopher J.
   Chesler, Alexander T.
   Sharif-Naeini, Reza
   Medzihradszky, Katalin F.
   Zhou, Sharleen
   King, David
   Sanchez, Elda E.
   Burlingame, Alma L.
   Basbaum, Allan I.
   Julius, David
TI A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain
SO NATURE
LA English
DT Article
ID capsaicin receptor; sensory neurons; venoms; mice; contributes; currents; stimuli; asics; trpv1
AB Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation(1). Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations(2-6). As such, venoms provide a rich and varied source of small molecule and protein pharmacophores(7,8) that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain(9), excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH < 6.5), MitTx massively potenti ates (>100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception.
C1 [Bohlen, Christopher J.; Chesler, Alexander T.; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Sharif-Naeini, Reza; Basbaum, Allan I.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA.
   [Medzihradszky, Katalin F.; Burlingame, Alma L.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Zhou, Sharleen; King, David] Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Berkeley, CA 94720 USA.
   [Sanchez, Elda E.] Texas A&M Univ, Dept Chem, Kingsville, TX 78363 USA.
   [Sanchez, Elda E.] Texas A&M Univ, Natl Nat Toxins Res Ctr, Kingsville, TX 78363 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Texas A&M University System; Texas A&M University Kingsville; Texas A&M University System; Texas A&M University Kingsville
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM david.julius@ucsf.edu
FU Ruth Kirschstein NIH [F31NS065597]; NIH from the UCSF Cardiovascular Research Institute; Canadian Institutes of Health Research; Howard Hughes Medical Institute; NIH [NCRR P41RR001614, NCRR P40RR018300-09, NINDS R01NS065071]
NR 30
TC 284
Z9 327
U1 2
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 NOV 17
PY 2011
VL 479
IS 7373
BP 410
EP U167
DI 10.1038/nature10607
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700048
PM 22094702
DA 2026-03-09
ER

PT J
AU Letzkus, JJ
   Wolff, SBE
   Meyer, EMM
   Tovote, P
   Courtin, J
   Herry, C
   Lüthi, A
AF Letzkus, Johannes J.
   Wolff, Steffen B. E.
   Meyer, Elisabeth M. M.
   Tovote, Philip
   Courtin, Julien
   Herry, Cyril
   Luethi, Andreas
TI A disinhibitory microcircuit for associative fear learning in the auditory cortex
SO NATURE
LA English
DT Article
ID gabaergic cell subtypes; layer-i interneurons; rat neocortex; gaba release; plasticity; neurons; modulation; inhibition; receptors; amygdala
AB Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits.
C1 [Letzkus, Johannes J.; Wolff, Steffen B. E.; Meyer, Elisabeth M. M.; Tovote, Philip; Luethi, Andreas] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Wolff, Steffen B. E.; Meyer, Elisabeth M. M.] Univ Basel, CH-4003 Basel, Switzerland.
   [Courtin, Julien; Herry, Cyril] INSERM, U862, F-33077 Bordeaux, France.
C3 Friedrich Miescher Institute for Biomedical Research; University of Basel; Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Letzkus, JJ (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM johannes.letzkus@fmi.ch; andreas.luthi@fmi.ch
FU Swiss National Science Foundation; National Competence Center in Research (NCCR) of the Swiss Confederation on the synaptic basis of mental disorders; French National Research Agency [ANR-2010-BLAN-1442-01]; Marie-Curie fellowship; Schering Foundation; Fonds AXA pour la Recherche; Aquitaine Regional Council; Novartis Research Foundation
NR 47
TC 657
Z9 786
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 DEC 15
PY 2011
VL 480
IS 7377
BP 331
EP U76
DI 10.1038/nature10674
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000043
PM 22158104
DA 2026-03-09
ER

PT J
AU Stefater, JA
   Lewkowich, I
   Rao, S
   Mariggi, G
   Carpenter, AC
   Burr, AR
   Fan, JQ
   Ajima, R
   Molkentin, JD
   Williams, BO
   Wills-Karp, M
   Pollard, JW
   Yamaguchi, T
   Ferrara, N
   Gerhardt, H
   Lang, RA
AF Stefater, James A., III
   Lewkowich, Ian
   Rao, Sujata
   Mariggi, Giovanni
   Carpenter, April C.
   Burr, Adam R.
   Fan, Jieqing
   Ajima, Rieko
   Molkentin, Jeffery D.
   Williams, Bart O.
   Wills-Karp, Marsha
   Pollard, Jeffrey W.
   Yamaguchi, Terry
   Ferrara, Napoleone
   Gerhardt, Holger
   Lang, Richard A.
TI Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells
SO NATURE
LA English
DT Article
ID endothelial growth-factor; retinal neovascularization; mouse; mechanism; vasculature; macrophages; tumorigenesis; heterogeneity; inhibition; receptor-1
AB Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally(1), somatic deletion in RMCs of the Wnt ligand transporter Wntless(2,3) results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF)(4-6). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.
C1 [Stefater, James A., III; Rao, Sujata; Carpenter, April C.; Fan, Jieqing; Lang, Richard A.] Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA.
   [Stefater, James A., III; Rao, Sujata; Carpenter, April C.; Fan, Jieqing; Lang, Richard A.] Cincinnati Childrens Hosp, Div Dev Biol, Med Ctr, Cincinnati, OH 45229 USA.
   [Stefater, James A., III; Rao, Sujata] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA.
   [Lewkowich, Ian; Wills-Karp, Marsha] Cincinnati Childrens Hosp, Div Immunobiol, Med Ctr, Cincinnati, OH 45229 USA.
   [Mariggi, Giovanni; Gerhardt, Holger] Canc Res UK, Vasc Biol Lab, London Res Inst, London WC2 3PX, England.
   [Burr, Adam R.; Molkentin, Jeffery D.] Univ Cincinnati, Div Mol Cardiovasc Biol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA.
   [Ajima, Rieko; Yamaguchi, Terry] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
   [Molkentin, Jeffery D.] Univ Cincinnati, Med Ctr, Howard Hughes Med Inst, Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA.
   [Williams, Bart O.] Van Andel Res Inst, Ctr Skeletal Dis Res, Grand Rapids, MI 49503 USA.
   [Pollard, Jeffrey W.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA.
   [Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA.
   [Gerhardt, Holger] VIB, Vasc Patterning Lab, Vesalius Res Ctr, B-3000 Louvain, Belgium.
C3 Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cancer Research UK; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University System of Ohio; University of Cincinnati; Howard Hughes Medical Institute; Cincinnati Children's Hospital Medical Center; Van Andel Institute; Van Andel Research Institute; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Roche Holding; Genentech; Roche Holding USA; Flanders Institute for Biotechnology (VIB)
RP Lang, RA (corresponding author), Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA.
EM richard.lang@cchmc.org
FU NIH; HHMI; Cancer Research UK; Medical Research Council [G1002033] Funding Source: researchfish; MRC [G1002033] Funding Source: UKRI
NR 35
TC 233
Z9 265
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 JUN 23
PY 2011
VL 474
IS 7352
BP 511
EP 515
DI 10.1038/nature10085
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700049
PM 21623369
DA 2026-03-09
ER

PT J
AU Pornillos, O
   Ganser-Pornillos, BK
   Yeager, M
AF Pornillos, Owen
   Ganser-Pornillos, Barbie K.
   Yeager, Mark
TI Atomic-level modelling of the HIV capsid
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; c-terminal domain; rous-sarcoma-virus; dimerization domain; in-vitro; structure validation; assembly property; protein; type-1; core
AB The mature capsids of human immunodeficiency virus type 1 (HIV-1) and other retroviruses are fullerene shells, composed of the viral CA protein, that enclose the viral genome and facilitate its delivery into new host cells(1). Retroviral CA proteins contain independently folded amino (N)- and carboxy (C)-terminal domains (NTD and CTD) that are connected by a flexible linker(2-4). The NTD forms either hexameric or pentameric rings, whereas the CTD forms symmetric homodimers that connect the rings into a hexagonal lattice(3,5-13). We previously used a disulphide crosslinking strategy to enable isolation and crystallization of soluble HIV-1 CA hexamers(11,14). Here we use the same approach to solve the X-ray structure of the HIV-1 CA pentamer at 2.5 angstrom resolution. Two mutant CA proteins with engineered disulphides at different positions (P17C/T19C and N21C/A22C) converged onto the same quaternary structure, indicating that the disulphide-crosslinked proteins recapitulate the structure of the native pentamer. Assembly of the quasi-equivalent hexamers and pentamers requires remarkably subtle rearrangements in subunit interactions, and appears to be controlled by an electrostatic switch that favours hexamers over pentamers. This study completes the gallery of substructures describing the components of the HIV-1 capsid and enables atomic-level modelling of the complete capsid. Rigid-body rotations around two assembly interfaces appear sufficient to generate the full range of continuously varying lattice curvature in the fullerene cone.
C1 [Pornillos, Owen; Ganser-Pornillos, Barbie K.; Yeager, Mark] Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
   [Pornillos, Owen; Ganser-Pornillos, Barbie K.; Yeager, Mark] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Yeager, Mark] Univ Virginia Hlth Syst, Dept Med, Div Cardiovasc Med, Charlottesville, VA 22908 USA.
C3 University of Virginia; Scripps Research Institute; University of Virginia; University of Virginia (UVA) Health System
RP Yeager, M (corresponding author), Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
EM yeager@virginia.edu
FU US National Institutes of Health [R01-GM066087, P50-GM082545]
NR 37
TC 317
Z9 409
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 20
PY 2011
VL 469
IS 7330
BP 424
EP +
DI 10.1038/nature09640
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600058
PM 21248851
DA 2026-03-09
ER

PT J
AU Wang, W
   Barnaby, JY
   Tada, Y
   Li, H
   Tör, M
   Caldelari, D
   Lee, DU
   Fu, XD
   Dong, XN
AF Wang, Wei
   Barnaby, Jinyoung Yang
   Tada, Yasuomi
   Li, Hairi
   Toer, Mahmut
   Caldelari, Daniela
   Lee, Dae-un
   Fu, Xiang-Dong
   Dong, Xinnian
TI Timing of plant immune responses by a central circadian regulator
SO NATURE
LA English
DT Article
ID downy mildew resistance; peronospora-parasitica; cell-death; arabidopsis; rhythms; genes; transcription; expression; mutant; bak1
AB The principal immune mechanism against biotrophic pathogens in plants is the resistance (R)-gene-mediated defence(1). It was proposed to share components with the broad-spectrum basal defence machinery(2). However, the underlying molecular mechanism is largely unknown. Here we report the identification of novel genes involved in R-gene-mediated resistance against downy mildew in Arabidopsis and their regulatory control by the circadian regulator, CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). Numerical clustering based on phenotypes of these gene mutants revealed that programmed cell death (PCD) is the major contributor to resistance. Mutants compromised in the R-gene-mediated PCD were also defective in basal resistance, establishing an interconnection between these two distinct defence mechanisms. Surprisingly, we found that these new defence genes are under circadian control by CCA1, allowing plants to 'anticipate' infection at dawn when the pathogen normally disperses the spores and time immune responses according to the perception of different pathogenic signals upon infection. Temporal control of the defence genes by CCA1 differentiates their involvement in basal and R-gene-mediated defence. Our study has revealed a key functional link between the circadian clock and plant immunity.
C1 [Wang, Wei; Barnaby, Jinyoung Yang; Tada, Yasuomi; Caldelari, Daniela; Lee, Dae-un; Dong, Xinnian] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Li, Hairi; Fu, Xiang-Dong] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Toer, Mahmut] Univ Worcester, NPARU, Henwick Grove WR2 6AJ, Worcester, England.
C3 Duke University; University of California System; University of California San Diego; University of Worcester
RP Dong, XN (corresponding author), Duke Univ, Dept Biol, POB 90338, Durham, NC 27708 USA.
EM xdong@duke.edu
FU NSF [MCB-0519898, HG004659]; National Human Genome Research Institute [R01HG004659] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0929226] Funding Source: National Science Foundation
NR 27
TC 371
Z9 453
U1 2
U2 212
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 110
EP U126
DI 10.1038/nature09766
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400044
PM 21293378
DA 2026-03-09
ER

PT J
AU Maekawa, M
   Yamaguchi, K
   Nakamura, T
   Shibukawa, R
   Kodanaka, I
   Ichisaka, T
   Kawamura, Y
   Mochizuki, H
   Goshima, N
   Yamanaka, S
AF Maekawa, Momoko
   Yamaguchi, Kei
   Nakamura, Tomonori
   Shibukawa, Ran
   Kodanaka, Ikumi
   Ichisaka, Tomoko
   Kawamura, Yoshifumi
   Mochizuki, Hiromi
   Goshima, Naoki
   Yamanaka, Shinya
TI Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; generation; protein; mouse; fibroblasts
AB Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4(1). However, the conversion to iPSCs is inefficient. The protooncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs(2). Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
C1 [Maekawa, Momoko; Nakamura, Tomonori; Shibukawa, Ran; Kodanaka, Ikumi; Ichisaka, Tomoko; Yamanaka, Shinya] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto 6068507, Japan.
   [Maekawa, Momoko; Shibukawa, Ran; Kodanaka, Ikumi; Yamanaka, Shinya] JST, Yamanaka iPS Cell Special Project, Kawaguchi, Saitama 3320012, Japan.
   [Yamaguchi, Kei; Kawamura, Yoshifumi; Mochizuki, Hiromi] Japan Biol Informat Consortium, Tokyo 1350064, Japan.
   [Nakamura, Tomonori; Ichisaka, Tomoko; Yamanaka, Shinya] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto 6068507, Japan.
   [Goshima, Naoki] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Tokyo 1350064, Japan.
   [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
C3 Kyoto University; Japan Science & Technology Agency (JST); Kyoto University; National Institute of Advanced Industrial Science & Technology (AIST); University of California System; University of California San Francisco; The J David Gladstone Institutes
RP Yamanaka, S (corresponding author), Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto 6068507, Japan.
EM n-goshima@aist.go.jp; yamanaka@cira.kyoto-u.ac.jp
FU New Energy and Industrial Technology Development Organization (NEDO); Ministry of Education, Culture, Sports, Science and Technology (MEXT); Japanese Society for the Promotion of Science (JSPS); Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO); Grants-in-Aid for Scientific Research [19002014] Funding Source: KAKEN
NR 25
TC 311
Z9 395
U1 1
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 225
EP U268
DI 10.1038/nature10106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800053
PM 21654807
DA 2026-03-09
ER

PT J
AU Wojtak, R
   Hansen, SH
   Hjorth, J
AF Wojtak, Radoslaw
   Hansen, Steen H.
   Hjorth, Jens
TI Gravitational redshift of galaxies in clusters as predicted by general relativity
SO NATURE
LA English
DT Article
ID newtonian dynamics; nuclear resonance; sirius-b; scales
AB The theoretical framework of cosmology is mainly defined by gravity, of which general relativity is the current model. Recent tests of general relativity within the Lambda Cold Dark Matter (Lambda CDM) model have found a concordance between predictions and the observations of the growth rate and clustering of the cosmic web(1,2). General relativity has not hitherto been tested on cosmological scales independently of the assumptions of the Lambda CDM model. Here we report an observation of the gravitational redshift of light coming from galaxies in clusters at the 99 per cent confidence level, based on archival data(3). Our measurement agrees with the predictions of general relativity and its modification created to explain cosmic acceleration without the need for dark energy (the f(R) theory(4)), but is inconsistent with alternative models designed to avoid the presence of dark matter(5,6).
C1 [Wojtak, Radoslaw; Hansen, Steen H.; Hjorth, Jens] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
C3 University of Copenhagen; Niels Bohr Institute
RP Wojtak, R (corresponding author), Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, Juliane Maries Vej 30, DK-2100 Copenhagen O, Denmark.
EM wojtak@dark-cosmology.dk
FU Danish National Research Foundation
NR 21
TC 104
Z9 112
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 567
EP 569
DI 10.1038/nature10445
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900034
PM 21956329
DA 2026-03-09
ER

PT J
AU Winslow, MM
   Dayton, TL
   Verhaak, RGW
   Kim-Kiselak, C
   Snyder, EL
   Feldser, DM
   Hubbard, DD
   DuPage, MJ
   Whittaker, CA
   Hoersch, S
   Yoon, S
   Crowley, D
   Bronson, RT
   Chiang, DY
   Meyerson, M
   Jacks, T
AF Winslow, Monte M.
   Dayton, Talya L.
   Verhaak, Roel G. W.
   Kim-Kiselak, Caroline
   Snyder, Eric L.
   Feldser, David M.
   Hubbard, Diana D.
   DuPage, Michel J.
   Whittaker, Charles A.
   Hoersch, Sebastian
   Yoon, Stephanie
   Crowley, Denise
   Bronson, Roderick T.
   Chiang, Derek Y.
   Meyerson, Matthew
   Jacks, Tyler
TI Suppression of lung adenocarcinoma progression by Nkx2-1
SO NATURE
LA English
DT Article
ID embryonic stem-cells; clinical-significance; protein expression; breast-cancer; self-renewal; hmgi-c; k-ras; metastasis; p53; oncogene
AB Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS(1) and inactivation of the p53 pathway(2), using conditional alleles in mice(3-5). Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras(LSL-G12D/+); p53(flox/flox) mice initiates lung adenocarcinoma development(4). Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain-and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limits metastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga(2). Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function(6-9), our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumour type substantiate its role as a dual function lineage factor.
C1 [Winslow, Monte M.; Dayton, Talya L.; Kim-Kiselak, Caroline; Snyder, Eric L.; Feldser, David M.; DuPage, Michel J.; Whittaker, Charles A.; Hoersch, Sebastian; Yoon, Stephanie; Crowley, Denise; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Winslow, Monte M.; Kim-Kiselak, Caroline; Jacks, Tyler] MIT, Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA.
   [Verhaak, Roel G. W.; Hubbard, Diana D.; Chiang, Derek Y.; Meyerson, Matthew] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02115 USA.
   [Verhaak, Roel G. W.; Hubbard, Diana D.; Chiang, Derek Y.; Meyerson, Matthew] Broad Inst, Cambridge, MA 02142 USA.
   [Bronson, Roderick T.] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA 01536 USA.
   [Chiang, Derek Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Tufts University; University of North Carolina; University of North Carolina Chapel Hill; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Jacks, T (corresponding author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tjacks@mit.edu
FU Genentech; Dutch Cancer Society KWF; Alfred P. Sloan Foundation; National Institutes of Health [U01-CA84306, K99-CA151968]; Howard Hughes Medical Institute; Ludwig Center for Molecular Oncology at MIT; National Cancer Institute [P30-CA14051];  [T32-HL007627]; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 49
TC 370
Z9 452
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 101
EP U120
DI 10.1038/nature09881
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300039
PM 21471965
DA 2026-03-09
ER

PT J
AU Alexandrou, MA
   Oliveira, C
   Maillard, M
   McGill, RAR
   Newton, J
   Creer, S
   Taylor, MI
AF Alexandrou, Markos A.
   Oliveira, Claudio
   Maillard, Marjorie
   McGill, Rona A. R.
   Newton, Jason
   Creer, Simon
   Taylor, Martin I.
TI Competition and phylogeny determine community structure in Mullerian co-mimics
SO NATURE
LA English
DT Article
ID positive interactions; stable-isotopes; dna content; fish; conspicuousness; facilitation; evolution
AB Until recently, the study of negative and antagonistic interactions (for example, competition and predation) has dominated our understanding of community structure, maintenance and assembly(1). Nevertheless, a recent theoretical model suggests that positive interactions (for example, mutualisms) may counterbalance competition, facilitating long-term coexistence even among ecologically undifferentiated species(2). Mullerian mimics are mutualists that share the costs of predator education(3) and are therefore ideally suited for the investigation of positive and negative interactions in community dynamics. The sole empirical test of this model in a Mullerian mimetic community supports the prediction that positive interactions outweigh the negative effects of spatial overlap(4) (without quantifying resource acquisition). Understanding the role of trophic niche partitioning in facilitating the evolution and stability of Mullerian mimetic communities is now of critical importance, but has yet to be formally investigated. Here we show that resource partitioning and phylogeny determine community structure and outweigh the positive effects of Mullerian mimicry in a species-rich group of neotropical catfishes. From multiple, independent reproductively isolated allopatric communities displaying convergently evolved colour patterns, 92% consist of species that do not compete for resources. Significant differences in phylogenetically conserved traits (snout morphology and body size) were consistently linked to trait-specific resource acquisition. Thus, we report the first evidence, to our knowledge, that competition for trophic resources and phylogeny are pivotal factors in the stable evolution of Mullerian mimicry rings. More generally, our work demonstrates that competition for resources is likely to have a dominant role in the structuring of communities that are simultaneously subject to the effects of both positive and negative interactions.
C1 [Alexandrou, Markos A.; Maillard, Marjorie; Creer, Simon; Taylor, Martin I.] Bangor Univ, Coll Nat Sci, Sch Biol Sci, Mol Ecol & Fisheries Genet Lab,Environm Ctr Wales, Bangor LL57 2UW, Gwynedd, Wales.
   [Oliveira, Claudio] Univ Estadual Paulista, Inst Biociencias, Dept Morfol, BR-18618970 Botucatu, SP, Brazil.
   [McGill, Rona A. R.; Newton, Jason] Scottish Univ Environm Res Ctr, NERC Life Sci Mass Spectrometry Facil, E Kilbride G75 0QF, Lanark, Scotland.
C3 Bangor University; Universidade Estadual Paulista; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); Scottish Universities Research & Reactor Center
RP Taylor, MI (corresponding author), Bangor Univ, Coll Nat Sci, Sch Biol Sci, Mol Ecol & Fisheries Genet Lab,Environm Ctr Wales, Bangor LL57 2UW, Gwynedd, Wales.
EM m.taylor@bangor.ac.uk
FU NERC [NE/C001168/1, NE/F007205/1]; UNESP, Brazil; NERC [NE/C001168/2, lsmsf010002] Funding Source: UKRI; Natural Environment Research Council [lsmsf010002, NE/C001168/2] Funding Source: researchfish
NR 42
TC 120
Z9 135
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 JAN 6
PY 2011
VL 469
IS 7328
BP 84
EP U97
DI 10.1038/nature09660
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600036
PM 21209663
DA 2026-03-09
ER

PT J
AU Liu, GH
   Barkho, BZ
   Ruiz, S
   Diep, D
   Qu, J
   Yang, SL
   Panopoulos, AD
   Suzuki, K
   Kurian, L
   Walsh, C
   Thompson, J
   Boue, S
   Fung, HL
   Sancho-Martinez, I
   Zhang, K
   Yates, J
   Belmonte, JCI
AF Liu, Guang-Hui
   Barkho, Basam Z.
   Ruiz, Sergio
   Diep, Dinh
   Qu, Jing
   Yang, Sheng-Lian
   Panopoulos, Athanasia D.
   Suzuki, Keiichiro
   Kurian, Leo
   Walsh, Christopher
   Thompson, James
   Boue, Stephanie
   Fung, Ho Lim
   Sancho-Martinez, Ignacio
   Zhang, Kun
   Yates, John, III
   Izpisua Belmonte, Juan Carlos
TI Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome
SO NATURE
LA English
DT Article
ID muscle-cell senescence; human somatic-cells; tumor-suppressor; yeast proteome; lamin; prelamin; defects; atherosclerosis; differentiation; phenotype
AB Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease(1-5), characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs)(6-8). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin(9-12). Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing(6,12,13), our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.
C1 [Liu, Guang-Hui; Barkho, Basam Z.; Ruiz, Sergio; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D.; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Sancho-Martinez, Ignacio; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Diep, Dinh; Fung, Ho Lim; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Thompson, James; Yates, John, III] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Boue, Stephanie; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
C3 Salk Institute; University of California System; University of California San Diego; Scripps Research Institute; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; University of Barcelona
RP Belmonte, JCI (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM belmonte@salk.edu
FU CIRM [TG2-01158]; AFAR/Ellison Medical Foundation; NIH [T32 CA009370, R01-DA025779, P41 RR011823]; G. Harold and Leila Y. Mathers Charitable Foundation; Sanofi-Aventis; Ellison Medical Foundation; MICINN; Fundacion Cellex (JCIB); National Cancer Institute [T32CA009370] Funding Source: NIH RePORTER
NR 41
TC 465
Z9 543
U1 2
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 221
EP 225
DI 10.1038/nature09879
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100043
PM 21346760
DA 2026-03-09
ER

PT J
AU Copeland, SR
   Sponheimer, M
   de Ruiter, DJ
   Lee-Thorp, JA
   Codron, D
   le Roux, PJ
   Grimes, V
   Richards, MP
AF Copeland, Sandi R.
   Sponheimer, Matt
   de Ruiter, Darryl J.
   Lee-Thorp, Julia A.
   Codron, Daryl
   le Roux, Petrus J.
   Grimes, Vaughan
   Richards, Michael P.
TI Strontium isotope evidence for landscape use by early hominins
SO NATURE
LA English
DT Article
ID human-evolution; life-history; ratios; body; australopithecus; sr-87/sr-86; patterns; africa; origin; homo
AB Ranging and residence patterns among early hominins have been indirectly inferred from morphology(1,2), stone-tool sourcing(3), referential models(4,5) and phylogenetic models(6-8). However, the highly uncertain nature of such reconstructions limits our understanding of early hominin ecology, biology, social structure and evolution. We investigated landscape use in Australopithecus africanus and Paranthropus robustus from the Sterkfontein and Swartkrans cave sites in South Africa using strontium isotope analysis, a method that can help to identify the geological substrate on which an animal lived during tooth mineralization. Here we show that a higher proportion of small hominins than large hominins had non-local strontium isotope compositions. Given the relatively high levels of sexual dimorphism in early hominins, the smaller teeth are likely to represent female individuals, thus indicating that females were more likely than males to disperse from their natal groups. This is similar to the dispersal pattern found in chimpanzees(9), bonobos(10) and many human groups(11), but dissimilar from that of most gorillas and other primates(12). The small proportion of demonstrably non-local large hominin individuals could indicate that male australopiths had relatively small home ranges, or that they preferred dolomitic landscapes.
C1 [Copeland, Sandi R.; Grimes, Vaughan; Richards, Michael P.] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Copeland, Sandi R.; Sponheimer, Matt] Univ Colorado, Dept Anthropol, Boulder, CO 80309 USA.
   [de Ruiter, Darryl J.] Texas A&M Univ, Dept Anthropol, College Stn, TX 77843 USA.
   [Lee-Thorp, Julia A.] Univ Oxford, Res Lab Archaeol & Hist Art, Oxford OX1 3QY, England.
   [Lee-Thorp, Julia A.; le Roux, Petrus J.] Univ Cape Town, Dept Geol Sci, AEON EarthLAB, ZA-7701 Rondebosch, South Africa.
   [Codron, Daryl] Univ Zurich, Vetsuisse Fac, Clin Zoo Anim Exot Pets & Wildlife, CH-8057 Zurich, Switzerland.
   [Grimes, Vaughan] Mem Univ, Dept Archaeol, St John, NF A1C 5S7, Canada.
   [Richards, Michael P.] Univ British Columbia, Dept Anthropol, Vancouver, BC V6T 1Z1, Canada.
C3 Max Planck Society; University of Colorado System; University of Colorado Boulder; Texas A&M University System; Texas A&M University College Station; University of Oxford; University of Cape Town; University of Zurich; Memorial University Newfoundland; University of British Columbia
RP Copeland, SR (corresponding author), Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, Deutsch Pl 6, D-04103 Leipzig, Germany.
EM sandi.copeland@colorado.edu
FU National Science Foundation, USA [0609963]; Max Planck Society; University of Colorado; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [0609963] Funding Source: National Science Foundation
NR 29
TC 170
Z9 199
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 JUN 2
PY 2011
VL 474
IS 7349
BP 76
EP U100
DI 10.1038/nature10149
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700040
PM 21637256
DA 2026-03-09
ER

PT J
AU Klinakis, A
   Lobry, C
   Abdel-Wahab, O
   Oh, P
   Haeno, H
   Buonamici, S
   van De Walle, I
   Cathelin, S
   Trimarchi, T
   Araldi, E
   Liu, C
   Ibrahim, S
   Beran, M
   Zavadil, J
   Efstratiadis, A
   Taghon, T
   Michor, F
   Levine, RL
   Aifantis, I
AF Klinakis, Apostolos
   Lobry, Camille
   Abdel-Wahab, Omar
   Oh, Philmo
   Haeno, Hiroshi
   Buonamici, Silvia
   van De Walle, Inge
   Cathelin, Severine
   Trimarchi, Thomas
   Araldi, Elisa
   Liu, Cynthia
   Ibrahim, Sherif
   Beran, Miroslav
   Zavadil, Jiri
   Efstratiadis, Argiris
   Taghon, Tom
   Michor, Franziska
   Levine, Ross L.
   Aifantis, Iannis
TI A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia
SO NATURE
LA English
DT Article
ID t-cell development; mice; differentiation; specification; activation; expression; progenitor; complex
AB Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types(1). Its activity is controlled by the multisubunit gamma-secretase (gamma SE) complex(2). Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations(3). Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue.
C1 [Lobry, Camille; Oh, Philmo; Buonamici, Silvia; Cathelin, Severine; Trimarchi, Thomas; Araldi, Elisa; Liu, Cynthia; Ibrahim, Sherif; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Lobry, Camille; Oh, Philmo; Buonamici, Silvia; Cathelin, Severine; Trimarchi, Thomas; Araldi, Elisa; Liu, Cynthia; Ibrahim, Sherif; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Klinakis, Apostolos; Efstratiadis, Argiris] Acad Athens, Biomed Res Fdn, Athens, Greece.
   [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10016 USA.
   [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10016 USA.
   [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [van De Walle, Inge; Taghon, Tom] Univ Ghent, State Univ Ghent Hosp, Dept Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium.
   [Beran, Miroslav] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
   [Zavadil, Jiri] NYU Canc Inst, Dept Pathol, New York, NY 10016 USA.
   [Zavadil, Jiri] NYU Langone Med Ctr, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA.
   [Buonamici, Silvia] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; New York University; New York University; Academy of Athens; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Ghent University; Ghent University Hospital; University of Texas System; UTMD Anderson Cancer Center; New York University; NYU Langone Medical Center; Novartis; Novartis USA
RP Aifantis, I (corresponding author), NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
EM aklinakis@bioacademy.gr; iannis.aifantis@nyumc.org
FU National Institutes of Health [RO1CA133379, RO1CA105129, R21CA141399, RO1CA149655, R01CA1328234, U54CA143798]; Leukemia & Lymphoma Society; American Cancer Society; Irma T. Hirschl Trust; Dana Foundation; Mallinckrodt Foundation; Alex's Lemonade Stand Foundation; Fund for Scientific Research Flanders (Fonds Wetenschappelijk Onderzoek); National Cancer Institute [1P01CA97403]; EU; Institute for the Promotion of Innovation by Science and Technology in Flanders (Agentschap voor Innovatie door Wetenschap en Technologie); Hope Street Kids Foundations; New York University; Fonds Wetenschappelijk Onderzoek; Memorial Sloan Kettering Cancer Center; American Society of Hematology; Howard Hughes Medical Institute
NR 32
TC 310
Z9 363
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 12
PY 2011
VL 473
IS 7346
BP 230
EP +
DI 10.1038/nature09999
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200042
PM 21562564
DA 2026-03-09
ER

PT J
AU Lioy, DT
   Garg, SK
   Monaghan, CE
   Raber, J
   Foust, KD
   Kaspar, BK
   Hirrlinger, PG
   Kirchhoff, F
   Bissonnette, JM
   Ballas, N
   Mandel, G
AF Lioy, Daniel T.
   Garg, Saurabh K.
   Monaghan, Caitlin E.
   Raber, Jacob
   Foust, Kevin D.
   Kaspar, Brian K.
   Hirrlinger, Petra G.
   Kirchhoff, Frank
   Bissonnette, John M.
   Ballas, Nurit
   Mandel, Gail
TI A role for glia in the progression of Rett's syndrome
SO NATURE
LA English
DT Article
ID mecp2 deficiency; mouse model; neurons; expression; astrocytes; abnormality; defects; release
AB Rett's syndrome (RTT) is an X-chromosome-linked autism spectrum disorder caused by loss of function of the transcription factor methyl-CpG-binding protein 2 (MeCP2)(1). Although MeCP2 is expressed in most tissues(2), loss of MeCP2 expression results primarily in neurological symptoms(1,3,4). Earlier studies suggested the idea that RTT is due exclusively to loss of MeCP2 function in neurons(2,4-10). Although defective neurons clearly underlie the aberrant behaviours, we and others showed recently that the loss of MECP2 from glia negatively influences neurons in a non-cell-autonomous fashion(11-13). Here we show that in globally MeCP2-deficient mice, re-expression of Mecp2 preferentially in astrocytes significantly improved locomotion and anxiety levels, restored respiratory abnormalities to a normal pattern, and greatly prolonged lifespan compared to globally null mice. Furthermore, restoration of MeCP2 in the mutant astrocytes exerted a non-cell-autonomous positive effect on mutant neurons in vivo, restoring normal dendritic morphology and increasing levels of the excitatory glutamate transporter VGLUT1. Our study shows that glia, like neurons, are integral components of the neuropathology of RTT, and supports the targeting of glia as a strategy for improving the associated symptoms.
C1 [Lioy, Daniel T.; Garg, Saurabh K.; Monaghan, Caitlin E.; Mandel, Gail] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Lioy, Daniel T.; Garg, Saurabh K.; Monaghan, Caitlin E.; Mandel, Gail] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
   [Raber, Jacob] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
   [Raber, Jacob] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Foust, Kevin D.; Kaspar, Brian K.] Ohio State Univ, Dept Pediat, Ctr Gene Therapy, Nationwide Childrens Hosp, Columbus, OH 43205 USA.
   [Hirrlinger, Petra G.] Paul Flechsig Inst Brain Res, D-04109 Leipzig, Germany.
   [Kirchhoff, Frank] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany.
   [Kirchhoff, Frank] Univ Saarland, Inst Pathol, D-37075 Homburg, Germany.
   [Bissonnette, John M.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97202 USA.
   [Bissonnette, John M.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97202 USA.
   [Ballas, Nurit] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
C3 Oregon Health & Science University; Howard Hughes Medical Institute; Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University; Oregon National Primate Research Center; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; Center for Gene Therapy; Max Planck Society; Saarland University; Oregon Health & Science University; Oregon Health & Science University; State University of New York (SUNY) System; Stony Brook University
RP Mandel, G (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
EM mandelg@ohsu.edu
FU National Institutes of Health; International Rett Syndrome Foundation; Rett Syndrome Research Trust; Oregon Brain Institute; OHSU
NR 29
TC 378
Z9 480
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 JUL 28
PY 2011
VL 475
IS 7357
BP 497
EP U90
DI 10.1038/nature10214
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900040
PM 21716289
DA 2026-03-09
ER

PT J
AU Chang, HC
   Paek, J
   Kim, DH
AF Chang, Howard C.
   Paek, Jennifer
   Kim, Dennis H.
TI Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; social-behavior; bacteria; pathway; kinase; homolog; system
AB Heritable variation in behavioural traits generally has a complex genetic basis(1), and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances(2,3). The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species(4) and provided insights into its diverse microbial ecology(5). C. elegans responds to bacterial infection with conserved innate immune responses(6-8) and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria(9). Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour(11). Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.
C1 [Chang, Howard C.; Paek, Jennifer; Kim, Dennis H.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Kim, DH (corresponding author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM dhkim@mit.edu
FU NIH-National Center for Research Resources; NIH [GM084477]
NR 30
TC 76
Z9 97
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 525
EP U148
DI 10.1038/nature10643
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000061
PM 22089131
DA 2026-03-09
ER

PT J
AU Imasaki, T
   Calero, G
   Cai, G
   Tsai, KL
   Yamada, K
   Cardelli, F
   Erdjument-Bromage, H
   Tempst, P
   Berger, I
   Kornberg, GL
   Asturias, FJ
   Kornberg, RD
   Takagi, Y
AF Imasaki, Tsuyoshi
   Calero, Guillermo
   Cai, Gang
   Tsai, Kuang-Lei
   Yamada, Kentaro
   Cardelli, Francesco
   Erdjument-Bromage, Hediye
   Tempst, Paul
   Berger, Imre
   Kornberg, Guy Lorch
   Asturias, Francisco J.
   Kornberg, Roger D.
   Takagi, Yuichiro
TI Architecture of the Mediator head module
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; repeat domain; complex; yeast; protein; initiation; subunit; binding; ctd
AB Mediator is a key regulator of eukaryotic transcription(1), connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II1-4 (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail(7-9). Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 angstroms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.
C1 [Imasaki, Tsuyoshi; Yamada, Kentaro; Cardelli, Francesco; Takagi, Yuichiro] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
   [Calero, Guillermo; Kornberg, Guy Lorch; Kornberg, Roger D.] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94350 USA.
   [Cai, Gang; Tsai, Kuang-Lei; Asturias, Francisco J.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Erdjument-Bromage, Hediye; Tempst, Paul] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA.
   [Berger, Imre] European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France.
C3 Indiana University System; Indiana University Bloomington; Stanford University; Scripps Research Institute; Memorial Sloan Kettering Cancer Center; European Molecular Biology Laboratory (EMBL)
RP Takagi, Y (corresponding author), Indiana Univ Sch Med, Dept Biochem & Mol Biol, 635 Barnhill Dr, Indianapolis, IN 46202 USA.
EM ytakagi@iupui.edu
FU NCI [Y1-CO-1020]; NIGMS [Y1-GM-1104]; US National Science Foundation [MCB 0843026]; American Heart Association [0735395N]; Human Frontier Science Program; NIH [Y1-CO-1020, Y1-GM-1104, R01 GM67167, GM36659]; NCI Cancer Center [P30 CA08748]; European Commission; DOE [DE-AC02-06CH11357, DE-AC02-05CH11231]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM067167] Funding Source: NIH RePORTER; American Heart Association (AHA) [0735395N] Funding Source: American Heart Association (AHA)
NR 42
TC 95
Z9 125
U1 0
U2 24
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 240
EP U45
DI 10.1038/nature10162
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500053
PM 21725323
DA 2026-03-09
ER

PT J
AU Ficz, G
   Branco, MR
   Seisenberger, S
   Santos, F
   Krueger, F
   Hore, TA
   Marques, CJ
   Andrews, S
   Reik, W
AF Ficz, Gabriella
   Branco, Miguel R.
   Seisenberger, Stefanie
   Santos, Fatima
   Krueger, Felix
   Hore, Timothy A.
   Marques, C. Joana
   Andrews, Simon
   Reik, Wolf
TI Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
SO NATURE
LA English
DT Article
ID dna methylation; self-renewal; stem-cells; genome; wide; pluripotent; conversion; proteins
AB Methylation at the 59 position of cytosine in DNA has important roles in genome function and is dynamically reprogrammed during early embryonic and germ cell development(1). The mammalian genome also contains 5-hydroxymethylcytosine (5hmC), which seems to be generated by oxidation of 5-methylcytosine (5mC) by the TET family of enzymes that are highly expressed in embryonic stem(ES) cells(2-4). Here we use antibodies against 5hmC and 5mC together with high throughput sequencing to determine genome-wide patterns of methylation and hydroxymethylation in mouse wild-type and mutant ES cells and differentiating embryoid bodies. We find that 5hmC is mostly associated with euchromatin and that whereas 5mC is under-represented at gene promoters and CpG islands, 5hmC is enriched and is associated with increased transcriptional levels. Most, if not all, 5hmC in the genome depends on pre-existing 5mC and the balance between these two modifications is different between genomic regions. Knockdown of Tet1 and Tet2 causes downregulation of a group of genes that includes pluripotency-related genes (including Esrrb, Prdm14, Dppa3, Klf2, Tcl1 and Zfp42) and a concomitant increase in methylation of their promoters, together with an increased propensity of ES cells for extraembryonic lineage differentiation. Declining levels of TETs during differentiation are associated with decreased hydroxymethylation levels at the promoters of ES cell-specific genes together with increased methylation and gene silencing. We propose that the balance between hydroxymethylation and methylation in the genome is inextricably linked with the balance between pluripotency and lineage commitment.
C1 [Ficz, Gabriella; Branco, Miguel R.; Seisenberger, Stefanie; Santos, Fatima; Hore, Timothy A.; Marques, C. Joana; Reik, Wolf] Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB22 3AT, England.
   [Krueger, Felix; Andrews, Simon] Babraham Inst, Bioinformat Grp, Cambridge CB22 3AT, England.
   [Reik, Wolf] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; University of Cambridge
RP Reik, W (corresponding author), Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB22 3AT, England.
EM wolf.reik@bbsrc.ac.uk
FU BBSRC; MRC; EU NoE The Epigenome; BBSRC [BBS/E/B/0000M236] Funding Source: UKRI; MRC [G0801727, G0801156] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/B/0000M236] Funding Source: researchfish; Medical Research Council [G0801156, G0801727] Funding Source: researchfish
NR 37
TC 920
Z9 1115
U1 0
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 19
PY 2011
VL 473
IS 7347
BP 398
EP U589
DI 10.1038/nature10008
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400054
PM 21460836
DA 2026-03-09
ER

PT J
AU Zhao, YF
   Terry, DS
   Shi, L
   Quick, M
   Weinstein, H
   Blanchard, SC
   Javitch, JA
AF Zhao, Yongfang
   Terry, Daniel S.
   Shi, Lei
   Quick, Matthias
   Weinstein, Harel
   Blanchard, Scott C.
   Javitch, Jonathan A.
TI Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue
SO NATURE
LA English
DT Article
ID bacterial homolog; dopamine transporter; molecular-mechanism; sodium symporter; binding-site; leut; ion; conformation; state; identification
AB Neurotransmitter/Na+ symporters (NSSs) terminate neuronal signalling by recapturing neurotransmitter released into the synapse in a co-transport (symport) mechanism driven by the Na+ electrochemical gradient(1-6). NSSs for dopamine, noradrenaline and serotonin are targeted by the psychostimulants cocaine and amphetamine(1), as well as by antidepressants(7). The crystal structure of LeuT, a prokaryotic NSS homologue, revealed an occluded conformation in which a leucine (Leu) and two Na+ are bound deep within the protein(8). This structure has been the basis for extensive structural and computational exploration of the functional mechanisms of proteins with a LeuT-like fold(9-22). Subsequently, an 'outward-open' conformation was determined in the presence of the inhibitor tryptophan(23), and the Na+-dependent formation of a dynamic outward-facing intermediate was identified using electron paramagnetic resonance spectroscopy(24). In addition, single-molecule fluorescence resonance energy transfer imaging has been used to reveal reversible transitions to an inward-open LeuT conformation, which involve the movement of transmembrane helix TM1a away from the transmembrane helical bundle(22). We investigated how substrate binding is coupled to structural transitions in LeuT during Na+-coupled transport. Here we report a process whereby substrate binding from the extracellular side of LeuT facilitates intracellular gate opening and substrate release at the intracellular face of the protein. In the presence of alanine, a substrate that is transported 10-fold faster than leucine(15,25), we observed alanine-induced dynamics in the intracellular gate region of LeuT that directly correlate with transport efficiency. Collectively, our data reveal functionally relevant and previously hidden aspects of the NSS transport mechanism that emphasize the functional importance of a second substrate (S2) binding site within the extracellular vestibule(15,20). Substrate binding in this S2 site appears to act cooperatively with the primary substrate (S1) binding site to control intracellular gating more than 30 angstrom away, in a manner that allows the Na+ gradient to power the transport mechanism.
C1 [Zhao, Yongfang; Quick, Matthias; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA.
   [Zhao, Yongfang; Quick, Matthias; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
   [Zhao, Yongfang; Quick, Matthias; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
   [Terry, Daniel S.; Shi, Lei; Weinstein, Harel; Blanchard, Scott C.] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
   [Shi, Lei; Weinstein, Harel] Cornell Univ, Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA.
C3 Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine
RP Javitch, JA (corresponding author), Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, 630 W 168th St, New York, NY 10032 USA.
EM scb2005@med.cornell.edu; jaj2@columbia.edu
FU National Institutes of Health [DA17293, DA022413, DA12408, DA023694]; Irma T. Hirschl/Monique Weill-Caulier trusts; Lieber Center for Schizophrenia Research and Treatment; Tri-Institutional Training Program in Computational Biology and Medicine
NR 33
TC 199
Z9 240
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 109
EP U11
DI 10.1038/nature09971
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700048
PM 21516104
DA 2026-03-09
ER

PT J
AU Regot, S
   Macia, J
   Conde, N
   Furukawa, K
   Kjellén, J
   Peeters, T
   Hohmann, S
   de Nadal, E
   Posas, F
   Solé, R
AF Regot, Sergi
   Macia, Javier
   Conde, Nuria
   Furukawa, Kentaro
   Kjellen, Jimmy
   Peeters, Tom
   Hohmann, Stefan
   de Nadal, Eulalia
   Posas, Francesc
   Sole, Ricard
TI Distributed biological computation with multicellular engineered networks
SO NATURE
LA English
DT Article
ID synthetic biology; communication; parts
AB Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices(1) using engineered biological units as basic building blocks(2,3). Such efforts, inspired in the standard design of electronic circuits(4-7), are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.
C1 [Macia, Javier; Conde, Nuria; Sole, Ricard] UPF, ICREA Complex Syst Lab, E-08003 Barcelona, Spain.
   [Regot, Sergi; Conde, Nuria; Peeters, Tom; de Nadal, Eulalia; Posas, Francesc] UPF, Dept Ciencies Expt & Salut, Cell Signaling Unit, E-08003 Barcelona, Spain.
   [Furukawa, Kentaro; Kjellen, Jimmy; Hohmann, Stefan] Univ Gothenburg, Dept Cell & Mol Biol Microbiol, S-40530 Gothenburg, Sweden.
   [Sole, Ricard] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Sole, Ricard] UPF, CSIC, Inst Biol Evolut, E-08003 Barcelona, Spain.
C3 Pompeu Fabra University; ICREA; Pompeu Fabra University; University of Gothenburg; The Santa Fe Institute; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE)
RP Solé, R (corresponding author), UPF, ICREA Complex Syst Lab, E-08003 Barcelona, Spain.
EM francesc.posas@upf.edu; ricard.sole@upf.edu
FU FPU (Spanish Government); James McDonnell Foundation; MICINN [BIO2009-07762, FIS2009-12365]; Consolider Ingenio 2010 programme [CSD2007-0015]; ESF [ERAS-CT-2003-980409]; CELLCOMPUT (FP6) project; FP7 UNICELLSYS [201142]; Santa Fe Institute; Fundacion Marcelino Botin (FMB); ICREA Academia (Generalitat de Catalunya); ICREA Funding Source: Custom
NR 27
TC 260
Z9 313
U1 2
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 207
EP 211
DI 10.1038/nature09679
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400037
PM 21150900
DA 2026-03-09
ER

PT J
AU Hayden, EJ
   Ferrada, E
   Wagner, A
AF Hayden, Eric J.
   Ferrada, Evandro
   Wagner, Andreas
TI Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme
SO NATURE
LA English
DT Article
ID group-i ribozyme; protein; evolvability; stability; epistasis; mechanism; azoarcus; intron; vitro; core
AB Cryptic variation is caused by the robustness of phenotypes to mutations(1). Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change(2-5). Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation(6-8). This is possible if the cryptic variation happens to be pre-adapted, or "exapted"(9), to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution(10,11).
C1 [Hayden, Eric J.; Ferrada, Evandro; Wagner, Andreas] Univ Zurich, Inst Evolutionary Biol & Environm Studies, CH-8057 Zurich, Switzerland.
   [Hayden, Eric J.; Ferrada, Evandro; 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 Studies, CH-8057 Zurich, Switzerland.
EM andreas.wagner@ieu.uzh.ch
FU Swiss National Science Foundation [315200-116814, 315200-119697, 315230-129708]; SystemsX.ch; University of Zurich
NR 37
TC 174
Z9 204
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 92
EP U120
DI 10.1038/nature10083
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700044
PM 21637259
DA 2026-03-09
ER

PT J
AU Deng, HX
   Chen, WJ
   Hong, ST
   Boycott, KM
   Gorrie, GH
   Siddique, N
   Yang, Y
   Fecto, F
   Shi, Y
   Zhai, H
   Jiang, HJ
   Hirano, M
   Rampersaud, E
   Jansen, GH
   Donkervoort, S
   Bigio, EH
   Brooks, BR
   Ajroud, K
   Sufit, RL
   Haines, JL
   Mugnaini, E
   Pericak-Vance, MA
   Siddique, T
AF Deng, Han-Xiang
   Chen, Wenjie
   Hong, Seong-Tshool
   Boycott, Kym M.
   Gorrie, George H.
   Siddique, Nailah
   Yang, Yi
   Fecto, Faisal
   Shi, Yong
   Zhai, Hong
   Jiang, Hujun
   Hirano, Makito
   Rampersaud, Evadnie
   Jansen, Gerard H.
   Donkervoort, Sandra
   Bigio, Eileen H.
   Brooks, Benjamin R.
   Ajroud, Kaouther
   Sufit, Robert L.
   Haines, Jonathan L.
   Mugnaini, Enrico
   Pericak-Vance, Margaret A.
   Siddique, Teepu
TI Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
SO NATURE
LA English
DT Article
ID amyotrophic-lateral-sclerosis; frontotemporal lobar degeneration; protein aggregation; superoxide-dismutase; gene-mutations; tdp-43; criteria; domains; fus; proteasome
AB Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder caused by motor-neuron degeneration in the brain and spinal cord. Most cases of ALS are sporadic but about 5-10% are familial. Mutations in superoxide dismutase 1 (SOD1)(1,2), TAR DNA-binding protein (TARDBP, also known as TDP43)(3,4) and fused in sarcoma (FUS, also known as translocated in liposarcoma (TLS))(5,6) account for approximately 30% of classic familial ALS. Mutations in several other genes have also been reported as rare causes of ALS or ALS-like syndromes(7-15). The causes of the remaining cases of familial ALS and of the vast majority of sporadic ALS are unknown. Despite extensive studies of previously identified ALS-causing genes, the pathogenic mechanism underlying motor-neuron degeneration in ALS remains largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in some ALS cases. It is unclear whether ALS and dementia share common aetiology and pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which regulates the degradation of ubiquitinated proteins. Functional analysis showed that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.
C1 [Deng, Han-Xiang; Chen, Wenjie; Hong, Seong-Tshool; Gorrie, George H.; Siddique, Nailah; Yang, Yi; Fecto, Faisal; Shi, Yong; Zhai, Hong; Jiang, Hujun; Hirano, Makito; Donkervoort, Sandra; Ajroud, Kaouther; Sufit, Robert L.; Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA.
   [Boycott, Kym M.] Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON K1H 8L1, Canada.
   [Boycott, Kym M.] Univ Ottawa, Dept Pediat, Ottawa, ON K1H 8L1, Canada.
   [Fecto, Faisal; Mugnaini, Enrico; Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Interdept Neurosci Program, Chicago, IL 60611 USA.
   [Rampersaud, Evadnie; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [Jansen, Gerard H.] Ottawa Hosp, Div Anat Pathol, Ottawa, ON K1Y 4E9, Canada.
   [Bigio, Eileen H.] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Div Neuropathol, Chicago, IL 60611 USA.
   [Brooks, Benjamin R.] Carolinas Med Ctr, Dept Neurol, Neurosci & Spine Inst, Charlotte, NC 28207 USA.
   [Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Mugnaini, Enrico; Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine; University of Ottawa; Children's Hospital of Eastern Ontario; University of Ottawa; Northwestern University; Feinberg School of Medicine; University of Miami; University of Ottawa; Ottawa Hospital Research Institute; Northwestern University; Feinberg School of Medicine; Carolinas Medical Center; Vanderbilt University; Northwestern University; Feinberg School of Medicine
RP Siddique, T (corresponding author), Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA.
EM t-siddique@northwestern.edu
FU National Institute of Neurological Disorders and Stroke [NS050641]; Les Turner ALS Foundation; Vena E. Schaff ALS Research Fund; Herbert and Florence C. Wenske Foundation; David C. Asselin MD Memorial Fund; Help America Foundation; Les Turner ALS Foundation/Herbert C. Wenske Foundation; NIH [T32AG20506]; MND Scotland; NCI [CCSG P30 CA060553]; National Cancer Institute [P30CA060553] Funding Source: NIH RePORTER; National Institute on Aging [T32AG020506] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [21591097] Funding Source: KAKEN
NR 36
TC 947
Z9 1134
U1 2
U2 125
PU 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 8
PY 2011
VL 477
IS 7363
BP 211
EP U113
DI 10.1038/nature10353
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900036
PM 21857683
DA 2026-03-09
ER

PT J
AU Borgia, MB
   Borgia, A
   Best, RB
   Steward, A
   Nettels, D
   Wunderlich, B
   Schuler, B
   Clarke, J
AF Borgia, Madeleine B.
   Borgia, Alessandro
   Best, Robert B.
   Steward, Annette
   Nettels, Daniel
   Wunderlich, Bengt
   Schuler, Benjamin
   Clarke, Jane
TI Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins
SO NATURE
LA English
DT Article
ID folding mechanism; domain; aggregation; energy; titin; intermediate; spectroscopy; collapse
AB A large range of debilitating medical conditions(1) is linked to protein misfolding, which may compete with productive folding particularly in proteins containing multiple domains(2). Seventy-five per cent of the eukaryotic proteome consists of multidomain proteins, yet it is not understood how interdomain misfolding is avoided. It has been proposed that maintaining low sequence identity between covalently linked domains is a mechanism to avoid misfolding(3). Here we use single-molecule Forster resonance energy transfer(4,5) to detect and quantify rare misfolding events in tandem immunoglobulin domains from the I band of titin under native conditions. About 5.5 per cent of molecules with identical domains misfold during refolding in vitro and form an unexpectedly stable state with an unfolding half-time of several days. Tandem arrays of immunoglobulin-like domains in humans show significantly lower sequence identity between neighbouring domains than between non-adjacent domains(3). In particular, the sequence identity of neighbouring domains has been found to be preferentially below 40 per cent(3). We observe no misfolding for a tandem of naturally neighbouring domains with low sequence identity (24 per cent), whereas misfolding occurs between domains that are 42 per cent identical. Coarse-grained molecular simulations predict the formation of domain-swapped structures that are in excellent agreement with the observed transfer efficiency of the misfolded species. We infer that the interactions underlying misfolding are very specific and result in a sequence-specific domain-swapping mechanism. Diversifying the sequence between neighbouring domains seems to be a successful evolutionary strategy to avoid misfolding in multidomain proteins.
C1 [Borgia, Madeleine B.; Best, Robert B.; Steward, Annette; Clarke, Jane] Univ Cambridge, Chem Lab, Cambridge CB2 1EW, England.
   [Borgia, Madeleine B.; Borgia, Alessandro; Nettels, Daniel; Wunderlich, Bengt; Schuler, Benjamin] Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland.
C3 University of Cambridge; University of Zurich
RP Clarke, J (corresponding author), Univ Cambridge, Chem Lab, Lensfield Rd, Cambridge CB2 1EW, England.
EM schuler@bioc.uzh.ch; jc162@cam.ac.uk
FU Wellcome Trust [064417]; Swiss National Science Foundation; Swiss National Center of Competence in Research in Structural Biology; UK Medical Research Council; Marie Curie Intra-European Fellowship; Royal Society; MRC [MC_U105485808] Funding Source: UKRI; Medical Research Council [MC_U105485808] Funding Source: researchfish
CR Arora P, 2006, BIOCHEMISTRY-US, V45, P12312, DOI 10.1021/bi060923s
   Balamurali MM, 2008, PROTEIN SCI, V17, P1815, DOI 10.1110/ps.036376.108
   Bennett MJ, 2006, STRUCTURE, V14, P811, DOI 10.1016/j.str.2006.03.011
   Borgia A, 2008, ANGEW CHEM INT EDIT, V47, P6900
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   Gianni S, 2010, NAT STRUCT MOL BIOL, V17, P1431, DOI 10.1038/nsmb.1956
   Gregersen N, 2006, ANNU REV GENOM HUM G, V7, P103, DOI 10.1146/annurev.genom.7.080505.115737
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   Hoffmann A, 2007, P NATL ACAD SCI USA, V104, P105, DOI 10.1073/pnas.0604353104
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   Karanicolas J, 2003, J MOL BIOL, V334, P309, DOI 10.1016/j.jmb.2003.09.047
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   Li HB, 2002, NATURE, V418, P998, DOI 10.1038/nature00938
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   Schuler Benjamin, 2007, V350, V0, P115
   Scott KA, 2002, J MOL BIOL, V315, P819, DOI 10.1006/jmbi.2001.5260
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   Straub JE, 2010, CURR OPIN STRUC BIOL, V20, P187, DOI 10.1016/j.sbi.2009.12.017
   STRYER L, 1978, ANNU REV BIOCHEM, V47, P819, DOI 10.1146/annurev.bi.47.070178.004131
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   Yang SC, 2004, P NATL ACAD SCI USA, V101, P13786, DOI 10.1073/pnas.0403724101
NR 37
TC 152
Z9 170
U1 0
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 662
EP U142
DI 10.1038/nature10099
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300044
PM 21623368
DA 2026-03-09
ER

PT J
AU Cymes, GD
   Grosman, C
AF Cymes, Gisela D.
   Grosman, Claudio
TI Tunable pKa values and the basis of opposite charge selectivities in nicotinic-type receptors
SO NATURE
LA English
DT Article
ID congenital myasthenic syndrome; gated ion channels; acetylcholine-receptor; single-channel; dielectric-constants; chloride channel; m2 domain; mutations; pore; subunit
AB Among ion channels, only the nicotinic-receptor superfamily has evolved to generate both cation-and anion-selective members. Although other, structurally unrelated, neurotransmitter-gated cation channels exist, no other type of neurotransmitter-gated anion channel, and thus no other source of fast synaptic inhibitory signals, has been described so far. In addition to the seemingly straightforward electrostatic effect of the presence (in the cation-selective members) or absence (in the anion-selective ones) of a ring of pore-facing carboxylates, mutational studies have identified other features of the amino-acid sequence near the intracellular end of the pore-lining transmembrane segments (M2) that are also required to achieve the high charge selectivity shown by native channels(1-10). However, the mechanism underlying this more subtle effect has remained elusive(11) and a subject of speculation. Here we show, using single-channel electrophysiological recordings to estimate the protonation state of native ionizable side chains, that anion-selective-type sequences favour whereas cation-selective-type sequences prevent the protonation of the conserved, buried basic residues at the intracellular entrance of the pore (the M2 0' position). We conclude that the previously unrecognized tunable charge state of the 0' ring of buried basic side chains is an essential feature of these channels' versatile charge-selectivity filter.
C1 [Cymes, Gisela D.; Grosman, Claudio] Univ Illinois, Ctr Biophys & Computat Biol, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
   [Cymes, Gisela D.; Grosman, Claudio] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Grosman, C (corresponding author), Univ Illinois, Ctr Biophys & Computat Biol, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
EM grosman@illinois.edu
FU US National Institutes of Health [R01-NS042169]; National Institute of Neurological Disorders and Stroke [R01NS042169] Funding Source: NIH RePORTER
NR 32
TC 24
Z9 27
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 JUN 23
PY 2011
VL 474
IS 7352
BP 526
EP U160
DI 10.1038/nature10015
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700052
PM 21602825
DA 2026-03-09
ER

PT J
AU Letessier, A
   Millot, GA
   Koundrioukoff, S
   Lachagès, AM
   Vogt, N
   Hansen, RS
   Malfoy, B
   Brison, O
   Debatisse, M
AF Letessier, Anne
   Millot, Gael A.
   Koundrioukoff, Stephane
   Lachages, Anne-Marie
   Vogt, Nicolas
   Hansen, R. Scott
   Malfoy, Bernard
   Brison, Olivier
   Debatisse, Michelle
TI Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site
SO NATURE
LA English
DT Article
ID dna-replication; molecular-basis; origin choice; common; genome; fork; cancer; chromosm; instability; induction
AB Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress(1). They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions(2) and hotspots for chromosomal rearrangements in various cancers(3). Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks(4). Here we show, in contrast to this view, that the fragility of FRA3B-the most active common fragile site in human lymphocytes-does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting(5,6) and replication timing are highly plastic(7,8) in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes(1). Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.
C1 [Letessier, Anne; Millot, Gael A.; Koundrioukoff, Stephane; Lachages, Anne-Marie; Vogt, Nicolas; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle] Inst Curie, Ctr Rech, F-75248 Paris, France.
   [Letessier, Anne; Millot, Gael A.; Koundrioukoff, Stephane; Lachages, Anne-Marie; Vogt, Nicolas; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle] Univ Paris 06, F-75005 Paris, France.
   [Letessier, Anne; Millot, Gael A.; Koundrioukoff, Stephane; Lachages, Anne-Marie; Vogt, Nicolas; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle] CNRS, UMR 3244, F-75248 Paris, France.
   [Hansen, R. Scott] Univ Washington, Div Med Genet, Dept Med, Sch Med, Seattle, WA 98195 USA.
C3 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; Sorbonne Universite; University of Washington; University of Washington Seattle
RP Debatisse, M (corresponding author), Inst Curie, Ctr Rech, 26 Rue Ulm, F-75248 Paris, France.
EM michelle.debatisse@curie.fr
FU ARC(Association pour la recherche sur le cancer); La Ligue Nationale contre le Cancer (LNCC); INCa (Institut National du Cancer) [2009-1-PLBIO-10-IC-1]; PIC Replication, Instabilite Chromosomique et Cancer (Institut Curie)
NR 32
TC 338
Z9 394
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 120
EP U138
DI 10.1038/nature09745
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400046
PM 21258320
DA 2026-03-09
ER

PT J
AU del Rio, L
   Åberg, J
   Renner, R
   Dahlsten, O
   Vedral, V
AF del Rio, Lidia
   Aberg, Johan
   Renner, Renato
   Dahlsten, Oscar
   Vedral, Vlatko
TI The thermodynamic meaning of negative entropy
SO NATURE
LA English
DT Article
ID quantum information; maxwells demon; computation; principle; physics; erasure
AB The heat generated by computations is not only an obstacle to circuit miniaturization but also a fundamental aspect of the relationship between information theory and thermodynamics. In principle, reversible operations may be performed at no energy cost; given that irreversible computations can always be decomposed into reversible operations followed by the erasure of data(1,2), the problem of calculating their energy cost is reduced to the study of erasure. Landauer's principle states that the erasure of data stored in a system has an inherent work cost and therefore dissipates heat(3-8). However, this consideration assumes that the information about the system to be erased is classical, and does not extend to the general case where an observer may have quantum information about the system to be erased, for instance by means of a quantum memory entangled with the system. Here we show that the standard formulation and implications of Landauer's principle are no longer valid in the presence of quantum information. Our main result is that the work cost of erasure is determined by the entropy of the system, conditioned on the quantum information an observer has about it. In other words, the more an observer knows about the system, the less it costs to erase it. This result gives a direct thermodynamic significance to conditional entropies, originally introduced in information theory. Furthermore, it provides new bounds on the heat generation of computations: because conditional entropies can become negative in the quantum case, an observer who is strongly correlated with a system may gain work while erasing it, thereby cooling the environment.
C1 [del Rio, Lidia; Aberg, Johan; Renner, Renato; Dahlsten, Oscar] ETH, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
   [Dahlsten, Oscar; Vedral, Vlatko] Univ Oxford, Clarendon Lab, Oxford OX1 3PU, England.
   [Dahlsten, Oscar; Vedral, Vlatko] Natl Univ Singapore, Ctr Quantum Technol, Singapore 117543, Singapore.
   [Vedral, Vlatko] Natl Univ Singapore, Dept Phys, Singapore 117542, Singapore.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Oxford; National University of Singapore; National University of Singapore
RP del Rio, L (corresponding author), ETH, Inst Theoret Phys, CH-8093 Zurich, Switzerland.
EM delrio@phys.ethz.ch
FU Swiss National Science Foundation [200021-119868]; Portuguese Fundacao para a Ciencia e Tecnologia [SFRH/BD/43263/2008]; European Research Council [258932]; Singapore's National Research Foundation and Ministry of Education; Fundação para a Ciência e a Tecnologia [SFRH/BD/43263/2008] Funding Source: FCT
NR 28
TC 289
Z9 306
U1 1
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 61
EP 63
DI 10.1038/nature10123
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700036
PM 21637254
DA 2026-03-09
ER

PT J
AU Oberst, A
   Dillon, CP
   Weinlich, R
   McCormick, LL
   Fitzgerald, P
   Pop, C
   Hakem, R
   Salvesen, GS
   Green, DR
AF Oberst, Andrew
   Dillon, Christopher P.
   Weinlich, Ricardo
   McCormick, Laura L.
   Fitzgerald, Patrick
   Pop, Cristina
   Hakem, Razq
   Salvesen, Guy S.
   Green, Douglas R.
TI Catalytic activity of the caspase-8-FLIPL complex inhibits RIPK3-dependent necrosis
SO NATURE
LA English
DT Article
ID cell-death; rip1 kinase; activation; requirement; apoptosis; homeostasis; expression; receptors; regulator; cleavage
AB Caspase-8 has two opposing biological functions-it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development(1), T-lymphocyte activation(2), and resistance to necrosis induced by tumour necrosis factor-alpha (TNF-alpha) and related family ligands(3,4). Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIPL, also known as CFLAR), and this complex is required for the protective function.
C1 [Oberst, Andrew; Dillon, Christopher P.; Weinlich, Ricardo; McCormick, Laura L.; Fitzgerald, Patrick; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Pop, Cristina; Salvesen, Guy S.] Sanford Burnham Med Res Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA.
   [Hakem, Razq] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
C3 St Jude Children's Research Hospital; Sanford Burnham Prebys Medical Discovery Institute; University of Toronto; University Health Network Toronto
RP Green, DR (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM douglas.green@stjude.org
FU NIH [AI44828, CA69381]; CIHR [MOP 36537]; Sass Foundation for Medical Research; ALSAC
NR 32
TC 1073
Z9 1221
U1 1
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 17
PY 2011
VL 471
IS 7338
BP 363
EP +
DI 10.1038/nature09852
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000042
PM 21368763
DA 2026-03-09
ER

PT J
AU Esplugues, E
   Huber, S
   Gagliani, N
   Hauser, AE
   Town, T
   Wan, YSY
   O'Connor, W
   Rongvaux, A
   Van Rooijen, N
   Haberman, AM
   Iwakura, Y
   Kuchroo, VK
   Kolls, JK
   Bluestone, JA
   Herold, KC
   Flavell, RA
AF Esplugues, Enric
   Huber, Samuel
   Gagliani, Nicola
   Hauser, Anja E.
   Town, Terrence
   Wan, Yisong Y.
   O'Connor, William, Jr.
   Rongvaux, Anthony
   Van Rooijen, Nico
   Haberman, Ann M.
   Iwakura, Yoichiro
   Kuchroo, Vijay K.
   Kolls, Jay K.
   Bluestone, Jeffrey A.
   Herold, Kevan C.
   Flavell, Richard A.
TI Control of TH17 cells occurs in the small intestine
SO NATURE
LA English
DT Article
ID growth-factor-beta; experimental autoimmune encephalomyelitis; t-cells; th17 cells; monoclonal-antibody; t-h-17 cells; tgf-beta; mice; differentiation; interleukin-10
AB Interleukin (IL)-17-producing T helper cells (T(H)17) are a recently identified CD4(+) T cell subset distinct from T helper type 1 (T(H)1) and T helper type 2 (T(H)2) cells(1). T(H)17 cells can drive antigen-specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE)(2), the mouse model for multiple sclerosis. The factors that are needed for the generation of T(H)17 cells have been well characterized(3-6). However, where and how the immune system controls T(H)17 cells in vivo remains unclear. Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory T(H)17 cells can be redirected to and controlled in the small intestine. T(H)17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that T(H)17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen; second, pro-inflammatory T(H)17 cells simultaneously acquire a regulatory phenotype within vitro and in vivo immune-suppressive properties (rT(H)17). These results identify mechanisms limiting T(H)17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of T(H)17 cells.
C1 [Esplugues, Enric; Huber, Samuel; O'Connor, William, Jr.; Rongvaux, Anthony; Herold, Kevan C.; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Esplugues, Enric; Hauser, Anja E.] German Rheumatism Res Ctr DRFZ, D-10117 Berlin, Germany.
   [Esplugues, Enric] Charite, D-10117 Berlin, Germany.
   [Huber, Samuel] Univ Klinikum Hamburg Eppendorf, Med Klin 1, D-20246 Hamburg, Germany.
   [Gagliani, Nicola] San Raffaele Diabet Res Inst HSR DRI, I-20132 Milan, Italy.
   [Town, Terrence] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
   [Town, Terrence] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA.
   [Town, Terrence] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90048 USA.
   [Wan, Yisong Y.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Van Rooijen, Nico] Vrije Univ Amsterdam, Fac Med, Dept Mol Cell Biol, NL-1081 BT Amsterdam, Netherlands.
   [Haberman, Ann M.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan.
   [Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Kolls, Jay K.] LSU Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA.
   [Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
   [Flavell, Richard A.] Howard Hughes Med Inst, New Haven, CT 06510 USA.
C3 Yale University; Leibniz Association; Deutsches Rheuma-Forschungszentrum (DRFZ); Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; University of Hamburg; University Medical Center Hamburg-Eppendorf; Cedars Sinai Medical Center; Cedars Sinai Medical Center; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Vrije Universiteit Amsterdam; Yale University; University of Tokyo; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Louisiana State University System; Louisiana State University Health Sciences Center New Orleans; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Esplugues, E (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
EM enric.esplugues@yale.edu; richard.flavell@yale.edu
FU National Multiple Sclerosis Society; DFG [HU 1714/1-1]; James Hudson Brown-Alexander B. Coxe Fellowship; Spanish Ministry of Science; Transgenic Core of the Yale DERC [DK45735]; JDRF; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK045735] Funding Source: NIH RePORTER
NR 33
TC 546
Z9 625
U1 1
U2 80
PU 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 28
PY 2011
VL 475
IS 7357
BP 514
EP U114
DI 10.1038/nature10228
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900044
PM 21765430
DA 2026-03-09
ER

PT J
AU Lamia, KA
   Papp, SJ
   Yu, RT
   Barish, GD
   Uhlenhaut, NH
   Jonker, JW
   Downes, M
   Evans, RM
AF Lamia, Katja A.
   Papp, Stephanie J.
   Yu, Ruth T.
   Barish, Grant D.
   Uhlenhaut, N. Henriette
   Jonker, Johan W.
   Downes, Michael
   Evans, Ronald M.
TI Cryptochromes mediate rhythmic repression of the glucocorticoid receptor
SO NATURE
LA English
DT Article
ID circadian clock; gene-expression; peripheral-tissue; transcription; liver; component; binding; mouse; mice; time
AB Mammalian metabolism is highly circadian and major hormonal circuits involving nuclear hormone receptors display interlinked diurnal cycling(1,2). However, mechanisms that logically explain the coordination of nuclear hormone receptors and the clock are poorly understood. Here we show that two circadian co-regulators, cryptochromes 1 and 2, interact with the glucocorticoid receptor in a ligand-dependent fashion and globally alter the transcriptional response to glucocorticoids in mouse embryonic fibroblasts: cryptochrome deficiency vastly decreases gene repression and approximately doubles the number of dexamethasone-induced genes, suggesting that cryptochromes broadly oppose glucocorticoid receptor activation and promote repression. In mice, genetic loss of cryptochrome 1 and/or 2 results in glucose intolerance and constitutively high levels of circulating corticosterone, suggesting reduced suppression of the hypothalamic-pituitary-adrenal axis coupled with increased glucocorticoid transactivation in the liver. Genomically, cryptochromes 1 and 2 associate with a glucocorticoid response element in the phosphoenolpyruvate carboxykinase 1 promoter in a hormone-dependent manner, and dexamethasone-induced transcription of the phosphoenolpyruvate carboxykinase 1 gene was strikingly increased in cryptochrome-deficient livers. These results reveal a specific mechanism through which cryptochromes couple the activity of clock and receptor target genes to complex genomic circuits underpinning normal metabolic homeostasis.
C1 [Lamia, Katja A.; Yu, Ruth T.; Barish, Grant D.; Uhlenhaut, N. Henriette; Jonker, Johan W.; Downes, Michael; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Lamia, Katja A.; Papp, Stephanie J.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
C3 Salk Institute; Scripps Research Institute
RP Evans, RM (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM klamia@scripps.edu; evans@salk.edu
FU National Institutes of Health [DK057978, DK062434, DK090188]; Glenn Foundation for Aging Research; Helmsley Trust; Life Sciences Research Foundation; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK057978] Funding Source: NIH RePORTER
NR 29
TC 483
Z9 594
U1 0
U2 79
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 552
EP 556
DI 10.1038/nature10700
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000067
PM 22170608
DA 2026-03-09
ER

PT J
AU Philippe, H
   Brinkmann, H
   Copley, RR
   Moroz, LL
   Nakano, H
   Poustka, AJ
   Wallberg, A
   Peterson, KJ
   Telford, MJ
AF Philippe, Herve
   Brinkmann, Henner
   Copley, Richard R.
   Moroz, Leonid L.
   Nakano, Hiroaki
   Poustka, Albert J.
   Wallberg, Andreas
   Peterson, Kevin J.
   Telford, Maximilian J.
TI Acoelomorph flatworms are deuterostomes related to Xenoturbella
SO NATURE
LA English
DT Article
ID phylogenetic distribution; basal position; sequences; phylum; nemertodermatida; micrornas; evolution; alignment; supports; package
AB Xenoturbellida and Acoelomorpha are marine worms with contentious ancestry. Both were originally associated with the flatworms (Platyhelminthes), but molecular data have revised their phylogenetic positions, generally linking Xenoturbellida to the deuterostomes(1,2) and positioning the Acoelomorpha as the most basally branching bilaterian group(s)(3-6). Recent phylogenomic data suggested that Xenoturbellida and Acoelomorpha are sister taxa and together constitute an early branch of Bilateria(7). Here we assemble three independent data sets-mitochondrial genes, a phylogenomic data set of 38,330 amino-acid positions and new microRNA (miRNA) complements-and show that the position of Acoelomorpha is strongly affected by a long-branch attraction (LBA) artefact. When we minimize LBA we find consistent support for a position of both acoelomorphs and Xenoturbella within the deuterostomes. The most likely phylogeny links Xenoturbella and Acoelomorpha in a clade we call Xenacoelomorpha. The Xenacoelomorpha is the sister group of the Ambulacraria (hemichordates and echinoderms). We show that analyses of miRNA complements(8) have been affected by character loss in the acoels and that both groups possess one miRNA and the gene Rsb66 otherwise specific to deuterostomes. In addition, Xenoturbella shares one miRNA with the ambulacrarians, and two with the acoels. This phylogeny makes sense of the shared characteristics of Xenoturbellida and Acoelomorpha, such as ciliary ultrastructure and diffuse nervous system, and implies the loss of various deuterostome characters in the Xenacoelomorpha including coelomic cavities, through gut and gill slits.
C1 [Telford, Maximilian J.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Philippe, Herve; Brinkmann, Henner] Univ Montreal, Dept Biochim, Ctr Robert Cedergren, Montreal, PQ H3C 3J7, Canada.
   [Copley, Richard R.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Moroz, Leonid L.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
   [Moroz, Leonid L.] Univ Florida, Dept Neurosci, St Augustine, FL 32080 USA.
   [Moroz, Leonid L.] Univ Florida, Whitney Lab Marine Biosci, Gainesville, FL 32080 USA.
   [Moroz, Leonid L.] Univ Florida, Dept Neurosci, Gainesville, FL 32080 USA.
   [Nakano, Hiroaki] Univ Gothenburg, Dept Marine Ecol Kristineberg, S-45034 Fiskebackskil, Sweden.
   [Poustka, Albert J.] Max Planck Inst Mol Genet, Evolut & Dev Grp, D-14195 Berlin, Germany.
   [Wallberg, Andreas] Uppsala Univ, Dept Systemat Biol, Evolutionary Biol Ctr, Uppsala, Sweden.
   [Peterson, Kevin J.] Dartmouth Coll, Dept Biol, Hanover, NH 03755 USA.
C3 University of London; University College London; Universite de Montreal; University of Oxford; Wellcome Centre for Human Genetics; State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; University of Gothenburg; Max Planck Society; Uppsala University; Dartmouth College
RP Telford, MJ (corresponding author), UCL, Dept Genet Evolut & Environm, Darwin Bldg,Gower St, London WC1E 6BT, England.
EM m.telford@ucl.ac.uk
FU Canada Research Chairs; Natural Sciences and Engineering Research Council; Reseau Quebecois de Calcul de Haute Performance; Biotechnology and Biological Sciences Research Council; National Science Foundation; NASA Ames; Wellcome Trust [075491/Z/04]; Max-Planck Society for the Advancement of Sciences; Direct For Computer & Info Scie & Enginr; Division Of Computer and Network Systems [0821622] Funding Source: National Science Foundation
NR 47
TC 341
Z9 398
U1 2
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 FEB 10
PY 2011
VL 470
IS 7333
BP 255
EP +
DI 10.1038/nature09676
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200043
PM 21307940
DA 2026-03-09
ER

PT J
AU Stiopkin, IV
   Weeraman, C
   Pieniazek, PA
   Shalhout, FY
   Skinner, JL
   Benderskii, AV
AF Stiopkin, Igor V.
   Weeraman, Champika
   Pieniazek, Piotr A.
   Shalhout, Fadel Y.
   Skinner, James L.
   Benderskii, Alexander V.
TI Hydrogen bonding at the water surface revealed by isotopic dilution spectroscopy
SO NATURE
LA English
DT Article
ID ultrafast infrared-spectroscopy; sum-frequency generation; molecular-dynamics simulations; liquid water; vibrational spectroscopy; line-shapes; interface; spectrum; h2o; d2o
AB The air-water interface is perhaps the most common liquid interface. It covers more than 70 per cent of the Earth's surface and strongly affects atmospheric, aerosol and environmental chemistry. The air-water interface has also attracted much interest as a model system that allows rigorous tests of theory, with one fundamental question being just how thin it is. Theoretical studies have suggested a surprisingly short 'healing length' of about 3 angstroms (1 angstrom = 0.1 nm), with the bulk-phase properties of water recovered within the top few monolayers(1-3). However, direct experimental evidence has been elusive owing to the difficulty of depth-profiling the liquid surface on the angstrom scale. Most physical, chemical and biological properties of water, such as viscosity, solvation, wetting and the hydrophobic effect, are determined by its hydrogen-bond network. This can be probed by observing the lineshape of the OH-stretch mode, the frequency shift of which is related to the hydrogen-bond strength(4-6). Here we report a combined experimental and theoretical study of the air-water interface using surface-selective heterodyne-detected vibrational sum frequency spectroscopy to focus on the 'free OD' transition found only in the topmost water layer. By using deuterated water and isotopic dilution to reveal the vibrational coupling mechanism, we find that the free OD stretch is affected only by intramolecular coupling to the stretching of the other OD group on the same molecule. The other OD stretch frequency indicates the strength of one of the first hydrogen bonds encountered at the surface; this is the donor hydrogen bond of the water molecule straddling the interface, which we find to be only slightly weaker than bulk-phase water hydrogen bonds. We infer from this observation a remarkably fast onset of bulk-phase behaviour on crossing from the air into the water phase.
C1 [Stiopkin, Igor V.; Weeraman, Champika; Shalhout, Fadel Y.; Benderskii, Alexander V.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA.
   [Pieniazek, Piotr A.; Skinner, James L.] Univ Wisconsin, Dept Chem, Madison, WI 53705 USA.
C3 Wayne State University; University of Wisconsin System; University of Wisconsin Madison
RP Benderskii, AV (corresponding author), Wayne State Univ, Dept Chem, Detroit, MI 48202 USA.
EM alex.benderskii@usc.edu
FU NSF [CHE-0449720, CHE-0750307]; DOE [DE-FG02-09ER16110]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1058752] Funding Source: National Science Foundation
NR 30
TC 390
Z9 446
U1 7
U2 365
PU 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 9
PY 2011
VL 474
IS 7350
BP 192
EP 195
DI 10.1038/nature10173
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800045
PM 21654801
DA 2026-03-09
ER

PT J
AU Lederbogen, F
   Kirsch, P
   Haddad, L
   Streit, F
   Tost, H
   Schuch, P
   Wüst, S
   Pruessner, JC
   Rietschel, M
   Deuschle, M
   Meyer-Lindenberg, A
AF Lederbogen, Florian
   Kirsch, Peter
   Haddad, Leila
   Streit, Fabian
   Tost, Heike
   Schuch, Philipp
   Wuest, Stefan
   Pruessner, Jens C.
   Rietschel, Marcella
   Deuschle, Michael
   Meyer-Lindenberg, Andreas
TI City living and urban upbringing affect neural social stress processing in humans
SO NATURE
LA English
DT Article
ID early-life stress; psychosocial stress; genetic risk; limbic system; schizophrenia; brain; mechanisms; amygdala; cortex; responses
AB More than half of the world's population now lives in cities, making the creation of a healthy urban environment amajor policy priority(1). Cities have both health risks and benefits(1), but mental health is negatively affected: mood and anxiety disorders are more prevalent in city dwellers(2) and the incidence of schizophrenia is strongly increased in people born and raised in cities(3-6). Although these findings have been widely attributed to the urban social environment(2,3,7,8), the neural processes that could mediate such associations are unknown. Here we show, using functional magnetic resonance imaging in three independent experiments, that urban upbringing and city living have dissociable impacts on social evaluative stress processing in humans. Current city living was associated with increased amygdala activity, whereas urban upbringing affected the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect(9) and stress(10). These findings were regionally and behaviourally specific, as no other brain structures were affected and no urbanicity effect was seen during control experiments invoking cognitive processing without stress. Our results identify distinct neural mechanisms for an established environmental risk factor, link the urban environment for the first time to social stress processing, suggest that brain regions differ in vulnerability to this risk factor across the lifespan, and indicate that experimental interrogation of epidemiological associations is a promising strategy in social neuroscience.
C1 [Lederbogen, Florian; Kirsch, Peter; Haddad, Leila; Streit, Fabian; Tost, Heike; Schuch, Philipp; Wuest, Stefan; Rietschel, Marcella; Deuschle, Michael; Meyer-Lindenberg, Andreas] Univ Heidelberg, Cent Inst Mental Hlth, Fac Med, D-68159 Mannheim, Germany.
   [Pruessner, Jens C.] McGill Univ, Douglas Mental Hlth Univ Inst, Verdun, PQ H4H 1R3, Canada.
C3 Central Institute of Mental Health; Ruprecht Karls University Heidelberg; McGill University
RP Meyer-Lindenberg, A (corresponding author), Univ Heidelberg, Cent Inst Mental Hlth, Fac Med, D-68159 Mannheim, Germany.
EM a.meyer-lindenberg@zi-mannheim.de
FU European Community [HEALTH-F2-2010-241909]; German Research Foundation (Deutsche Forschungsgemeinschaft) [SFB 636-B7]; Federal Ministry of Education and Research (MooDS)
NR 30
TC 1097
Z9 1312
U1 23
U2 547
PU 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 23
PY 2011
VL 474
IS 7352
BP 498
EP 501
DI 10.1038/nature10190
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700046
PM 21697947
DA 2026-03-09
ER

PT J
AU Rohwer, T
   Hellmann, S
   Wiesenmayer, M
   Sohrt, C
   Stange, A
   Slomski, B
   Carr, A
   Liu, YW
   Miaja-Avila, L
   Kalläne, M
   Mathias, S
   Kipp, L
   Rossnagel, K
   Bauer, M
AF Rohwer, Timm
   Hellmann, Stefan
   Wiesenmayer, Martin
   Sohrt, Christian
   Stange, Ankatrin
   Slomski, Bartosz
   Carr, Adra
   Liu, Yanwei
   Miaja-Avila, Luis
   Kallaene, Matthias
   Mathias, Stefan
   Kipp, Lutz
   Rossnagel, Kai
   Bauer, Michael
TI Collapse of long-range charge order tracked by time-resolved photoemission at high momenta
SO NATURE
LA English
DT Article
ID superlattice formation; electronic-structure; density-wave; phase; superconductivity; particle; surface
AB Intense femtosecond (10(-15) s) light pulses can be used to transform electronic, magnetic and structural order in condensed-matter systems on timescales of electronic and atomic motion(1,2,3). This technique is particularly useful in the study(4,5) and in the control(6) of materials whose physical properties are governed by the interactions between multiple degrees of freedom. Time- and angle-resolved photoemission spectroscopy is in this context a direct and comprehensive, energy- and momentum-selective probe of the ultrafast processes that couple to the electronic degrees of freedom(7-10). Previously, the capability of such studies to access electron momentum space away from zero momentum was, however, restricted owing to limitations of the available probing photon energy(10,11). Here, using femtosecond extreme-ultraviolet pulses delivered by a high-harmonic-generation source, we use time- and angle-resolved photoemission spectroscopy to measure the photoinduced vaporization of a charge-ordered state in the potential excitonic insulator 1T-TiSe2 (refs 12, 13). By way of stroboscopic imaging of electronic band dispersions at large momentum, in the vicinity of the edge of the first Brillouin zone, we reveal that the collapse of atomic-scale periodic long-range order happens on a timescale as short as 20 femtoseconds. The surprisingly fast response of the system is assigned to screening by the transient generation of free charge carriers. Similar screening scenarios are likely to be relevant in other photoinduced solid-state transitions and may generally determine the response times. Moreover, as electron states with large momenta govern fundamental electronic properties in condensed matter systems(14), we anticipate that the experimental advance represented by the present study will be useful to study the ultrafast dynamics and microscopic mechanisms of electronic phenomena in a wide range of materials.
C1 [Rohwer, Timm; Hellmann, Stefan; Wiesenmayer, Martin; Sohrt, Christian; Stange, Ankatrin; Slomski, Bartosz; Kallaene, Matthias; Kipp, Lutz; Rossnagel, Kai; Bauer, Michael] Univ Kiel, Inst Expt & Appl Phys, D-24118 Kiel, Germany.
   [Carr, Adra; Mathias, Stefan] Univ Colorado, JILA, Boulder, CO 80309 USA.
   [Carr, Adra; Mathias, Stefan] NIST, Boulder, CO 80309 USA.
   [Liu, Yanwei] Univ Calif Berkeley, NSF ERC Extreme Ultraviolet Sci & Technol, Berkeley, CA 94720 USA.
   [Liu, Yanwei] Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Xray Opt, Berkeley, CA 94720 USA.
   [Miaja-Avila, Luis] Univ Texas Austin, Ctr Nano & Mol Sci, Austin, TX 78722 USA.
   [Mathias, Stefan] Univ Kaiserslautern, Dept Phys, D-67663 Kaiserslautern, Germany.
   [Mathias, Stefan] Univ Kaiserslautern, Res Ctr OPTIMAS, D-67663 Kaiserslautern, Germany.
C3 University of Kiel; University of Colorado System; University of Colorado Boulder; National Institute of Standards & Technology (NIST) - USA; National Science Foundation (NSF); NSF - Engineering Research Centers (ERC); University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of Texas System; University of Texas Austin; RPTU University Kaiserslautern; RPTU University Kaiserslautern
RP Bauer, M (corresponding author), Univ Kiel, Inst Expt & Appl Phys, Olshaussenstr 40, D-24118 Kiel, Germany.
EM rossnagel@physik.uni-kiel.de; bauer@physik.uni-kiel.de
FU JILA Physics Frontier Center; German Science Foundation (DFG) [SFB 855]; European Community [GA 253316]; US Department of Energy, Office of Basic Energy Sciences; NSF EUV ERC; Direct For Mathematical & Physical Scien; Division Of Physics [1125844] Funding Source: National Science Foundation
NR 30
TC 429
Z9 481
U1 1
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 MAR 24
PY 2011
VL 471
IS 7339
BP 490
EP +
DI 10.1038/nature09829
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200057
PM 21389987
DA 2026-03-09
ER

PT J
AU Specht, HP
   Nölleke, C
   Reiserer, A
   Uphoff, M
   Figueroa, E
   Ritter, S
   Rempe, G
AF Specht, Holger P.
   Nolleke, Christian
   Reiserer, Andreas
   Uphoff, Manuel
   Figueroa, Eden
   Ritter, Stephan
   Rempe, Gerhard
TI A single-atom quantum memory
SO NATURE
LA English
DT Article
ID entanglement; photon; cavity; qubit
AB The faithful storage of a quantum bit (qubit) of light is essential for long-distance quantum communication, quantum networking and distributed quantum computing(1). The required optical quantum memory must be able to receive and recreate the photonic qubit; additionally, it must store an unknown quantum state of light better than any classical device. So far, these two requirements have been met only by ensembles of material particles that store the information in collective excitations(2-7). Recent developments, however, have paved the way for an approach in which the information exchange occurs between single quanta of light and matter(8-13). This single-particle approach allows the material qubit to be addressed, which has fundamental advantages for realistic implementations. First, it enables a heralding mechanism that signals the successful storage of a photon by means of state detection(14-16); this can be used to combat inevitable losses and finite efficiencies. Second, it allows for individual qubit manipulations, opening up avenues for in situ processing of the stored quantum information. Here we demonstrate the most fundamental implementation of such a quantum memory, by mapping arbitrary polarization states of light into and out of a single atom trapped inside an optical cavity. The memory performance is tested with weak coherent pulses and analysed using full quantum process tomography. The average fidelity is measured to be 93%, and low decoherence rates result in qubit coherence times exceeding 180 microseconds. This makes our system a versatile quantum node with excellent prospects for applications in optical quantum gates(17) and quantum repeaters(18).
C1 [Specht, Holger P.; Nolleke, Christian; Reiserer, Andreas; Uphoff, Manuel; Figueroa, Eden; Ritter, Stephan; Rempe, Gerhard] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Max Planck Society
RP Ritter, S (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM stephan.ritter@mpq.mpg.de
FU Deutsche Forschungsgemeinschaft [635]; European Union; Bundesministerium fur Bildung und Forschung; Alexander von Humboldt Foundation
NR 32
TC 368
Z9 415
U1 0
U2 141
PU 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 12
PY 2011
VL 473
IS 7346
BP 190
EP 193
DI 10.1038/nature09997
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200033
PM 21532588
DA 2026-03-09
ER

PT J
AU Smart, N
   Bollini, S
   Dubé, KN
   Vieira, JM
   Zhou, B
   Davidson, S
   Yellon, D
   Riegler, J
   Price, AN
   Lythgoe, MF
   Pu, WT
   Riley, PR
AF Smart, Nicola
   Bollini, Sveva
   Dube, Karina N.
   Vieira, Joaquim M.
   Zhou, Bin
   Davidson, Sean
   Yellon, Derek
   Riegler, Johannes
   Price, Anthony N.
   Lythgoe, Mark F.
   Pu, William T.
   Riley, Paul R.
TI De novo cardiomyocytes from within the activated adult heart after injury
SO NATURE
LA English
DT Article
ID epicardial progenitors; smooth-muscle; neovascularization; lineage; cells; tbx18
AB A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction(1). A therapeutic ideal-relative to cell transplantation-would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm's tumour 1 (Wt1), through priming by thymosin beta 4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells(2) with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.
C1 [Smart, Nicola; Bollini, Sveva; Dube, Karina N.; Vieira, Joaquim M.; Riley, Paul R.] UCL Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England.
   [Zhou, Bin; Pu, William T.] Childrens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Zhou, Bin; Pu, William T.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   [Zhou, Bin; Pu, William T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Zhou, Bin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Beijing 20031, Peoples R China.
   [Davidson, Sean; Yellon, Derek] UCL, Hatter Cardiovasc Inst, London WC1E 6HX, England.
   [Riegler, Johannes; Lythgoe, Mark F.] UCL, Dept Med, Ctr Adv Biomed Imaging CABI, London WC1E 6DD, England.
   [Riegler, Johannes; Lythgoe, Mark F.] UCL, Inst Child Hlth, London WC1E 6DD, England.
   [Riegler, Johannes] UCL, Ctr Math & Phys Life Sci & Expt Biol CoMPLEX, London WC1E 6BT, England.
   [Price, Anthony N.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Fac Med, London W12 0NN, England.
C3 University of London; University College London; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Chinese Academy of Sciences; University of London; University College London; University of London; University College London; University of London; University College London; University of London; University College London; Imperial College London
RP Riley, PR (corresponding author), UCL Inst Child Hlth, Mol Med Unit, London WC1N 1EH, England.
EM p.riley@ich.ucl.ac.uk
FU British Heart Foundation; British Heart Foundation [RG/08/003/25264, RG/08/015/26411, FS/08/004/23625, PG/10/005/28175] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/I014667/1] Funding Source: researchfish; Medical Research Council [G0700933] Funding Source: researchfish; EPSRC [EP/I014667/1] Funding Source: UKRI; MRC [G0700933] Funding Source: UKRI
NR 24
TC 517
Z9 605
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 640
EP U117
DI 10.1038/nature10188
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300039
PM 21654746
DA 2026-03-09
ER

PT J
AU Kaiser, WJ
   Upton, JW
   Long, AB
   Livingston-Rosanoff, D
   Daley-Bauer, LP
   Hakem, R
   Caspary, T
   Mocarski, ES
AF Kaiser, William J.
   Upton, Jason W.
   Long, Alyssa B.
   Livingston-Rosanoff, Devon
   Daley-Bauer, Lisa P.
   Hakem, Razqallah
   Caspary, Tamara
   Mocarski, Edward S.
TI RIP3 mediates the embryonic lethality of caspase-8-deficient mice
SO NATURE
LA English
DT Article
ID receptor-interacting protein; homotypic interaction motif; cell-death; programmed necrosis; immune-system; tnf-alpha; t-cells; in-vivo; caspase-8; expression
AB Apoptosis and necroptosis are complementary pathways controlled by common signalling adaptors, kinases and proteases; among these, caspase-8 (Casp8) is critical for death receptor-induced apoptosis. This caspase has also been implicated in non-apoptotic pathways that regulate Fas-associated via death domain (FADD)dependent signalling and other less defined biological processes as diverse as innate immune signalling and myeloid or lymphoid differentiation patterns(1). Casp8 suppresses RIP3-RIP1 (also known as RIPK3-RIPK1) kinase complex-dependent(2-4) necroptosis(5) that follows death receptor activation as well as a RIP3-dependent, RIP(1)-independent necrotic pathway that has emerged as a host defence mechanism against murine cytomegalovirus(6). Disruption of Casp8 expression leads to embryonic lethality in mice between embryonic days 10.5 and 11.5 (ref. 7). Thus, Casp8 may naturally hold alternative RIP3-dependent death pathways in check in addition to promoting apoptosis. We find that RIP3 is responsible for the mid-gestational death of Casp8-deficient embryos. Remarkably, Casp8(-/-)Rip3(-/-) double mutant mice are viable and mature into fertile adults with a full immune complement of myeloid and lymphoid cell types. These mice seem immunocompetent but develop lymphadenopathy by four months of age marked by accumulation of abnormal T cells in the periphery, a phenotype reminiscent of mice with Fas-deficiency (lpr/lpr; also known as Fas). Thus, Casp8 contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development.
C1 [Kaiser, William J.; Upton, Jason W.; Livingston-Rosanoff, Devon; Daley-Bauer, Lisa P.; Mocarski, Edward S.] Emory Univ, Sch Med, Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
   [Long, Alyssa B.; Caspary, Tamara] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
   [Hakem, Razqallah] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
   [Hakem, Razqallah] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
C3 Emory University; Emory University; University of Toronto; University of Toronto; University Health Network Toronto
RP Kaiser, WJ (corresponding author), Emory Univ, Sch Med, Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
EM wkaiser@emory.edu
FU Georgia Cancer Coalition; NIH [R01 AI20211, AI30363]; National Institute of Allergy and Infectious Diseases [R01AI020211] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008169] Funding Source: NIH RePORTER
NR 30
TC 906
Z9 1035
U1 3
U2 104
PU 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 17
PY 2011
VL 471
IS 7338
BP 368
EP +
DI 10.1038/nature09857
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000043
PM 21368762
DA 2026-03-09
ER

PT J
AU Wang, J
   Genack, AZ
AF Wang, Jing
   Genack, Azriel Z.
TI Transport through modes in random media
SO NATURE
LA English
DT Article
ID nonlinear least-squares; anderson localization; intensity distributions; disordered-systems; transmission; waves; ultrasound; diffusion; lattices; absence
AB Excitations in complex media are superpositions of eigenstates that are referred to as 'levels' for quantum systems and 'modes' for classical waves. Although the Hamiltonian of a complex system may not be known or solvable, Wigner conjectured(1) that the statistics of energy level spacings would be the same as for the eigenvalues of large randommatrices. This has explained key characteristics of neutron scattering spectra(2). Subsequently, Thouless and co-workers argued(3,4) that the metal-insulator transition in disordered systems(4-6) could be described by a single parameter, the ratio of the average width and spacing of electronic energy levels: when this dimension-less ratio falls below unity, conductivity is suppressed by Anderson localization(5) of the electronic wave function. However, because of spectral congestion due to the overlap of modes(7-9), even for localized waves, a comprehensive modal description of wave propagation has not been realized. Here we show that the field speckle pattern(10) of transmitted radiation-in this case, a microwave field transmitted through randomly packed alumina spheres-can be decomposed into a sum of the patterns of the individual modes of the medium and the central frequency and linewidth of each mode can be found. We find strong correlation between modal field speckle patterns, which leads to destructive interference between modes. This allows us to explain complexities of steady state and pulsed transmission of localized waves and to harmonize wave and particle descriptions of diffusion.
C1 [Wang, Jing; Genack, Azriel Z.] CUNY Queens Coll, Dept Phys, Flushing, NY 11367 USA.
C3 City University of New York (CUNY) System; Queens College NY (CUNY)
RP Genack, AZ (corresponding author), CUNY Queens Coll, Dept Phys, Flushing, NY 11367 USA.
EM genack@qc.edu
FU National Science Foundation [DMR0907285]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0907285] Funding Source: National Science Foundation
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NR 33
TC 110
Z9 126
U1 1
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 17
PY 2011
VL 471
IS 7338
BP 345
EP +
DI 10.1038/nature09824
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000038
PM 21412335
DA 2026-03-09
ER

PT J
AU Capitanio, FA
   Faccenna, C
   Zlotnik, S
   Stegman, DR
AF Capitanio, F. A.
   Faccenna, C.
   Zlotnik, S.
   Stegman, D. R.
TI Subduction dynamics and the origin of Andean orogeny and the Bolivian orocline
SO NATURE
LA English
DT Article
ID altiplano-puna; tectonics; plateau; evolution; geometry; climate; uplift; zones; rise
AB The building of the Andes results from the subduction of the oceanic Nazca plate underneath the South American continent(1,2). However, how and why the Andes and their curvature, the Bolivian orocline, formed in the Cenozoic era (65.5 million years (Myr) ago to present), despite subduction continuing since the Mesozoic era(3) (251.0-65.5 Myr ago), is still unknown. Three-dimensional numerical subduction models demonstrate that variations in slab thickness, arising from the Nazca plate's age at the trench, produce a cordilleran morphology consistent with that observed(1,2). The age-dependent sinking of the slab in the mantle drives traction towards the trench at the base of the upper plate, causing it to thicken. Thus, subducting older Nazca plate below the Central Andes can explain the locally thickened crust and higher elevations. Here we demonstrate that resultant thickening of the South American plate modifies both shear force gradients and migration rates along the trench to produce a concave margin that matches the Bolivian orocline. Additionally, the varying forcing along the margin allows stress belts to form in the upper-plate interior, explaining the widening of the Central Andes and the different tectonic styles found on their margins, the Eastern and Western Cordilleras(2). The rise of the Central Andes and orocline formation are directly related to the local increase of Nazca plate age and an age distribution along the margin similar to that found today; the onset of these conditions only occurred in the Eocene epoch(4). This may explain the enigmatic delay of the Andean orogeny, that is, the formation of the modern Andes.
C1 [Capitanio, F. A.; Zlotnik, S.] Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
   [Faccenna, C.] Univ Roma Tre, Dipartimento Sci Geog, I-00146 Rome, Italy.
   [Zlotnik, S.] Monash Univ, Sch Math Sci, Clayton, Vic 3800, Australia.
   [Zlotnik, S.] UPC Barcelona Tech, Dept Matemat Aplicada 3, Lab Calcul Numer, E-08034 Barcelona, Spain.
   [Stegman, D. R.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
C3 Monash University; Roma Tre University; Monash University; Universitat Politecnica de Catalunya; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Capitanio, FA (corresponding author), Monash Univ, Sch Geosci, Clayton, Vic 3800, Australia.
EM fabio.capitanio@monash.edu
FU Australian Research Council [DP0987374]; G. Unger Vetlesen Foundation; Australian Research Council [DP0987374] Funding Source: Australian Research Council
NR 29
TC 162
Z9 173
U1 1
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 83
EP 86
DI 10.1038/nature10596
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900038
PM 22113613
DA 2026-03-09
ER

PT J
AU Zhao, Y
   Yang, JL
   Shi, JJ
   Gong, YN
   Lu, QH
   Xu, H
   Liu, LP
   Shao, F
AF Zhao, Yue
   Yang, Jieling
   Shi, Jianjin
   Gong, Yi-Nan
   Lu, Qiuhe
   Xu, Hao
   Liu, Liping
   Shao, Feng
TI The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus
SO NATURE
LA English
DT Article
ID induced cell-death; phagosome maturation; activates caspase-1; legionella; recognition; domain; interleukin-1-beta; susceptibility; il-1-beta; infection
AB Inflammasomes are large cytoplasmic complexes that sense microbial infections/danger molecules and induce caspase-1 activation-dependent cytokine production and macrophage inflammatory death(1,2). The inflammasome assembled by the NOD-like receptor (NLR) protein NLRC4 responds to bacterial flagellin and a conserved type III secretion system (TTSS) rod component(3-5). How the NLRC4 inflammasome detects the two bacterial products and the molecular mechanism of NLRC4 inflammasome activation are not understood. Here we show that NAIP5, a BIR-domain NLR protein required for Legionella pneumophila replication in mouse macrophages(6), is a universal component of the flagellin-NLRC4 pathway. NAIP5 directly and specifically interacted with flagellin, which determined the inflammasome-stimulation activities of different bacterial flagellins. NAIP5 engagement by flagellin promoted a physical NAIP5-NLRC4 association, rendering full reconstitution of a flagellin-responsive NLRC4 inflammasome in non-macrophage cells. The related NAIP2 functioned analogously to NAIP5, serving as a specific inflammasome receptor for TTSS rod proteins such as Salmonella PrgJ and Burkholderia BsaK. Genetic analysis of Chromobacterium violaceum infection revealed that the TTSS needle protein CprI can stimulate NLRC4 inflammasome activation in human macrophages. Similarly, CprI is specifically recognized by human NAIP, the sole NAIP family member in human. The finding that NAIP proteins are inflammasome receptors for bacterial flagellin and TTSS apparatus components further predicts that the remaining NAIP family members may recognize other unidentified microbial products to activate NLRC4 inflammasome-mediated innate immunity.
C1 [Zhao, Yue; Yang, Jieling; Shi, Jianjin; Gong, Yi-Nan; Lu, Qiuhe; Xu, Hao; Liu, Liping; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Zhao, Yue; Yang, Jieling] Peking Union Med Coll, Beijing 100730, Peoples R China.
   [Zhao, Yue; Yang, Jieling] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College
RP Shao, F (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM shaofeng@nibs.ac.cn
FU National Basic Research Program of China (973 Programs) [2010CB835400, 2012CB518700]
NR 37
TC 1041
Z9 1239
U1 3
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 SEP 29
PY 2011
VL 477
IS 7366
BP 596
EP U257
DI 10.1038/nature10510
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900041
PM 21918512
DA 2026-03-09
ER

PT J
AU Alföldi, J
   Di Palma, F
   Grabherr, M
   Williams, C
   Kong, LS
   Mauceli, E
   Russell, P
   Lowe, CB
   Glor, RE
   Jaffe, JD
   Ray, DA
   Boissinot, S
   Shedlock, AM
   Botka, C
   Castoe, TA
   Colbourne, JK
   Fujita, MK
   Moreno, RG
   ten Hallers, BF
   Haussler, D
   Heger, A
   Heiman, D
   Janes, DE
   Johnson, J
   de Jong, PJ
   Koriabine, MY
   Lara, M
   Novick, PA
   Organ, CL
   Peach, SE
   Poe, S
   Pollock, DD
   de Queiroz, K
   Sanger, T
   Searle, S
   Smith, JD
   Smith, Z
   Swofford, R
   Turner-Maier, J
   Wade, J
   Young, S
   Zadissa, A
   Edwards, SV
   Glenn, TC
   Schneider, CJ
   Losos, JB
   Lander, ES
   Breen, M
   Ponting, CP
   Lindblad-Toh, K
AF Alfoeldi, Jessica
   Di Palma, Federica
   Grabherr, Manfred
   Williams, Christina
   Kong, Lesheng
   Mauceli, Evan
   Russell, Pamela
   Lowe, Craig B.
   Glor, Richard E.
   Jaffe, Jacob D.
   Ray, David A.
   Boissinot, Stephane
   Shedlock, Andrew M.
   Botka, Christopher
   Castoe, Todd A.
   Colbourne, John K.
   Fujita, Matthew K.
   Moreno, Ricardo Godinez
   ten Hallers, Boudewijn F.
   Haussler, David
   Heger, Andreas
   Heiman, David
   Janes, Daniel E.
   Johnson, Jeremy
   de Jong, Pieter J.
   Koriabine, Maxim Y.
   Lara, Marcia
   Novick, Peter A.
   Organ, Chris L.
   Peach, Sally E.
   Poe, Steven
   Pollock, David D.
   de Queiroz, Kevin
   Sanger, Thomas
   Searle, Steve
   Smith, Jeremy D.
   Smith, Zachary
   Swofford, Ross
   Turner-Maier, Jason
   Wade, Juli
   Young, Sarah
   Zadissa, Amonida
   Edwards, Scott V.
   Glenn, Travis C.
   Schneider, Christopher J.
   Losos, Jonathan B.
   Lander, Eric S.
   Breen, Matthew
   Ponting, Chris P.
   Lindblad-Toh, Kerstin
TI The genome of the green anole lizard and a comparative analysis with birds and mammals
SO NATURE
LA English
DT Article
ID chicken; evolution
AB The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments(1). Among amniotes, genome sequences are available for mammals and birds(2-4), but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes(2). Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds(5). We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
C1 [Alfoeldi, Jessica; Di Palma, Federica; Grabherr, Manfred; Mauceli, Evan; Russell, Pamela; Jaffe, Jacob D.; Heiman, David; Johnson, Jeremy; Lara, Marcia; Peach, Sally E.; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Lander, Eric S.; Lindblad-Toh, Kerstin] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Williams, Christina; Breen, Matthew] N Carolina State Univ, Dept Mol Biomed Sci, Coll Vet Med, Raleigh, NC 27606 USA.
   [Kong, Lesheng; Fujita, Matthew K.; Heger, Andreas; Ponting, Chris P.] Univ Oxford, MRC, Funct Genom Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Lowe, Craig B.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Glor, Richard E.] Univ Rochester, Rochester, NY 14607 USA.
   [Ray, David A.; Smith, Jeremy D.] Mississippi State Univ, Dept Biochem Mol Biol Entomol & Plant Pathol, Mississippi State, MS 39762 USA.
   [Boissinot, Stephane] CUNY, Dept Biol, Queens Coll, New York, NY 11367 USA.
   [Shedlock, Andrew M.] Coll Charleston, Dept Biol, Charleston, SC 29424 USA.
   [Shedlock, Andrew M.] Coll Charleston, Grad Program Marine Genom, Charleston, SC 29424 USA.
   [Botka, Christopher] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Castoe, Todd A.; Pollock, David D.] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
   [Colbourne, John K.; Smith, Zachary] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA.
   [Fujita, Matthew K.; Moreno, Ricardo Godinez; Janes, Daniel E.; Organ, Chris L.; Sanger, Thomas; Edwards, Scott V.; Losos, Jonathan B.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Fujita, Matthew K.; Moreno, Ricardo Godinez; Janes, Daniel E.; Organ, Chris L.; Sanger, Thomas; Edwards, Scott V.; Losos, Jonathan B.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
   [ten Hallers, Boudewijn F.; de Jong, Pieter J.; Koriabine, Maxim Y.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
   [Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Novick, Peter A.] Queensborough Community Coll, Dept Biol Sci & Geol, Bayside, NY 11364 USA.
   [Poe, Steven] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA.
   [Pollock, David D.] Univ Colorado, Program Computat Biosci, Sch Med, Aurora, CO 80045 USA.
   [de Queiroz, Kevin] Smithsonian Inst, Natl Museum Nat Hist, Dept Vertebrate Zool, Washington, DC 20560 USA.
   [Wade, Juli] Michigan State Univ, Dept Psychol, Program Neurosci, E Lansing, MI 48824 USA.
   [Wade, Juli] Michigan State Univ, Dept Zool, Program Neurosci, E Lansing, MI 48824 USA.
   [Glenn, Travis C.] Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA.
   [Glenn, Travis C.] Univ Georgia, Georgia Genom Facil, Athens, GA 30602 USA.
   [Schneider, Christopher J.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
   [Breen, Matthew] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27695 USA.
   [Breen, Matthew] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
   [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab Uppsala, S-75123 Uppsala, Sweden.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; North Carolina State University; University of Oxford; Stanford University; University of Rochester; Mississippi State University; City University of New York (CUNY) System; Queens College NY (CUNY); College of Charleston; College of Charleston; Harvard University; Harvard Medical School; University of Colorado System; University of Colorado Anschutz Medical Campus; Indiana University System; Indiana University Bloomington; Harvard University; Harvard University; Children's Hospital Los Angeles; Children's Hospital Oakland Research Institute; University of California System; University of California Santa Cruz; University of New Mexico; University of Colorado System; University of Colorado Anschutz Medical Campus; Smithsonian Institution; Smithsonian National Museum of Natural History; Michigan State University; Michigan State University; University System of Georgia; University of Georgia; University System of Georgia; University of Georgia; Boston University; North Carolina State University; University of North Carolina; University of North Carolina Chapel Hill; Uppsala University
RP Alföldi, J (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM jalfoldi@broadinstitute.org; kersli@broadinstitute.org
FU National Human Genome Research Institute (NHGRI); NSF [DEB-0844624, DEB-0920892]; David and Lucile Packard Foundation; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0841821] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0817687] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0742833] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0905714] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BB/F007590/1] Funding Source: researchfish; Medical Research Council [MC_U137761446] Funding Source: researchfish; BBSRC [BB/F007590/1] Funding Source: UKRI; MRC [MC_U137761446] Funding Source: UKRI
CR Axelsson E, 2005, GENOME RES, V15, P120, DOI 10.1101/gr.3021305
   Benton MJ, 2007, MOL BIOL EVOL, V24, P26, DOI 10.1093/molbev/msl150
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   Farinazzo A, 2009, J CHROMATOGR A, V1216, P1241, DOI 10.1016/j.chroma.2008.11.051
   Fujita MK, 2011, GENOME BIOL EVOL, V3, P974, DOI 10.1093/gbe/evr072
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   Gorman GC, 1973, CYTOTAXONOMY VERTEBR, V0, P349
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   Kordis D, 2009, CYTOGENET GENOME RES, V127, P94, DOI 10.1159/000294999
   Losos JB, 2009, ORGANISM ENVIRON, V10, P1
   Lowe CB, 2010, J HERED, V101, P437, DOI 10.1093/jhered/esq016
   Mann K, 2007, PROTEOMICS, V7, P3558, DOI 10.1002/pmic.200700397
   Novick PA, 2011, GENOME BIOL EVOL, V3, P1, DOI 10.1093/gbe/evq080
   Novick PA, 2009, MOL BIOL EVOL, V26, P1811, DOI 10.1093/molbev/msp090
   Organ CL, 2008, INTEGR COMP BIOL, V48, P512, DOI 10.1093/icb/icn041
   Potrzebowski L, 2008, PLOS BIOL, V6, P709, DOI 10.1371/journal.pbio.0060080
   Shedlock AM, 2007, P NATL ACAD SCI USA, V104, P2767, DOI 10.1073/pnas.0606204104
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   Warren WC, 2010, NATURE, V464, P757, DOI 10.1038/nature08819
NR 26
TC 528
Z9 610
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 SEP 29
PY 2011
VL 477
IS 7366
BP 587
EP 591
DI 10.1038/nature10390
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900039
PM 21881562
DA 2026-03-09
ER

PT J
AU Du, J
   Say, RF
   Lü, W
   Fuchs, G
   Einsle, O
AF Du, Juan
   Say, Rafael F.
   Lu, Wei
   Fuchs, Georg
   Einsle, Oliver
TI Active-site remodelling in the bifunctional fructose-1,6-bisphosphate aldolase/phosphatase
SO NATURE
LA English
DT Article
ID crystal-structure; aldolase; evolution; mechanism; muscle; archaebacteria; expression; enzymes; cloning; gene
AB Fructose-1,6-bisphosphate (FBP) aldolase/phosphatase is a bifunctional, thermostable enzyme that catalyses two subsequent steps in gluconeogenesis in most archaea and in deeply branching bacterial lineages(1-3). It mediates the aldol condensation of heat-labile dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP) to FBP4, as well as the subsequent, irreversible hydrolysis of the product to yield the stable fructose-6-phosphate (F6P) and inorganic phosphate; no reaction intermediates are released. Here we present a series of structural snapshots of the reaction that reveal a substantial remodelling of the active site through the movement of loop regions that create different catalytic functionalities at the same location. We have solved the three-dimensional structures of FBP aldolase/phosphatase from thermophilic Thermoproteus neutrophilus(5,6) in a ligand-free state as well as in complex with the substrates DHAP and FBP and the product F6P to resolutions up to 1.3 angstrom. In conjunction with mutagenesis data, this pinpoints the residues required for the two reaction steps and shows that the sequential binding of additional Mg2+ cations reversibly facilitates the reaction. FBP aldolase/phosphatase is an ancestral gluconeogenic enzyme optimized for high ambient temperatures(1,2), and our work resolves how consecutive structural rearrangements reorganize the catalytic centre of the protein to carry out two canonical reactions in a very non-canonical type of bifunctionality.
C1 [Du, Juan; Lu, Wei; Einsle, Oliver] Univ Freiburg, Inst Organ Chem & Biochem, Lehrstuhl Biochem, D-79104 Freiburg, Germany.
   [Say, Rafael F.; Fuchs, Georg] Univ Freiburg, Lehrstuhl Mikrobiol, D-79104 Freiburg, Germany.
   [Einsle, Oliver] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany.
C3 University of Freiburg; University of Freiburg; University of Freiburg
RP Einsle, O (corresponding author), Univ Freiburg, Inst Organ Chem & Biochem, Lehrstuhl Biochem, Albertstr 21, D-79104 Freiburg, Germany.
EM einsle@biochemie.uni-freiburg.de
FU Deutsche Forschungsgemeinschaft [Ei520/3-2, Fu118/15-4, Fu118/15-5]
NR 37
TC 54
Z9 65
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 534
EP U134
DI 10.1038/nature10458
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200047
PM 21983965
DA 2026-03-09
ER

PT J
AU Xu, GZ
   Lo, YC
   Li, QB
   Napolitano, G
   Wu, XF
   Jiang, XL
   Dreano, M
   Karin, M
   Wu, H
AF Xu, Guozhou
   Lo, Yu-Chih
   Li, Qiubai
   Napolitano, Gennaro
   Wu, Xuefeng
   Jiang, Xuliang
   Dreano, Michel
   Karin, Michael
   Wu, Hao
TI Crystal structure of inhibitor of κB kinase β
SO NATURE
LA English
DT Article
ID ubiquitin-like domain; protein-kinase; catalytic subunit; ikk-beta; docking interactions; complex; phosphorylation; activation; alpha; binding
AB Inhibitor of kappa B (I kappa B) kinase (IKK) phosphorylates I kappa B proteins, leading to their degradation and the liberation of nuclear factor kappa B for gene transcription. Here we report the crystal structure of IKK beta in complex with an inhibitor, at a resolution of 3.6 angstrom. The structure reveals a trimodular architecture comprising the kinase domain, a ubiquitin-like domain (ULD) and an elongated, alpha-helical scaffold/dimerization domain (SDD). Unexpectedly, the predicted leucine zipper and helix-loop-helix motifs do not form these structures but are part of the SDD. The ULD and SDD mediate a critical interaction with I kappa B alpha that restricts substrate specificity, and the ULD is also required for catalytic activity. The SDD mediates IKK beta dimerization, but dimerization per se is not important for maintaining IKK beta activity and instead is required for IKK beta activation. Other IKK family members, IKK alpha, TBK1 and IKK-i, may have a similar trimodular architecture and function.
C1 [Xu, Guozhou; Lo, Yu-Chih; Li, Qiubai; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA.
   [Napolitano, Gennaro; Wu, Xuefeng; Karin, Michael] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Jiang, Xuliang] EMD Serono Res Inst, Billerica, MA 01821 USA.
   [Dreano, Michel] Merck Serono, CH-1211 Geneva, Switzerland.
C3 Cornell University; Weill Cornell Medicine; University of California System; University of California San Diego; Merck KGaA; EMD Serono Inc.
RP Wu, H (corresponding author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA.
EM haowu@med.cornell.edu
FU National Institutes of Health; American Heart Association; Cancer Research Institute; American Cancer Society
NR 50
TC 178
Z9 207
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 APR 21
PY 2011
VL 472
IS 7343
BP 325
EP U222
DI 10.1038/nature09853
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600034
PM 21423167
DA 2026-03-09
ER

PT J
AU Jain, A
   Liu, RJ
   Ramani, B
   Arauz, E
   Ishitsuka, Y
   Ragunathan, K
   Park, J
   Chen, J
   Xiang, YK
   Ha, T
AF Jain, Ankur
   Liu, Ruijie
   Ramani, Biswarathan
   Arauz, Edwin
   Ishitsuka, Yuji
   Ragunathan, Kaushik
   Park, Jeehae
   Chen, Jie
   Xiang, Yang K.
   Ha, Taekjip
TI Probing cellular protein complexes using single-molecule pull-down
SO NATURE
LA English
DT Article
ID resonance energy-transfer; living cells; escherichia-coli; gene-expression; live cells; stoichiometry; mtor; fret; dna; microscopy
AB Proteins perform most cellular functions in macromolecular complexes. The same protein often participates in different complexes to exhibit diverse functionality. Current ensemble approaches of identifying cellular protein interactions cannot reveal physiological permutations of these interactions. Here we describe a single-molecule pull-down (SiMPull) assay that combines the principles of a conventional pull-down assay with single-molecule fluorescence microscopy and enables direct visualization of individual cellular protein complexes. SiMPull can reveal how many proteins and of which kinds are present in the in vivo complex, as we show using protein kinase A. We then demonstrate a wide applicability to various signalling proteins found in the cytosol, membrane and cellular organelles, and to endogenous protein complexes from animal tissue extracts. The pulled-down proteins are functional and are used, without further processing, for single-molecule biochemical studies. SiMPull should provide a rapid, sensitive and robust platform for analysing protein assemblies in biological pathways.
C1 [Jain, Ankur; Ragunathan, Kaushik; Park, Jeehae; Ha, Taekjip] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA.
   [Jain, Ankur; Ragunathan, Kaushik; Park, Jeehae; Ha, Taekjip] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Liu, Ruijie; Ramani, Biswarathan; Xiang, Yang K.] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
   [Arauz, Edwin; Chen, Jie] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
   [Ishitsuka, Yuji; Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Ishitsuka, Yuji; Ha, Taekjip] Univ Illinois, Ctr Phys Living Cells, Urbana, IL 61801 USA.
   [Ishitsuka, Yuji; Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
C3 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; 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; Howard Hughes Medical Institute
RP Ha, T (corresponding author), Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA.
EM kevinyx@illinois.edu; tjha@illinois.edu
FU NIH [AI083025, GM065367, HL082846, AR048914]; NSF [0646550, 0822613]; Direct For Mathematical & Physical Scien; Division Of Physics [0646550] Funding Source: National Science Foundation
NR 42
TC 366
Z9 432
U1 0
U2 204
PU 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 26
PY 2011
VL 473
IS 7348
BP 484
EP U322
DI 10.1038/nature10016
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300034
PM 21614075
DA 2026-03-09
ER

PT J
AU Dupont, S
   Morsut, L
   Aragona, M
   Enzo, E
   Giulitti, S
   Cordenonsi, M
   Zanconato, F
   Le Digabel, J
   Forcato, M
   Bicciato, S
   Elvassore, N
   Piccolo, S
AF Dupont, Sirio
   Morsut, Leonardo
   Aragona, Mariaceleste
   Enzo, Elena
   Giulitti, Stefano
   Cordenonsi, Michelangelo
   Zanconato, Francesca
   Le Digabel, Jimmy
   Forcato, Mattia
   Bicciato, Silvio
   Elvassore, Nicola
   Piccolo, Stefano
TI Role of YAP/TAZ in mechanotransduction
SO NATURE
LA English
DT Article
ID epithelial-mesenchymal transition; cell self-renewal; contact inhibition; actin dynamics; growth-control; breast-cancer; hippo pathway; metastasis; taz; force
AB Cells perceive their microenvironment not only through soluble signals but also through physical and mechanical cues, such as extracellular matrix (ECM) stiffness or confined adhesiveness. By mechanotransduction systems, cells translate these stimuli into biochemical signals controlling multiple aspects of cell behaviour, including growth, differentiation and cancer malignant progression, but how rigidity mechanosensing is ultimately linked to activity of nuclear transcription factors remains poorly understood. Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals exerted by ECM rigidity and cell shape. This regulation requires Rho GTPase activity and tension of the actomyosin cytoskeleton, but is independent of the Hippo/LATS cascade. Crucially, YAP/TAZ are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry; conversely, expression of activated YAP overrules physical constraints in dictating cell behaviour. These findings identify YAP/TAZ as sensors and mediators of mechanical cues instructed by the cellular microenvironment.
C1 [Dupont, Sirio; Morsut, Leonardo; Aragona, Mariaceleste; Enzo, Elena; Cordenonsi, Michelangelo; Zanconato, Francesca; Piccolo, Stefano] Univ Padua, Sch Med, Dept Histol Microbiol & Med Biotechnol, I-35131 Padua, Italy.
   [Giulitti, Stefano; Elvassore, Nicola] Univ Padua, Dept Chem Engn DIPIC, I-35131 Padua, Italy.
   [Le Digabel, Jimmy] Univ Paris Diderot, Lab MSC, F-75205 Paris, France.
   [Le Digabel, Jimmy] CNRS, UMR 7057, F-75205 Paris, France.
   [Forcato, Mattia; Bicciato, Silvio] Univ Modena & Reggio Emilia, Dept Biomed Sci, Ctr Genome Res, I-41100 Modena, Italy.
C3 University of Padua; University of Padua; Universite Paris Cite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universita di Modena e Reggio Emilia
RP Dupont, S (corresponding author), Univ Padua, Sch Med, Dept Histol Microbiol & Med Biotechnol, Viale Colombo 3, I-35131 Padua, Italy.
EM dupont@bio.unipd.it; piccolo@bio.unipd.it
FU Telethon and Progetti di Eccellenza; AIRC (Italian Association for Cancer Research); University of Padua; IIT; Telethon; MIUR (Italian Minister of University)
NR 44
TC 4590
Z9 5502
U1 53
U2 1201
PU 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 9
PY 2011
VL 474
IS 7350
BP 179
EP U212
DI 10.1038/nature10137
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800042
PM 21654799
DA 2026-03-09
ER

PT J
AU Faelber, K
   Posor, Y
   Gao, S
   Held, M
   Roske, Y
   Schulze, D
   Haucke, V
   Noé, F
   Daumke, O
AF Faelber, Katja
   Posor, York
   Gao, Song
   Held, Martin
   Roske, Yvette
   Schulze, Dennis
   Haucke, Volker
   Noe, Frank
   Daumke, Oliver
TI Crystal structure of nucleotide-free dynamin
SO NATURE
LA English
DT Article
ID pleckstrin homology domain; particle mesh ewald; gtpase domain; middle domain; ph domain; model; phosphorylation; identification; resolution; mechanism
AB Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function.
C1 [Faelber, Katja; Gao, Song; Roske, Yvette; Schulze, Dennis; Daumke, Oliver] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Posor, York; Gao, Song; Haucke, Volker] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany.
   [Held, Martin; Noe, Frank] Free Univ Berlin, Inst Math, D-14195 Berlin, Germany.
   [Daumke, Oliver] Charite, Inst Med Phys & Biophys, D-10117 Berlin, Germany.
C3 Helmholtz Association; Max Delbruck Center for Molecular Medicine; Free University of Berlin; Free University of Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Daumke, O (corresponding author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany.
EM katja.faelber@mdc-berlin.de; oliver.daumke@mdc-berlin.de
FU Deutsche Forschungsgemeinschaft [SFB 740/C7, SFB958/A12, SFB740/D7, SFB958/A04, SFB740/C8, SFB 958/A7]; International Human Frontier Science Program Organization; EMBO
NR 57
TC 244
Z9 280
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 SEP 29
PY 2011
VL 477
IS 7366
BP 556
EP U318
DI 10.1038/nature10369
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900032
PM 21927000
DA 2026-03-09
ER

PT J
AU Campana, S
   Lodato, G
   D'Avanzo, P
   Panagia, N
   Rossi, EM
   Della Valle, M
   Tagliaferri, G
   Antonelli, LA
   Covino, S
   Ghirlanda, G
   Ghisellini, G
   Melandri, A
   Pian, E
   Salvaterra, R
   Cusumano, G
   D'Elia, V
   Fugazza, D
   Palazzi, E
   Sbarufatti, B
   Vergani, SD
AF Campana, S.
   Lodato, G.
   D'Avanzo, P.
   Panagia, N.
   Rossi, E. M.
   Della Valle, M.
   Tagliaferri, G.
   Antonelli, L. A.
   Covino, S.
   Ghirlanda, G.
   Ghisellini, G.
   Melandri, A.
   Pian, E.
   Salvaterra, R.
   Cusumano, G.
   D'Elia, V.
   Fugazza, D.
   Palazzi, E.
   Sbarufatti, B.
   Vergani, S. D.
TI The unusual gamma-ray burst GRB 101225A explained as a minor body falling onto a neutron star
SO NATURE
LA English
DT Article
ID massive black-hole; tidally disrupted star; white-dwarf; comets; accretion; outburst; disk
AB The tidal disruption of a solar-mass star around a supermassive black hole has been extensively studied analytically(1,2) and numerically(3). In these events, the star develops into an elongated banana-shaped structure. After completing an eccentric orbit, the bound debris falls into the black hole, forming an accretion disk and emitting radiation(4-6). The same process may occur on planetary scales if a minor body passes too close to its star. In the Solar System, comets fall directly into our Sun(7) or onto planets(8). If the star is a compact object, the minor body can become tidally disrupted. Indeed, one of the first mechanisms invoked to produce strong gamma-ray emission involved accretion of comets onto neutron stars in our Galaxy(9). Here we report that the peculiarities of the 'Christmas' gamma-ray burst (GRB 101225A(10)) can be explained by a tidal disruption event of a minor body around an isolated Galactic neutron star. This would indicate either that minor bodies can be captured by compact stellar remnants more frequently than occurs in the Solar System or that minor-body formation is relatively easy around millisecond radio pulsars. A peculiar supernova associated with a gamma-ray burst provides an alternative explanation(11).
C1 [Campana, S.; D'Avanzo, P.; Tagliaferri, G.; Covino, S.; Ghirlanda, G.; Ghisellini, G.; Melandri, A.; Fugazza, D.; Sbarufatti, B.; Vergani, S. D.] INAF Osservatorio Astron Brera, I-23807 Merate, LC, Italy.
   [Lodato, G.] Univ Milan, Dipartimento Fis, I-20133 Milan, Italy.
   [Panagia, N.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Panagia, N.] INAF Osservatorio Astrofis Catania, I-95123 Catania, Italy.
   [Rossi, E. M.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Della Valle, M.] INAF Osservatorio Astron Capodimonte, I-80131 Naples, Italy.
   [Antonelli, L. A.; D'Elia, V.] INAF Osservatorio Astron Roma, I-00044 Rome, Italy.
   [Pian, E.] Scuola Normale Super Pisa, I-56126 Pisa, Italy.
   [Pian, E.] INAF Osservatorio Astron Trieste, I-34143 Trieste, Italy.
   [Salvaterra, R.] Univ Insubria, Dipartimento Fis & Matemat, I-22100 Como, Italy.
   [Cusumano, G.] INAF Ist Astrofis Spaziale & Fis Cosm, I-90146 Palermo, Italy.
   [D'Elia, V.] ASI Sci Data Ctr, I-00044 Frascati, Roma, Italy.
   [Palazzi, E.] INAF Ist Astrofis Spaziale & Fis Cosm, Sez Bologna, I-40129 Bologna, Italy.
C3 Istituto Nazionale Astrofisica (INAF); University of Milan; Space Telescope Science Institute; Istituto Nazionale Astrofisica (INAF); Leiden University - Excl LUMC; Leiden University; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); Scuola Normale Superiore di Pisa; Istituto Nazionale Astrofisica (INAF); University of Insubria; Istituto Nazionale Astrofisica (INAF); Agenzia Spaziale Italiana (ASI); Istituto Nazionale Astrofisica (INAF)
RP Campana, S (corresponding author), INAF Osservatorio Astron Brera, Via E Bianchi 46, I-23807 Merate, LC, Italy.
EM sergio.campana@brera.inaf.it
FU ASI; INAF
NR 27
TC 58
Z9 60
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 DEC 1
PY 2011
VL 480
IS 7375
BP 69
EP 71
DI 10.1038/nature10592
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900034
PM 22129725
DA 2026-03-09
ER

PT J
AU Jones, JTA
   Hasell, T
   Wu, XF
   Bacsa, J
   Jelfs, KE
   Schmidtmann, M
   Chong, SY
   Adams, DJ
   Trewin, A
   Schiffman, F
   Cora, F
   Slater, B
   Steiner, A
   Day, GM
   Cooper, AI
AF Jones, James T. A.
   Hasell, Tom
   Wu, Xiaofeng
   Bacsa, John
   Jelfs, Kim E.
   Schmidtmann, Marc
   Chong, Samantha Y.
   Adams, Dave J.
   Trewin, Abbie
   Schiffman, Florian
   Cora, Furio
   Slater, Ben
   Steiner, Alexander
   Day, Graeme M.
   Cooper, Andrew I.
TI Modular and predictable assembly of porous organic molecular crystals
SO NATURE
LA English
DT Article
ID framework; chemistry; hydrogen; methane; design
AB Nanoporous molecular frameworks(1-7) are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores(7) rather than, for example, the functional group localization found in the reactive sites of enzymes(8). This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores(9-15). In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally(16,17), allowing in silico materials design strategies(18). The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules.
C1 [Jones, James T. A.; Hasell, Tom; Wu, Xiaofeng; Bacsa, John; Jelfs, Kim E.; Schmidtmann, Marc; Chong, Samantha Y.; Adams, Dave J.; Trewin, Abbie; Steiner, Alexander; Cooper, Andrew I.] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Merseyside, England.
   [Jones, James T. A.; Hasell, Tom; Wu, Xiaofeng; Bacsa, John; Jelfs, Kim E.; Schmidtmann, Marc; Chong, Samantha Y.; Adams, Dave J.; Trewin, Abbie; Steiner, Alexander; Cooper, Andrew I.] Univ Liverpool, Ctr Mat Discovery, Liverpool L69 7ZD, Merseyside, England.
   [Schiffman, Florian; Cora, Furio; Slater, Ben] UCL, Dept Chem, London WC1H 0AJ, England.
   [Day, Graeme M.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
C3 University of Liverpool; University of Liverpool; University of London; University College London; University of Cambridge
RP Cooper, AI (corresponding author), Univ Liverpool, Dept Chem, Crown St, Liverpool L69 7ZD, Merseyside, England.
EM aicooper@liv.ac.uk
FU EPSRC [EP/F067496/1, EP/H000925/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F067496/1, EP/H000925/1] Funding Source: researchfish
NR 32
TC 456
Z9 508
U1 3
U2 724
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 367
EP 371
DI 10.1038/nature10125
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100043
PM 21677756
DA 2026-03-09
ER

PT J
AU Wollmann, P
   Cui, S
   Viswanathan, R
   Berninghausen, O
   Wells, MN
   Moldt, M
   Witte, G
   Butryn, A
   Wendler, P
   Beckmann, R
   Auble, DT
   Hopfner, KP
AF Wollmann, Petra
   Cui, Sheng
   Viswanathan, Ramya
   Berninghausen, Otto
   Wells, Melissa N.
   Moldt, Manuela
   Witte, Gregor
   Butryn, Agata
   Wendler, Petra
   Beckmann, Roland
   Auble, David T.
   Hopfner, Karl-Peter
TI Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP
SO NATURE
LA English
DT Article
ID tata-binding protein; rna-polymerase-ii; chromatin; transcription; dna; software; nc2; architecture; expression; generation
AB Swi2/Snf2-type ATPases regulate genome-associated processes such as transcription, replication and repair by catalysing the disruption, assembly or remodelling of nucleosomes or other protein-DNA complexes(1,2). It has been suggested that ATP-driven motor activity along DNA disrupts target protein-DNA interactions in the remodelling reaction(3-5). However, the complex and highly specific remodelling reactions are poorly understood, mostly because of a lack of high-resolution structural information about how remodellers bind to their substrate proteins. Mot1 (modifier of transcription 1 in Saccharomyces cerevisiae, denoted BTAF1 in humans) is a Swi2/Snf2 enzyme that specifically displaces the TATA box binding protein (TBP) from the promoter DNA and regulates transcription globally by generating a highly dynamic TBP pool in the cell(6,7). As a Swi2/Snf2 enzyme that functions as a single polypeptide and interacts with a relatively simple substrate, Mot1 offers an ideal system from which to gain a better understanding of this important enzyme family. To reveal how Mot1 specifically disrupts TBP-DNA complexes, we combined crystal and electron microscopy structures of Mot1-TBP from Encephalitozoon cuni-culi with biochemical studies. Here we show that Mot1 wraps around TBP and seems to act like a bottle opener: a spring-like array of 16 HEAT(huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats grips the DNA-distal side of TBP via loop insertions, and the Swi2/Snf2 domain binds to upstream DNA, positioned to weaken the TBP-DNA interaction by DNA translocation. A 'latch' subsequently blocks the DNA-binding groove of TBP, acting as a chaperone to prevent DNA re-association and ensure efficient promoter clearance. This work shows how a remodelling enzyme can combine both motor and chaperone activities to achieve functional specificity using a conserved Swi2/Snf2 translocase.
C1 [Wollmann, Petra; Cui, Sheng; Berninghausen, Otto; Moldt, Manuela; Witte, Gregor; Butryn, Agata; Wendler, Petra; Beckmann, Roland; Hopfner, Karl-Peter] Univ Munich, Dept Biochem, D-81377 Munich, Germany.
   [Wollmann, Petra; Witte, Gregor; Hopfner, Karl-Peter] Gene Ctr Munich, Munich Ctr Adv Photon, D-81377 Munich, Germany.
   [Viswanathan, Ramya; Wells, Melissa N.; Auble, David T.] Univ Virginia Hlth Syst, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
   [Witte, Gregor; Beckmann, Roland; Hopfner, Karl-Peter] Gene Ctr Munich, Ctr Integrated Prot Sci, D-81377 Munich, Germany.
C3 University of Munich; University of Munich; University of Virginia; University of Virginia (UVA) Health System; University of Munich
RP Hopfner, KP (corresponding author), Univ Munich, Dept Biochem, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM auble@virginia.edu; hopfner@lmb.uni-muenchen.de
FU German Research Council [SFB 646, SFB/TR5]; Excellence Initiative (Center for Integrated Protein Science, Munich); DFG [WE4628/1]; NIH [GM55763]; National Institute of General Medical Sciences [R01GM055763] Funding Source: NIH RePORTER
NR 44
TC 60
Z9 73
U1 0
U2 13
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 403
EP U168
DI 10.1038/nature10215
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200048
PM 21734658
DA 2026-03-09
ER

PT J
AU Slade, D
   Dunstan, MS
   Barkauskaite, E
   Weston, R
   Lafite, P
   Dixon, N
   Ahel, M
   Leys, D
   Ahel, I
AF Slade, Dea
   Dunstan, Mark S.
   Barkauskaite, Eva
   Weston, Ria
   Lafite, Pierre
   Dixon, Neil
   Ahel, Marijan
   Leys, David
   Ahel, Ivan
TI The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase
SO NATURE
LA English
DT Article
ID identification; chromatin; binding; model; metabolites; field
AB Post-translational modification of proteins by poly(ADP-ribosyl) ation regulates many cellular pathways that are critical for genome stability, including DNA repair, chromatin structure, mitosis and apoptosis(1). Poly(ADP-ribose) (PAR) is composed of repeating ADPribose units linked via a unique glycosidic ribose-ribose bond, and is synthesized from NAD by PAR polymerases(1,2). PAR glycohydrolase (PARG) is the only protein capable of specific hydrolysis of the ribose-ribose bonds present in PAR chains; its deficiency leads to cell death(3,4). Here we show that filamentous fungi and a number of bacteria possess a divergent form of PARG that has all the main characteristics of the human PARG enzyme. We present the first PARG crystal structure (derived from the bacterium Thermomonospora curvata), which reveals that the PARG catalytic domain is a distant member of the ubiquitous ADP-ribose-binding macrodomain family(5,6). High-resolution structures of T. curvata PARG in complexes with ADP-ribose and the PARG inhibitor ADP-HPD, complemented by biochemical studies, allow us to propose a model for PAR binding and catalysis by PARG. The insights into the PARG structure and catalytic mechanism should greatly improve our understanding of how PARG activity controls reversible protein poly(ADP-ribosyl) ation and potentially of how the defects in this regulation are linked to human disease.
C1 [Slade, Dea; Barkauskaite, Eva; Weston, Ria; Ahel, Ivan] Univ Manchester, Paterson Inst Canc Res, Canc Res UK, Manchester M20 4BX, Lancs, England.
   [Slade, Dea] Univ Paris 05, Fac Med, INSERM, U1001, F-75015 Paris, France.
   [Dunstan, Mark S.; Dixon, Neil; Leys, David] Manchester Interdisciplinary Bioctr, Manchester M1 7DN, Lancs, England.
   [Lafite, Pierre] Univ Orleans, ICOA, CNRS, UMR 6005, F-45067 Orleans, France.
   [Ahel, Marijan] Rudjer Boskovic Inst, HR-10000 Zagreb, Croatia.
C3 Paterson Institute for Cancer Research; Cancer Research UK; University of Manchester; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; University of Manchester; CEA; Centre National de la Recherche Scientifique (CNRS); Universite de Orleans; Rudjer Boskovic Institute
RP Ahel, I (corresponding author), Univ Manchester, Paterson Inst Canc Res, Canc Res UK, Wilmslow Rd, Manchester M20 4BX, Lancs, England.
EM iahel@picr.man.ac.uk
FU Cancer Research UK; AXA Research Fund
NR 30
TC 329
Z9 383
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 SEP 29
PY 2011
VL 477
IS 7366
BP 616
EP U150
DI 10.1038/nature10404
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900045
PM 21892188
DA 2026-03-09
ER

PT J
AU Saavedra, S
   Stouffer, DB
   Uzzi, B
   Bascompte, J
AF Saavedra, Serguei
   Stouffer, Daniel B.
   Uzzi, Brian
   Bascompte, Jordi
TI Strong contributors to network persistence are the most vulnerable to extinction
SO NATURE
LA English
DT Article
ID mutualistic networks; architecture; systems
AB The architecture of mutualistic networks facilitates coexistence of individual participants by minimizing competition relative to facilitation(1,2). However, it is not known whether this benefit is received by each participant node in proportion to its overall contribution to network persistence. This issue is critical to understanding the trade-offs faced by individual nodes in a network(3-5). We address this question by applying a suite of structural and dynamic methods to an ensemble of flowering plant/insect pollinator networks. Here we report two main results. First, nodes contribute heterogeneously to the overall nested architecture of the network. From simulations, we confirm that the removal of a strong contributor tends to decrease overall network persistence more than the removal of a weak contributor. Second, strong contributors to collective persistence do not gain individual survival benefits but are in fact the nodes most vulnerable to extinction. We explore the generality of these results to other cooperative networks by analysing a 15-year time series of the interactions between designer and contractor firms in the New York City garment industry. As with the ecological networks, a firm's survival probability decreases as its individual nestedness contribution increases. Our results, therefore, introduce a new paradox into the study of the persistence of cooperative networks, and potentially address questions about the impact of invasive species in ecological systems and new competitors in economic systems.
C1 [Stouffer, Daniel B.; Bascompte, Jordi] CSIC, Estn Biol Donana, Integrat Ecol Grp, E-41092 Seville, Spain.
   [Saavedra, Serguei; Uzzi, Brian] Northwestern Univ, NW Inst Complex Syst, Evanston, IL 60208 USA.
   [Saavedra, Serguei; Uzzi, Brian] Northwestern Univ, Kellogg Sch Management, Evanston, IL 60208 USA.
   [Saavedra, Serguei] Northwestern Univ, Clin & Translat Sci Inst, Chicago, IL 60611 USA.
   [Stouffer, Daniel B.] Univ Canterbury, Sch Biol Sci, Christchurch 8140, New Zealand.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); Northwestern University; Northwestern University; Northwestern University; University of Canterbury
RP Bascompte, J (corresponding author), CSIC, Estn Biol Donana, Integrat Ecol Grp, Calle Americo Vespucio S-N, E-41092 Seville, Spain.
EM bascompte@ebd.csic.es
FU Kellogg School of Management, Northwestern University; Northwestern University Institute on Complex Systems; NUCATS [UL1RR025741]; CSIC-JAE postdoctoral fellowship; Army Research Laboratory [W911NF-09-2-0053]; European Research Council under the European Community [268543]; European Research Council (ERC) [268543] Funding Source: European Research Council (ERC); Academy of Finland (AKA) [268543] Funding Source: Academy of Finland (AKA)
NR 22
TC 262
Z9 294
U1 6
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 OCT 13
PY 2011
VL 478
IS 7368
BP 233
EP 235
DI 10.1038/nature10433
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800048
PM 21918515
DA 2026-03-09
ER

PT J
AU Jaskelioff, M
   Muller, FL
   Paik, JH
   Thomas, E
   Jiang, S
   Adams, AC
   Sahin, E
   Kost-Alimova, M
   Protopopov, A
   Cadiñanos, J
   Horner, JW
   Maratos-Flier, E
   DePinho, RA
AF Jaskelioff, Mariela
   Muller, Florian L.
   Paik, Ji-Hye
   Thomas, Emily
   Jiang, Shan
   Adams, Andrew C.
   Sahin, Ergun
   Kost-Alimova, Maria
   Protopopov, Alexei
   Cadinanos, Juan
   Horner, James W.
   Maratos-Flier, Eleftheria
   DePinho, Ronald A.
TI Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
SO NATURE
LA English
DT Article
ID neural stem-cells; olfactory-bulb; dna-damage; chromosomal instability; life-span; cancer; neurogenesis; adult; mouse; recombination
AB An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo(1). Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses(1). Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-oestrogen receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2(+) neural progenitors, Dcx(+) newborn neurons, and Olig2(+) oligodendrocyte populations. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons(2), this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk(1,3) and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.
C1 [Jaskelioff, Mariela; Muller, Florian L.; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadinanos, Juan; Horner, James W.; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Jaskelioff, Mariela; Muller, Florian L.; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadinanos, Juan; Horner, James W.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Jaskelioff, Mariela; Muller, Florian L.; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadinanos, Juan; Horner, James W.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
   [Jaskelioff, Mariela; Muller, Florian L.; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadinanos, Juan; Horner, James W.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA.
   [Adams, Andrew C.; Maratos-Flier, Eleftheria] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP DePinho, RA (corresponding author), Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM ron_depinho@dfci.harvard.edu
FU Susan G. Komen for the Cure fellowship [PDF060881]; NIH National Cancer Institute [R01CA84628, U01CA141508]; Belfer Foundation; American Cancer Society (ACS) [PF-08-261-01-TBE]
NR 35
TC 622
Z9 737
U1 1
U2 202
PU 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 6
PY 2011
VL 469
IS 7328
BP 102
EP U1700
DI 10.1038/nature09603
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600040
PM 21113150
DA 2026-03-09
ER

PT J
AU Yunker, PJ
   Still, T
   Lohr, MA
   Yodh, AG
AF Yunker, Peter J.
   Still, Tim
   Lohr, Matthew A.
   Yodh, A.G.
TI Suppression of the coffee-ring effect by shape-dependent capillary interactions
SO NATURE
LA English
DT Article
ID air-water-interface; ellipsoidal particles; pattern-formation; evaporation; droplets; drops
AB When a drop of liquid dries on a solid surface, its suspended particulate matter is deposited in ring-like fashion. This phenomenon, known as the coffee-ring effect(1-3), is familiar to anyone who has observed a drop of coffee dry. During the drying process, drop edges become pinned to the substrate, and capillary flow outward from the centre of the drop brings suspended particles to the edge as evaporation proceeds. After evaporation, suspended particles are left highly concentrated along the original drop edge. The coffee-ring effect is manifested in systems with diverse constituents, ranging from large colloids(1,4,5) to nanoparticles(6) and individual molecules(7). In fact-despite the many practical applications for uniform coatings in printing(8), biology(9,10) and complex assembly(11)-the ubiquitous nature of the effect has made it difficult to avoid(6,12-16). Here we show experimentally that the shape of the suspended particles is important and can be used to eliminate the coffee-ring effect: ellipsoidal particles are deposited uniformly during evaporation. The anisotropic shape of the particles significantly deforms interfaces, producing strong interparticle apillary interactions(17-23). Thus, after the ellipsoids are carried to the air-water interface by the same outward flow that causes the coffee-ring effect for spheres, strong long-ranged interparticle attractions between ellipsoids lead to the formation of loosely packed or arrested structures on the air-water interface(17,18,21,24). These structures prevent the suspended particles from reaching the drop edge and ensure uniform deposition. Interestingly, under appropriate conditions, suspensions of spheres mixed with a small number of ellipsoids also produce uniform deposition. Thus, particle shape provides a convenient parameter to control the deposition of particles, without modification of particle or solvent chemistry.
C1 Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   CNRS Rhodia Univ Pennsylvania, Complex Assemblies Soft Matter, UMI 3254, Bristol, PA 19007 USA.
C3 University of Pennsylvania; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC)
RP Yunker, PJ (corresponding author), Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
EM pyunker@sas.upenn.edu
FU Division Of Materials Research; Direct For Mathematical & Physical Scien [0804881, 1120901] Funding Source: National Science Foundation
NR 29
TC 1357
Z9 1544
U1 25
U2 1379
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 308
EP 311
DI 10.1038/nature10344
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500047
PM 21850105
DA 2026-03-09
ER

PT J
AU Itzhaki, I
   Maizels, L
   Huber, I
   Zwi-Dantsis, L
   Caspi, O
   Winterstern, A
   Feldman, O
   Gepstein, A
   Arbel, G
   Hammerman, H
   Boulos, M
   Gepstein, L
AF Itzhaki, Ilanit
   Maizels, Leonid
   Huber, Irit
   Zwi-Dantsis, Limor
   Caspi, Oren
   Winterstern, Aaron
   Feldman, Oren
   Gepstein, Amira
   Arbel, Gil
   Hammerman, Haim
   Boulos, Monther
   Gepstein, Lior
TI Modelling the long QT syndrome with induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID cardiomyocytes; induction; ranolazine; mechanism; myocytes; block
AB The ability to generate patient-specific human induced pluripotent stem cells (iPSCs)(1-3) offers a new paradigm for modelling human disease and for individualizing drug testing(4). Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death(5-7). Here we report the development of a patient/disease-specific human iPSC line from a patient with type-2 LQTS (which is due to the A614V missense mutation in the KCNH2 gene). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes (the characteristic LQTS phenotype) when compared to healthy control cells. Voltage-clamp studies confirmed that this action-potential-duration prolongation stems from a significant reduction of the cardiac potassium current I-Kr. Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. We then used the LQTS human iPSC-derived cardiac-tissue model to evaluate the potency of existing and novel pharmacological agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K-ATP-channel openers and late sodium-channel blockers) the disease phenotype. Our study illustrates the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. As such, it represents a promising paradigm to study disease mechanisms, optimize patient care (personalized medicine), and aid in the development of new therapies.
C1 [Itzhaki, Ilanit; Maizels, Leonid; Huber, Irit; Zwi-Dantsis, Limor; Caspi, Oren; Winterstern, Aaron; Feldman, Oren; Gepstein, Amira; Arbel, Gil; Gepstein, Lior] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Sohnis Family Res Lab Cardiac Electrophysiol & Re, IL-31096 Haifa, Israel.
   [Hammerman, Haim; Boulos, Monther; Gepstein, Lior] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Rambam Med Ctr, Dept Cardiol, IL-31096 Haifa, Israel.
C3 Technion Israel Institute of Technology; Rappaport Faculty of Medicine; Technion Israel Institute of Technology; Rappaport Faculty of Medicine; Rambam Health Care Campus
RP Gepstein, L (corresponding author), Technion Israel Inst Technol, Bruce Rappaport Fac Med, Sohnis Family Res Lab Cardiac Electrophysiol & Re, POB9649, IL-31096 Haifa, Israel.
EM mdlior@techunix.technion.ac.il
FU Israel Science Foundation; Legacy Heritage Foundation [1225/09]; Yad Hanadiv Foundation; Lorry Lokey research fund; Nancy and Stephen Grand Philanthropic Fund
NR 28
TC 805
Z9 969
U1 0
U2 9
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 225
EP U113
DI 10.1038/nature09747
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200039
PM 21240260
DA 2026-03-09
ER

PT J
AU Mardis, ER
AF Mardis, Elaine R.
TI A decade's perspective on DNA sequencing technology
SO NATURE
LA English
DT Article
ID human genome; structural variation; copy number; colorectal cancers; haplotype map; human breast; evolution; inhibitors; mutations; insights
AB The decade since the Human Genome Project ended has witnessed a remarkable sequencing technology explosion that has permitted a multitude of questions about the genome to be asked and answered, at unprecedented speed and resolution. Here I present examples of how the resulting information has both enhanced our knowledge and expanded the impact of the genome on biomedical research. New sequencing technologies have also introduced exciting new areas of biological endeavour. The continuing upward trajectory of sequencing technology development is enabling clinical applications that are aimed at improving medical diagnosis and treatment.
C1 Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
C3 Washington University (WUSTL)
RP Mardis, ER (corresponding author), Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
EM emardis@wustl.edu
NR 46
TC 610
Z9 862
U1 1
U2 220
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 198
EP 203
DI 10.1038/nature09796
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200033
PM 21307932
DA 2026-03-09
ER

PT J
AU Spence, JR
   Mayhew, CN
   Rankin, SA
   Kuhar, MF
   Vallance, JE
   Tolle, K
   Hoskins, EE
   Kalinichenko, VV
   Wells, SI
   Zorn, AM
   Shroyer, NF
   Wells, JM
AF Spence, Jason R.
   Mayhew, Christopher N.
   Rankin, Scott A.
   Kuhar, Matthew F.
   Vallance, Jefferson E.
   Tolle, Kathryn
   Hoskins, Elizabeth E.
   Kalinichenko, Vladimir V.
   Wells, Susanne I.
   Zorn, Aaron M.
   Shroyer, Noah F.
   Wells, James M.
TI Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
SO NATURE
LA English
DT Article
ID efficient differentiation; endocrine-cells; endoderm; neurogenin-3; specification; generation; culture; liver; fate
AB Studies in embryonic development have guided successful efforts to direct the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into specific organ cell types in vitro(1,2). For example, human PSCs have been differentiated into monolayer cultures of liver hepatocytes and pancreatic endocrine cells(3-6) that have therapeutic efficacy in animal models of liver disease(7,8) and diabetes(9), respectively. However, the generation of complex three-dimensional organ tissues in vitro remains a major challenge for translational studies. Here we establish a robust and efficient process to direct the differentiation of human PSCs into intestinal tissue in vitro using a temporal series of growth factor manipulations to mimic embryonic intestinal development(10). This involved activin-induced definitive endoderm formation(11), FGF/Wnt-induced posterior endoderm pattering, hindgut specification and morphogenesis(12-14), and a pro-intestinal culture system(15,16) to promote intestinal growth, morphogenesis and cytodifferentiation. The resulting three-dimensional intestinal 'organoids' consisted of a polarized, columnar epithelium that was patterned into villus-like structures and crypt-like proliferative zones that expressed intestinal stem cell markers(17). The epithelium contained functional enterocytes, as well as goblet, Paneth and enteroendocrine cells. Using this culture system as a model to study human intestinal development, we identified that the combined activity of WNT3A and FGF4 is required for hindgut specification whereas FGF4 alone is sufficient to promote hindgut morphogenesis. Our data indicate that human intestinal stem cells form de novo during development. We also determined that NEUROG3, a pro-endocrine transcription factor that is mutated in enteric anendocrinosis(18), is both necessary and sufficient for human enteroendocrine cell development in vitro. PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development and disease.
C1 [Spence, Jason R.; Mayhew, Christopher N.; Rankin, Scott A.; Kuhar, Matthew F.; Tolle, Kathryn; Kalinichenko, Vladimir V.; Zorn, Aaron M.; Shroyer, Noah F.; Wells, James M.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Vallance, Jefferson E.; Shroyer, Noah F.] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.
   [Hoskins, Elizabeth E.; Wells, Susanne I.] Cincinnati Childrens Hosp Med Ctr, Div Hematol & Oncol, Cincinnati, OH 45229 USA.
   [Kalinichenko, Vladimir V.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA.
C3 Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center
RP Wells, JM (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM james.wells@cchmc.org
FU Juvenile Diabetes Research Foundation [JDRF-2-2003-530]; NIH [R01GM072915, R01DK080823A1 and S1, R03 DK084167, R01 CA142826, F32 DK83202-01, T32 HD07463];  [P30 DK078392];  [U54 RR025216]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK078392] Funding Source: NIH RePORTER
NR 38
TC 1533
Z9 1892
U1 6
U2 339
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 105
EP U120
DI 10.1038/nature09691
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400043
PM 21151107
DA 2026-03-09
ER

PT J
AU Lathrop, SK
   Bloom, SM
   Rao, SM
   Nutsch, K
   Lio, CW
   Santacruz, N
   Peterson, DA
   Stappenbeck, TS
   Hsieh, CS
AF Lathrop, Stephanie K.
   Bloom, Seth M.
   Rao, Sindhuja M.
   Nutsch, Katherine
   Lio, Chan-Wang
   Santacruz, Nicole
   Peterson, Daniel A.
   Stappenbeck, Thaddeus S.
   Hsieh, Chyi-Song
TI Peripheral education of the immune system by colonic commensal microbiota
SO NATURE
LA English
DT Article
ID regulatory t-cells; differentiation; self; gene
AB The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T-reg) cells(1). However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease(2-4). Here we show that encounter with commensal microbiota results in the peripheral generation of T-reg cells rather than pathogenic effectors. We observed that colonic T-reg cells used T-cell antigen receptors (TCRs) different from those used by T-reg cells in other locations, implying an important role for local antigens in shaping the colonic T-reg-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon T-reg TCRs. These TCRs did not facilitate thymic T-reg-cell development, implying that many colonic T-reg cells arise instead by means of antigen-driven peripheral T-reg-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic T-reg cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo T-reg-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of T-reg cells in response to an individual's microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.
C1 [Lathrop, Stephanie K.; Rao, Sindhuja M.; Nutsch, Katherine; Lio, Chan-Wang; Santacruz, Nicole; Hsieh, Chyi-Song] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA.
   [Bloom, Seth M.; Stappenbeck, Thaddeus S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Peterson, Daniel A.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of Nebraska System; University of Nebraska Lincoln
RP Hsieh, CS (corresponding author), Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA.
EM chsieh@wustl.edu
FU National Institute of Allergy and Infectious Diseases; Burroughs-Wellcome Fund; National Institutes of Health [5T32AI0071632]; National Institute of Allergy and Infectious Diseases [T32AI007163, R01AI079187] Funding Source: NIH RePORTER
NR 34
TC 829
Z9 1039
U1 1
U2 116
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 250
EP U142
DI 10.1038/nature10434
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800052
PM 21937990
DA 2026-03-09
ER

PT J
AU Zuber, J
   Shi, JW
   Wang, E
   Rappaport, AR
   Herrmann, H
   Sison, EA
   Magoon, D
   Qi, J
   Blatt, K
   Wunderlich, M
   Taylor, MJ
   Johns, C
   Chicas, A
   Mulloy, JC
   Kogan, SC
   Brown, P
   Valent, P
   Bradner, JE
   Lowe, SW
   Vakoc, CR
AF Zuber, Johannes
   Shi, Junwei
   Wang, Eric
   Rappaport, Amy R.
   Herrmann, Harald
   Sison, Edward A.
   Magoon, Daniel
   Qi, Jun
   Blatt, Katharina
   Wunderlich, Mark
   Taylor, Meredith J.
   Johns, Christopher
   Chicas, Agustin
   Mulloy, James C.
   Kogan, Scott C.
   Brown, Patrick
   Valent, Peter
   Bradner, James E.
   Lowe, Scott W.
   Vakoc, Christopher R.
TI RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
SO NATURE
LA English
DT Article
ID transcriptional program; h3k79 methylation; stem-cells; in-vivo; c-myc; classification; leukemogenesis; expression; mll-af9; inhibition
AB Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs(1). Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states(2). By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.
C1 [Lowe, Scott W.; Vakoc, Christopher R.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Zuber, Johannes] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
   [Shi, Junwei] SUNY Stony Brook, Mol & Cellular Biol Program, Stony Brook, NY 11794 USA.
   [Rappaport, Amy R.; Lowe, Scott W.] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Sison, Edward A.; Magoon, Daniel; Brown, Patrick] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Baltimore, MD 21231 USA.
   [Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Blatt, Katharina; Valent, Peter] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria.
   [Wunderlich, Mark; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
   [Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
C3 Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); State University of New York (SUNY) System; Stony Brook University; Cold Spring Harbor Laboratory; Johns Hopkins University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Medical University of Vienna; Cincinnati Children's Hospital Medical Center; University of California System; University of California San Francisco
RP Vakoc, CR (corresponding author), Cold Spring Harbor Lab, Howard Hughes Med Inst, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM lowe@cshl.edu; vakoc@cshl.edu
FU Don Monti Memorial Research Foundation; Laurie Strauss Leukemia Foundation; German Research Foundation (DFG); CSHL; NIH; Barbara McClintock fellowship; Damon-Runyon Cancer Research Foundation; Smith Family Foundation; Damon Runyon-Lilly Clinical Investigator Award; Leukemia and Lymphoma Society (LLS); Leukemia and Lymphoma Society of America; National Cancer Institute; Howard Hughes Medical Institute; CSHL President's Council; SASS Foundation for Medical Research
NR 42
TC 1585
Z9 1953
U1 2
U2 301
PU 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 27
PY 2011
VL 478
IS 7370
BP 524
EP U124
DI 10.1038/nature10334
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200045
PM 21814200
DA 2026-03-09
ER

PT J
AU Lim, C
   Lee, J
   Choi, C
   Kilman, VL
   Kim, J
   Park, SM
   Jang, SK
   Allada, R
   Choe, J
AF Lim, Chunghun
   Lee, Jongbin
   Choi, Changtaek
   Kilman, Valerie L.
   Kim, Juwon
   Park, Sung Mi
   Jang, Sung Key
   Allada, Ravi
   Choe, Joonho
TI The novel gene twenty-four defines a critical translational step in the Drosophila clock
SO NATURE
LA English
DT Article
ID messenger-rna translation; circadian-rhythms; binding-protein; period protein; molecular oscillations; expression; neurons; system; ablation; orange
AB Daily oscillations of gene expression underlie circadian behaviours in multicellular organisms(1). While attention has been focused on transcriptional and post-translational mechanisms(1-3), other post-transcriptional modes have been less clearly delineated. Here we report mutants of a novel Drosophila gene twenty-four (tyf) that show weak behavioural rhythms. Weak rhythms are accompanied by marked reductions in the levels of the clock protein Period (PER) as well as more modest effects on Timeless (TIM). Nonetheless, PER induction in pacemaker neurons can rescue tyf mutant rhythms. TYF associates with a 5'-cap-binding complex, poly(A)-binding protein (PABP), as well as per and tim transcripts. Furthermore, TYF activates reporter expression when tethered to reporter messenger RNA even in vitro. Taken together, these data indicate that TYF potently activates PER translation in pacemaker neurons to sustain robust rhythms, revealing a new and important role for translational control in the Drosophila circadian clock.
C1 [Lim, Chunghun; Kilman, Valerie L.; Allada, Ravi] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA.
   [Lee, Jongbin; Choi, Changtaek; Kim, Juwon; Choe, Joonho] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
   [Park, Sung Mi; Jang, Sung Key] Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea.
C3 Northwestern University; Korea Advanced Institute of Science & Technology (KAIST); Pohang University of Science & Technology (POSTECH)
RP Allada, R (corresponding author), Northwestern Univ, Dept Neurobiol & Physiol, 2153 Sheridan Rd, Evanston, IL 60208 USA.
EM r-allada@northwestern.edu; jchoe@kaist.ac.kr
FU Ministry of Education, Science and Technology, the Republic of Korea; National Institutes of Health [R01NS059042, R01NS052903, R01MH067870]
NR 51
TC 69
Z9 81
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 FEB 17
PY 2011
VL 470
IS 7334
BP 399
EP U152
DI 10.1038/nature09728
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100043
PM 21331043
DA 2026-03-09
ER

PT J
AU Ernst, J
   Kheradpour, P
   Mikkelsen, TS
   Shoresh, N
   Ward, LD
   Epstein, CB
   Zhang, XL
   Wang, L
   Issner, R
   Coyne, M
   Ku, MC
   Durham, T
   Kellis, M
   Bernstein, BE
AF Ernst, Jason
   Kheradpour, Pouya
   Mikkelsen, Tarjei S.
   Shoresh, Noam
   Ward, Lucas D.
   Epstein, Charles B.
   Zhang, Xiaolan
   Wang, Li
   Issner, Robbyn
   Coyne, Michael
   Ku, Manching
   Durham, Timothy
   Kellis, Manolis
   Bernstein, Bradley E.
TI Mapping and analysis of chromatin state dynamics in nine human cell types
SO NATURE
LA English
DT Article
ID genome-wide association; transcription-factor-binding; embryonic stem-cells; gene-expression; histone modifications; susceptibility loci; enhancers; population; metaanalysis; promoters
AB Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.
C1 [Ernst, Jason; Kheradpour, Pouya; Mikkelsen, Tarjei S.; Shoresh, Noam; Ward, Lucas D.; Epstein, Charles B.; Zhang, Xiaolan; Wang, Li; Issner, Robbyn; Coyne, Michael; Ku, Manching; Durham, Timothy; Kellis, Manolis; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Ernst, Jason; Kheradpour, Pouya; Ward, Lucas D.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02114 USA.
   [Ku, Manching; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
   [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Kellis, M (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM manoli@mit.edu
FU National Human Genome Research Institute [U54 HG004570, R01 HG004037, RC1 HG005334]; Howard Hughes Medical Institute; National Science Foundation [0644282, 0905968]; Sloan Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0644282, 0905968] Funding Source: National Science Foundation
NR 65
TC 2203
Z9 2706
U1 1
U2 210
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 43
EP U52
DI 10.1038/nature09906
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300027
PM 21441907
DA 2026-03-09
ER

PT J
AU Siracusa, MC
   Saenz, SA
   Hill, DA
   Kim, BS
   Headley, MB
   Doering, TA
   Wherry, EJ
   Jessup, HK
   Siegel, LA
   Kambayashi, T
   Dudek, EC
   Kubo, M
   Cianferoni, A
   Spergel, JM
   Ziegler, SF
   Comeau, MR
   Artis, D
AF Siracusa, Mark C.
   Saenz, Steven A.
   Hill, David A.
   Kim, Brian S.
   Headley, Mark B.
   Doering, Travis A.
   Wherry, E. John
   Jessup, Heidi K.
   Siegel, Lori A.
   Kambayashi, Taku
   Dudek, Emily C.
   Kubo, Masato
   Cianferoni, Antonella
   Spergel, Jonathan M.
   Ziegler, Steven F.
   Comeau, Michael R.
   Artis, David
TI TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation
SO NATURE
LA English
DT Article
ID thymic stromal lymphopoietin; cell; expression; immunity; sufficient; induction; infection; associate; variants; asthma
AB CD4(+) T-helper type 2 (T(H)2) cells, characterized by their expression of interleukin (IL)-4, IL-5, IL-9 and IL-13, are required for immunity to helminth parasites(1) and promote the pathological inflammation associated with asthma and allergic diseases(2). Polymorphisms in the gene encoding the cytokine thymic stromal lymphopoietin (TSLP) are associated with the development of multiple allergic disorders in humans, indicating that TSLP is a critical regulator of T(H)2 cytokine-associated inflammatory diseases(3-6). In support of genetic analyses, exaggerated TSLP production is associated with asthma, atopic dermatitis and food allergies in patients, and studies in murine systems demonstrated that TSLP promotes T(H)2 cytokine-mediated immunity and inflammation(5,7-12). However, the mechanisms through which TSLP induces T(H)2 cytokine responses remain poorly defined. Here we demonstrate that TSLP promotes systemic basophilia, that disruption of TSLP-TSLPR interactions results in defective basophil responses, and that TSLPR-sufficient basophils can restore T(H)2-cell-dependent immunity in vivo. TSLP acted directly on bone-marrow-resident progenitors to promote basophil responses selectively. Critically, TSLP could elicit basophil responses in both IL-3-IL-3R-sufficient and -deficient environments, and genome-wide transcriptional profiling and functional analyses identified heterogeneity between TSLP-elicited versus IL-3-elicited basophils. Furthermore, activated human basophils expressed TSLPR, and basophils isolated from eosinophilic oesophagitis patients were distinct from classical basophils. Collectively, these studies identify previously unrecognized heterogeneity within the basophil cell lineage and indicate that expression of TSLP may influence susceptibility to multiple allergic diseases by regulating basophil haematopoiesis and eliciting a population of functionally distinct basophils that promote T(H)2 cytokine-mediated inflammation.
C1 [Siracusa, Mark C.; Saenz, Steven A.; Hill, David A.; Kim, Brian S.; Doering, Travis A.; Wherry, E. John; Artis, David] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Siracusa, Mark C.; Saenz, Steven A.; Hill, David A.; Kim, Brian S.; Doering, Travis A.; Wherry, E. John; Artis, David] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Headley, Mark B.; Ziegler, Steven F.] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA.
   [Headley, Mark B.; Ziegler, Steven F.] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98195 USA.
   [Jessup, Heidi K.; Siegel, Lori A.; Comeau, Michael R.] Amgen Inc, Inflammat Res, Seattle, WA 98119 USA.
   [Kambayashi, Taku] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Dudek, Emily C.; Cianferoni, Antonella; Spergel, Jonathan M.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Allergy & Immunol,Dept Pediat, Philadelphia, PA 19104 USA.
   [Kubo, Masato] RIKEN, Yokohama Inst, Res Ctr Allergy & Immunol, Lab Signal Network, Yokohama, Kanagawa 2300045, Japan.
   [Kubo, Masato] Tokyo Univ Sci, Res Inst Biol Sci, Div Mol Pathol, Chiba 2780022, Japan.
   [Artis, David] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; Benaroya Research Institute; University of Washington; University of Washington Seattle; Amgen; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; RIKEN; Tokyo University of Science; University of Pennsylvania
RP Artis, D (corresponding author), Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM dartis@mail.med.upenn.edu
FU National Institutes of Health [AI61570, AI74878, AI87990, AI083480, AI085828, GM082187, AI060516]; Burroughs Wellcome Fund; National Institute of Allergy and Infectious Diseases [R01AI095466, U01AI095608] Funding Source: NIH RePORTER
NR 32
TC 421
Z9 475
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 SEP 8
PY 2011
VL 477
IS 7363
BP 229
EP U138
DI 10.1038/nature10329
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900040
PM 21841801
DA 2026-03-09
ER

PT J
AU Weiss, J
   Pyrski, M
   Jacobi, E
   Bufe, B
   Willnecker, V
   Schick, B
   Zizzari, P
   Gossage, SJ
   Greer, CA
   Leinders-Zufall, T
   Woods, CG
   Wood, JN
   Zufall, F
AF Weiss, Jan
   Pyrski, Martina
   Jacobi, Eric
   Bufe, Bernd
   Willnecker, Vivienne
   Schick, Bernhard
   Zizzari, Philippe
   Gossage, Samuel J.
   Greer, Charles A.
   Leinders-Zufall, Trese
   Woods, C. Geoffrey
   Wood, John N.
   Zufall, Frank
TI Loss-of-function mutations in sodium channel Nav1.7 cause anosmia
SO NATURE
LA English
DT Article
ID mouse olfactory-bulb; pain; expression; system; rat; receptor; organization; deletion; subunit; reveals
AB Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.
C1 [Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Leinders-Zufall, Trese; Zufall, Frank] Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany.
   [Willnecker, Vivienne; Schick, Bernhard] Univ Saarland, Dept Otolaryngol, Sch Med, D-66421 Homburg, Germany.
   [Zizzari, Philippe] Univ Paris 05, Fac Med, INSERM, Ctr Psychiat & Neurosci,UMR 894, F-75014 Paris, France.
   [Gossage, Samuel J.; Wood, John N.] UCL, Wolfson Inst Biomed Res, Mol Nocicept Grp, London WC1E 6BT, England.
   [Greer, Charles A.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA.
   [Woods, C. Geoffrey] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England.
   [Wood, John N.] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea.
C3 Saarland University; Saarland University; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); University of London; University College London; Yale University; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Seoul National University (SNU)
RP Zufall, F (corresponding author), Univ Saarland, Dept Physiol, Sch Med, D-66421 Homburg, Germany.
EM frank.zufall@uks.eu
FU Deutsche Forschungsgemeinschaft (DFG) [SFB 530, SFB 894, GK 1326]; Biotechnology and Biological Sciences Research Council; Medical Research Council; Wellcome Trust; Korean Ministry of Education, Science and Technology [R31-2008-000-10103-0]; National Research Foundation of Korea; BBSRC [BB/F000227/1] Funding Source: UKRI; MRC [G0901905] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F000227/1] Funding Source: researchfish; Medical Research Council [G0901905] Funding Source: researchfish
NR 37
TC 246
Z9 298
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 APR 14
PY 2011
VL 472
IS 7342
BP 186
EP 190
DI 10.1038/nature09975
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100035
PM 21441906
DA 2026-03-09
ER

PT J
AU Suhre, K
   Shin, SY
   Petersen, AK
   Mohney, RP
   Meredith, D
   Wägele, B
   Altmaier, E
   Deloukas, P
   Erdmann, J
   Grundberg, E
   Hammond, CJ
   de Angelis, MH
   Kastenmüller, G
   Köttgen, A
   Kronenberg, F
   Mangino, M
   Meisinger, C
   Meitinger, T
   Mewes, HW
   Milburn, MV
   Prehn, C
   Raffler, J
   Ried, JS
   Römisch-Margl, W
   Samani, NJ
   Small, KS
   Wichmann, HE
   Zhai, GJ
   Illig, T
   Spector, TD
   Adamski, J
   Soranzo, N
   Gieger, C
AF Suhre, Karsten
   Shin, So-Youn
   Petersen, Ann-Kristin
   Mohney, Robert P.
   Meredith, David
   Waegele, Brigitte
   Altmaier, Elisabeth
   Deloukas, Panos
   Erdmann, Jeanette
   Grundberg, Elin
   Hammond, Christopher J.
   Hrabe de Angelis, Martin
   Kastenmueller, Gabi
   Koettgen, Anna
   Kronenberg, Florian
   Mangino, Massimo
   Meisinger, Christa
   Meitinger, Thomas
   Mewes, Hans-Werner
   Milburn, Michael V.
   Prehn, Cornelia
   Raffler, Johannes
   Ried, Janina S.
   Roemisch-Margl, Werner
   Samani, Nilesh J.
   Small, Kerrin S.
   Wichmann, H. -Erich
   Zhai, Guangju
   Illig, Thomas
   Spector, Tim D.
   Adamski, Jerzy
   Soranzo, Nicole
   Gieger, Christian
TI Human metabolic individuality in biomedical and pharmaceutical research
SO NATURE
LA English
DT Article
ID genome-wide association; genetic-variation; kidney-function; loci; transporter; variants; metaanalysis; contribute; risk; tool
AB Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.
C1 [Suhre, Karsten; Waegele, Brigitte; Altmaier, Elisabeth; Kastenmueller, Gabi; Raffler, Johannes; Roemisch-Margl, Werner] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, D-85764 Neuherberg, Germany.
   [Suhre, Karsten; Raffler, Johannes] Univ Munich, Fac Biol, D-82152 Planegg Martinsried, Germany.
   [Suhre, Karsten] Qatar Fdn, Weill Cornell Med Coll Qatar, Dept Physiol & Biophys, Doha, Qatar.
   [Shin, So-Youn; Deloukas, Panos; Grundberg, Elin; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Petersen, Ann-Kristin; Ried, Janina S.; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
   [Mohney, Robert P.; Milburn, Michael V.] Metabolon Inc, Res Triangle Pk, NC 27709 USA.
   [Meredith, David] Oxford Brookes Univ, Sch Life Sci, Oxford OX3 0BP, England.
   [Waegele, Brigitte; Mewes, Hans-Werner] Tech Univ Munich, Dept Genome Oriented Bioinformat, Life & Food Sci Ctr Weihenstephan, D-85354 Freising Weihenstephan, Germany.
   [Erdmann, Jeanette] Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
   [Grundberg, Elin; Hammond, Christopher J.; Mangino, Massimo; Small, Kerrin S.; Zhai, Guangju; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Hrabe de Angelis, Martin; Prehn, Cornelia; Adamski, Jerzy] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Genome Anal Ctr, Inst Expt Genet, D-85764 Neuherberg, Germany.
   [Hrabe de Angelis, Martin; Adamski, Jerzy] Tech Univ Munich, Life & Food Sci Ctr Weihenstephan, Inst Expt Genet, D-85354 Freising Weihenstephan, Germany.
   [Koettgen, Anna] Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany.
   [Kronenberg, Florian] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
   [Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
   [Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
   [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
   [Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE1 7RH, Leics, England.
   [Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
   [Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, D-80539 Munich, Germany.
   [Wichmann, H. -Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
   [Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; Qatar Foundation (QF); Weill Cornell Medical College Qatar; Wellcome Trust Sanger Institute; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Metabolon; Oxford Brookes University; Technical University of Munich; University of Lubeck; University of London; King's College London; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; University of Freiburg; Medical University of Innsbruck; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; University of Leicester; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health
RP Suhre, K (corresponding author), German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM karsten@suhre.fr; ns6@sanger.ac.uk
FU Helmholtz Zentrum Munchen; National Research Center for Environmental Health; German Federal Ministry of Education, Science, Research and Technology; State of Bavaria; German Federal Ministry of Education and Research (BMBF) [0315494A, 03IS2061B, 0315442A]; German National Genome Research Network [01GS0823]; Munich Center of Health Sciences (MC Health) aspart of LMUinnovativ; Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities [h1231]; Wellcome Trust; European Community [HEALTH-F2-2008-201865-GEFOS, QLG2-CT-2002-01254]; Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; Biotechnology and Biological Sciences Research Council (BBSRC) [G20234]; ENGAGE project [HEALTH-F4-2007-201413]; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease; National Eye Institute via an NIH/CIDR; Oxford Brookes University; DFG [Graduiertenkolleg GRK 1563]; German Research Foundation (DFG) [KO-3598/2-1]; Genomics of Lipid-associated Disorders (GOLD) of the Austrian Genome Research Programme (GEN-AU); Wellcome Trust [091746/Z/10/Z]
NR 50
TC 829
Z9 903
U1 0
U2 262
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 54
EP U60
DI 10.1038/nature10354
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300029
PM 21886157
DA 2026-03-09
ER

PT J
AU Giri, G
   Verploegen, E
   Mannsfeld, SCB
   Atahan-Evrenk, S
   Kim, DH
   Lee, SY
   Becerril, HA
   Aspuru-Guzik, A
   Toney, MF
   Bao, ZA
AF Giri, Gaurav
   Verploegen, Eric
   Mannsfeld, Stefan C. B.
   Atahan-Evrenk, Sule
   Kim, Do Hwan
   Lee, Sang Yoon
   Becerril, Hector A.
   Aspuru-Guzik, Alan
   Toney, Michael F.
   Bao, Zhenan
TI Tuning charge transport in solution-sheared organic semiconductors using lattice strain
SO NATURE
LA English
DT Article
ID field-effect transistors; thin-film transistors; pentacene derivatives; high-performance; electronics; mobility
AB Circuits based on organic semiconductors are being actively explored for flexible, transparent and low-cost electronic applications(1-5). But to realize such applications, the charge carrier mobilities of solution-processed organic semiconductors must be improved. For inorganic semiconductors, a general method of increasing charge carrier mobility is to introduce strain within the crystal lattice(6). Here we describe a solution-processing technique for organic semiconductors in which lattice strain is used to increase charge carrier mobilities by introducing greater electron orbital overlap between the component molecules. For organic semiconductors, the spacing between cofacially stacked, conjugated backbones (the pi-pi stacking distance) greatly influences electron orbital overlap and therefore mobility(7). Using our method to incrementally introduce lattice strain, we alter the pi-pi stacking distance of 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene) from 3.33 angstrom to 3.08 angstrom. We believe that 3.08 angstrom is the shortest pi-pi stacking distance that has been achieved in an organic semiconductor crystal lattice (although a pi-pi distance of 3.04 angstrom has been achieved through intramolecular bonding(8-10)). The positive charge carrier (hole) mobility in TIPS-pentacene transistors increased from 0.8 cm(2) V-1 s(-1) for unstrained films to a high mobility of 4.6 cm(2) V-1 s(-1) for a strained film. Using solution processing to modify molecular packing through lattice strain should aid the development of high-performance, low-cost organic semiconducting devices.
C1 [Giri, Gaurav; Verploegen, Eric; Kim, Do Hwan; Bao, Zhenan] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
   [Verploegen, Eric; Mannsfeld, Stefan C. B.; Toney, Michael F.] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
   [Atahan-Evrenk, Sule; Aspuru-Guzik, Alan] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Lee, Sang Yoon] Samsung Adv Inst Technol, Display Device Lab, Yongin 449712, Kyunggi Do, South Korea.
   [Becerril, Hector A.] Brigham Young Univ Idaho, Dept Chem, Rexburg, ID 83460 USA.
C3 Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Harvard University; Samsung; Brigham Young University
RP Bao, ZA (corresponding author), Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
EM zbao@stanford.edu
FU National Science Foundation DMR-Solid State Chemistry [DMR-0705687-002]; Samsung Advanced Institute of Technology; Stanford University [SPO 25591130-45282-A]; Air Force Office of Scientific Research [FA9550-09-1-0256]; Eastman Kodak Corporation
NR 30
TC 1020
Z9 1147
U1 14
U2 1026
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 504
EP U124
DI 10.1038/nature10683
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000056
PM 22193105
DA 2026-03-09
ER

PT J
AU Garcia, V
   Phelps, SEL
   Gray, S
   Neale, MJ
AF Garcia, Valerie
   Phelps, Sarah E. L.
   Gray, Stephen
   Neale, Matthew J.
TI Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1
SO NATURE
LA English
DT Article
ID rad32(mre11) nuclease; meiosis; ctp1(ctip); mutation; removal; repair; roles; axis; sae2
AB Repair of DNA double-strand breaks (DSBs) by homologous recombination requires resection of 5'-termini to generate 3'-single-strand DNA tails(1). Key components of this reaction are exonuclease 1 and the bifunctional endo/exonuclease, Mre11 (refs 2-4). Mre11 endonuclease activity is critical when DSB termini are blocked by bound protein-such as by the DNA end-joining complex(5), topoisomerases(6) or the meiotic transesterase Spo11 (refs 7-13)-but a specific function for the Mre11 3'-5' exonuclease activity has remained elusive. Here we use Saccharomyces cerevisiae to reveal a role for the Mre11 exonuclease during the resection of Spo11-linked 5'-DNA termini in vivo. We show that the residual resection observed in Exo1-mutant cells is dependent on Mre11, and that both exonuclease activities are required for efficient DSB repair. Previous work has indicated that resection traverses unidirectionally(1). Using a combination of physical assays for 5'-end processing, our results indicate an alternative mechanism involving bidirectional resection. First, Mre11 nicks the strand to be resected up to 300 nucleotides from the 5'-terminus of the DSB-much further away than previously assumed. Second, this nick enables resection in a bidirectional manner, using Exo1 in the 5'-3' direction away from the DSB, and Mre11 in the 3'-5' direction towards the DSB end. Mre11 exonuclease activity also confers resistance to DNA damage in cycling cells, suggesting that Mre11-catalysed resection may be a general feature of various DNA repair pathways.
C1 [Garcia, Valerie; Phelps, Sarah E. L.; Gray, Stephen; Neale, Matthew J.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
C3 University of Sussex
RP Neale, MJ (corresponding author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
EM m.neale@sussex.ac.uk
FU MRC; Royal Society; Human Frontiers Science Program Organisation; MRC [G0800005] Funding Source: UKRI; Medical Research Council [G0800005] Funding Source: researchfish
NR 30
TC 349
Z9 456
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 NOV 10
PY 2011
VL 479
IS 7372
BP 241
EP U123
DI 10.1038/nature10515
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800045
PM 22002605
DA 2026-03-09
ER

PT J
AU Locke, DP
   Hillier, LW
   Warren, WC
   Worley, KC
   Nazareth, LV
   Muzny, DM
   Yang, SP
   Wang, ZY
   Chinwalla, AT
   Minx, P
   Mitreva, M
   Cook, L
   Delehaunty, KD
   Fronick, C
   Schmidt, H
   Fulton, LA
   Fulton, RS
   Nelson, JO
   Magrini, V
   Pohl, C
   Graves, TA
   Markovic, C
   Cree, A
   Dinh, HH
   Hume, J
   Kovar, CL
   Fowler, GR
   Lunter, G
   Meader, S
   Heger, A
   Ponting, CP
   Marques-Bonet, T
   Alkan, C
   Chen, L
   Cheng, Z
   Kidd, JM
   Eichler, EE
   White, S
   Searle, S
   Vilella, AJ
   Chen, YA
   Flicek, P
   Ma, JA
   Raney, B
   Suh, B
   Burhans, R
   Herrero, J
   Haussler, D
   Faria, R
   Fernando, O
   Darré, F
   Farré, D
   Gazave, E
   Oliva, M
   Navarro, A
   Roberto, R
   Capozzi, O
   Archidiacono, N
   Della Valle, G
   Purgato, S
   Rocchi, M
   Konkel, MK
   Walker, JA
   Ullmer, B
   Batzer, MA
   Smit, AFA
   Hubley, R
   Casola, C
   Schrider, DR
   Hahn, MW
   Quesada, V
   Puente, XS
   Ordoñez, GR
   López-Otín, C
   Vinar, T
   Brejova, B
   Ratan, A
   Harris, RS
   Miller, W
   Kosiol, C
   Lawson, HA
   Taliwal, V
   Martins, AL
   Siepel, A
   RoyChoudhury, A
   Ma, X
   Degenhardt, J
   Bustamante, CD
   Gutenkunst, RN
   Mailund, T
   Dutheil, JY
   Hobolth, A
   Schierup, MH
   Ryder, OA
   Yoshinaga, Y
   de Jong, PJ
   Weinstock, GM
   Rogers, J
   Mardis, ER
   Gibbs, RA
   Wilson, RK
AF Locke, Devin P.
   Hillier, LaDeana W.
   Warren, Wesley C.
   Worley, Kim C.
   Nazareth, Lynne V.
   Muzny, Donna M.
   Yang, Shiaw-Pyng
   Wang, Zhengyuan
   Chinwalla, Asif T.
   Minx, Pat
   Mitreva, Makedonka
   Cook, Lisa
   Delehaunty, Kim D.
   Fronick, Catrina
   Schmidt, Heather
   Fulton, Lucinda A.
   Fulton, Robert S.
   Nelson, Joanne O.
   Magrini, Vincent
   Pohl, Craig
   Graves, Tina A.
   Markovic, Chris
   Cree, Andy
   Dinh, Huyen H.
   Hume, Jennifer
   Kovar, Christie L.
   Fowler, Gerald R.
   Lunter, Gerton
   Meader, Stephen
   Heger, Andreas
   Ponting, Chris P.
   Marques-Bonet, Tomas
   Alkan, Can
   Chen, Lin
   Cheng, Ze
   Kidd, Jeffrey M.
   Eichler, Evan E.
   White, Simon
   Searle, Stephen
   Vilella, Albert J.
   Chen, Yuan
   Flicek, Paul
   Ma, Jian
   Raney, Brian
   Suh, Bernard
   Burhans, Richard
   Herrero, Javier
   Haussler, David
   Faria, Rui
   Fernando, Olga
   Darre, Fleur
   Farre, Domenec
   Gazave, Elodie
   Oliva, Meritxell
   Navarro, Arcadi
   Roberto, Roberta
   Capozzi, Oronzo
   Archidiacono, Nicoletta
   Della Valle, Giuliano
   Purgato, Stefania
   Rocchi, Mariano
   Konkel, Miriam K.
   Walker, Jerilyn A.
   Ullmer, Brygg
   Batzer, Mark A.
   Smit, Arian F. A.
   Hubley, Robert
   Casola, Claudio
   Schrider, Daniel R.
   Hahn, Matthew W.
   Quesada, Victor
   Puente, Xose S.
   Ordonez, Gonzalo R.
   Lopez-Otin, Carlos
   Vinar, Tomas
   Brejova, Brona
   Ratan, Aakrosh
   Harris, Robert S.
   Miller, Webb
   Kosiol, Carolin
   Lawson, Heather A.
   Taliwal, Vikas
   Martins, Andre L.
   Siepel, Adam
   RoyChoudhury, Arindam
   Ma, Xin
   Degenhardt, Jeremiah
   Bustamante, Carlos D.
   Gutenkunst, Ryan N.
   Mailund, Thomas
   Dutheil, Julien Y.
   Hobolth, Asger
   Schierup, Mikkel H.
   Ryder, Oliver A.
   Yoshinaga, Yuko
   de Jong, Pieter J.
   Weinstock, George M.
   Rogers, Jeffrey
   Mardis, Elaine R.
   Gibbs, Richard A.
   Wilson, Richard K.
TI Comparative and demographic analysis of orang-utan genomes
SO NATURE
LA English
DT Article
ID low nucleotide diversity; retrotransposons; chimpanzees; evolution; humans; ancestor; sequence
AB 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal(1), far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (Ne) expanded exponentially relative to the ancestral Ne after the split, while Bornean Ne declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.
C1 [Locke, Devin P.; Hillier, LaDeana W.; Warren, Wesley C.; Yang, Shiaw-Pyng; Wang, Zhengyuan; Chinwalla, Asif T.; Minx, Pat; Mitreva, Makedonka; Cook, Lisa; Delehaunty, Kim D.; Fronick, Catrina; Schmidt, Heather; Fulton, Lucinda A.; Fulton, Robert S.; Nelson, Joanne O.; Magrini, Vincent; Pohl, Craig; Graves, Tina A.; Markovic, Chris; Weinstock, George M.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [Worley, Kim C.; Nazareth, Lynne V.; Muzny, Donna M.; Cree, Andy; Dinh, Huyen H.; Hume, Jennifer; Kovar, Christie L.; Fowler, Gerald R.; Rogers, Jeffrey; Gibbs, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Lunter, Gerton; Meader, Stephen; Heger, Andreas; Ponting, Chris P.] Univ Oxford, MRC, Funct Genom Unit, Oxford OX1 3QX, England.
   [Lunter, Gerton; Meader, Stephen; Heger, Andreas; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Marques-Bonet, Tomas; Alkan, Can; Chen, Lin; Cheng, Ze; Kidd, Jeffrey M.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Marques-Bonet, Tomas; Faria, Rui; Fernando, Olga; Darre, Fleur; Farre, Domenec; Gazave, Elodie; Oliva, Meritxell; Navarro, Arcadi] Univ Pompeu Fabra, PRBB, CSIC, IBE, Barcelona 08003, Spain.
   [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [White, Simon; Searle, Stephen] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Vilella, Albert J.; Chen, Yuan; Flicek, Paul; Herrero, Javier] European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Ma, Jian; Raney, Brian; Suh, Bernard; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Burhans, Richard; Ratan, Aakrosh; Harris, Robert S.; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Faria, Rui] Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO, P-4485661 Vairao, Portugal.
   [Fernando, Olga] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780157 Oeiras, Portugal.
   [Navarro, Arcadi] ICREA, Barcelona 08003, Spain.
   [Navarro, Arcadi] PRBB, INB, Barcelona 08003, Spain.
   [Roberto, Roberta; Capozzi, Oronzo; Archidiacono, Nicoletta; Rocchi, Mariano] Univ Bari, Dept Biol, I-70125 Bari, Italy.
   [Della Valle, Giuliano; Purgato, Stefania] Univ Bologna, Dept Biol, I-40126 Bologna, Italy.
   [Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Ullmer, Brygg] Louisiana State Univ, Dept Comp Sci, Ctr Computat & Technol, Baton Rouge, LA 70803 USA.
   [Smit, Arian F. A.; Hubley, Robert] Inst Syst Biol, Seattle, WA 98103 USA.
   [Casola, Claudio; Schrider, Daniel R.; Hahn, Matthew W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Casola, Claudio; Schrider, Daniel R.; Hahn, Matthew W.] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
   [Quesada, Victor; Puente, Xose S.; Ordonez, Gonzalo R.; Lopez-Otin, Carlos] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, E-33006 Oviedo, Spain.
   [Vinar, Tomas; Brejova, Brona] Comenius Univ, Fac Math Phys & Informat, Bratislava 84248, Slovakia.
   [Kosiol, Carolin] Vetmeduni Vienna, Inst Populat Genet, A-1210 Vienna, Austria.
   [Lawson, Heather A.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [Taliwal, Vikas; Martins, Andre L.; Siepel, Adam; Ma, Xin; Degenhardt, Jeremiah] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [RoyChoudhury, Arindam] Columbia Univ, Dept Biostat, New York, NY 10032 USA.
   [Bustamante, Carlos D.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Gutenkunst, Ryan N.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA.
   [Mailund, Thomas; Dutheil, Julien Y.; Hobolth, Asger; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
   [Ryder, Oliver A.] San Diego Zoos Inst Conservat Res, Escondido, CA 92027 USA.
   [Yoshinaga, Yuko; de Jong, Pieter J.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
C3 Washington University (WUSTL); Baylor College of Medicine; University of Oxford; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; University of Washington; University of Washington Seattle; Pompeu Fabra University; Barcelona Biomedical Research Park; Consejo Superior de Investigaciones Cientificas (CSIC); University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of California System; University of California Santa Cruz; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Universidade do Porto; Universidade Nova de Lisboa; ICREA; Pompeu Fabra University; Barcelona Biomedical Research Park; Universita degli Studi di Bari Aldo Moro; University of Bologna; Louisiana State University System; Louisiana State University; Louisiana State University System; Louisiana State University; Institute for Systems Biology (ISB); Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington; University of Oviedo; Instituto Universitario de Oncologia de Asturias; Comenius University Bratislava; University of Veterinary Medicine Vienna; Washington University (WUSTL); Cornell University; Columbia University; Stanford University; University of Arizona; Aarhus University; Zoological Society of San Diego; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute
RP Locke, DP (corresponding author), Washington Univ, Sch Med, Genome Ctr, 4444 Forest Pk Ave, St Louis, MO 63108 USA.
EM dlocke@wustl.edu; wwarren@wustl.edu
FU National Human Genome Research Institute (NHGRI) [U54 HG003079, U54 HG003273]; National Institutes of Health [R01 GM59290, PO1 AG022064, HG002385, HG002238]; National Science Foundation [DBI-0644111]; David and Lucile Packard Foundation; Cornell University; UK Medical Research Council; Marie Curie Fellowship; Ministerio de Ciencia e Innovacion-Spain (MCI-Spain); Fundacion M. Botin; MCI-Spain [BFU2006-15413-C02-01, BFU2009-13409-C02-02]; Spanish National Institute for Bioinformatics (INAB); Fundacao para a Ciencia e a Tecnologia (Portugal) [SFRH/BPD/26384/2006, SFRH/BD/15856/2005]; PRIN; CEGBA; Commission of the European Communities [IRG-224885, IRG-231025]; Fundação para a Ciência e a Tecnologia [SFRH/BD/15856/2005, SFRH/BPD/26384/2006] Funding Source: FCT; ICREA Funding Source: Custom; National Human Genome Research Institute [R01HG002385, R01HG002939] Funding Source: NIH RePORTER; Medical Research Council [MC_U137761446, G0501331] Funding Source: researchfish; MRC [G0501331, MC_U137761446] Funding Source: UKRI
NR 30
TC 410
Z9 508
U1 3
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 27
PY 2011
VL 469
IS 7331
BP 529
EP 533
DI 10.1038/nature09687
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500032
PM 21270892
DA 2026-03-09
ER

PT J
AU Allison, KR
   Brynildsen, MP
   Collins, JJ
AF Allison, Kyle R.
   Brynildsen, Mark P.
   Collins, James J.
TI Metabolite-enabled eradication of bacterial persisters by aminoglycosides
SO NATURE
LA English
DT Article
ID escherichia-coli; pseudomonas-aeruginosa; antibiotic tolerance; cells; resistance; mechanism; biofilms; roles; death; antimicrobials
AB Bacterial persistence is a state in which a sub-population of dormant cells, or 'persisters', tolerates antibiotic treatment(1-4). Bacterial persisters have been implicated in biofilms and in chronic and recurrent infections(5-7). Despite this clinical relevance, there are currently no viable means for eradicating persisters. Here we show that specific metabolic stimuli enable the killing of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) persisters with aminoglycosides. This potentiation is aminoglycoside-specific, it does not rely on growth resumption and it is effective in both aerobic and anaerobic conditions. It proceeds by the generation of a proton-motive force which facilitates aminoglycoside uptake. Our results demonstrate that persisters, although dormant, are primed for metabolite uptake, central metabolism and respiration. We show that aminoglycosides can be used in combination with specific metabolites to treat E. coli and S. aureus biofilms. Furthermore, we demonstrate that this approach can improve the treatment of chronic infections in a mouse urinary tract infection model. This work establishes a strategy for eradicating bacterial persisters that is based on metabolism, and highlights the importance of the metabolic environment to antibiotic treatment.
C1 [Allison, Kyle R.; Brynildsen, Mark P.; Collins, James J.] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Ctr Biodynam, Boston, MA 02215 USA.
   [Collins, James J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02118 USA.
C3 Howard Hughes Medical Institute; Boston University; Boston University; Harvard University
RP Collins, JJ (corresponding author), Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Ctr Biodynam, Boston, MA 02215 USA.
EM jcollins@bu.edu
FU NIH; Howard Hughes Medical Institute
NR 30
TC 805
Z9 954
U1 8
U2 335
PU 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 12
PY 2011
VL 473
IS 7346
BP 216
EP +
DI 10.1038/nature10069
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200039
PM 21562562
DA 2026-03-09
ER

PT J
AU Huh, JR
   Leung, MWL
   Huang, PX
   Ryan, DA
   Krout, MR
   Malapaka, RRV
   Chow, J
   Manel, N
   Ciofani, M
   Kim, SV
   Cuesta, A
   Santori, FR
   Lafaille, JJ
   Xu, HE
   Gin, DY
   Rastinejad, F
   Littman, DR
AF Huh, Jun R.
   Leung, Monica W. L.
   Huang, Pengxiang
   Ryan, Daniel A.
   Krout, Michael R.
   Malapaka, Raghu R. V.
   Chow, Jonathan
   Manel, Nicolas
   Ciofani, Maria
   Kim, Sangwon V.
   Cuesta, Adolfo
   Santori, Fabio R.
   Lafaille, Juan J.
   Xu, H. Eric
   Gin, David Y.
   Rastinejad, Fraydoon
   Littman, Dan R.
TI Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity
SO NATURE
LA English
DT Article
ID genome-wide association; sodium/potassium-atpase; cardiac-glycosides; ligand-binding; beta; il-23; alpha; populations; digitalis; gut
AB CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in T(H)17 cell differentiation and function with susceptibility to Crohn's disease, rheumatoid arthritis and psoriasis(1-3). Thus, the pathway towards differentiation of T(H)17 cells and, perhaps, of related innate lymphoid cells with similar effector functions(4,5), is an attractive target for therapeutic applications. Mouse and human T(H)17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor ROR gamma t, which is required for induction of IL-17 transcription and for the manifestation of T(H)17-dependent autoimmune disease in mice(6). By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of ROR gamma t transcriptional activity. Digoxin inhibited murine T(H)17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives 20,22-dihydrodigoxin-21,23-diol and digoxin-21-salicylidene specifically inhibited induction of IL-17 in human CD4(+) T cells. Using these small-molecule compounds, we demonstrate that ROR gamma t is important for the maintenance of IL-17 expression in mouse and human effector T cells. These data indicate that derivatives of digoxin can be used as chemical templates for the development of ROR gamma t-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
C1 [Huh, Jun R.; Leung, Monica W. L.; Chow, Jonathan; Manel, Nicolas; Ciofani, Maria; Kim, Sangwon V.; Cuesta, Adolfo; Santori, Fabio R.; Lafaille, Juan J.; Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA.
   [Huang, Pengxiang; Rastinejad, Fraydoon] Sanford Burnham Med Res Inst Lake Nona, Orlando, FL 32827 USA.
   [Ryan, Daniel A.; Krout, Michael R.; Gin, David Y.] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
   [Malapaka, Raghu R. V.; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
   [Chow, Jonathan; Cuesta, Adolfo; Littman, Dan R.] NYU, Howard Hughes Med Inst, Sch Med, New York, NY 10016 USA.
C3 New York University; Sanford Burnham Prebys Medical Discovery Institute; Memorial Sloan Kettering Cancer Center; Van Andel Institute; Van Andel Research Institute; Howard Hughes Medical Institute; New York University
RP Littman, DR (corresponding author), NYU, Sch Med, Mol Pathogenesis Program, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA.
EM Dan.Littman@med.nyu.edu
FU Jane Coffin Childs Memorial Funds; Howard Hughes Medical Institute; National Institutes of Health [F32GM0860552, RO1GM058833, RO1GM067659, 2RO1GM55217, RO1AI080885]
NR 30
TC 474
Z9 552
U1 1
U2 68
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 486
EP 490
DI 10.1038/nature09978
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600037
PM 21441909
DA 2026-03-09
ER

PT J
AU O'Neill, JS
   van Ooijen, G
   Dixon, LE
   Troein, C
   Corellou, F
   Bouget, FY
   Reddy, AB
   Millar, AJ
AF O'Neill, John S.
   van Ooijen, Gerben
   Dixon, Laura E.
   Troein, Carl
   Corellou, Florence
   Bouget, Francois-Yves
   Reddy, Akhilesh B.
   Millar, Andrew J.
TI Circadian rhythms persist without transcription in a eukaryote
SO NATURE
LA English
DT Article
ID clock; phosphorylation; ostreococcus; system; plants
AB Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants(1,2). This daily timekeeping is thought to be driven by transcriptional-translational feedback loops, whereby rhythmic expression of 'clock' gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms(3). The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes(4). Given that recent observations in animals and plants have revealed prominent post-translational contributions to time-keeping(5), a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals(6). Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria(7), and are conserved across kingdoms.
C1 [O'Neill, John S.; Reddy, Akhilesh B.] Univ Cambridge, Metab Res Labs, Addenbrookes Hosp, Inst Metab Sci,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
   [O'Neill, John S.; van Ooijen, Gerben; Dixon, Laura E.; Millar, Andrew J.] Ctr Syst Biol Edinburgh, Edinburgh EH9 3JD, Midlothian, Scotland.
   [Troein, Carl; Millar, Andrew J.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JH, Midlothian, Scotland.
   [Corellou, Florence; Bouget, Francois-Yves] Univ Paris 06, UMR7621, Lab Oceanog Microbienne, Observ Oceanol, F-66651 Banyuls Sur Mer, France.
   [Corellou, Florence; Bouget, Francois-Yves] CNRS, UMR7621, Lab Observ Oceanog Microbienne, Observ Oceanol, F-66651 Banyuls Sur Mer, France.
C3 University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Edinburgh; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Reddy, AB (corresponding author), Univ Cambridge, Metab Res Labs, Addenbrookes Hosp, Inst Metab Sci,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
EM areddy@cantab.net; Andrew.Millar@ed.ac.uk
FU BBSRC; EPSRC [D019621]; BBSRC/ANR [F005466]; HFSP; Wellcome Trust [083643/Z/07/Z]; MRC Centre for Obesity and Related metabolic Disorders (MRC CORD); Biotechnology and Biological Sciences Research Council [BB/F005466/1, BB/D019621/1] Funding Source: researchfish; BBSRC [BB/F005466/1, BB/D019621/1] Funding Source: UKRI; Wellcome Trust [083643/Z/07/Z] Funding Source: Wellcome Trust
NR 29
TC 406
Z9 464
U1 3
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 JAN 27
PY 2011
VL 469
IS 7331
BP 554
EP 558
DI 10.1038/nature09654
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500037
PM 21270895
DA 2026-03-09
ER

PT J
AU Madhusudhan, N
   Harrington, J
   Stevenson, KB
   Nymeyer, S
   Campo, CJ
   Wheatley, PJ
   Deming, D
   Blecic, J
   Hardy, RA
   Lust, NB
   Anderson, DR
   Collier-Cameron, A
   Britt, CBT
   Bowman, WC
   Hebb, L
   Hellier, C
   Maxted, PFL
   Pollacco, D
   West, RG
AF Madhusudhan, Nikku
   Harrington, Joseph
   Stevenson, Kevin B.
   Nymeyer, Sarah
   Campo, Christopher J.
   Wheatley, Peter J.
   Deming, Drake
   Blecic, Jasmina
   Hardy, Ryan A.
   Lust, Nate B.
   Anderson, David R.
   Collier-Cameron, Andrew
   Britt, Christopher B. T.
   Bowman, William C.
   Hebb, Leslie
   Hellier, Coel
   Maxted, Pierre F. L.
   Pollacco, Don
   West, Richard G.
TI A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b
SO NATURE
LA English
DT Article
ID giant planets; hot jupiters; hd 189733b; temperature; emission; photochemistry; chemistry; spectra; dwarfs; stars
AB The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth(1); the atmosphere can also differ from those in the Solar System(1,2). The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry(4,5) of the transiting hot Jupiter WASP-12b (ref. 6) that reveals C/O >= 1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T > 2,500 K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres(7-9).
C1 [Madhusudhan, Nikku] MIT, Cambridge, MA 02139 USA.
   [Harrington, Joseph; Stevenson, Kevin B.; Nymeyer, Sarah; Campo, Christopher J.; Blecic, Jasmina; Hardy, Ryan A.; Lust, Nate B.; Britt, Christopher B. T.; Bowman, William C.] Univ Cent Florida, Dept Phys, Planetary Sci Grp, Orlando, FL 32816 USA.
   [Wheatley, Peter J.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Deming, Drake] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Anderson, David R.; Hellier, Coel; Maxted, Pierre F. L.] Univ Keele, Astrophys Grp, Keele ST5 5BG, Staffs, England.
   [Collier-Cameron, Andrew] Univ St Andrews, Sch Phys & Astron, Haugh KY16 9SS, Fife, Scotland.
   [Hebb, Leslie] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA.
   [Pollacco, Don] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [West, Richard G.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
C3 Massachusetts Institute of Technology (MIT); State University System of Florida; University of Central Florida; University of Warwick; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Keele University; University of St Andrews; Vanderbilt University; Queens University Belfast; University of Leicester
RP Madhusudhan, N (corresponding author), Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
EM nmadhu@mit.edu
FU NASA; JPL/Caltech; STFC [PP/F000065/1, PP/F000073/1, PP/D000955/1, ST/I002308/1, PP/F000057/1, ST/F002599/1, PP/F000081/1, ST/G002355/1, ST/J000035/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/G002355/1, PP/F000081/1, PP/D000955/1, ST/I002308/1, PP/F000073/1, PP/F000057/1, ST/J000035/1, PP/F000065/1, ST/F002599/1] Funding Source: researchfish
NR 30
TC 257
Z9 304
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 64
EP 67
DI 10.1038/nature09602
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600031
PM 21150901
DA 2026-03-09
ER

PT J
AU Hansen, SB
   Tao, X
   MacKinnon, R
AF Hansen, Scott B.
   Tao, Xiao
   MacKinnon, Roderick
TI Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2
SO NATURE
LA English
DT Article
ID potassium channels; proteins
AB The regulation of ion channel activity by specific lipid molecules is widely recognized as an integral component of electrical signalling in cells(1,2). In particular, phosphatidylinositol 4,5-bisphosphate (PIP2), a minor yet dynamic phospholipid component of cell membranes, is known to regulate many different ion channels(2-8). PIP2 is the primary agonist for classical inward rectifier (Kir2) channels, through which this lipid can regulate a cell's resting membrane potential(2,7-9). However, the molecular mechanism by which PIP2 exerts its action is unknown. Here we present the X-ray crystal structure of a Kir2.2 channel in complex with a short-chain (dioctanoyl) derivative of PIP2. We found that PIP2 binds at an interface between the transmembrane domain (TMD) and the cytoplasmic domain (CTD). The PIP2-binding site consists of a conserved non-specific phospholipid-binding region in the TMD and a specific phosphatidylinositol-binding region in the CTD. On PIP2 binding, a flexible expansion linker contracts to a compact helical structure, the CTD translates 6 angstrom and becomes tethered to the TMD and the inner helix gate begins to open. In contrast, the small anionic lipid dioctanoyl glycerol pyrophosphatidic acid (PPA) also binds to the non-specific TMD region, but not to the specific phosphatidylinositol region, and thus fails to engage the CTD or open the channel. Our results show how PIP2 can control the resting membrane potential through a specific ion-channel-receptor-ligand interaction that brings about a large conformational change, analogous to neurotransmitter activation of ion channels at synapses.
C1 [Hansen, Scott B.; Tao, Xiao; MacKinnon, Roderick] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA.
C3 Rockefeller University; Howard Hughes Medical Institute
RP MacKinnon, R (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, 1230 York Ave, New York, NY 10065 USA.
EM mackinn@rockefeller.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIBIB NIH HHS [P30 EB009998] Funding Source: Medline
NR 30
TC 509
Z9 557
U1 0
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 495
EP U152
DI 10.1038/nature10370
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500047
PM 21874019
DA 2026-03-09
ER

PT J
AU Yoo, SK
   Starnes, TW
   Deng, Q
   Huttenlocher, A
AF Yoo, Sa Kan
   Starnes, Taylor W.
   Deng, Qing
   Huttenlocher, Anna
TI Lyn is a redox sensor that mediates leukocyte wound attraction in vivo
SO NATURE
LA English
DT Article
ID tyrosine kinase; src; zebrafish; neutrophils; activation; chemotaxis; resolution; adhesion
AB Tissue wounding induces the rapid recruitment of leukocytes(1). Wounds and tumours-a type of 'unhealed wound'(2)-generate hydrogen peroxide (H2O2) through an NADPH oxidase (NOX). This extracellular H2O2 mediates recruitment of leukocytes, particularly the first responders of innate immunity, neutrophils, to injured tissue(3-6). However, the sensor that neutrophils use to detect the redox state at wounds is unknown. Here we identify the Src family kinase (SFK) Lyn as a redox sensor that mediates initial neutrophil recruitment to wounds in zebrafish larvae. Lyn activation in neutrophils is dependent on wound-derived H2O2 after tissue injury, and inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of SFKs also disrupted H2O2-mediated chemotaxis of primary human neutrophils. In vitro analysis identified a single cysteine residue, C466, as being responsible for direct oxidation-mediated activation of Lyn. Furthermore, transgenic-tissue-specific reconstitution with wild-type Lyn and a cysteine mutant revealed that Lyn C466 is important for the neutrophil wound response and downstream signalling in vivo. This is the first identification, to our knowledge, of a physiological redox sensor that mediates leukocyte wound attraction in multicellular organisms.
C1 [Starnes, Taylor W.; Deng, Qing; Huttenlocher, Anna] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
   [Yoo, Sa Kan] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53706 USA.
   [Huttenlocher, Anna] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Huttenlocher, A (corresponding author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
EM huttenlocher@wisc.edu
FU American Heart Association [11PRE4890041]; National Institutes of Health [GM074827, 5T32 HL07899]; UW MSTP; National Heart Lung and Blood Institute [T32HL007899] Funding Source: NIH RePORTER; American Heart Association (AHA) [11PRE4890041] Funding Source: American Heart Association (AHA)
NR 39
TC 366
Z9 422
U1 0
U2 68
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 109
EP U278
DI 10.1038/nature10632
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900044
PM 22101434
DA 2026-03-09
ER

PT J
AU Wiedenheft, B
   Lander, GC
   Zhou, KH
   Jore, MM
   Brouns, SJJ
   van der Oost, J
   Doudna, JA
   Nogales, E
AF Wiedenheft, Blake
   Lander, Gabriel C.
   Zhou, Kaihong
   Jore, Matthijs M.
   Brouns, Stan J. J.
   van der Oost, John
   Doudna, Jennifer A.
   Nogales, Eva
TI Structures of the RNA-guided surveillance complex from a bacterial immune system
SO NATURE
LA English
DT Article
ID crispr rna; electron-microscopy; target recognition; seed sequence; prokaryotes; interference; repeats; dna; endoribonuclease; maturation
AB Bacteria and archaea acquire resistance to viruses and plasmids by integrating short fragments of foreign DNA into clustered regularly interspaced short palindromic repeats (CRISPRs). These repetitive loci maintain a genetic record of all prior encounters with foreign transgressors(1-6). CRISPRs are transcribed and the long primary transcript is processed into a library of short CRISPR-derived RNAs (crRNAs) that contain a unique sequence complementary to a foreign nucleic-acid challenger(7-12). In Escherichia coli, crRNAs are incorporated into a multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defence), which is required for protection against bacteriophages(13,14). Here we use cryo-electron microscopy to determine the subnanometre structures of Cascade before and after binding to a target sequence. These structures reveal a sea-horse-shaped architecture in which the crRNA is displayed along a helical arrangement of protein subunits that protect the crRNA from degradation while maintaining its availability for base pairing. Cascade engages invading nucleic acids through high-affinity base-pairing interactions near the 5' end of the crRNA. Base pairing extends along the crRNA, resulting in a series of short helical segments that trigger a concerted conformational change. This conformational rearrangement may serve as a signal that recruits a trans-acting nuclease (Cas3) for destruction of invading nucleic-acid sequences.
C1 [Wiedenheft, Blake; Zhou, Kaihong; Doudna, Jennifer A.; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Wiedenheft, Blake; Zhou, Kaihong; Doudna, Jennifer A.; Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Lander, Gabriel C.; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Jore, Matthijs M.; Brouns, Stan J. J.; van der Oost, John] Wageningen Univ, Dept Agrotechnol & Food Sci, Microbiol Lab, NL-6703 HB Wageningen, Netherlands.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Doudna, Jennifer A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Wageningen University & Research; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Doudna, JA (corresponding author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
EM doudna@berkeley.edu; enogales@lbl.gov
FU National Science Foundation; Veni grant [863.08.014]; NWO [865.05.001]; Damon Runyon Cancer Research Foundation
NR 31
TC 303
Z9 414
U1 2
U2 127
PU 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 22
PY 2011
VL 477
IS 7365
BP 486
EP U141
DI 10.1038/nature10402
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500045
PM 21938068
DA 2026-03-09
ER

PT J
AU Lange, J
   Pan, J
   Cole, F
   Thelen, MP
   Jasin, M
   Keeney, S
AF Lange, Julian
   Pan, Jing
   Cole, Francesca
   Thelen, Michael P.
   Jasin, Maria
   Keeney, Scott
TI ATM controls meiotic double-strand-break formation
SO NATURE
LA English
DT Article
ID mouse spermatocytes; chromosome synapsis; prophase arrest; recombination; mice; surveillance; defects; spo11; gene; phosphorylation
AB In many organisms, developmentally programmed double-strand breaks (DSBs) formed by the SPO11 transesterase initiate meiotic recombination, which promotes pairing and segregation of homologous chromosomes(1). Because every chromosome must receive a minimum number of DSBs, attention has focused on factors that support DSB formation(2). However, improperly repaired DSBs can cause meiotic arrest or mutation(3,4); thus, having too many DSBs is probably as deleterious as having too few. Only a small fraction of SPO11 protein ever makes a DSB in yeast or mouse(5) and SPO11 and its accessory factors remain abundant long after most DSB formation ceases(1), implying the existence of mechanisms that restrain SPO11 activity to limit DSB numbers. Here we report that the number of meiotic DSBs in mouse is controlled by ATM, a kinase activated by DNA damage to trigger checkpoint signalling and promote DSB repair. Levels of SPO11-oligonucleotide complexes, by-products of meiotic DSB formation, are elevated at least tenfold in spermatocytes lacking ATM. Moreover, Atm mutation renders SPO11-oligonucleotide levels sensitive to genetic manipulations that modulate SPO11 protein levels. We propose that ATM restrains SPO11 via a negative feedback loop in which kinase activation by DSBs suppresses further DSB formation. Our findings explain previously puzzling phenotypes of Atm-null mice and provide a molecular basis for the gonadal dysgenesis observed in ataxia telangiectasia, the human syndrome caused by ATM deficiency.
C1 [Lange, Julian; Pan, Jing; Keeney, Scott] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
   [Cole, Francesca; Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Thelen, Michael P.] Lawrence Livermore Natl Lab, Phys & Life Sci Directorate, Livermore, CA 94550 USA.
   [Keeney, Scott] 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; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center
RP Keeney, S (corresponding author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10065 USA.
EM m-jasin@ski.mskcc.org; s-keeney@ski.mskcc.org
FU NIH [HD040916, HD053855, GM058673]; Leukemia and Lymphoma Society; Ruth L. Kirschstein NRSA [F32HD51392]
NR 30
TC 197
Z9 220
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 237
EP U117
DI 10.1038/nature10508
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800044
PM 22002603
DA 2026-03-09
ER

PT J
AU Fernández, A
   Lynch, M
AF Fernandez, Ariel
   Lynch, Michael
TI Non-adaptive origins of interactome complexity
SO NATURE
LA English
DT Article
ID protein; dynamics; algorithms; evolution
AB The boundaries between prokaryotes, unicellular eukaryotes and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift and mutation(1). The resultant decline in the efficiency of selection seems to be sufficient to influence a wide range of attributes at the genomic level in a non-adaptive manner(2). A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels(2-4). Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relation between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein-protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by non-adaptive mechanisms.
C1 [Lynch, Michael] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Fernandez, Ariel] Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA.
   [Fernandez, Ariel] Rice Univ, Dept Bioengn, Houston, TX 77005 USA.
C3 Indiana University System; Indiana University Bloomington; University of Chicago; Rice University
RP Lynch, M (corresponding author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
EM ariel@uchicago.edu; milynch@indiana.edu
FU National Institutes of Health [R01GM072614, R01GM036827]; Institute of Biophysical Dynamics; Department of Computer Science at The University of Chicago; National Science Foundation [EF-0827411]
NR 30
TC 94
Z9 108
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2011
VL 474
IS 7352
BP 502
EP U130
DI 10.1038/nature09992
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700047
PM 21593762
DA 2026-03-09
ER

PT J
AU Wan, CH
   Zhang, XZ
   Gao, XL
   Wang, JM
   Tan, XY
AF Wan, Caihua
   Zhang, Xiaozhong
   Gao, Xili
   Wang, Jimin
   Tan, Xinyu
TI Geometrical enhancement of low-field magnetoresistance in silicon
SO NATURE
LA English
DT Article
ID giant magnetoresistance; hall-coefficient; room-temperature; semiconductors; inhomogeneity; nanostructures; metals
AB Inhomogeneity-induced magnetoresistance (IMR) reported in some non-magnetic semiconductors(1-8), particularly silicon(1,6-8), has generated considerable interest owing to the large magnitude of the effect and its linear field dependence (albeit at high magnetic fields). Various theories implicate(9-18) spatial variation of the carrier mobility as being responsible for IMR. Here we show that IMR in lightly doped silicon can be significantly enhanced through hole injection, and then tuned by an applied current to arise at low magnetic fields. In our devices, the 'inhomogeneity' is provided by the p-n boundary formed between regions where conduction is dominated by the minority and majority charge carriers (holes and electrons) respectively; application of a magnetic field distorts the current in the boundary region, resulting in large magnetoresistance. Because this is an intrinsically spatial effect, the geometry of the device can be used to enhance IMR further: we designed an IMR device whose room-temperature field sensitivity at low fields was greatly improved, with magnetoresistance reaching 10% at 0.07 T and 100% at 0.2 T, approaching the performance of commercial giant-magnetoresistance devices(19,20). The combination of high sensitivity to low magnetic fields and large high-field response should make this device concept attractive to the magnetic-field sensing industry. Moreover, because our device is based on a conventional silicon platform, it should be possible to integrate it with existing silicon devices and so aid the development of silicon-based magnetoelectronics.
C1 [Wan, Caihua; Zhang, Xiaozhong; Gao, Xili; Wang, Jimin; Tan, Xinyu] Tsinghua Univ, Dept Mat Sci & Engn, Adv Mat Lab, Beijing 100084, Peoples R China.
   [Wan, Caihua; Zhang, Xiaozhong; Gao, Xili; Wang, Jimin; Tan, Xinyu] Tsinghua Univ, Beijing Natl Ctr Electron Microscopy, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University
RP Zhang, XZ (corresponding author), Tsinghua Univ, Dept Mat Sci & Engn, Adv Mat Lab, Beijing 100084, Peoples R China.
EM xzzhang@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2009CB929202]; National Science Foundation of China [11074141, U0734001]
NR 25
TC 89
Z9 97
U1 1
U2 160
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 304
EP U68
DI 10.1038/nature10375
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400025
PM 21921912
DA 2026-03-09
ER

PT J
AU Shapiro, ND
   Rauniyar, V
   Hamilton, GL
   Wu, J
   Toste, FD
AF Shapiro, Nathan D.
   Rauniyar, Vivek
   Hamilton, Gregory L.
   Wu, Jeffrey
   Toste, F. Dean
TI Asymmetric additions to dienes catalysed by a dithiophosphoric acid
SO NATURE
LA English
DT Article
ID o,o-diethyldithiophosphoric acid; phosphoric-acid; hydroamination; alkenes
AB Chiral Bronsted acids (proton donors) have been shown to facilitate a broad range of asymmetric chemical transformations under catalytic conditions without requiring additional toxic or expensive metals(1-8). Although the catalysts developed thus far are remarkably effective at activating polarized functional groups, it is not clear whether organic Bronsted acids can be used to catalyse highly enantioselective transformations of unactivated carbon-carbon multiple bonds. This deficiency persists despite the fact that racemic acid-catalysed 'Markovnikov' additions to alkenes are well known chemical transformations. Here we show that chiral dithiophosphoric acids can catalyse the intramolecular hydroamination and hydroarylation of dienes and allenes to generate heterocyclic products in exceptional yield and enantiomeric excess. We present a mechanistic hypothesis that involves the addition of the acid catalyst to the diene, followed by nucleophilic displacement of the resulting dithiophosphate intermediate; we also report mass spectroscopic and deuterium labelling studies in support of the proposed mechanism. The catalysts and concepts revealed in this study should prove applicable to other asymmetric functionalizations of unsaturated systems.
C1 [Shapiro, Nathan D.; Rauniyar, Vivek; Hamilton, Gregory L.; Wu, Jeffrey; Toste, F. Dean] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Toste, FD (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM fdtoste@berkeley.edu
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; NIHGMS [R01 GM074774]; Natural Sciences and Engineering Research Council of Canada (NSERC); Bristol-Myers/Squibb
NR 30
TC 183
Z9 212
U1 2
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 245
EP +
DI 10.1038/nature09723
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200041
PM 21307938
DA 2026-03-09
ER

PT J
AU Fritsch, J
   Scheerer, P
   Frielingsdorf, S
   Kroschinsky, S
   Friedrich, B
   Lenz, O
   Spahn, CMT
AF Fritsch, Johannes
   Scheerer, Patrick
   Frielingsdorf, Stefan
   Kroschinsky, Sebastian
   Friedrich, Baerbel
   Lenz, Oliver
   Spahn, Christian M. T.
TI The crystal structure of an oxygen-tolerant hydrogenase uncovers a novel iron-sulphur centre
SO NATURE
LA English
DT Article
ID membrane-bound hydrogenase; nife hydrogenase; alcaligenes-eutrophus; protein; crystallography; potentials; conversion; cluster; o-2; h-2
AB Hydrogenases are abundant enzymes that catalyse the reversible interconversion of H-2 into protons and electrons at high rates(1). Those hydrogenases maintaining their activity in the presence of O-2 are considered to be central to H-2-based technologies, such as enzymatic fuel cells and for light-driven H-2 production(2). Despite comprehensive genetic, biochemical, electrochemical and spectroscopic investigations(3-8), the molecular background allowing a structural interpretation of how the catalytic centre is protected from irreversible inactivation by O-2 has remained unclear. Here we present the crystal structure of an O-2-tolerant [NiFe]-hydrogenase from the aerobic H-2 oxidizer Ralstonia eutropha H16 at 1.5 angstrom resolution. The heterodimeric enzyme consists of a large subunit harbouring the catalytic centre in the H-2-reduced state and a small subunit containing an electron relay consisting of three different iron-sulphur clusters. The cluster proximal to the active site displays an unprecedented [4Fe-3S] structure and is coordinated by six cysteines. According to the current model, this cofactor operates as an electronic switch depending on the nature of the gas molecule approaching the active site. It serves as an electron acceptor in the course of H-2 oxidation and as an electron-delivering device upon O-2 attack at the active site. This dual function is supported by the capability of the novel iron-sulphur cluster to adopt three redox states at physiological redox potentials(7-9). The second structural feature is a network of extended water cavities that may act as a channel facilitating the removal of water produced at the [NiFe] active site. These discoveries will have an impact on the design of biological and chemical H-2-converting catalysts that are capable of cycling H-2 in air.
C1 [Scheerer, Patrick; Kroschinsky, Sebastian; Spahn, Christian M. T.] Charite, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Fritsch, Johannes; Frielingsdorf, Stefan; Friedrich, Baerbel; Lenz, Oliver] Humboldt Univ, Inst Biol, D-10115 Berlin, Germany.
   [Spahn, Christian M. T.] Humboldt Univ, Zentrum Biophys & Bioinformat, D-10115 Berlin, Germany.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Humboldt University of Berlin
RP Scheerer, P (corresponding author), Charite, Inst Med Phys & Biophys CC2, Charitepl 1, D-10117 Berlin, Germany.
EM patrick.scheerer@charite.de; oliver.lenz@cms.hu-berlin.de; christian.spahn@charite.de
FU EU; DFG Cluster of Excellence 'Unifying Concepts in Catalysis'; ERC [ERC-2009/249910-TUDOR];  [Sfb740]
NR 48
TC 310
Z9 343
U1 1
U2 228
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 249
EP U134
DI 10.1038/nature10505
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800047
PM 22002606
DA 2026-03-09
ER

PT J
AU Massel, F
   Heikkilä, TT
   Pirkkalainen, JM
   Cho, SU
   Saloniemi, H
   Hakonen, PJ
   Sillanpää, MA
AF Massel, F.
   Heikkila, T. T.
   Pirkkalainen, J. -M.
   Cho, S. U.
   Saloniemi, H.
   Hakonen, P. J.
   Sillanpaa, M. A.
TI Microwave amplification with nanomechanical resonators
SO NATURE
LA English
DT Article
ID parametric amplification; quantum-noise; ground-state; instability; motion; limits
AB The sensitive measurement of electrical signals is at the heart of modern technology. According to the principles of quantum mechanics, any detector or amplifier necessarily adds a certain amount of noise to the signal, equal to at least the noise added by quantum fluctuations(1,2). This quantum limit of added noise has nearly been reached in superconducting devices that take advantage of nonlinearities in Josephson junctions(3,4). Here we introduce the concept of the amplification of microwave signals using mechanical oscillation, which seems likely to enable quantum-limited operation. We drive a nanomechanical resonator with a radiation pressure force(5-7), and provide an experimental demonstration and an analytical description of how a signal input to a microwave cavity induces coherent stimulated emission and, consequently, signal amplification. This generic scheme, which is based on two linear oscillators, has the advantage of being conceptually and practically simpler than the Josephson junction devices. In our device, we achieve signal amplification of 25 decibels with the addition of 20 quanta of noise, which is consistent with the expected amount of added noise. The generality of the model allows for realization in other physical systems as well, and we anticipate that near-quantum-limited mechanical microwave amplification will soon be feasible in various applications involving integrated electrical circuits.
C1 [Massel, F.; Heikkila, T. T.; Pirkkalainen, J. -M.; Cho, S. U.; Hakonen, P. J.; Sillanpaa, M. A.] Aalto Univ, Low Temp Lab, FI-00076 Aalto, Finland.
   [Saloniemi, H.] VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland.
C3 Aalto University; VTT Technical Research Center Finland
RP Massel, F (corresponding author), Aalto Univ, Low Temp Lab, POB 15100, FI-00076 Aalto, Finland.
EM francesco.massel@aalto.fi
FU Academy of Finland; European Research Council [240362-Heattronics, 240387-NEMSQED];  [EU-FP7-NMP-246026]
NR 30
TC 275
Z9 302
U1 3
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 DEC 15
PY 2011
VL 480
IS 7377
BP 351
EP 354
DI 10.1038/nature10628
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000047
PM 22170682
DA 2026-03-09
ER

PT J
AU Di Toro, G
   Han, R
   Hirose, T
   De Paola, N
   Nielsen, S
   Mizoguchi, K
   Ferri, F
   Cocco, M
   Shimamoto, T
AF Di Toro, G.
   Han, R.
   Hirose, T.
   De Paola, N.
   Nielsen, S.
   Mizoguchi, K.
   Ferri, F.
   Cocco, M.
   Shimamoto, T.
TI Fault lubrication during earthquakes
SO NATURE
LA English
DT Article
ID coseismic slip; rock-friction; rates; propagation; mechanism; solids; zone; laws
AB The determination of rock friction at seismic slip rates (about 1 m s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip(1). Given the difficulty in determining friction by seismological methods(1), elucidating constraints are derived from experimental studies(2-9). Here we review a large set of published and unpublished experiments (similar to 300) performed in rotary shear apparatus at slip rates of 0.1-2.6 ms(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built(4-6), quartz-built(3) and carbonate-built(7,8)) rocks and non-cohesive rocks (clay-rich(9), anhydrite, gypsum and dolomite(10) gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger(11,12) a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates(13,14) suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15 km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.
C1 [Di Toro, G.; Ferri, F.] Univ Padua, Dipartimento Geosci, I-35131 Padua, Italy.
   [Di Toro, G.; Nielsen, S.; Cocco, M.] Ist Nazl Geofis & Vulcanol, I-00143 Rome, Italy.
   [Han, R.] Korea Inst Geosci & Mineral Resources, Taejon 305350, South Korea.
   [Hirose, T.] JAMSTEC, Kochi Inst Core Sample Res, Kochi 7838502, Japan.
   [De Paola, N.] Univ Durham, Dept Earth Sci, Durham DH1 3LE, England.
   [Mizoguchi, K.] Cent Res Inst Elect Power Ind, Civil Engn Res Lab, Chiba 2701194, Japan.
   [Shimamoto, T.] China Earthquake Adm, Inst Geol, Beijing 100029, Peoples R China.
C3 University of Padua; Istituto Nazionale Geofisica e Vulcanologia (INGV); Korea Institute of Geoscience & Mineral Resources (KIGAM); Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Durham University; Central Research Institute of Electric Power Industry - Japan; China Earthquake Administration; Institute of Geology, CEA
RP Di Toro, G (corresponding author), Univ Padua, Dipartimento Geosci, I-35131 Padua, Italy.
EM giulio.ditoro@unipd.it
FU Progetti di Eccellenza Fondazione Cassa di Risparmio di Padova e Rovigo; European Research Council [205175]
NR 36
TC 752
Z9 827
U1 11
U2 301
PU 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 24
PY 2011
VL 471
IS 7339
BP 494
EP +
DI 10.1038/nature09838
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200058
PM 21430777
DA 2026-03-09
ER

PT J
AU Ikeda, F
   Deribe, YL
   Skånland, SS
   Stieglitz, B
   Grabbe, C
   Franz-Wachtel, M
   van Wijk, SJL
   Goswami, P
   Nagy, V
   Terzic, J
   Tokunaga, F
   Androulidaki, A
   Nakagawa, T
   Pasparakis, M
   Iwai, K
   Sundberg, JP
   Schaefer, L
   Rittinger, K
   Macek, B
   Dikic, I
AF Ikeda, Fumiyo
   Deribe, Yonathan Lissanu
   Skanland, Sigrid S.
   Stieglitz, Benjamin
   Grabbe, Caroline
   Franz-Wachtel, Mirita
   van Wijk, Sjoerd J. L.
   Goswami, Panchali
   Nagy, Vanja
   Terzic, Janos
   Tokunaga, Fuminori
   Androulidaki, Ariadne
   Nakagawa, Tomoko
   Pasparakis, Manolis
   Iwai, Kazuhiro
   Sundberg, John P.
   Schaefer, Liliana
   Rittinger, Katrin
   Macek, Boris
   Dikic, Ivan
TI SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis
SO NATURE
LA English
DT Article
ID polyubiquitin chains; immune-system; proteins; activation; fractionation; dermatitis; proteomics; induction; nemo
AB SHARPIN is a ubiquitin-binding and ubiquitin-like-domain-containing protein which, when mutated in mice, results in immune system disorders and multi-organ inflammation(1,2). Here we report that SHARPIN functions as a novel component of the linear ubiquitin chain assembly complex (LUBAC) and that the absence of SHARPIN causes dysregulation of NF-kappa B and apoptotic signalling pathways, explaining the severe phenotypes displayed by chronic proliferative dermatitis (cpdm) in SHARPIN-deficient mice. Upon binding to the LUBAC subunit HOIP (also known as RNF31), SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo. Coexpression of SHARPIN and HOIP promotes linear ubiquitination of NEMO (also known as IKBKG), an adaptor of the I kappa B kinases (IKKs) and subsequent activation of NF-kappa B signalling, whereas SHARPIN deficiency in mice causes an impaired activation of the IKK complex and NF-kappa B in B cells, macrophages and mouse embryonic fibroblasts (MEFs). This effect is further enhanced upon concurrent downregulation of HOIL-1L (also known as RBCK1), another HOIP-binding component of LUBAC. In addition, SHARPIN deficiency leads to rapid cell death upon tumour-necrosis factor alpha (TNF-alpha) stimulation via FADD- and caspase-8-dependent pathways. SHARPIN thus activates NF kappa B and inhibits apoptosis via distinct pathways in vivo.
C1 [Ikeda, Fumiyo; Deribe, Yonathan Lissanu; Skanland, Sigrid S.; Grabbe, Caroline; van Wijk, Sjoerd J. L.; Goswami, Panchali; Dikic, Ivan] Goethe Univ Frankfurt, Sch Med, Frankfurt Inst Mol Life Sci, D-60590 Frankfurt, Germany.
   [Ikeda, Fumiyo; Deribe, Yonathan Lissanu; Skanland, Sigrid S.; Grabbe, Caroline; van Wijk, Sjoerd J. L.; Goswami, Panchali; Dikic, Ivan] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, D-60590 Frankfurt, Germany.
   [Stieglitz, Benjamin; Rittinger, Katrin] Natl Inst Med Res, MRC, London NW7 1AA, England.
   [Grabbe, Caroline] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
   [Franz-Wachtel, Mirita; Macek, Boris] Univ Tubingen, Interfac Inst Cell Biol, Proteome Ctr Tubingen, D-72076 Tubingen, Germany.
   [Nagy, Vanja] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Terzic, Janos; Dikic, Ivan] Univ Split, Sch Med, HR-21000 Split, Croatia.
   [Tokunaga, Fuminori; Nakagawa, Tomoko; Iwai, Kazuhiro] Osaka Univ, Grad Sch Med, Dept Biophys & Biochem, Suita, Osaka 5650871, Japan.
   [Androulidaki, Ariadne; Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50674 Cologne, Germany.
   [Androulidaki, Ariadne; Pasparakis, Manolis] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
   [Iwai, Kazuhiro] Osaka Univ, Grad Sch Frontier Biosci, Cell Biol & Metab Grp, Suita, Osaka 5650871, Japan.
   [Sundberg, John P.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Schaefer, Liliana] Klinikum Goethe Univ, Div Nephropharmakol, D-60590 Frankfurt, Germany.
C3 Goethe University Frankfurt; Goethe University Frankfurt; MRC National Institute for Medical Research; Umea University; Eberhard Karls University of Tubingen; Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); University of Split; University of Osaka; University of Cologne; University of Cologne; University of Osaka; Jackson Laboratory; Goethe University Frankfurt; Goethe University Frankfurt Hospital
RP Dikic, I (corresponding author), Goethe Univ Frankfurt, Sch Med, Frankfurt Inst Mol Life Sci, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM Ivan.Dikic@biochem2.de
FU Deutsche Forschungsgemeinschaft [DI 931/3-1]; Goethe University Frankfurt [EXC115]; Landesstiftung Baden-Wurttemberg; Medical Research Council UK; JSPS; EMBO; National Institutes of Health [AR049288]; Unity Through Knowledge Fund; International Human Frontier Science Program Organization; MRC [MC_U117565398] Funding Source: UKRI; Medical Research Council [MC_U117565398] Funding Source: researchfish; Grants-in-Aid for Scientific Research [22117006, 23657075] Funding Source: KAKEN
NR 27
TC 628
Z9 717
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 MAR 31
PY 2011
VL 471
IS 7340
BP 637
EP U120
DI 10.1038/nature09814
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200043
PM 21455181
DA 2026-03-09
ER

PT J
AU Ehrlicher, AJ
   Nakamura, F
   Hartwig, JH
   Weitz, DA
   Stossel, TP
AF Ehrlicher, A. J.
   Nakamura, F.
   Hartwig, J. H.
   Weitz, D. A.
   Stossel, T. P.
TI Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin A
SO NATURE
LA English
DT Article
ID molecular motors; auto-inhibition; cross-linking; living cells; mechanotransduction; proteins
AB Mechanical stresses elicit cellular reactions mediated by chemical signals. Defective responses to forces underlie human medical disorders(1-4) such as cardiac failure(5) and pulmonary injury(6). The actin cytoskeleton's connectivity enables it to transmit forces rapidly over large distances(7), implicating it in these physiological and pathological responses. Despite detailed knowledge of the cytoskeletal structure, the specific molecular switches that convert mechanical stimuli into chemical signals have remained elusive. Here we identify the actin-binding protein filamin A (FLNA)(8,9) as a central mechanotransduction element of the cytoskeleton. We reconstituted a minimal system consisting of actin filaments, FLNA and two FLNA-binding partners: the cytoplasmic tail of beta-integrin, and FilGAP. Integrins form an essential mechanical linkage between extracellular and intracellular environments, with beta-integrin tails connecting to the actin cytoskeleton by binding directly to filamin(4). FilGAP is an FLNA-binding GTPase-activating protein specific for RAC, which in vivo regulates cell spreading and bleb formation(10). Using fluorescence loss after photoconversion, a novel, high-speed alternative to fluorescence recovery after photobleaching(11), we demonstrate that both externally imposed bulk shear and myosin-II-driven forces differentially regulate the binding of these partners to FLNA. Consistent with structural predictions, strain increases beta-integrin binding to FLNA, whereas it causes FilGAP to dissociate from FLNA, providing a direct and specific molecular basis for cellular mechanotransduction. These results identify a molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signalling molecules.
C1 [Ehrlicher, A. J.; Nakamura, F.; Hartwig, J. H.; Stossel, T. P.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Translat Med Div, Boston, MA 02115 USA.
   [Ehrlicher, A. J.; Weitz, D. A.] Harvard Univ, Dept Phys, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University
RP Nakamura, F (corresponding author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Translat Med Div, Boston, MA 02115 USA.
EM aje@seas.harvard.edu; fnakamura@rics.bwh.harvard.edu
FU NIH [R01 HL19429, T32 HL07680]; Harvard University Science and Engineering Committee
NR 34
TC 295
Z9 342
U1 0
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 OCT 13
PY 2011
VL 478
IS 7368
BP 260
EP U154
DI 10.1038/nature10430
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800054
PM 21926999
DA 2026-03-09
ER

PT J
AU Frank, KT
   Petrie, B
   Fisher, JAD
   Leggett, WC
AF Frank, Kenneth T.
   Petrie, Brian
   Fisher, Jonathan A. D.
   Leggett, William C.
TI Transient dynamics of an altered large marine ecosystem
SO NATURE
LA English
DT Article
ID scotian-shelf; trophic cascades; continental-shelf; regime shifts; gadus-morhua; atlantic cod; fish; canada; recovery; collapse
AB Overfishing of large-bodied benthic fishes and their subsequent population collapses on the Scotian Shelf of Canada's east coast(1,2) and elsewhere(3,4) resulted in restructuring of entire food webs now dominated by planktivorous, forage fish species and macroinvertebrates. Despite the imposition of strict management measures in force since the early 1990s, the Scotian Shelf ecosystem has not reverted back to its former structure. Here we provide evidence of the transient nature of this ecosystem and its current return path towards benthic fish species domination. The prolonged duration of the altered food web, and its current recovery, was and is being governed by the oscillatory, runaway consumption dynamics of the forage fish complex. These erupting forage species, which reached biomass levels 900% greater than those prevalent during the pre-collapse years of large benthic predators, are now in decline, having outstripped their zooplankton food supply. This dampening, and the associated reduction in the intensity of predation, was accompanied by lagged increases in species abundances at both lower and higher trophic levels, first witnessed in zooplankton and then in large-bodied predators, all consistent with a return towards the earlier ecosystem structure. We conclude that the reversibility of perturbed ecosystems can occur and that this bodes well for other collapsed fisheries.
C1 [Frank, Kenneth T.; Petrie, Brian] Bedford Inst Oceanog, Ocean Sci Div, Dartmouth, NS B2Y 4A2, Canada.
   [Fisher, Jonathan A. D.; Leggett, William C.] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
C3 Bedford Institute of Oceanography; Fisheries & Oceans Canada; Queens University - Canada
RP Frank, KT (corresponding author), Bedford Inst Oceanog, Ocean Sci Div, POB 1006, Dartmouth, NS B2Y 4A2, Canada.
EM kenneth.frank@dfo-mpo.gc.ca
FU Fisheries and Oceans Canada; Natural Sciences and Engineering Research Council of Canada; Natural Environment Research Council [SAH01001] Funding Source: researchfish; NERC [SAH01001] Funding Source: UKRI
NR 50
TC 227
Z9 260
U1 0
U2 246
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 86
EP U98
DI 10.1038/nature10285
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300036
PM 21796120
DA 2026-03-09
ER

PT J
AU Gerlach, B
   Cordier, SM
   Schmukle, AC
   Emmerich, CH
   Rieser, E
   Haas, TL
   Webb, AI
   Rickard, JA
   Anderton, H
   Wong, WWL
   Nachbur, U
   Gangoda, L
   Warnken, U
   Purcell, AW
   Silke, J
   Walczak, H
AF Gerlach, Bjoern
   Cordier, Stefanie M.
   Schmukle, Anna C.
   Emmerich, Christoph H.
   Rieser, Eva
   Haas, Tobias L.
   Webb, Andrew I.
   Rickard, James A.
   Anderton, Holly
   Wong, Wendy W-L.
   Nachbur, Ueli
   Gangoda, Lahiru
   Warnken, Uwe
   Purcell, Anthony W.
   Silke, John
   Walczak, Henning
TI Linear ubiquitination prevents inflammation and regulates immune signalling
SO NATURE
LA English
DT Article
ID chronic proliferative dermatitis; k11-linked polyubiquitination; mediated regulation; structural basis; tnf; activation; nemo; recognition; mechanisms; chains
AB Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKK gamma or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1 beta was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.
C1 [Gerlach, Bjoern; Cordier, Stefanie M.; Schmukle, Anna C.; Emmerich, Christoph H.; Rieser, Eva; Walczak, Henning] Univ London Imperial Coll Sci Technol & Med, Dept Med, Tumour Immunol Unit, London W12 0NN, England.
   [Gerlach, Bjoern; Emmerich, Christoph H.; Haas, Tobias L.; Walczak, Henning] German Canc Res Ctr, Div Apoptosis Regulat, D-69120 Heidelberg, Germany.
   [Haas, Tobias L.] Mediterranean Inst Oncol, Dept Expt Oncol, I-95029 Viagrande, Italy.
   [Webb, Andrew I.; Purcell, Anthony W.] Bio21 Melbourne Univ, Dept Biochem, Melbourne, Vic 3010, Australia.
   [Rickard, James A.; Anderton, Holly; Wong, Wendy W-L.; Nachbur, Ueli; Gangoda, Lahiru; Silke, John] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia.
   [Warnken, Uwe] German Canc Res Ctr, Prot Anal Core Facil, D-69120 Heidelberg, Germany.
C3 Imperial College London; Helmholtz Association; German Cancer Research Center (DKFZ); Mediterranean Institute of Oncology; University of Melbourne; La Trobe University; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Walczak, H (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Med, Tumour Immunol Unit, London W12 0NN, England.
EM h.walczak@imperial.ac.uk
FU Cancer Research UK; AICR; BBSRC (ERASysBio PLUS); Ovarian Cancer Action; EU; NHMRC [541901, 541902, 602516]; HGF/SBCancer; Schweizer Nationalfonds (SNF); National Health and Medical Research Council (NHMRC) [602516, 541901, 541902] Funding Source: National Health and Medical Research Council (NHMRC); Biotechnology and Biological Sciences Research Council [BB/I004580/1] Funding Source: researchfish; Cancer Research UK [10950] Funding Source: researchfish; BBSRC [BB/I004580/1] Funding Source: UKRI
NR 37
TC 793
Z9 891
U1 1
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 591
EP +
DI 10.1038/nature09816
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200033
PM 21455173
DA 2026-03-09
ER

PT J
AU Chapman, I
AF Chapman, Ian
TI TURNING POINT
SO NATURE
LA English
DT Article
NR 0
TC 0
Z9 0
U1 0
U2 6
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 506
EP 506
DI 
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600043
DA 2026-03-09
ER

PT J
AU Zhou, Z
   Feng, HQ
   Zhou, BR
   Ghirlando, R
   Hu, KF
   Zwolak, A
   Jenkins, LMM
   Xiao, H
   Tjandra, N
   Wu, C
   Bai, YW
AF Zhou, Zheng
   Feng, Hanqiao
   Zhou, Bing-Rui
   Ghirlando, Rodolfo
   Hu, Kaifeng
   Zwolak, Adam
   Jenkins, Lisa M. Miller
   Xiao, Hua
   Tjandra, Nico
   Wu, Carl
   Bai, Yawen
TI Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3
SO NATURE
LA English
DT Article
ID fission yeast scm3; saccharomyces-cerevisiae; sedimentation-velocity; analytical ultracentrifugation; protein; nmr; nucleosm; chromatin; hjurp; cse4
AB The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore(1). The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4) 2 heterotetramer and are required for the deposition of CenH3 at centromeres in vivo(5-13). Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An alpha-helix and an irregular loop at the conserved amino terminus and a shorter alpha-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome.
C1 [Zhou, Zheng; Feng, Hanqiao; Zhou, Bing-Rui; Xiao, Hua; Wu, Carl; Bai, Yawen] NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA.
   [Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA.
   [Hu, Kaifeng] Univ Wisconsin, Natl Magnet Resonance Facil Madison, Madison, WI 53706 USA.
   [Zwolak, Adam; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
   [Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, 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 Diabetes & Digestive & Kidney Diseases (NIDDK); University of Wisconsin System; University of Wisconsin Madison; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Bai, YW (corresponding author), NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
FU NCI; NIDDK; NHLBI; National Cancer Institute [ZIABC010808] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [ZIAHL006064, ZIAHL001048] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK033007] Funding Source: NIH RePORTER
NR 39
TC 109
Z9 138
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 APR 14
PY 2011
VL 472
IS 7342
BP 234
EP 237
DI 10.1038/nature09854
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100046
PM 21412236
DA 2026-03-09
ER

PT J
AU Kofoed, EM
   Vance, RE
AF Kofoed, Eric M.
   Vance, Russell E.
TI Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
SO NATURE
LA English
DT Article
ID cell-death; caspase-1; activation; flagellin; interleukin-1-beta; secretion; birc1e
AB Inflammasomes are a family of cytosolic multiprotein complexes that initiate innate immune responses to pathogenic microbes by activating the caspase 1 protease(1,2). Although genetic data support a critical role for inflammasomes in immune defence and inflammatory diseases(3), the molecular basis by which individual inflammasomes respond to specific stimuli remains poorly understood. The inflammasome that contains the NLRC4 (NLR family, CARD domain containing 4) protein was previously shown to be activated in response to two distinct bacterial proteins, flagellin(4,5) and PrgJ(6), a conserved component of pathogen-associated type III secretion systems. However, direct binding between NLRC4 and flagellin or PrgJ has never been demonstrated. A homologue of NLRC4, NAIP5 (NLR family, apoptosis inhibitory protein 5), has been implicated in activation of NLRC4 (refs 7-11), but is widely assumed to have only an auxiliary role(1,2), as NAIP5 is often dispensable for NLRC4 activation(7,8). However, Naip5 is a member of a small multigene family(12), raising the possibility of redundancy and functional specialization among Naip genes. Here we show in mice that different NAIP paralogues determine the specificity of the NLRC4 inflammasome for distinct bacterial ligands. In particular, we found that activation of endogenous NLRC4 by bacterial PrgJ requires NAIP2, a previously uncharacterized member of the NAIP gene family, whereas NAIP5 and NAIP6 activate NLRC4 specifically in response to bacterial flagellin. We dissected the biochemical mechanism underlying the requirement for NAIP proteins by use of a reconstituted NLRC4 inflammasome system. We found that NAIP proteins control ligand-dependent oligomerization of NLRC4 and that the NAIP2-NLRC4 complex physically associates with PrgJ but not flagellin, whereas NAIP5-NLRC4 associates with flagellin but not PrgJ. Our results identify NAIPs as immune sensor proteins and provide biochemical evidence for a simple receptor-ligand model for activation of the NAIP-NLRC4 inflammasomes.
C1 [Kofoed, Eric M.; Vance, Russell E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Vance, RE (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM rvance@berkeley.edu
FU Burroughs Wellcome Fund; Cancer Research Institute; NIH [AI075039, AI080749, AI063302]; National Institute of Allergy and Infectious Diseases [P01AI063302] Funding Source: NIH RePORTER
NR 26
TC 724
Z9 862
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 592
EP U356
DI 10.1038/nature10394
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900040
PM 21874021
DA 2026-03-09
ER

PT J
AU White, RM
   Cech, J
   Ratanasirintrawoot, S
   Lin, CY
   Rahl, PB
   Burke, CJ
   Langdon, E
   Tomlinson, ML
   Mosher, J
   Kaufman, C
   Chen, F
   Long, HK
   Kramer, M
   Datta, S
   Neuberg, D
   Granter, S
   Young, RA
   Morrison, S
   Wheeler, GN
   Zon, LI
AF White, Richard Mark
   Cech, Jennifer
   Ratanasirintrawoot, Sutheera
   Lin, Charles Y.
   Rahl, Peter B.
   Burke, Christopher J.
   Langdon, Erin
   Tomlinson, Matthew L.
   Mosher, Jack
   Kaufman, Charles
   Chen, Frank
   Long, Hannah K.
   Kramer, Martin
   Datta, Sumon
   Neuberg, Donna
   Granter, Scott
   Young, Richard A.
   Morrison, Sean
   Wheeler, Grant N.
   Zon, Leonard I.
TI DHODH modulates transcriptional elongation in the neural crest and melanoma
SO NATURE
LA English
DT Article
ID carbamoyl-phosphate synthetase; zebrafish; leflunomide; expression; inhibitor; discovery; kinase; cells; gene
AB Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma(1). We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.
C1 [White, Richard Mark; Cech, Jennifer; Ratanasirintrawoot, Sutheera; Burke, Christopher J.; Langdon, Erin; Kaufman, Charles; Datta, Sumon; Zon, Leonard I.] Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [White, Richard Mark; Kaufman, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Lin, Charles Y.; Rahl, Peter B.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Lin, Charles Y.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Tomlinson, Matthew L.; Wheeler, Grant N.] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England.
   [Mosher, Jack; Morrison, Sean] Univ Michigan, Howard Hughes Med Inst, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
   [Chen, Frank] Harvard Univ, Cambridge, MA 02138 USA.
   [Long, Hannah K.] Univ Cambridge, Cambridge CB2 1TN, England.
   [Kramer, Martin] Genzyme Corp, Cambridge, MA 02142 USA.
   [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Granter, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); University of East Anglia; University of Michigan System; University of Michigan; Howard Hughes Medical Institute; Harvard University; University of Cambridge; Sanofi-Aventis; Genzyme Corporation; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Zon, LI (corresponding author), Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU Howard Hughes Medical Institute; National Cancer Institute (National Institutes of Health); American Society for Clinical Oncology; National Institute of Arthritis and Musculoskeletal and SkinDiseases (National Institutes of Health); Biotechnology and Biological Sciences Research Council/Pfizer; National Cancer Institute [T32CA009172, R01CA103846] Funding Source: NIH RePORTER
NR 26
TC 388
Z9 460
U1 2
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 518
EP 522
DI 10.1038/nature09882
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200063
PM 21430780
DA 2026-03-09
ER

PT J
AU Sandberg, MK
   Al-Doujaily, H
   Sharps, B
   Clarke, AR
   Collinge, J
AF Sandberg, Malin K.
   Al-Doujaily, Huda
   Sharps, Bernadette
   Clarke, Anthony R.
   Collinge, John
TI Prion propagation and toxicity in vivo occur in two distinct mechanistic phases
SO NATURE
LA English
DT Article
ID mouse scrapie; mice; disease; protein; prp; replication; pathogenesis; infectivity; resistant; strains
AB Mammalian prions cause fatal neurodegenerative conditions including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals(1). Prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. The relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. Prion incubation periods in experimental animals are known to vary inversely with expression level of cellular prion protein. Here we demonstrate that prion propagation in brain proceeds via two distinct phases: a clinically silent exponential phase not rate-limited by prion protein concentration which rapidly reaches a maximal prion titre, followed by a distinct switch to a plateau phase. The latter determines time to clinical onset in a manner inversely proportional to prion protein concentration. These findings demonstrate an uncoupling of infectivity and toxicity. We suggest that prions themselves are not neurotoxic but catalyse the formation of such species from PrPC. Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity (phase 1) to a toxic (phase 2) pathway.
C1 [Sandberg, Malin K.; Al-Doujaily, Huda; Sharps, Bernadette; Clarke, Anthony R.; Collinge, John] UCL Inst Neurol, MRC Prion Unit, London WC1N 3BG, England.
   [Sandberg, Malin K.; Al-Doujaily, Huda; Sharps, Bernadette; Clarke, Anthony R.; Collinge, John] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.
C3 University of London; University College London; University of London; University College London
RP Collinge, J (corresponding author), UCL Inst Neurol, MRC Prion Unit, Queen Sq, London WC1N 3BG, England.
EM j.collinge@prion.ucl.ac.uk
FU UK Medical Research Council; Medical Research Council [MC_U123160656, MC_U123192748] Funding Source: researchfish; MRC [MC_U123192748, MC_U123160656] Funding Source: UKRI
NR 30
TC 252
Z9 277
U1 1
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 FEB 24
PY 2011
VL 470
IS 7335
BP 540
EP 542
DI 10.1038/nature09768
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900043
PM 21350487
DA 2026-03-09
ER

PT J
AU Van Aert, S
   Batenburg, KJ
   Rossell, MD
   Erni, R
   Van Tendeloo, G
AF Van Aert, Sandra
   Batenburg, Kees J.
   Rossell, Marta D.
   Erni, Rolf
   Van Tendeloo, Gustaaf
TI Three-dimensional atomic imaging of crystalline nanoparticles
SO NATURE
LA English
DT Article
ID guinier-preston zones; internal structure; electron; tomography; prospects; images
AB Determining the three-dimensional (3D) arrangement of atoms in crystalline nanoparticles is important for nanometre-scale device engineering and also for applications involving nanoparticles, such as optoelectronics or catalysis. A nanoparticle's physical and chemical properties are controlled by its exact 3D morphology, structure and composition(1). Electron tomography enables the recovery of the shape of a nanoparticle from a series of projection images(2-4). Although atomic-resolution electron microscopy has been feasible for nearly four decades, neither electron tomography nor any other experimental technique has yet demonstrated atomic resolution in three dimensions. Here we report the 3D reconstruction of a complex crystalline nanoparticle at atomic resolution. To achieve this, we combined aberration-corrected scanning transmission electron microscopy(5-7), statistical parameter estimation theory(8,9) and discrete tomography(10,11). Unlike conventional electron tomography, only two images of the target-a silver nanoparticle embedded in an aluminium matrix-are sufficient for the reconstruction when combined with available knowledge about the particle's crystallographic structure. Additional projections confirm the reliability of the result. The results we present help close the gap between the atomic resolution achievable in two-dimensional electron micrographs and the coarser resolution that has hitherto been obtained by conventional electron tomography.
C1 [Van Aert, Sandra; Van Tendeloo, Gustaaf] Univ Antwerp, B-2020 Antwerp, Belgium.
   [Batenburg, Kees J.] Ctr Wiskunde & Informat, NL-1098 XG Amsterdam, Netherlands.
   [Batenburg, Kees J.] Univ Antwerp, IBBT Vis Lab, B-2610 Antwerp, Belgium.
   [Rossell, Marta D.] Swiss Fed Inst Technol, Dept Mat, CH-8093 Zurich, Switzerland.
   [Erni, Rolf] Empa, Swiss Fed Labs Mat Sci & Technol, Ctr Electron Microscopy, CH-8600 Dubendorf, Switzerland.
C3 University of Antwerp; University of Antwerp; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA)
RP Van Aert, S (corresponding author), Univ Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
EM sandra.vanaert@ua.ac.be
FU Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; European Union [026019 ESTEEM]
NR 30
TC 439
Z9 490
U1 3
U2 348
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 374
EP 377
DI 10.1038/nature09741
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100037
PM 21289625
DA 2026-03-09
ER

PT J
AU Noggle, S
   Fung, HL
   Gore, A
   Martinez, H
   Satriani, KC
   Prosser, R
   Oum, K
   Paull, D
   Druckenmiller, S
   Freeby, M
   Greenberg, E
   Zhang, K
   Goland, R
   Sauer, MV
   Leibel, RL
   Egli, D
AF Noggle, Scott
   Fung, Ho-Lim
   Gore, Athurva
   Martinez, Hector
   Satriani, Kathleen Crumm
   Prosser, Robert
   Oum, Kiboong
   Paull, Daniel
   Druckenmiller, Sarah
   Freeby, Matthew
   Greenberg, Ellen
   Zhang, Kun
   Goland, Robin
   Sauer, Mark V.
   Leibel, Rudolph L.
   Egli, Dieter
TI Human oocytes reprogram somatic cells to a pluripotent state
SO NATURE
LA English
DT Article
ID embryonic stem-cells; nuclear transfer; gene-expression; developmental competence; derivation; lines
AB The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange.
C1 [Noggle, Scott; Martinez, Hector; Paull, Daniel; Druckenmiller, Sarah; Egli, Dieter] New York Stem Cell Fdn Lab, New York, NY USA.
   [Fung, Ho-Lim; Gore, Athurva; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Satriani, Kathleen Crumm; Prosser, Robert; Oum, Kiboong; Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Ctr Womens Reprod Care, New York, NY USA.
   [Satriani, Kathleen Crumm; Prosser, Robert; Oum, Kiboong; Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY USA.
   [Freeby, Matthew; Greenberg, Ellen; Goland, Robin; Leibel, Rudolph L.] Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY USA.
   [Freeby, Matthew; Greenberg, Ellen; Goland, Robin; Leibel, Rudolph L.] Columbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY 10027 USA.
C3 The New York Stem Cell Foundation; University of California System; University of California San Diego; Columbia University; Columbia University; Columbia University; Columbia University
RP Egli, D (corresponding author), New York Stem Cell Fdn Lab, New York, NY USA.
EM d.egli@nyscf.org
FU UCSD; New York Stem Cell Foundation; Russell Berrie Foundation
NR 38
TC 156
Z9 198
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 OCT 6
PY 2011
VL 478
IS 7367
BP 70
EP U81
DI 10.1038/nature10397
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400036
PM 21979046
DA 2026-03-09
ER

PT J
AU Bouwens, RJ
   Illingworth, GD
   Labbe, I
   Oesch, PA
   Trenti, M
   Carollo, CM
   van Dokkum, PG
   Franx, M
   Stiavelli, M
   González, V
   Magee, D
   Bradley, L
AF Bouwens, R. J.
   Illingworth, G. D.
   Labbe, I.
   Oesch, P. A.
   Trenti, M.
   Carollo, C. M.
   van Dokkum, P. G.
   Franx, M.
   Stiavelli, M.
   Gonzalez, V.
   Magee, D.
   Bradley, L.
TI A candidate redshift z ≈ 10 galaxy and rapid changes in that population at an age of 500 Myr
SO NATURE
LA English
DT Article
ID lyman-break galaxy; stellar mass density; ultra deep field; star-forming galaxy; luminosity function; spectroscopic confirmation; evolution; reionization; epoch; z-similar-to-5
AB Searches for very-high-redshift galaxies over the past decade have yielded a large sample of more than 6,000 galaxies existing just 900-2,000 million years (Myr) after the Big Bang (redshifts 6 > z > 3; ref. 1). The Hubble Ultra Deep Field (HUDF09) data(2,3) have yielded the first reliable detections of z approximate to 8 galaxies(3-9) that, together with reports of a c-ray burst at z approximate to 8.2 (refs 10, 11), constitute the earliest objects reliably reported to date. Observations of z approximate to 7-8 galaxies suggest substantial star formation at z > 9-10 (refs 12, 13). Here we use the full two-year HUDF09 data to conduct an ultra-deep search for z approximate to 10 galaxies in the heart of the reionization epoch, only 500 Myr after the Big Bang. Not only do we find one possible z approximate to 10 galaxy candidate, but we show that, regardless of source detections, the star formation rate density is much smaller (similar to 10%) at this time than it is just similar to 200 Myr later at z approximate to 8. This demonstrates how rapid galaxy build-up was at z approximate to 10, as galaxies increased in both luminosity density and volume density from z approximate to 10 to z approximate to 8. The 100-200 Myr before z approximate to 10 is clearly a crucial phase in the assembly of the earliest galaxies.
C1 [Bouwens, R. J.; Illingworth, G. D.; Gonzalez, V.; Magee, D.] Univ Calif Santa Cruz, Dept Astron, Santa Cruz, CA 95064 USA.
   [Bouwens, R. J.; Franx, M.] Leiden Univ, Leiden Observ, NL-2333 Leiden, Netherlands.
   [Labbe, I.] Carnegie Observ, Pasadena, CA 91101 USA.
   [Oesch, P. A.; Carollo, C. M.] Swiss Fed Inst Technol, Inst Astron, CH-8093 Zurich, Switzerland.
   [Trenti, M.] Univ Colorado, Ctr Astrophys & Space Astron, Boulder, CO 80303 USA.
   [van Dokkum, P. G.] Yale Univ, Dept Astron, New Haven, CT 06520 USA.
   [Stiavelli, M.; Bradley, L.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
C3 University of California System; University of California Santa Cruz; Leiden University; Leiden University - Excl LUMC; Carnegie Institution for Science; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Colorado System; University of Colorado Boulder; Yale University; Space Telescope Science Institute
RP Bouwens, RJ (corresponding author), Univ Calif Santa Cruz, Dept Astron, Santa Cruz, CA 95064 USA.
EM bouwens@ucolick.org
FU NASA; Swiss National Science Foundation; Science and Technology Facilities Council [ST/H00243X/1] Funding Source: researchfish
NR 30
TC 258
Z9 283
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 504
EP 507
DI 10.1038/nature09717
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500026
PM 21270889
DA 2026-03-09
ER

PT J
AU Inuzuka, H
   Shaik, S
   Onoyama, I
   Gao, DM
   Tseng, A
   Maser, RS
   Zhai, B
   Wan, LX
   Gutierrez, A
   Lau, AW
   Xiao, YH
   Christie, AL
   Aster, J
   Settleman, J
   Gygi, SP
   Kung, AL
   Look, T
   Nakayama, KI
   DePinho, RA
   Wei, WY
AF Inuzuka, Hiroyuki
   Shaik, Shavali
   Onoyama, Ichiro
   Gao, Daming
   Tseng, Alan
   Maser, Richard S.
   Zhai, Bo
   Wan, Lixin
   Gutierrez, Alejandro
   Lau, Alan W.
   Xiao, Yonghong
   Christie, Amanda L.
   Aster, Jon
   Settleman, Jeffrey
   Gygi, Steven P.
   Kung, Andrew L.
   Look, Thomas
   Nakayama, Keiichi I.
   DePinho, Ronald A.
   Wei, Wenyi
TI SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction
SO NATURE
LA English
DT Article
ID fbw7 ubiquitin ligase; tumor-suppressor; phosphorylation; degradation; differentiation; complex; cancers; protein
AB The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer(1) and T-cell acute lymphoblastic leukaemia (T-ALL)(2). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL(3-5), validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun(6), Myc(7), cyclin E-8 and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth(10), overexpression of Jun, Myc or notch 1 can also induce programmed cell death(11). Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCFFBW7 (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL.
C1 [Inuzuka, Hiroyuki; Shaik, Shavali; Gao, Daming; Tseng, Alan; Wan, Lixin; Lau, Alan W.; Wei, Wenyi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
   [Onoyama, Ichiro; Nakayama, Keiichi I.] Kyushu Univ, Dept Mol & Cellular Biol, Med Inst Bioregulat, Fukuoka 8128582, Japan.
   [Maser, Richard S.; Xiao, Yonghong; DePinho, Ronald A.] Harvard Univ, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Med Oncol,Sch Med, Boston, MA 02115 USA.
   [Maser, Richard S.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Zhai, Bo; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Gutierrez, Alejandro; Christie, Amanda L.; Kung, Andrew L.; Look, Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Christie, Amanda L.; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
   [Aster, Jon] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med, Boston, MA 02129 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Kyushu University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Jackson Laboratory; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School
RP Wei, WY (corresponding author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM wwei2@bidmc.harvard.edu
FU Emerald Foundation; Leukemia and Lymphoma Society; National Institutes of Health [GM089763]; Robert A. and Renee E. Belfer Foundation Institute for Applied Cancer Science
NR 29
TC 559
Z9 649
U1 1
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 MAR 3
PY 2011
VL 471
IS 7336
BP 104
EP U128
DI 10.1038/nature09732
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100043
PM 21368833
DA 2026-03-09
ER

PT J
AU Shi, ML
   Zhu, JH
   Wang, R
   Chen, X
   Mi, LZ
   Walz, T
   Springer, TA
AF Shi, Minlong
   Zhu, Jianghai
   Wang, Rui
   Chen, Xing
   Mi, Lizhi
   Walz, Thomas
   Springer, Timothy A.
TI Latent TGF-β structure and activation
SO NATURE
LA English
DT Article
ID growth-factor-beta; binding-protein; crystal-structure; secretion; mature; tgf-beta-1; domain; factor-beta-1; inflammation; requirement
AB Transforming growth factor (TGF)-beta is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-beta 1 requires the binding of alpha(v) integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. Crystals of dimeric porcine proTGF-beta 1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between alpha(v)beta(6) integrin and the prodomain is insufficient for TGF-beta 1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-beta family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.
C1 [Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Springer, Timothy A.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
   [Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Walz, Thomas] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Springer, TA (corresponding author), Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NHLBI NIH HHS [P01 HL103526] Funding Source: Medline
NR 46
TC 846
Z9 1023
U1 4
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 16
PY 2011
VL 474
IS 7351
BP 343
EP U370
DI 10.1038/nature10152
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100038
PM 21677751
DA 2026-03-09
ER

PT J
AU Choi, JH
   Banks, AS
   Kamenecka, TM
   Busby, SA
   Chalmers, MJ
   Kumar, N
   Kuruvilla, DS
   Shin, YS
   He, YJ
   Bruning, JB
   Marciano, DP
   Cameron, MD
   Laznik, D
   Jurczak, MJ
   Schürer, SC
   Vidovic, D
   Shulman, GI
   Spiegelman, BM
   Griffin, PR
AF Choi, Jang Hyun
   Banks, Alexander S.
   Kamenecka, Theodore M.
   Busby, Scott A.
   Chalmers, Michael J.
   Kumar, Naresh
   Kuruvilla, Dana S.
   Shin, Youseung
   He, Yuanjun
   Bruning, John B.
   Marciano, David P.
   Cameron, Michael D.
   Laznik, Dina
   Jurczak, Michael J.
   Schuerer, Stephan C.
   Vidovic, Dusica
   Shulman, Gerald I.
   Spiegelman, Bruce M.
   Griffin, Patrick R.
TI Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation
SO NATURE
LA English
DT Article
ID activated-receptor-gamma; adipocyte differentiation; skeletal-muscle; rosiglitazone; expression; obesity; potent; thiazolidinedione; ppar-gamma-2; modulators
AB PPAR gamma is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone(1). These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPAR gamma-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPAR gamma by Cdk5 (ref. 2). Here we describe novel synthetic compounds that have a unique mode of binding to PPAR gamma, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPAR gamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPAR gamma.
C1 [Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA.
   [Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Kamenecka, Theodore M.; Shin, Youseung; He, Yuanjun; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
   [Busby, Scott A.; Chalmers, Michael J.; Kumar, Naresh; Kuruvilla, Dana S.; Marciano, David P.; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
   [Kamenecka, Theodore M.; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, SRMSC, Jupiter, FL 33458 USA.
   [Bruning, John B.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA.
   [Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06510 USA.
   [Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
   [Schuerer, Stephan C.; Vidovic, Dusica] Univ Miami, Ctr Computat Sci, Miami, FL 33136 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Texas A&M University System; Texas A&M University College Station; Howard Hughes Medical Institute; Yale University; Yale University; Howard Hughes Medical Institute; University of Miami
RP Spiegelman, BM (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu; pgriffin@scripps.edu
FU National Institutes of Health (NIH), National Institute of Mental Health [U54-MH074404]; National Institute of General Medical Sciences [R01-GM084041]; National Institute of Diabetes and Digestive and Kidney Diseases [1RC4DK090861]; NIH [DK31405]
NR 28
TC 451
Z9 526
U1 1
U2 64
PU 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 22
PY 2011
VL 477
IS 7365
BP 477
EP U131
DI 10.1038/nature10383
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500043
PM 21892191
DA 2026-03-09
ER

PT J
AU Lockner, DA
   Morrow, C
   Moore, D
   Hickman, S
AF Lockner, David A.
   Morrow, Carolyn
   Moore, Diane
   Hickman, Stephen
TI Low strength of deep San Andreas fault gouge from SAFOD core
SO NATURE
LA English
DT Article
ID heat-flow; stress; serpentinite; friction; zone
AB The San Andreas fault accommodates 28-34 mm yr(-1) of right lateral motion of the Pacific crustal plate northwestward past the North American plate. In California, the fault is composed of two distinct locked segments that have produced great earthquakes in historical times, separated by a 150-km-long creeping zone. The San Andreas Fault Observatory at Depth (SAFOD) is a scientific borehole located northwest of Parkfield, California, near the southern end of the creeping zone. Core was recovered from across the actively deforming San Andreas fault at a vertical depth of 2.7 km (ref. 1). Here we report laboratory strength measurements of these fault core materials at in situ conditions, demonstrating that at this locality and this depth the San Andreas fault is profoundly weak (coefficient of friction, 0.15) owing to the presence of the smectite clay mineral saponite, which is one of the weakest phyllosilicates known. This Mg-rich clay is the low-temperature product of metasomatic reactions between the quartzofeldspathic wall rocks and serpentinite blocks in the fault(2,3). These findings provide strong evidence that deformation of the mechanically unusual creeping portions of the San Andreas fault system is controlled by the presence of weak minerals rather than by high fluid pressure or other proposed mechanisms(1). The combination of these measurements of fault core strength with borehole observations(1,4,5) yields a self-consistent picture of the stress state of the San Andreas fault at the SAFOD site, in which the fault is intrinsically weak in an otherwise strong crust.
C1 [Lockner, David A.; Morrow, Carolyn; Moore, Diane; Hickman, Stephen] US Geol Survey, Menlo Pk, CA 94025 USA.
C3 United States Department of the Interior; United States Geological Survey
RP Lockner, DA (corresponding author), US Geol Survey, 345 Middlefield Rd, Menlo Pk, CA 94025 USA.
EM dlockner@usgs.gov
CR Boness NL, 2006, GEOPHYSICS, V71, PF131, DOI 10.1190/1.2231107
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   Solum JG, 2006, GEOPHYS RES LETT, V33, P0, DOI 10.1029/2006GL027285
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   Tembe S, 2010, J GEOPHYS RES-SOL EA, V115, P0, DOI 10.1029/2009JB006383
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   Tobin H, 2007, IODP ICDP WORKSH FAU, V0, P5
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NR 28
TC 335
Z9 382
U1 3
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 82
EP U107
DI 10.1038/nature09927
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400041
PM 21441903
DA 2026-03-09
ER

PT J
AU Meek, SJ
   O'Brien, RV
   Llaveria, J
   Schrock, RR
   Hoveyda, AH
AF Meek, Simon J.
   O'Brien, Robert V.
   Llaveria, Josep
   Schrock, Richard R.
   Hoveyda, Amir H.
TI Catalytic Z-selective olefin cross-metathesis for natural product synthesis
SO NATURE
LA English
DT Article
ID ring-closing metathesis; efficient; complexes; plasmalogen; molybdenum; krn7000
AB Alkenes are found in many biologically active molecules, and there are a large number of chemical transformations in which alkenes act as the reactants or products (or both) of the reaction. Many alkenes exist as either the E or the higher-energy Z stereoisomer. Catalytic procedures for the stereoselective formation of alkenes are valuable, yet methods enabling the synthesis of 1,2-disubstituted Z alkenes are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and of allylic amides, used until now only in E-selective processes. The corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. These transformations, promoted by catalysts that contain the highly abundant and inexpensive metal molybdenum, are amenable to gram-scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. The utility of this method is demonstrated by its use in syntheses of an anti-oxidant plasmalogen phospholipid, found in electrically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant KRN7000.
C1 [Meek, Simon J.; O'Brien, Robert V.; Llaveria, Josep; Hoveyda, Amir H.] Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA.
   [Schrock, Richard R.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Boston College; Massachusetts Institute of Technology (MIT)
RP Hoveyda, AH (corresponding author), Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU US National Institutes of Health, Institute of General Medical Sciences [GM-59426]; National Science Foundation [CHE-0715138]; US National Science Foundation [DBI-0619576]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1111074] Funding Source: National Science Foundation
NR 30
TC 333
Z9 388
U1 4
U2 233
PU 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 24
PY 2011
VL 471
IS 7339
BP 461
EP 466
DI 10.1038/nature09957
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200052
PM 21430774
DA 2026-03-09
ER

PT J
AU Brennand, KJ
   Simone, A
   Jou, J
   Gelboin-Burkhart, C
   Tran, N
   Sangar, S
   Li, Y
   Mu, YL
   Chen, G
   Yu, D
   McCarthy, S
   Sebat, J
   Gage, FH
AF Brennand, Kristen J.
   Simone, Anthony
   Jou, Jessica
   Gelboin-Burkhart, Chelsea
   Tran, Ngoc
   Sangar, Sarah
   Li, Yan
   Mu, Yangling
   Chen, Gong
   Yu, Diana
   McCarthy, Shane
   Sebat, Jonathan
   Gage, Fred H.
TI Modelling schizophrenia using human induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID rabies virus; receptors; pathways
AB Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%(1). Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue(2) and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD(3), the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood(4-6). We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder.
C1 [Brennand, Kristen J.; Simone, Anthony; Jou, Jessica; Gelboin-Burkhart, Chelsea; Tran, Ngoc; Sangar, Sarah; Li, Yan; Mu, Yangling; Yu, Diana; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Chen, Gong] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [McCarthy, Shane] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
C3 Salk Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Cold Spring Harbor Laboratory; University of California System; University of California San Diego; University of California System; University of California San Diego
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 California Institute for Regenerative Medicine; CIRM [RL1-00649-1]; Lookout and Mathers Foundation; Helmsley Foundation; Sanofi-Aventis
NR 25
TC 1063
Z9 1281
U1 0
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 MAY 12
PY 2011
VL 473
IS 7346
BP 221
EP +
DI 10.1038/nature09915
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200040
PM 21490598
DA 2026-03-09
ER

PT J
AU Williams, SE
   Beronja, S
   Pasolli, HA
   Fuchs, E
AF Williams, Scott E.
   Beronja, Slobodan
   Pasolli, H. Amalia
   Fuchs, Elaine
TI Asymmetric cell divisions promote Notch-dependent epidermal differentiation
SO NATURE
LA English
DT Article
ID regulates spindle orientation; stem-cells; planar divisions; drosophila; protein; numa; lgn; polarity; fate; pins
AB Stem and progenitor cells use asymmetric cell divisions to balance proliferation and differentiation. Evidence from invertebrates shows that this process is regulated by proteins asymmetrically distributed at the cell cortex during mitosis: Par3-Par6-aPKC, which confer polarity, and G alpha(i)-LGN/AGS3-NuMA-dynein/dynactin, which govern spindle positioning. Here we focus on developing mouse skin, where progenitor cells execute a switch from symmetric to predominantly asymmetric divisions concomitant with stratification. Using in vivo skin-specific lentiviral RNA interference, we investigate spindle orientation regulation and provide direct evidence that LGN (also called Gpsm2), NuMA and dynactin (Dctn1) are involved. In compromising asymmetric cell divisions, we uncover profound defects in stratification, differentiation and barrier formation, and implicate Notch signalling as an important effector. Our study demonstrates the efficacy of applying RNA interference in vivo to mammalian systems, and the ease of uncovering complex genetic interactions, here to gain insights into how changes in spindle orientation are coupled to establishing proper tissue architecture during skin development.
C1 [Williams, Scott E.; Beronja, Slobodan; Pasolli, H. Amalia; 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 National Institutes of Health [R01AR27883]; American Cancer Society; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR027883, R37AR027883, R01AR050452] Funding Source: NIH RePORTER
NR 49
TC 337
Z9 397
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 FEB 17
PY 2011
VL 470
IS 7334
BP 353
EP 358
DI 10.1038/nature09793
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100033
PM 21331036
DA 2026-03-09
ER

PT J
AU Mariappan, M
   Mateja, A
   Dobosz, M
   Bove, E
   Hegde, RS
   Keenan, RJ
AF Mariappan, Malaiyalam
   Mateja, Agnieszka
   Dobosz, Malgorzata
   Bove, Elia
   Hegde, Ramanujan S.
   Keenan, Robert J.
TI The mechanism of membrane-associated steps in tail-anchored protein insertion
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; translocation; yeast; complex; binding; model; get3
AB Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. Here we reconstitute the TA protein insertion cycle with purified components, present crystal structures of key complexes between these components and perform mutational analyses based on the structures. We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2. Once the targeting complex has been recruited, Get1 interacts with Get3 to drive TA protein release in an ATPase-dependent reaction. After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle.
C1 [Mateja, Agnieszka; Dobosz, Malgorzata; Bove, Elia; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
   [Mariappan, Malaiyalam; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
C3 University of Chicago; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
RP Keenan, RJ (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Room W238,929 E 57th St, Chicago, IL 60637 USA.
EM hegde.science@gmail.com; bkeenan@uchicago.edu
FU US DOE [DE-AC02-06CH11357]; NIH [R01 GM086487]; Camille and Henry Dreyfus Postdoctoral Program in Environmental Chemistry; Edward Mallinckrodt, Jr. Foundation; National Institute of General Medical Sciences [R01GM086487] Funding Source: NIH RePORTER
NR 39
TC 135
Z9 163
U1 2
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 SEP 1
PY 2011
VL 477
IS 7362
BP 61
EP U69
DI 10.1038/nature10362
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300030
PM 21866104
DA 2026-03-09
ER

PT J
AU Hrecka, K
   Hao, CL
   Gierszewska, M
   Swanson, SK
   Kesik-Brodacka, M
   Srivastava, S
   Florens, L
   Washburn, MP
   Skowronski, J
AF Hrecka, Kasia
   Hao, Caili
   Gierszewska, Magda
   Swanson, Selene K.
   Kesik-Brodacka, Malgorzata
   Srivastava, Smita
   Florens, Laurence
   Washburn, Michael P.
   Skowronski, Jacek
TI Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein
SO NATURE
LA English
DT Article
ID aicardi-goutieres syndrome; ubiquitin ligase; innate; gene; association; usurps; cells
AB Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses(1,2). Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA(3,4). In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism(5,6). Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection(7,8). Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutieres syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors(9,10). Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
C1 [Hrecka, Kasia; Hao, Caili; Kesik-Brodacka, Malgorzata; Skowronski, Jacek] Case Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
   [Hrecka, Kasia; Gierszewska, Magda; Srivastava, Smita; Skowronski, Jacek] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Swanson, Selene K.; Florens, Laurence; Washburn, Michael P.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Washburn, Michael P.] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Kansas City, KS 66160 USA.
C3 University System of Ohio; Case Western Reserve University; Cold Spring Harbor Laboratory; Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center
RP Skowronski, J (corresponding author), Case Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
EM jacek.skowronski@case.edu
FU NIH [R01 AI077459, R21 AI084694]; Case CFAR developmental funds; Stowers Institute for Medical Research
NR 30
TC 1016
Z9 1214
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 JUN 30
PY 2011
VL 474
IS 7353
BP 658
EP U137
DI 10.1038/nature10195
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300043
PM 21720370
DA 2026-03-09
ER

PT J
AU Angel, A
   Song, J
   Dean, C
   Howard, M
AF Angel, Andrew
   Song, Jie
   Dean, Caroline
   Howard, Martin
TI A Polycomb-based switch underlying quantitative epigenetic memory
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; vernalization; chromatin; protein; flc; methylation; information; propagation; inheritance; repressor
AB The conserved Polycomb repressive complex 2 (PRC2) generates trimethylation of histone 3 lysine 27 (H3K27me3)(1,2), a modification associated with stable epigenetic silencing(3,4). Much is known about PRC2-induced silencing but key questions remain concerning its nucleation and stability. Vernalization, the perception and memory of winter in plants, is a classic epigenetic process that, in Arabidopsis, involves PRC2-based silencing of the floral repressor FLC(5,6). The slow dynamics of vernalization, taking place over weeks in the cold, generate a level of stable silencing of FLC in the subsequent warm that depends quantitatively on the length of the prior cold. These features make vernalization an ideal experimental system to investigate both the maintenance of epigenetic states and the switching between them. Here, using mathematical modelling, chromatin immunoprecipitation and an FLC:GUS reporter assay, we show that the quantitative nature of vernalization is generated by H3K27me3-mediated FLC silencing in the warm in a subpopulation of cells whose number depends on the length of the prior cold. During the cold, H3K27me3 levels progressively increase at a tightly localized nucleation region within FLC. At the end of the cold, numerical simulations predict that such a nucleation region is capable of switching the bistable epigenetic state of an individual locus, with the probability of overall FLC coverage by silencing H3K27me3 marks depending on the length of cold exposure. Thus, the model predicts a bistable pattern of FLC gene expression in individual cells, a prediction we verify using the FLC: GUS reporter system. Our proposed switching mechanism, involving the local nucleation of an opposing histone modification, is likely to be widely relevant in epigenetic reprogramming.
C1 [Song, Jie; Dean, Caroline] John Innes Ctr, Dept Cell & Dev Biol, Norwich NR4 7UH, Norfolk, England.
   [Angel, Andrew; Howard, Martin] John Innes Ctr, Dept Computat & Syst Biol, Norwich NR4 7UH, Norfolk, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre
RP Dean, C (corresponding author), John Innes Ctr, Dept Cell & Dev Biol, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England.
EM caroline.dean@jic.ac.uk; martin.howard@jic.ac.uk
FU European Research Council; Biotechnology and Biological Sciences Research Council; Royal Society; BBSRC [BBS/E/J/000CA369, BBS/E/J/000C0637] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/J/000C0637, BBS/E/J/000CA369, BB/C519670/1] Funding Source: researchfish
NR 30
TC 359
Z9 390
U1 3
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 105
EP +
DI 10.1038/nature10241
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300039
PM 21785438
DA 2026-03-09
ER

PT J
AU Zhang, HB
   Zhou, XH
   McQuade, T
   Li, JH
   Chan, FKM
   Zhang, JK
AF Zhang, Haibing
   Zhou, Xiaohui
   McQuade, Thomas
   Li, Jinghe
   Chan, Francis Ka-Ming
   Zhang, Jianke
TI Functional complementation between FADD and RIP1 in embryos and lymphocytes
SO NATURE
LA English
DT Article
ID receptor-interacting protein; death domain protein; cell-death; kinase rip; programmed necrosis; fas; apoptosis; regulator; fas/apo1
AB FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). Death receptors are essential for immune homeostasis, but dispensable during embryogenesis. Surprisingly, Fadd(-/-) mice die in utero(4,5) and conditional deletion of FADD leads to impaired lymphocyte proliferation(6,7). How FADD regulates embryogenesis and lymphocyte responses has been a long-standing enigma. FADD could directly bind to RIP1 (also known as RIPK1), a serine/threonine kinase that mediates both necrosis and NF-kappa B activation. Here we show that Fadd(-/-) embryos contain raised levels of RIP1 and exhibit massive necrosis. To investigate a potential in vivo functional interaction between RIP1 and FADD, null alleles of RIP1 were crossed into Fadd(-/-) mice. Notably, RIP1 deficiency allowed normal embryogenesis of Fadd(-/-) mice. Conversely, the developmental defect of Rip1(-/-) lymphocytes was partially corrected by FADD deletion. Furthermore, RIP1 deficiency fully restored normal proliferation in Fadd(-/-) T cells but not in Fadd(-/-) B cells. Fadd(-/-)Rip1(-/-) double-knockout T cells are resistant to death induced by Fas or TNF-alpha and show reduced NF-kappa B activity. Therefore, our data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function.
C1 [Zhang, Haibing; Zhou, Xiaohui; Li, Jinghe; Zhang, Jianke] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA.
   [McQuade, Thomas; Chan, Francis Ka-Ming] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
C3 Thomas Jefferson University; University of Massachusetts System; University of Massachusetts Worcester
RP Zhang, JK (corresponding author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA.
EM francis.chan@umassmed.edu; jzhang@mail.jci.tju.edu
FU NIH [CA95454, AI083915, AI076788, AI083497, AI017672]; W. W. Smith Charitable Trust grant; TJU Enhancement grant; CONCERN Foundation
NR 23
TC 374
Z9 412
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2011
VL 471
IS 7338
BP 373
EP +
DI 10.1038/nature09878
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000044
PM 21368761
DA 2026-03-09
ER

PT J
AU DiMaio, F
   Terwilliger, TC
   Read, RJ
   Wlodawer, A
   Oberdorfer, G
   Wagner, U
   Valkov, E
   Alon, A
   Fass, D
   Axelrod, HL
   Das, D
   Vorobiev, SM
   Iwaï, H
   Pokkuluri, PR
   Baker, D
AF DiMaio, Frank
   Terwilliger, Thomas C.
   Read, Randy J.
   Wlodawer, Alexander
   Oberdorfer, Gustav
   Wagner, Ulrike
   Valkov, Eugene
   Alon, Assaf
   Fass, Deborah
   Axelrod, Herbert L.
   Das, Debanu
   Vorobiev, Sergey M.
   Iwai, Hideo
   Pokkuluri, P. Raj
   Baker, David
TI Improved molecular replacement by density- and energy-guided protein structure optimization
SO NATURE
LA English
DT Article
ID crystallographic refinement; prediction; accuracy; software
AB Molecular replacement(1-4) procedures, which search for placements of a starting model within the crystallographic unit cell that best account for the measured diffraction amplitudes, followed by automatic chain tracing methods(5-8), have allowed the rapid solution of large numbers of protein crystal structures. Despite extensive work(9-14), molecular replacement or the subsequent rebuilding usually fail with more divergent starting models based on remote homologues with less than 30% sequence identity. Here we show that this limitation can be substantially reduced by combining algorithms for protein structure modelling with those developed for crystallographic structure determination. An approach integrating Rosetta structure modelling with Autobuild chain tracing yielded high-resolution structures for 8 of 13 X-ray diffraction data sets that could not be solved in the laboratories of expert crystallographers and that remained unsolved after application of an extensive array of alternative approaches. We estimate that the new method should allow rapid structure determination without experimental phase information for over half the cases where current methods fail, given diffraction data sets of better than 3.2 angstrom resolution, four or fewer copies in the asymmetric unit, and the availability of structures of homologous proteins with >20% sequence identity.
C1 [Terwilliger, Thomas C.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [DiMaio, Frank; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [DiMaio, Frank; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Read, Randy J.] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
   [Oberdorfer, Gustav; Wagner, Ulrike] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria.
   [Valkov, Eugene] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
   [Alon, Assaf; Fass, Deborah] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
   [Axelrod, Herbert L.; Das, Debanu] SLAC Natl Accelerator Lab, Joint Ctr Struct Genom, Menlo Pk, CA 94025 USA.
   [Axelrod, Herbert L.; Das, Debanu] SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA.
   [Vorobiev, Sergey M.] Columbia Univ, NE Struct Genom Consortium, New York, NY 10027 USA.
   [Iwai, Hideo] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki, Finland.
   [Pokkuluri, P. Raj] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Cambridge; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Graz; University of Cambridge; Weizmann Institute of Science; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Columbia University; University of Helsinki; United States Department of Energy (DOE); Argonne National Laboratory
RP Terwilliger, TC (corresponding author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA.
EM terwilliger@lanl.gov; dabaker@u.washington.edu
FU NIH [5R01GM092802, P41RR002250]; Wellcome Trust; HHMI; Israel Science Foundation; DK Molecular Enzymology [W901]; Austrian Science Fund [P19858]; NIH, National Cancer Institute, Center for Cancer Research; academy of Finland [1131413]; Protein Structure Initiative of National Institute of General Medical Sciences [U54 GM074958]; US Department of Energy's Office of Science, Biological and Environmental Research [DE-AC02-06CH11357]; NIH, National Institutes of General Medical Sciences, Protein Structure Initiative [U54 GM094586, GM074898]; National Cancer Institute [ZIABC010348] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P01GM063210] Funding Source: NIH RePORTER; Austrian Science Fund (FWF) [P19858] Funding Source: Austrian Science Fund (FWF); Austrian Science Fund (FWF) [W 901] Funding Source: researchfish
NR 29
TC 197
Z9 222
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 MAY 26
PY 2011
VL 473
IS 7348
BP 540
EP U149
DI 10.1038/nature09964
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300047
PM 21532589
DA 2026-03-09
ER

PT J
AU Sundal, AV
   Shepherd, A
   Nienow, P
   Hanna, E
   Palmer, S
   Huybrechts, P
AF Sundal, Aud Venke
   Shepherd, Andrew
   Nienow, Peter
   Hanna, Edward
   Palmer, Steven
   Huybrechts, Philippe
TI Melt-induced speed-up of Greenland ice sheet offset by efficient subglacial drainage
SO NATURE
LA English
DT Article
ID mass-balance; surface melt; acceleration; dynamics; tracking; runoff; motion
AB Fluctuations in surface melting are known to affect the speed of glaciers and ice sheets(1-7), but their impact on the Greenland ice sheet in a warming climate remains uncertain(8). Although some studies suggest that greater melting produces greater ice-sheet acceleration(7,9), others have identified a long-term decrease in Greenland's flow despite increased melting(3). Here we use satellite observations of ice motion recorded in a land-terminating sector of southwest Greenland to investigate the manner in which ice flow develops during years of markedly different melting. Although peak rates of ice speed-up are positively correlated with the degree of melting, mean summer flow rates are not, because glacier slowdown occurs, on average, when a critical run-off threshold of about 1.4 centimetres a day is exceeded. In contrast to the first half of summer, when flow is similar in all years, speed-up during the latter half is 62 +/- 16 per cent less in warmer years. Consequently, in warmer years, the period of fast ice flow is three times shorter and, overall, summer ice flow is slower. This behaviour is at odds with that expected from basal lubrication alone(7,9). Instead, it mirrors that of mountain glaciers(10-12), where melt-induced acceleration of flow ceases during years of high melting once subglacial drainage becomes efficient. A model of ice-sheet flow that captures switching between cavity and channel drainage modes(13) is consistent with the run-off threshold, fast-flow periods, and later-summer speeds we have observed. Simulations of the Greenland ice-sheet flow under climate warming scenarios should account for the dynamic evolution of subglacial drainage; a simple model of basal lubrication alone misses key aspects of the ice sheet's response to climate warming.
C1 [Sundal, Aud Venke; Shepherd, Andrew; Palmer, Steven] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Nienow, Peter] Univ Edinburgh, Sch Geosci, Edinburgh EH8 9XP, Midlothian, Scotland.
   [Hanna, Edward] Univ Sheffield, Dept Geog, Sheffield S10 2TN, S Yorkshire, England.
   [Huybrechts, Philippe] Vrije Univ Brussel, Dept Geog, B-1050 Brussels, Belgium.
C3 University of Leeds; University of Edinburgh; University of Sheffield; Vrije Universiteit Brussel
RP Shepherd, A (corresponding author), Univ Leeds, Sch Earth & Environm, Woodhouse Lane, Leeds LS2 9JT, W Yorkshire, England.
EM a.shepherd@leeds.ac.uk
FU UK NERC National Centre for Earth Observation; EU [026]; Natural Environment Research Council [earth010006, cpom20001] Funding Source: researchfish; NERC [cpom20001] Funding Source: UKRI
NR 26
TC 277
Z9 330
U1 1
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 522
EP U83
DI 10.1038/nature09740
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500030
PM 21270891
DA 2026-03-09
ER

PT J
AU Weitenberg, C
   Endres, M
   Sherson, JF
   Cheneau, M
   Schauss, P
   Fukuhara, T
   Bloch, I
   Kuhr, S
AF Weitenberg, Christof
   Endres, Manuel
   Sherson, Jacob F.
   Cheneau, Marc
   Schauss, Peter
   Fukuhara, Takeshi
   Bloch, Immanuel
   Kuhr, Stefan
TI Single-spin addressing in an atomic Mott insulator
SO NATURE
LA English
DT Article
ID optically trapped atoms; controlled collisions; transition; superfluid; entanglement; microscopy; microtrap; lattices
AB Ultracold atoms in optical lattices provide a versatile tool with which to investigate fundamental properties of quantum many-body systems. In particular, the high degree of control of experimental parameters has allowed the study of many interesting phenomena, such as quantum phase transitions and quantum spin dynamics. Here we demonstrate how such control can be implemented at the most fundamental level of a single spin at a specific site of an optical lattice. Using a tightly focused laser beam together with a microwave field, we were able to flip the spin of individual atoms in a Mott insulator with sub-diffraction-limited resolution, well below the lattice spacing. The Mott insulator provided us with a large two-dimensional array of perfectly arranged atoms, in which we created arbitrary spin patterns by sequentially addressing selected lattice sites after freezing out the atom distribution. We directly monitored the tunnelling quantum dynamics of single atoms in the lattice prepared along a single line, and observed that our addressing scheme leaves the atoms in the motional ground state. The results should enable studies of entropy transport and the quantum dynamics of spin impurities, the implementation of novel cooling schemes, and the engineering of quantum many-body phases and various quantum information processing applications.
C1 [Weitenberg, Christof; Endres, Manuel; Sherson, Jacob F.; Cheneau, Marc; Schauss, Peter; Fukuhara, Takeshi; Bloch, Immanuel; Kuhr, Stefan] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Bloch, Immanuel] Univ Munich, D-80799 Munich, Germany.
C3 Max Planck Society; University of Munich
RP Kuhr, S (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM stefan.kuhr@mpq.mpg.de
FU MPG; DFG; Stiftung Rheinland-Pfalzfur Innovation; Carl-Zeiss Stiftung; EU; JSPS
NR 50
TC 600
Z9 673
U1 2
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 MAR 17
PY 2011
VL 471
IS 7338
BP 319
EP +
DI 10.1038/nature09827
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000033
PM 21412333
DA 2026-03-09
ER

PT J
AU Kormendy, J
   Bender, R
   Cornell, ME
AF Kormendy, John
   Bender, R.
   Cornell, M. E.
TI Supermassive black holes do not correlate with galaxy disks or pseudobulges
SO NATURE
LA English
DT Article
ID m-bh-sigma(asterisk) relation; mass; constraints; accretion; quasars; nuclei; bulges; origin; sigma
AB The masses of supermassive black holes are known to correlate with the properties of the bulge components of their host galaxies(1-5). In contrast, they seem not to correlate with galaxy disks(1). Disk-grown 'pseudobulges' are intermediate in properties between bulges and disks(6); it has been unclear whether they do(1,5) or do not(7-9) correlate with black holes in the same way that bulges do. At stake in this issue are conclusions about which parts of galaxies coevolve with black holes(10), possibly by being regulated by energy feedback from black holes(11). Here we report pseudobulge classifications for galaxies with dynamically detected black holes and combine them with recent measurements of velocity dispersions in the biggest bulgeless galaxies(12). These data confirm that black holes do not correlate with disks and show that they correlate little or not at all with pseudobulges. We suggest that there are two different modes of black-hole feeding. Black holes in bulges grow rapidly to high masses when mergers drive gas infall that feeds quasar-like events. In contrast, small black holes in bulgeless galaxies and in galaxies with pseudobulges grow as low-level Seyfert galaxies. Growth of the former is driven by global processes, so the biggest black holes coevolve with bulges, but growth of the latter is driven locally and stochastically, and they do not coevolve with disks and pseudobulges.
C1 [Kormendy, John; Cornell, M. E.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Bender, R.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Bender, R.] Univ Sternwarte, D-81679 Munich, Germany.
C3 University of Texas System; University of Texas Austin; Max Planck Society; University of Munich
RP Kormendy, J (corresponding author), Univ Texas Austin, Dept Astron, 1 Univ Stn, Austin, TX 78712 USA.
EM kormendy@astro.as.utexas.edu
FU NASA; National Science Foundation (NSF)
NR 30
TC 219
Z9 233
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 20
PY 2011
VL 469
IS 7330
BP 374
EP 376
DI 10.1038/nature09694
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600046
PM 21248845
DA 2026-03-09
ER

PT J
AU Chung, WJ
   Oh, JW
   Kwak, K
   Lee, BY
   Meyer, J
   Wang, E
   Hexemer, A
   Lee, SW
AF Chung, Woo-Jae
   Oh, Jin-Woo
   Kwak, Kyungwon
   Lee, Byung Yang
   Meyer, Joel
   Wang, Eddie
   Hexemer, Alexander
   Lee, Seung-Wuk
TI Biomimetic self-templating supramolecular structures
SO NATURE
LA English
DT Article
ID convergent evolution; liquid-crystals; phase; biomaterials; coloration; protein; skin
AB In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials(1-3). During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures(1,4). A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres(5), distinctively coloured skin tissues from cholesteric phase fibre bundles(6,7), and mineralized tissues from hierarchically organized fibres(8). Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods(9-12). However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.
C1 [Chung, Woo-Jae; Oh, Jin-Woo; Kwak, Kyungwon; Lee, Byung Yang; Meyer, Joel; Wang, Eddie; Lee, Seung-Wuk] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
   [Chung, Woo-Jae; Oh, Jin-Woo; Kwak, Kyungwon; Lee, Byung Yang; Meyer, Joel; Wang, Eddie; Lee, Seung-Wuk] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
   [Hexemer, Alexander] Univ Calif Berkeley, Lawrence Berkeley Lab, Adv Light Source, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Lee, SW (corresponding author), Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
EM leesw@berkeley.edu
FU National Science Foundation [DMR-0747713]; Center of Integrated Nanomechanical Systems (COINS) of the National Science Foundation [EEC-0832819]; National Institute of Dental and Craniofacial Research [R21DE018360]; Defense Advanced Research Projects Agency (DARPA); Nanoscience and Nanotechnology Institute at the University of California, Berkeley; Lawrence Berkeley National Laboratory; Korea Research Foundation; Korean government (MOEHRD) [KRF-2006-352-D00048]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0747713] Funding Source: National Science Foundation
NR 33
TC 392
Z9 446
U1 10
U2 761
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 364
EP 368
DI 10.1038/nature10513
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100041
PM 22012394
DA 2026-03-09
ER

PT J
AU Kwon, HB
   Sabatini, BL
AF Kwon, Hyung-Bae
   Sabatini, Bernardo L.
TI Glutamate induces de novo growth of functional spines in developing cortex
SO NATURE
LA English
DT Article
ID hippocampal slice cultures; single dendritic spines; synapse formation; pyramidal neurons; adult cortex; in-vivo; plasticity; synaptogenesis; activation; maturation
AB Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodelling, stabilization and pruning during development, and similar structural changes can be triggered by learning and changes in sensory experiences(1-4). However, the biochemical triggers and mechanisms of de novo spine formation in the developing brain and the functional significance of new spines to neuronal connectivity are largely unknown. Here we develop an approach to induce and monitor de novo spine formation in real time using combined two-photon laser-scanning microscopy and two-photon laser uncaging of glutamate. Our data demonstrate that, in mouse cortical layer 2/3 pyramidal neurons, glutamate is sufficient to trigger de novo spine growth from the dendrite shaft in a location-specific manner. We find that glutamate-induced spinogenesis requires opening of NMDARs (N-methyl-D-aspartate-type glutamate receptors) and activation of protein kinase A (PKA) but is independent of calcium-calmodulin-dependent kinase II (CaMKII) and tyrosine kinase receptor B (TrkB) receptors. Furthermore, newly formed spines express glutamate receptors and are rapidly functional such that they transduce presynaptic activity into postsynaptic signals. Together, our data demonstrate that early neural connectivity is shaped by activity in a spatially precise manner and that nascent dendrite spines are rapidly functionally incorporated into cortical circuits.
C1 [Kwon, Hyung-Bae; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Sabatini, BL (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
EM bsabatini@hms.harvard.edu
FU Simons Foundation; National Institute of Neurological Disorders and Stroke [NS046579]
NR 30
TC 282
Z9 366
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 100
EP 104
DI 10.1038/nature09986
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700046
PM 21552280
DA 2026-03-09
ER

PT J
AU Wang, Z
   Young, RL
   Xue, HL
   Wagner, GP
AF Wang, Zhe
   Young, Rebecca L.
   Xue, Huiling
   Wagner, Guenter P.
TI Transcriptomic analysis of avian digits reveals conserved and derived digit identities in birds
SO NATURE
LA English
DT Article
ID differential expression analysis; rna-seq data; gene-expression; wing digits; hox genes; r-package; evolution; homology; limb; patterns
AB Morphological characters are the result of developmental gene expression. The identity of a character is ultimately grounded in the gene regulatory network directing development and thus whole-genome gene expression data can provide evidence about character identity. This approach has been successfully used to assess cell-type identity(1-3). Here we use transcriptomic data to address a long-standing uncertainty in evolutionary biology, the identity of avian wing digits(4,5). Embryological evidence clearly identifies the three wing digits as developing from digit positions 2, 3 and 4 (ref. 6), whereas palaeontological data suggest that they are digits I, II and III7. We compare the transcriptomes of the wing and foot digits and find a strong signal that unites the first wing digit with the first foot digit, even though the first wing digit develops from embryological position 2. Interestingly, our transcriptomic data of the posterior digits show a higher degree of differentiation among forelimb digits compared with hindlimb digits. These data show that in the stem lineage of birds the first digit underwent a translocation from digit position 1 to position 2, and further indicate that the posterior wing digits have unique identities contrary to any model of avian digit identity proposed so far(5,8).
C1 [Wang, Zhe; Young, Rebecca L.; Wagner, Guenter P.] Yale Univ, Yale Syst Biol Inst, West Haven, CT 06516 USA.
   [Wang, Zhe; Young, Rebecca L.; Wagner, Guenter P.] Yale Univ, Dept Ecol & Evolutionary Biol, West Haven, CT 06516 USA.
   [Xue, Huiling] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
C3 Yale University; Yale University; Yale University
RP Wagner, GP (corresponding author), Yale Univ, Yale Syst Biol Inst, West Haven, CT 06516 USA.
EM gunter.wagner@yale.edu
FU Yale Science Development Fund
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   Robinson MD, 2010, GENOME BIOL, V11, P0, DOI 10.1186/gb-2010-11-3-r25
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   Sugino K, 2006, NAT NEUROSCI, V9, P99, DOI 10.1038/nn1618
   Suzuki R, 2006, BIOINFORMATICS, V22, P1540, DOI 10.1093/bioinformatics/btl117
   Suzuki T, 2008, P NATL ACAD SCI USA, V105, P4185, DOI 10.1073/pnas.0707899105
   Tamura K, 2011, SCIENCE, V331, P753, DOI 10.1126/science.1198229
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NR 38
TC 57
Z9 64
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 583
EP U345
DI 10.1038/nature10391
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900038
PM 21892187
DA 2026-03-09
ER

PT J
AU Zhu, XB
   Saito, S
   Kemp, A
   Kakuyanagi, K
   Karimoto, S
   Nakano, H
   Munro, WJ
   Tokura, Y
   Everitt, MS
   Nemoto, K
   Kasu, M
   Mizuochi, N
   Semba, K
AF Zhu, Xiaobo
   Saito, Shiro
   Kemp, Alexander
   Kakuyanagi, Kosuke
   Karimoto, Shin-ichi
   Nakano, Hayato
   Munro, William J.
   Tokura, Yasuhiro
   Everitt, Mark S.
   Nemoto, Kae
   Kasu, Makoto
   Mizuochi, Norikazu
   Semba, Kouichi
TI Coherent coupling of a superconducting flux qubit to an electron spin ensemble in diamond
SO NATURE
LA English
DT Article
ID quantum state; cavity; dynamics
AB During the past decade, research into superconducting quantum bits (qubits) based on Josephson junctions has made rapid progress(1). Many foundational experiments have been performed(2-8), and superconducting qubits are now considered one of the most promising systems for quantum information processing. However, the experimentally reported coherence times are likely to be insufficient for future large-scale quantum computation. A natural solution to this problem is a dedicated engineered quantum memory based on atomic and molecular systems. The question of whether coherent quantum coupling is possible between such natural systems and a single macroscopic artificial atom has attracted considerable attention(9-12) since the first demonstration of macroscopic quantum coherence in Josephson junction circuits(2). Here we report evidence of coherent strong coupling between a single macroscopic superconducting artificial atom (a flux qubit) and an ensemble of electron spins in the form of nitrogen-vacancy colour centres in diamond. Furthermore, we have observed coherent exchange of a single quantum of energy between a flux qubit and a macroscopic ensemble consisting of about 3 x 10(7) such colour centres. This provides a foundation for future quantum memories and hybrid devices coupling microwave and optical systems.
C1 [Zhu, Xiaobo; Saito, Shiro; Kemp, Alexander; Kakuyanagi, Kosuke; Karimoto, Shin-ichi; Nakano, Hayato; Munro, William J.; Tokura, Yasuhiro; Kasu, Makoto; Semba, Kouichi] NTT Corp, NTT Basic Res Labs, Kanagawa 2430198, Japan.
   [Everitt, Mark S.; Nemoto, Kae] Res Org Informat & Syst, Natl Inst Informat, Chiyoda Ku, Tokyo 1018430, Japan.
   [Mizuochi, Norikazu] Osaka Univ, Grad Sch Engn Sci, Osaka 5608531, Japan.
   [Mizuochi, Norikazu] PRESTO JST, Kawaguchi, Saitama 3320012, Japan.
C3 NTT, Inc; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan; University of Osaka; Japan Science & Technology Agency (JST)
RP Semba, K (corresponding author), NTT Corp, NTT Basic Res Labs, 3-1 Morinosato Wakamiya, Kanagawa 2430198, Japan.
EM semba.kouichi@lab.ntt.co.jp
FU Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST); MEXT [18001002]; Japanese Society for the Promotion of Science (JSPS) [22102502, 22241025]; Grants-in-Aid for Scientific Research [22102502, 23681017, 21102003, 09F09770, 21102002, 22241025] Funding Source: KAKEN
NR 30
TC 392
Z9 419
U1 1
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 221
EP 224
DI 10.1038/nature10462
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800045
PM 21993757
DA 2026-03-09
ER

PT J
AU Gaston, MA
   Zhang, LW
   Green-Church, KB
   Krzycki, JA
AF Gaston, Marsha A.
   Zhang, Liwen
   Green-Church, Kari B.
   Krzycki, Joseph A.
TI The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine
SO NATURE
LA English
DT Article
ID transfer-rna synthetase; m methyl transfer; methanosarcina-barkeri; corrinoid protein; methyltransferases; code; reconstitution; uag; expansion; analogs
AB Pyrrolysine, the twenty-second amino acid found to be encoded in the natural genetic code(1-4), is necessary for all of the known pathways by which methane is formed from methylamines(5,6). Pyrrolysine comprises a methylated pyrroline carboxylate in amide linkage to the e-amino group of L-lysine(2,7,8). In certain Archaea, three methyltransferases initiate methanogenesis from the various methylamines(9-11), and these enzymes are encoded by genes with an in-frame amber codon(12,13) that is translated as pyrrolysine(2,7,8). Escherichia coli that has been transformed with the pylTSBCD genes from methanogenic Archaea can incorporate endogenously biosynthesized pyrrolysine into proteins(14). The decoding of UAG as pyrrolysine requires pylT(1,6), which produces tRNA(Pyl) (also called tRNA(CUA)), and pylS(1), which encodes a pyrrolysyl-tRNA synthetase(4,15,16). The pylB, pylC and pylD genes(1) are each required for tRNA-independent pyrrolysine synthesis(14). Pyrrolysine is the last remaining genetically encoded amino acid with an unknown biosynthetic pathway. Here we provide genetic and mass spectrometric evidence for a pylBCD-dependent pathway in which pyrrolysine arises from two lysines. We show that a newly uncovered UAG-encoded amino acid, desmethylpyrrolysine, is made from lysine and exogenous D-ornithine in a pylC-dependent process followed by a pylD-dependent process, but it is not further converted to pyrrolysine. These results indicate that the radical S-adenosyl-L-methionine (SAM) protein PylB mediates a lysine mutase reaction that produces 3-methylornithine, which is then ligated to a second molecule of lysine by PylC before oxidation by PylD results in pyrrolysine. The discovery of lysine as the sole precursor to pyrrolysine will further inform discussions of the evolution of the genetic code and amino acid biosynthetic pathways. Furthermore, intermediates of the pathway may provide new avenues by which the pyl system can be exploited to produce recombinant proteins with useful modified residues.
C1 [Gaston, Marsha A.; Krzycki, Joseph A.] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.
   [Zhang, Liwen; Green-Church, Kari B.] Ohio State Univ, Mass Spectrometry & Prote Facil, CCIC, Columbus, OH 43210 USA.
   [Krzycki, Joseph A.] Ohio State Univ, Biochem Program, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University
RP Krzycki, JA (corresponding author), Ohio State Univ, Dept Microbiol, 484 W 12th Ave, Columbus, OH 43210 USA.
EM krzycki.1@osu.edu
FU National Institutes of Health; US Department of Energy
NR 30
TC 103
Z9 144
U1 2
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 647
EP U131
DI 10.1038/nature09918
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200045
PM 21455182
DA 2026-03-09
ER

PT J
AU Puente, XS
   Pinyol, M
   Quesada, V
   Conde, L
   Ordóñez, GR
   Villamor, N
   Escaramis, G
   Jares, P
   Beà, S
   González-Díaz, M
   Bassaganyas, L
   Baumann, T
   Juan, M
   López-Guerra, M
   Colomer, D
   Tubío, JMC
   López, C
   Navarro, A
   Tornador, C
   Aymerich, M
   Rozman, M
   Hernández, JM
   Puente, DA
   Freije, JMP
   Velasco, G
   Gutiérrez-Fernández, A
   Costa, D
   Carrió, A
   Guijarro, S
   Enjuanes, A
   Hernández, L
   Yagüe, J
   Nicolás, P
   Romeo-Casabona, CM
   Himmelbauer, H
   Castillo, E
   Dohm, JC
   de Sanjosé, S
   Piris, MA
   de Alava, E
   Miguel, JS
   Royo, R
   Gelpí, JL
   Torrents, D
   Orozco, M
   Pisano, DG
   Valencia, A
   Guigó, R
   Bayés, M
   Heath, S
   Gut, M
   Klatt, P
   Marshall, J
   Raine, K
   Stebbings, LA
   Futreal, PA
   Stratton, MR
   Campbell, PJ
   Gut, I
   López-Guillermo, A
   Estivill, X
   Montserrat, E
   López-Otín, C
   Campo, E
AF Puente, Xose S.
   Pinyol, Magda
   Quesada, Victor
   Conde, Laura
   Ordonez, Gonzalo R.
   Villamor, Neus
   Escaramis, Georgia
   Jares, Pedro
   Bea, Silvia
   Gonzalez-Diaz, Marcos
   Bassaganyas, Laia
   Baumann, Tycho
   Juan, Manel
   Lopez-Guerra, Monica
   Colomer, Dolors
   Tubio, Jose M. C.
   Lopez, Cristina
   Navarro, Alba
   Tornador, Cristian
   Aymerich, Marta
   Rozman, Maria
   Hernandez, Jesus M.
   Puente, Diana A.
   Freije, Jose M. P.
   Velasco, Gloria
   Gutierrez-Fernandez, Ana
   Costa, Dolors
   Carrio, Anna
   Guijarro, Sara
   Enjuanes, Anna
   Hernandez, Lluis
   Yaguee, Jordi
   Nicolas, Pilar
   Romeo-Casabona, Carlos M.
   Himmelbauer, Heinz
   Castillo, Ester
   Dohm, Juliane C.
   de Sanjose, Silvia
   Piris, Miguel A.
   de Alava, Enrique
   Miguel, Jesus San
   Royo, Romina
   Gelpi, Josep L.
   Torrents, David
   Orozco, Modesto
   Pisano, David G.
   Valencia, Alfonso
   Guigo, Roderic
   Bayes, Monica
   Heath, Simon
   Gut, Marta
   Klatt, Peter
   Marshall, John
   Raine, Keiran
   Stebbings, Lucy A.
   Futreal, P. Andrew
   Stratton, Michael R.
   Campbell, Peter J.
   Gut, Ivo
   Lopez-Guillermo, Armando
   Estivill, Xavier
   Montserrat, Emili
   Lopez-Otin, Carlos
   Campo, Elias
TI Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
SO NATURE
LA English
DT Article
ID cancer genome; cell; expression; notch1; hypermutation; network
AB Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution(1,2). Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes(3,4). The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
C1 [Conde, Laura; Villamor, Neus; Jares, Pedro; Bea, Silvia; Lopez-Guerra, Monica; Colomer, Dolors; Lopez, Cristina; Navarro, Alba; Aymerich, Marta; Rozman, Maria; Costa, Dolors; Carrio, Anna; Guijarro, Sara; Enjuanes, Anna; Hernandez, Lluis; Campo, Elias] Univ Barcelona, IDIBAPS, Hosp Clin, Serv Anat Patol,Unidad Hematopatol, E-08036 Barcelona, Spain.
   [Puente, Xose S.; Quesada, Victor; Ordonez, Gonzalo R.; Puente, Diana A.; Freije, Jose M. P.; Velasco, Gloria; Gutierrez-Fernandez, Ana; Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain.
   [Pinyol, Magda] IDIBAPS, Unidad Genom, Barcelona 08036, Spain.
   [Escaramis, Georgia; Bassaganyas, Laia; Tubio, Jose M. C.; Tornador, Cristian; Estivill, Xavier] Pompeu Fabra Univ, Ctr Genom Regulat, Genes & Dis Programme, Barcelona 08003, Spain.
   [Gonzalez-Diaz, Marcos; Hernandez, Jesus M.; de Alava, Enrique; Miguel, Jesus San] Univ Salamanca, Ctr Invest Canc IBMCC USAL CSIC, Univ Hosp, Serv Hematol, Salamanca 37007, Spain.
   [Baumann, Tycho; Lopez-Guillermo, Armando; Montserrat, Emili] Univ Barcelona, IDIBAPS, Hosp Clin, Serv Hematol, E-08036 Barcelona, Spain.
   [Juan, Manel; Yaguee, Jordi] IDIBAPS, Hosp Clin, Serv Inmunol, Barcelona 08036, Spain.
   [Tubio, Jose M. C.] Hosp Clin Univ Santiago de Compostela, Santiago De Compostela 15706, Spain.
   [Nicolas, Pilar; Romeo-Casabona, Carlos M.] Univ Basque Country, Univ Deusto, Catedra Interuniv Derechoy Genoma Humano, Bilbao 48007, Spain.
   [Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.] Pompeii Fabra Univ, Ctr Genom Regulat, Ultrasequencing Unit, Barcelona 08003, Spain.
   [de Sanjose, Silvia] IDIBELL, Inst Catala Oncol, Unidad Infecc & Canc, Lhospitalet De Llobregat 08907, Spain.
   [Piris, Miguel A.] Spanish Natl Canc Res Ctr CNIO, Mol Pathol Programme, Madrid 28029, Spain.
   [Royo, Romina; Gelpi, Josep L.; Torrents, David; Orozco, Modesto] Univ Barcelona, Spanish Natl Bioinformat Inst, IRB, Programa Conjunto Biol Computac,BSC, E-08028 Barcelona, Spain.
   [Pisano, David G.; Valencia, Alfonso] Spanish Natl Bioinformat Inst, Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Madrid 28029, Spain.
   [Guigo, Roderic] Pompeu Fabra Univ, Ctr Genom Regulat, Spanish Natl Bioinformat Inst, Genom Bioinformat Programme, Barcelona 08003, Spain.
   [Bayes, Monica; Heath, Simon; Gut, Marta; Gut, Ivo] Ctr Nacl Anal Genom, Barcelona 08028, Spain.
   [Klatt, Peter] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain.
   [Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
C3 University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; University of Oviedo; Instituto Universitario de Oncologia de Asturias; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-USAL - Instituto de Biologia Molecular y Celular del Cancer de Salamanca (IBMCC); CSIC - Centro de Investigacion del Cancer (CIC); University of Salamanca; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Complexo Hospitalario Universitario de Santiago de Compostela; University of Deusto; University of Basque Country; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro Nacional de Investigaciones Oncologicas (CNIO); Barcelona Institute of Science & Technology; Institute for Research in Biomedicine - IRB Barcelona; University of Barcelona; Centro Nacional de Investigaciones Oncologicas (CNIO); Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); Wellcome Trust Sanger Institute
RP Campo, E (corresponding author), Univ Barcelona, IDIBAPS, Hosp Clin, Serv Anat Patol,Unidad Hematopatol, E-08036 Barcelona, Spain.
EM ecampo@clinic.ub.es
FU Spanish Ministry of Science and Innovation (MICINN) through the Institut de Salud Carlos III (ISCIII); Red Tematica de Investigacion del Cancer (RTICC) del ISCIII
NR 26
TC 1242
Z9 1407
U1 0
U2 167
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 101
EP 105
DI 10.1038/nature10113
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300053
PM 21642962
DA 2026-03-09
ER

PT J
AU Hada, K
   Doi, A
   Kino, M
   Nagai, H
   Hagiwara, Y
   Kawaguchi, N
AF Hada, Kazuhiro
   Doi, Akihiro
   Kino, Motoki
   Nagai, Hiroshi
   Hagiwara, Yoshiaki
   Kawaguchi, Noriyuki
TI An origin of the radio jet in M87 at the location of the central black hole
SO NATURE
LA English
DT Article
ID active galactic nuclei; gamma-ray emission; inner jet; relativistic jets; central engine; galaxy m87; 3c 279; accretion; motion; flare
AB Powerful radio jets from active galactic nuclei are thought to be powered by the accretion of material onto the supermassive black hole (the 'central engine')(1,2). M87 is one of the closest examples of this phenomenon, and the structure of its jet has been probed on a scale of about 100 Schwarzschild radii (R(s), the radius of the event horizon)(3). However, the location of the central black hole relative to the jet base (a bright compact radio 'core') remains elusive(4,5). Observations of other jets indicate that the central engines are located about 10(4)-10(6)R(s) upstream from the radio core(6-9). Here we report radio observations of M87 at six frequencies that allow us to achieve a positional accuracy of about 20 microarcseconds. As the jet base becomes more transparent at higher frequencies, the multifrequency position measurements of the radio core enable us to determine the upstream end of the jet. The data reveal that the central engine of M87 is located within 14-23R(s) of the radio core at 43 GHz. This implies that the site of material infall onto the black hole and the eventual origin of the jet reside in the bright compact region seen on the image at 43 GHz.
C1 [Hada, Kazuhiro; Hagiwara, Yoshiaki; Kawaguchi, Noriyuki] Grad Univ Adv Studies SOKENDAI, Dept Astron Sci, Tokyo 1818588, Japan.
   [Hada, Kazuhiro; Kino, Motoki; Nagai, Hiroshi; Hagiwara, Yoshiaki; Kawaguchi, Noriyuki] Natl Astron Observ Japan, Tokyo 1818588, Japan.
   [Doi, Akihiro; Nagai, Hiroshi] Japan Aerosp Explorat Agcy, Inst Space & Astronaut Sci, Chuo Ku, Kanagawa 2525210, Japan.
   [Doi, Akihiro] Grad Univ Adv Studies SOKENDAI, Dept Space & Astronaut Sci, Chuo Ku, Kanagawa 2525210, Japan.
C3 Graduate University for Advanced Studies - Japan; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); Graduate University for Advanced Studies - Japan
RP Hada, K (corresponding author), Grad Univ Adv Studies SOKENDAI, Dept Astron Sci, 2-21-1 Osawa, Tokyo 1818588, Japan.
EM kazuhiro.hada@nao.ac.jp
FU Graduate University for Advanced Studies (Sokendai)
NR 29
TC 249
Z9 266
U1 0
U2 9
PU 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 8
PY 2011
VL 477
IS 7363
BP 185
EP 187
DI 10.1038/nature10387
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900029
PM 21901008
DA 2026-03-09
ER

PT J
AU Shevenell, AE
   Ingalls, AE
   Domack, EW
   Kelly, C
AF Shevenell, A. E.
   Ingalls, A. E.
   Domack, E. W.
   Kelly, C.
TI Holocene Southern Ocean surface temperature variability west of the Antarctic Peninsula
SO NATURE
LA English
DT Article
ID sea-ice; spatiotemporal variability; atmospheric co2; palmer-deep; climate; record; mechanisms; vegetation; insolation; atlantic
AB The disintegration of ice shelves, reduced sea-ice and glacier extent, and shifting ecological zones observed around Antarctica(1,2) highlight the impact of recent atmospheric(3) and oceanic warming(4) on the cryosphere. Observations(1,2) and models(5,6) suggest that oceanic and atmospheric temperature variations at Antarctica's margins affect global cryosphere stability, ocean circulation, sea levels and carbon cycling. In particular, recent climate changes on the Antarctic Peninsula have been dramatic, yet the Holocene climate variability of this region is largely unknown, limiting our ability to evaluate ongoing changes within the context of historical variability and underlying forcing mechanisms. Here we show that surface ocean temperatures at the continental margin of the western Antarctic Peninsula cooled by 3-4 degrees C over the past 12,000 years, tracking the Holocene decline of local (65 degrees S) spring insolation. Our results, based on TEX(86) sea surface temperature (SST) proxy evidence from a marine sediment core, indicate the importance of regional summer duration as a driver of Antarctic seasonal sea-ice fluctuations(7). On millennial timescales, abrupt SST fluctuations of 2-4 degrees C coincide with globally recognized climate variability(8). Similarities between our SSTs, Southern Hemisphere westerly wind reconstructions(9) and El Nino/Southern Oscillation variability(10) indicate that present climate teleconnections between the tropical Pacific Ocean and the western Antarctic Peninsula(11) strengthened late in the Holocene epoch. We conclude that during the Holocene, Southern Ocean temperatures at the western Antarctic Peninsula margin were tied to changes in the position of the westerlies, which have a critical role in global carbon cycling(9,12).
C1 [Shevenell, A. E.; Ingalls, A. E.; Kelly, C.] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
   [Domack, E. W.] Hamilton Coll, Dept Geosci, Clinton, NY 13323 USA.
C3 University of Washington; University of Washington Seattle; Hamilton College
RP Shevenell, AE (corresponding author), UCL, Dept Geog, Gower St, London WC1E 6BT, England.
EM a.shevenell@ucl.ac.uk
FU NSF [OPP-0620099, OPP-0732467]
NR 32
TC 171
Z9 199
U1 2
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 250
EP 254
DI 10.1038/nature09751
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200042
PM 21307939
DA 2026-03-09
ER

PT J
AU Brown, KR
   Ospelkaus, C
   Colombe, Y
   Wilson, AC
   Leibfried, D
   Wineland, DJ
AF Brown, K. R.
   Ospelkaus, C.
   Colombe, Y.
   Wilson, A. C.
   Leibfried, D.
   Wineland, D. J.
TI Coupled quantized mechanical oscillators
SO NATURE
LA English
DT Article
ID quantum computer; ions; state; entanglement; atom
AB The harmonic oscillator is one of the simplest physical systems but also one of the most fundamental. It is ubiquitous in nature, often serving as an approximation for a more complicated system or as a building block in larger models. Realizations of harmonic oscillators in the quantum regime include electromagnetic fields in a cavity(1-3) and the mechanical modes of a trapped atom(4) or macroscopic solid(5). Quantized interaction between two motional modes of an individual trapped ion has been achieved by coupling through optical fields(6), and entangled motion of two ions in separate locations has been accomplished indirectly through their internal states(7). However, direct controllable coupling between quantized mechanical oscillators held in separate locations has not been realized previously. Here we implement such coupling through the mutual Coulomb interaction of two ions held in trapping potentials separated by 40 mm (similar work is reported in a related paper(8)). By tuning the confining wells into resonance, energy is exchanged between the ions at the quantum level, establishing that direct coherent motional coupling is possible for separately trapped ions. The system demonstrates a building block for quantum information processing and quantum simulation. More broadly, this work is a natural precursor to experiments in hybrid quantum systems, such as coupling a trapped ion to a quantized macroscopic mechanical or electrical oscillator(9-13).
C1 [Brown, K. R.; Ospelkaus, C.; Colombe, Y.; Wilson, A. C.; Leibfried, D.; Wineland, D. J.] NIST, Div Time & Frequency, Boulder, CO 80305 USA.
C3 National Institute of Standards & Technology (NIST) - USA
RP Brown, KR (corresponding author), NIST, Div Time & Frequency, 325 Broadway, Boulder, CO 80305 USA.
EM kenton.brown@nist.gov
FU IARPA; DARPA; ONR; NIST
NR 30
TC 232
Z9 256
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 10
PY 2011
VL 471
IS 7337
BP 196
EP 199
DI 10.1038/nature09721
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200032
PM 21346762
DA 2026-03-09
ER

PT J
AU Sayrin, C
   Dotsenko, I
   Zhou, XX
   Peaudecerf, B
   Rybarczyk, T
   Gleyzes, S
   Rouchon, P
   Mirrahimi, M
   Amini, H
   Brune, M
   Raimond, JM
   Haroche, S
AF Sayrin, Clement
   Dotsenko, Igor
   Zhou, Xingxing
   Peaudecerf, Bruno
   Rybarczyk, Theo
   Gleyzes, Sebastien
   Rouchon, Pierre
   Mirrahimi, Mazyar
   Amini, Hadis
   Brune, Michel
   Raimond, Jean-Michel
   Haroche, Serge
TI Real-time quantum feedback prepares and stabilizes photon number states
SO NATURE
LA English
DT Article
ID radiation-field; error; coherent; entanglement; circuit; cavity
AB Feedback loops are central to most classical control procedures. A controller compares the signal measured by a sensor (system output) with the target value or set-point. It then adjusts an actuator (system input) to stabilize the signal around the target value. Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback(1-3), which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system. An optimal compromise uses weak measurements(4,5), providing partial information with minimal perturbation. The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target. Although some aspects of this scenario have been experimentally demonstrated for the control of quantum(6-9) or classical(10,11) micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized. Here we have implemented such a real-time stabilizing quantum feedback scheme(12) following a method inspired by ref. 13. It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps(14-16). The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number(14). The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements. The microwave field is a quantum oscillator usable as a quantum memory(17) or as a quantum bus swapping information between atoms(18). Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence(15,16), and is a significant step towards the implementation of complex quantum information operations.
C1 [Sayrin, Clement; Dotsenko, Igor; Zhou, Xingxing; Peaudecerf, Bruno; Rybarczyk, Theo; Gleyzes, Sebastien; Brune, Michel; Raimond, Jean-Michel; Haroche, Serge] UPMC Paris 6, ENS, CNRS, Lab Kastler Brossel, F-75005 Paris, France.
   [Rouchon, Pierre; Amini, Hadis] Mines ParisTech, Ctr Automat & Syst Math & Syst, F-75272 Paris 6, France.
   [Mirrahimi, Mazyar] INRIA Paris Rocquencourt, F-78153 Le Chesnay, France.
   [Haroche, Serge] Coll France, F-75231 Paris 05, France.
C3 Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite PSL; MINES ParisTech; Universite PSL; College de France
RP Haroche, S (corresponding author), UPMC Paris 6, ENS, CNRS, Lab Kastler Brossel, 24 Rue Lhomond, F-75005 Paris, France.
EM haroche@lkb.ens.fr
FU Agence Nationale de la Recherche (ANR); EU; ERC
NR 30
TC 473
Z9 528
U1 3
U2 145
PU 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 1
PY 2011
VL 477
IS 7362
BP 73
EP 77
DI 10.1038/nature10376
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300033
PM 21886159
DA 2026-03-09
ER

PT J
AU Morin, RD
   Mendez-Lago, M
   Mungall, AJ
   Goya, R
   Mungall, KL
   Corbett, RD
   Johnson, NA
   Severson, TM
   Chiu, R
   Field, M
   Jackman, S
   Krzywinski, M
   Scott, DW
   Trinh, DL
   Tamura-Wells, J
   Li, S
   Firme, MR
   Rogic, S
   Griffith, M
   Chan, S
   Yakovenko, O
   Meyer, IM
   Zhao, EY
   Smailus, D
   Moksa, M
   Chittaranjan, S
   Rimsza, L
   Brooks-Wilson, A
   Spinelli, JJ
   Ben-Neriah, S
   Meissner, B
   Woolcock, B
   Boyle, M
   McDonald, H
   Tam, A
   Zhao, YJ
   Delaney, A
   Zeng, T
   Tse, K
   Butterfield, Y
   Birol, I
   Holt, R
   Schein, J
   Horsman, DE
   Moore, R
   Jones, SJM
   Connors, JM
   Hirst, M
   Gascoyne, RD
   Marra, MA
AF Morin, Ryan D.
   Mendez-Lago, Maria
   Mungall, Andrew J.
   Goya, Rodrigo
   Mungall, Karen L.
   Corbett, Richard D.
   Johnson, Nathalie A.
   Severson, Tesa M.
   Chiu, Readman
   Field, Matthew
   Jackman, Shaun
   Krzywinski, Martin
   Scott, David W.
   Trinh, Diane L.
   Tamura-Wells, Jessica
   Li, Sa
   Firme, Marlo R.
   Rogic, Sanja
   Griffith, Malachi
   Chan, Susanna
   Yakovenko, Oleksandr
   Meyer, Irmtraud M.
   Zhao, Eric Y.
   Smailus, Duane
   Moksa, Michelle
   Chittaranjan, Suganthi
   Rimsza, Lisa
   Brooks-Wilson, Angela
   Spinelli, John J.
   Ben-Neriah, Susana
   Meissner, Barbara
   Woolcock, Bruce
   Boyle, Merrill
   McDonald, Helen
   Tam, Angela
   Zhao, Yongjun
   Delaney, Allen
   Zeng, Thomas
   Tse, Kane
   Butterfield, Yaron
   Birol, Inanc
   Holt, Rob
   Schein, Jacqueline
   Horsman, Douglas E.
   Moore, Richard
   Jones, Steven J. M.
   Connors, Joseph M.
   Hirst, Martin
   Gascoyne, Randy D.
   Marra, Marco A.
TI Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
SO NATURE
LA English
DT Article
ID b-cell lymphoma; nf-kappa-b; follicular lymphoma; somatic mutations; rna-seq; inactivation; cancer; expression; subtypes; phosphorylation
AB Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.
C1 [Morin, Ryan D.; Mendez-Lago, Maria; Mungall, Andrew J.; Goya, Rodrigo; Mungall, Karen L.; Corbett, Richard D.; Severson, Tesa M.; Chiu, Readman; Field, Matthew; Jackman, Shaun; Krzywinski, Martin; Trinh, Diane L.; Tamura-Wells, Jessica; Li, Sa; Firme, Marlo R.; Griffith, Malachi; Chan, Susanna; Yakovenko, Oleksandr; Zhao, Eric Y.; Smailus, Duane; Moksa, Michelle; Chittaranjan, Suganthi; Brooks-Wilson, Angela; McDonald, Helen; Tam, Angela; Zhao, Yongjun; Delaney, Allen; Zeng, Thomas; Tse, Kane; Butterfield, Yaron; Birol, Inanc; Holt, Rob; Schein, Jacqueline; Moore, Richard; Jones, Steven J. M.; Hirst, Martin; Marra, Marco A.] BC Canc Agcy Vancouver, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Johnson, Nathalie A.; Scott, David W.; Rogic, Sanja; Ben-Neriah, Susana; Meissner, Barbara; Woolcock, Bruce; Boyle, Merrill; Horsman, Douglas E.; Connors, Joseph M.; Gascoyne, Randy D.] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada.
   [Meyer, Irmtraud M.] Centre High Throughput Biol, Dept Comp Sci, Vancouver, BC V6T 1Z4, Canada.
   [Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
   [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
   [Connors, Joseph M.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
   [Gascoyne, Randy D.] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 2B5, Canada.
   [Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
C3 British Columbia Cancer Agency; British Columbia Cancer Agency; University of Arizona; Simon Fraser University; University of British Columbia; University of British Columbia; University of British Columbia
RP Marra, MA (corresponding author), BC Canc Agcy Vancouver, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
EM mmarra@bcgsc.ca
FU National Cancer Institute Office of Cancer Genomics [HHSN261200800001E]; Terry Fox Foundation [019001, NCIC 019005]; Genome Canada/Genome British Columbia; NIH [P50CA130805-01, 1U01CA114778]; Michael Smith Foundation for Health Research [ST-PDF-01793]; MSFHR; Spanish Ministry of Education; Terry Fox Foundation at Canadian Institutes of Health Research [TGT-53912]; Canadian Cancer Society; Canadian Institutes of Health Research; UBC Four Year Fellowship; Canadian Foundation for Innovation
NR 50
TC 1333
Z9 1533
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 AUG 18
PY 2011
VL 476
IS 7360
BP 298
EP 303
DI 10.1038/nature10351
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500031
PM 21796119
DA 2026-03-09
ER

PT J
AU Duy, C
   Hurtz, C
   Shojaee, S
   Cerchietti, L
   Geng, HM
   Swaminathan, S
   Klemm, L
   Kweon, SM
   Nahar, R
   Braig, M
   Park, E
   Kim, YM
   Hofmann, WK
   Herzog, S
   Jumaa, H
   Koeffler, HP
   Yu, JJ
   Heisterkamp, N
   Graeber, TG
   Wu, H
   Ye, BH
   Melnick, A
   Müschen, M
AF Duy, Cihangir
   Hurtz, Christian
   Shojaee, Seyedmehdi
   Cerchietti, Leandro
   Geng, Huimin
   Swaminathan, Srividya
   Klemm, Lars
   Kweon, Soo-mi
   Nahar, Rahul
   Braig, Melanie
   Park, Eugene
   Kim, Yong-mi
   Hofmann, Wolf-Karsten
   Herzog, Sebastian
   Jumaa, Hassan
   Koeffler, H. Phillip
   Yu, J. Jessica
   Heisterkamp, Nora
   Graeber, Thomas G.
   Wu, Hong
   Ye, B. Hilda
   Melnick, Ari
   Mueschen, Markus
TI BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition
SO NATURE
LA English
DT Article
ID chronic myeloid-leukemia; germinal-center formation; imatinib resistance; initiating cells; in-vitro; b-cells; expression; stat5; proliferation; inflammation
AB Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases(2,3). Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases(4,5). However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs)(6-8), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones.
C1 [Duy, Cihangir; Hurtz, Christian; Shojaee, Seyedmehdi; Swaminathan, Srividya; Klemm, Lars; Nahar, Rahul; Mueschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   [Duy, Cihangir; Kweon, Soo-mi; Nahar, Rahul; Park, Eugene; Kim, Yong-mi; Heisterkamp, Nora; Mueschen, Markus] Univ So Calif, Dept Pediat, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
   [Cerchietti, Leandro; Geng, Huimin; Melnick, Ari] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
   [Cerchietti, Leandro; Geng, Huimin; Melnick, Ari] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
   [Braig, Melanie] Univ Klinikum Hamburg Eppendorf, Dept Hematol & Oncol, Hamburg, Germany.
   [Hofmann, Wolf-Karsten] Heidelberg Univ, Klinikum Mannheim, Dept Hematol & Oncol, Mannheim, Germany.
   [Hurtz, Christian; Herzog, Sebastian; Jumaa, Hassan] Univ Freiburg, Fac Biol, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany.
   [Hurtz, Christian; Herzog, Sebastian; Jumaa, Hassan] Max Planck Inst Immunobiol, Freiburg, Germany.
   [Koeffler, H. Phillip] Cedars Sinai Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Yu, J. Jessica; Ye, B. Hilda] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
   [Graeber, Thomas G.; Wu, Hong] Univ Calif Los Angeles, Dept Mol Pharmacol, Los Angeles, CA 90095 USA.
C3 University of California System; University of California San Francisco; Children's Hospital Los Angeles; University of Southern California; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; University of Hamburg; University Medical Center Hamburg-Eppendorf; Ruprecht Karls University Heidelberg; University of Freiburg; Max Planck Society; Cedars Sinai Medical Center; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; University of California System; University of California Los Angeles
RP Müschen, M (corresponding author), Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
EM markus.muschen@ucsf.edu
FU National Institutes of Health/National Cancer Institute [R01CA104348, R01CA085573, R01CA026038, R01CA090321, R01CA137060, R01CA139032, R01CA157664, R21CA152497]; Leukemia and Lymphoma Society [SCOR 7005-11]; Alex's Lemonade Stand Foundation for Pediatric Cancer Research; California Institute for Regenerative Medicine [TR02-1816]; William Laurence and Blanche Hughes Foundation; Stand Up To Cancer-American Association for Cancer Research [IRG00909]; National Cancer Institute [R01CA157644] Funding Source: NIH RePORTER
NR 45
TC 164
Z9 193
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 MAY 19
PY 2011
VL 473
IS 7347
BP 384
EP U572
DI 10.1038/nature09883
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400051
PM 21593872
DA 2026-03-09
ER

PT J
AU Wenzel, DM
   Lissounov, A
   Brzovic, PS
   Klevit, RE
AF Wenzel, Dawn M.
   Lissounov, Alexei
   Brzovic, Peter S.
   Klevit, Rachel E.
TI UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids
SO NATURE
LA English
DT Article
ID ubiquitin-conjugating enzyme; crystal-structure; protein; ligase; ring; expression; activation; residues; insights; complex
AB Although the functional interaction between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) is essential in ubiquitin (Ub) signalling, the criteria that define an active E2-E3 pair are not well established. The human E2 UBCH7 (also known as UBE2L3) shows broad specificity for HECT-type E3s(1), but often fails to function with RING E3s in vitro despite forming specific complexes(2-4). Structural comparisons of inactive UBCH7-RING complexes with active UBCH5-RING complexes reveal no defining differences(3,4), highlighting a gap in our understanding of Ub transfer. Here we show that, unlike many E2s that transfer Ub with RINGs, UBCH7 lacks intrinsic, E3-independent reactivity with lysine, explaining its preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits activity with the RING-inbetween-RING (RBR) family of E3s that includes parkin (also known as PARK2) and human homologue of ariadne (HHARI; also known as ARIH1)(5,6). Found in all eukaryotes(7), RBRs regulate processes such as translation(8) and immune signalling(9). RBRs contain a canonical C3HC4-type RING, followed by two conserved Cys/His-rich Zn2+-binding domains, in-between-RING (IBR) and RING2 domains, which together define this E3 family(7). We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted Ub), requiring a conserved cysteine residue in RING2. Our results define the functional cadre of E3s for UBCH7, an E2 involved in cell proliferation(10) and immune function(11), and indicate a novel mechanism for an entire class of E3s.
C1 [Wenzel, Dawn M.; Lissounov, Alexei; Brzovic, Peter S.; Klevit, Rachel E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Klevit, RE (corresponding author), Univ Washington, Dept Biochem, Box 357350, Seattle, WA 98195 USA.
EM klevit@u.washington.edu
FU National Institute of General Medical Sciences [5R01 GM088055, T32 GM07270]; National Science Foundation [MCB0615632]
NR 35
TC 465
Z9 596
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 JUN 2
PY 2011
VL 474
IS 7349
BP 105
EP U136
DI 10.1038/nature09966
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700047
PM 21532592
DA 2026-03-09
ER

PT J
AU Park, JE
   Heo, I
   Tian, Y
   Simanshu, DK
   Chang, H
   Jee, D
   Patel, DJ
   Kim, VN
AF Park, Jong-Eun
   Heo, Inha
   Tian, Yuan
   Simanshu, Dhirendra K.
   Chang, Hyeshik
   Jee, David
   Patel, Dinshaw J.
   Kim, V. Narry
TI Dicer recognizes the 5′ end of RNA for efficient and accurate processing
SO NATURE
LA English
DT Article
ID c-elegans; microrna biogenesis; binding-protein; interference; drosophila; cells; maturation; uridylation; mechanisms; pathways
AB A hallmark of RNA silencing is a class of approximately 22-nucleotide RNAs that are processed from double-stranded RNA precursors by Dicer. Accurate processing by Dicer is crucial for the functionality of microRNAs (miRNAs). The current model posits that Dicer selects cleavage sites by measuring a set distance from the 3' overhang of the double-stranded RNA terminus. Here we report that human Dicer anchors not only the 3' end but also the 5' end, with the cleavage site determined mainly by the distance (similar to 2 nucleotides) from the 5' end (5' counting rule). This cleavage requires a 5'-terminal phosphate group. Further, we identify a novel basic motif (5' pocket) in human Dicer that recognizes the 5'-phosphorylated end. The 5' counting rule and the 5' anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5' pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5'-pocket mutant. Thus, 5'-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs.
C1 [Park, Jong-Eun; Heo, Inha; Chang, Hyeshik; Jee, David; Kim, V. Narry] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea.
   [Tian, Yuan; Simanshu, Dhirendra K.; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
C3 Seoul National University (SNU); Memorial Sloan Kettering Cancer Center
RP Kim, VN (corresponding author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea.
EM narrykim@snu.ac.kr
FU National Research Foundation [2010000021, 20100020415]; Ministry of Education, Science and Technology; National Institutes of Health; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 41
TC 396
Z9 516
U1 0
U2 92
PU 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 14
PY 2011
VL 475
IS 7355
BP 201
EP U107
DI 10.1038/nature10198
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500044
PM 21753850
DA 2026-03-09
ER

PT J
AU Bouvignies, G
   Vallurupalli, P
   Hansen, DF
   Correia, BE
   Lange, O
   Bah, A
   Vernon, RM
   Dahlquist, FW
   Baker, D
   Kay, LE
AF Bouvignies, Guillaume
   Vallurupalli, Pramodh
   Hansen, D. Flemming
   Correia, Bruno E.
   Lange, Oliver
   Bah, Alaji
   Vernon, Robert M.
   Dahlquist, Frederick W.
   Baker, David
   Kay, Lewis E.
TI Solution structure of a minor and transiently formed state of a T4 lysozyme mutant
SO NATURE
LA English
DT Article
ID relaxation dispersion nmr; excited protein states; nuclear-magnetic-resonance; chemical-shifts; heteronuclear correlation; spectroscopy; exchange; flexibility; angles; resolution
AB Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers)(1-3). However, a rigorous understanding of the relation between a protein's structure, dynamics and function remains elusive. This is because many of the conformers on its energy landscape are only transiently formed and marginally populated (less than a few per cent of the total number of molecules), so that they cannot be individually characterized by most biophysical tools. Here we study a lysozyme mutant from phage T4 that binds hydrophobic molecules(4) and populates an excited state transiently (about 1 ms) to about 3% at 25 degrees C (ref. 5). We show that such binding occurs only via the ground state, and present the atomic-level model of the 'invisible', excited state obtained using a combined strategy of relaxation-dispersion NMR (ref. 6) and CS-Rosetta(7) model building that rationalizes this observation. The model was tested using structure-based design calculations identifying point mutants predicted to stabilize the excited state relative to the ground state. In this way a pair of mutations were introduced, inverting the relative populations of the ground and excited states and altering function. Our results suggest a mechanism for the evolution of a protein's function by changing the delicate balance between the states on its energy landscape. More generally, they show that our approach can generate and validate models of excited protein states.
C1 [Bouvignies, Guillaume; Vallurupalli, Pramodh; Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Bouvignies, Guillaume; Vallurupalli, Pramodh; Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Bouvignies, Guillaume; Vallurupalli, Pramodh; Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada.
   [Correia, Bruno E.; Lange, Oliver; Vernon, Robert M.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Correia, Bruno E.] Inst Gulbenkian Ciencias, Program Computat Biol, P-2780156 Oeiras, Portugal.
   [Bah, Alaji; Vernon, Robert M.; Kay, Lewis E.] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada.
   [Dahlquist, Frederick W.] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
C3 University of Toronto; University of Toronto; University of Toronto; University of Washington; University of Washington Seattle; Instituto Gulbenkian de Ciencia; University of Toronto; Hospital for Sick Children (SickKids); University of California System; University of California Santa Barbara
RP Kay, LE (corresponding author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada.
EM kay@pound.med.utoronto.ca
FU European Molecular Biology Organization; Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council of Canada
NR 51
TC 251
Z9 291
U1 0
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 1
PY 2011
VL 477
IS 7362
BP 111
EP U134
DI 10.1038/nature10349
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300042
PM 21857680
DA 2026-03-09
ER

PT J
AU Le Bars, M
   Wieczorek, MA
   Karatekin, Ö
   Cébron, D
   Laneuville, M
AF Le Bars, M.
   Wieczorek, M. A.
   Karatekin, O.
   Cebron, D.
   Laneuville, M.
TI An impact-driven dynamo for the early Moon
SO NATURE
LA English
DT Article
ID tidal instability; elliptic instability; magnetic-fields; precession; core; dissipation; convection
AB The origin of lunar magnetic anomalies(1-5) remains unresolved after their discovery more than four decades ago. A commonly invoked hypothesis is that the Moon might once have possessed a thermally driven core dynamo(3), but this theory is problematical given the small size of the core and the required surface magnetic field strengths(6). An alternative hypothesis is that impact events might have amplified ambient fields near the antipodes of the largest basins(7), but many magnetic anomalies exist that are not associated with basin antipodes. Here we propose a new model for magnetic field generation, in which dynamo action comes from impact-induced changes in the Moon's rotation rate. Basin-forming impact events are energetic enough to have unlocked the Moon from synchronous rotation(8), and we demonstrate that the subsequent large-scale fluid flows in the core, excited by the tidal distortion of the core-mantle boundary(9), could have powered a lunar dynamo. Predicted surface magnetic field strengths are on the order of several microteslas, consistent with palaeomagnetic measurements(5), and the duration of these fields is sufficient to explain the central magnetic anomalies associated with several large impact basins.
C1 [Le Bars, M.; Cebron, D.] CNRS, IRPHE, F-13384 Marseille 13, France.
   [Le Bars, M.; Cebron, D.] Aix Marseille Univ, F-13384 Marseille 13, France.
   [Wieczorek, M. A.; Laneuville, M.] Univ Paris Diderot, Inst Phys Globe Paris, F-94100 St Maur Des Fosses, France.
   [Karatekin, O.] Royal Observ Belgium, BE-1180 Uccle, Belgium.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Universite Paris Cite
RP Le Bars, M (corresponding author), CNRS, IRPHE, 49 Rue F Joliot Curie,BP 146, F-13384 Marseille 13, France.
EM lebars@irphe.univ-mrs.fr
FU Belgian PRODEX
NR 37
TC 135
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 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 215
EP U90
DI 10.1038/nature10565
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800039
PM 22071767
DA 2026-03-09
ER

PT J
AU Liu, J
   Renault, L
   Veaute, X
   Fabre, F
   Stahlberg, H
   Heyer, WD
AF Liu, Jie
   Renault, Ludovic
   Veaute, Xavier
   Fabre, Francis
   Stahlberg, Henning
   Heyer, Wolf-Dietrich
TI Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation
SO NATURE
LA English
DT Article
ID double-strand-break; saccharomyces-cerevisiae; homologous recombination; mitotic recombination; dna-repair; protein; helicase; gene; mutations; exchange
AB Homologous recombination is a high-fidelity DNA repair pathway. Besides a critical role in accurate chromosome segregation during meiosis, recombination functions in DNA repair and in the recovery of stalled or broken replication forks to ensure genomic stability. In contrast, inappropriate recombination contributes to genomic instability, leading to loss of heterozygosity, chromosome rearrangements and cell death. The RecA/UvsX/RadA/Rad51 family of proteins catalyses the signature reactions of recombination, homology search and DNA strand invasion(1,2). Eukaryotes also possess Rad51 paralogues, whose exact role in recombination remains to be defined(3). Here we show that the Saccharomyces cerevisiae Rad51 paralogues, the Rad55-Rad57 heterodimer, counteract the antirecombination activity of the Srs2 helicase. The Rad55-Rad57 heterodimer associates with the Rad51-single-stranded DNA filament, rendering it more stable than a nucleoprotein filament containing Rad51 alone. The Rad51-Rad55-Rad57 co-filament resists disruption by the Srs2 antirecombinase by blocking Srs2 translocation, involving a direct protein interaction between Rad55-Rad57 and Srs2. Our results demonstrate an unexpected role of the Rad51 paralogues in stabilizing the Rad51 filament against a biologically important antagonist, the Srs2 antirecombination helicase. The biological significance of this mechanism is indicated by a complete suppression of the ionizing radiation sensitivity of rad55 or rad57 mutants by concomitant deletion of SRS2, as expected for biological antagonists. We propose that the Rad51 presynaptic filament is a meta-stable reversible intermediate, whose assembly and disassembly is governed by the balance between Rad55-Rad57 and Srs2, providing a key regulatory mechanism controlling the initiation of homologous recombination. These data provide a paradigm for the potential function of the human RAD51 paralogues, which are known to be involved in cancer predisposition and human disease.
C1 [Liu, Jie; Heyer, Wolf-Dietrich] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Renault, Ludovic; Stahlberg, Henning; Heyer, Wolf-Dietrich] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Veaute, Xavier; Fabre, Francis] CEA, CNRS, UMR217, CEA DSV Inst Radiobiol Cellulaire & Mol, F-92265 Fontenay Aux Roses, France.
   [Stahlberg, Henning] Univ Basel, Ctr Cellular Imaging & Nanoanalyt, CH-4056 Basel, Switzerland.
C3 University of California System; University of California Davis; University of California System; University of California Davis; Centre National de la Recherche Scientifique (CNRS); CEA; University of Basel
RP Heyer, WD (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM wdheyer@ucdavis.edu
FU Tobacco-Related Disease Research Program [17FT-0046]; European Community [LSHG-CT-2003-503303]; Centre National de la Recherche Scientifique; Commissariat a l'Energie Atomique; SystemsX.ch; National Institutes of Health [U54GM74929, CA92267, GM58015]; National Institute of General Medical Sciences [R01GM058015] Funding Source: NIH RePORTER
NR 39
TC 162
Z9 197
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 245
EP U129
DI 10.1038/nature10522
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800046
PM 22020281
DA 2026-03-09
ER

PT J
AU Harlander, M
   Lechner, R
   Brownnutt, M
   Blatt, R
   Hänsel, W
AF Harlander, M.
   Lechner, R.
   Brownnutt, M.
   Blatt, R.
   Haensel, W.
TI Trapped-ion antennae for the transmission of quantum information
SO NATURE
LA English
DT Article
ID atom; oscillators; decoherence; computation; computer; photon; cavity; state
AB More than 100 years ago, Hertz succeeded in transmitting signals over a few metres to a receiving antenna using an electromagnetic oscillator, thus proving the electromagnetic theory(1) developed by Maxwell. Since this seminal work, technology has developed, and various oscillators are now available at the quantum mechanical level. For quantized electromagnetic oscillations, atoms in cavities can be used to couple electric fields(2,3). However, a quantum mechanical link between two mechanical oscillators (such as cantilevers(4,5) or the vibrational modes of trapped atoms(6) or ions(7,8)) has been rarely demonstrated and has been achieved only indirectly. Examples include the mechanical transport of atoms carrying quantum information(9) or the use of spontaneously emitted photons(10). Here we achieve direct coupling between the motional dipoles of separately trapped ions over a distance of 54 micrometres, using the dipole-dipole interaction as a quantum mechanical transmission line(11). This interaction is small between single trapped ions, but the coupling is amplified by using additional trapped ions as antennae. With three ions in each well, the interaction is increased by a factor of seven compared to the single-ion case. This enhancement facilitates bridging of larger distances and relaxes the constraints on the miniaturization of trap electrodes. The system provides a building block for quantum computers and opportunities for coupling different types of quantum systems.
C1 [Harlander, M.; Lechner, R.; Brownnutt, M.; Blatt, R.; Haensel, W.] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Blatt, R.; Haensel, W.] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
C3 University of Innsbruck; Austrian Academy of Sciences
RP Blatt, R (corresponding author), Univ Innsbruck, Inst Expt Phys, Technikerstr 25, A-6020 Innsbruck, Austria.
EM rainer.blatt@uibk.ac.at
FU EU; Austrian Science Fund (FWF); European Research Council (ERC); Institut fur Quanteninformation GmbH
NR 29
TC 143
Z9 149
U1 1
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 200
EP 203
DI 10.1038/nature09800
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200033
PM 21346764
DA 2026-03-09
ER

PT J
AU Hopkins, R
   Rausher, MD
AF Hopkins, Robin
   Rausher, Mark D.
TI Identification of two genes causing reinforcement in the Texas wildflower Phlox drummondii
SO NATURE
LA English
DT Article
ID character displacement; reproductive isolation; speciation genetics; hybridization; evolution
AB Species formation generates biological diversity and occurs when traits evolve that prevent gene flow between populations. Discerning the number and distribution of genes underlying these traits and, in a few cases, identifying the genes involved, has greatly enhanced our understanding over the past 15 years of species formation (reviewed by Noor and Feder(1) and Wolf et al.(2)). However, this work has almost exclusively focused on traits that restrict gene flow between populations that have evolved as a by-product of genetic divergence between geographically isolated populations. By contrast, little is known about the characteristics of genes associated with reinforcement, the process by which natural selection directly favours restricted gene flow during the formation of species. Here we identify changes in two genes that appear to cause a flower colour change in Phlox drummondii, which previous work has shown contributes to reinforcement. Both changes involve cis-regulatory mutations to genes in the anthocyanin biosynthetic pathway (ABP). Because one change is recessive whereas the other is dominant, hybrid offspring produce an intermediate flower colour that is visited less by pollinators, and is presumably maladaptive. Thus genetic change selected to increase prezygotic isolation also appears to result in increased postzygotic isolation.
C1 [Hopkins, Robin; Rausher, Mark D.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
C3 Duke University
RP Hopkins, R (corresponding author), Duke Univ, Dept Biol, Box 90338, Durham, NC 27708 USA.
EM robin.hopkins@duke.edu; mrausher@duke.edu
FU National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0841521] Funding Source: National Science Foundation
NR 34
TC 145
Z9 169
U1 2
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 JAN 20
PY 2011
VL 469
IS 7330
BP 411
EP +
DI 10.1038/nature09641
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600055
PM 21217687
DA 2026-03-09
ER

PT J
AU Sawcer, S
   Hellenthal, G
   Pirinen, M
   Spencer, CCA
   Patsopoulos, NA
   Moutsianas, L
   Dilthey, A
   Su, Z
   Freeman, C
   Hunt, SE
   Edkins, S
   Gray, E
   Booth, DR
   Potter, SC
   Goris, A
   Band, G
   Oturai, AB
   Strange, A
   Saarela, J
   Bellenguez, C
   Fontaine, B
   Gillman, M
   Hemmer, B
   Gwilliam, R
   Zipp, F
   Jayakumar, A
   Martin, R
   Leslie, S
   Hawkins, S
   Giannoulatou, E
   D'alfonso, S
   Blackburn, H
   Boneschi, FM
   Liddle, J
   Harbo, HF
   Perez, ML
   Spurkland, A
   Waller, MJ
   Mycko, MP
   Ricketts, M
   Comabella, M
   Hammond, N
   Kockum, I
   McCann, OT
   Ban, M
   Whittaker, P
   Kemppinen, A
   Weston, P
   Hawkins, C
   Widaa, S
   Zajicek, J
   Dronov, S
   Robertson, N
   Bumpstead, SJ
   Barcellos, LF
   Ravindrarajah, R
   Abraham, R
   Alfredsson, L
   Ardlie, K
   Aubin, C
   Baker, A
   Baker, K
   Baranzini, SE
   Bergamaschi, L
   Bergamaschi, R
   Bernstein, A
   Berthele, A
   Boggild, M
   Bradfield, JP
   Brassat, D
   Broadley, SA
   Buck, D
   Butzkueven, H
   Capra, R
   Carroll, WM
   Cavalla, P
   Celius, EG
   Cepok, S
   Chiavacci, R
   Clerget-Darpoux, F
   Clysters, K
   Comi, G
   Cossburn, M
   Cournu-Rebeix, I
   Cox, MB
   Cozen, W
   Cree, BAC
   Cross, AH
   Cusi, D
   Daly, MJ
   Davis, E
   de Bakker, PIW
   Debouverie, M
   D'hooghe, MB
   Dixon, K
   Dobosi, R
   Dubois, B
   Ellinghaus, D
   Elovaara, I
   Esposito, F
   Fontenille, C
   Foote, S
   Franke, A
   Galimberti, D
   Ghezzi, A
   Glessner, J
   Gomez, R
   Gout, O
   Graham, C
   Grant, SFA
   Guerini, FR
   Hakonarson, H
   Hall, P
   Hamsten, A
   Hartung, HP
   Heard, RN
   Heath, S
   Hobart, J
   Hoshi, M
   Infante-Duarte, C
   Ingram, G
   Ingram, W
   Islam, T
   Jagodic, M
   Kabesch, M
   Kermode, AG
   Kilpatrick, TJ
   Kim, C
   Klopp, N
   Koivisto, K
   Larsson, M
   Lathrop, M
   Lechner-Scott, JS
   Leone, MA
   Leppä, V
   Liljedahl, U
   Bomfim, IL
   Lincoln, RR
   Link, J
   Liu, JJ
   Lorentzen, ÅR
   Lupoli, S
   Macciardi, F
   Mack, T
   Marriott, M
   Martinelli, V
   Mason, D
   McCauley, JL
   Mentch, F
   Mero, IL
   Mihalova, T
   Montalban, X
   Mottershead, J
   Myhr, KM
   Naldi, P
   Ollier, W
   Page, A
   Palotie, A
   Pelletier, J
   Piccio, L
   Pickersgill, T
   Piehl, F
   Pobywajlo, S
   Quach, HL
   Ramsay, PP
   Reunanen, M
   Reynolds, R
   Rioux, J
   Rodegher, M
   Roesner, S
   Rubio, JP
   Rückert, IM
   Salvetti, M
   Salvi, E
   Santaniello, A
   Schaefer, CA
   Schreiber, S
   Schulze, C
   Scott, RJ
   Sellebjerg, F
   Selmaj, KW
   Sexton, D
   Shen, L
   Simms-Acuna, B
   Skidmore, S
   Sleiman, PMA
   Smestad, C
   Sorensen, PS
   Sondergaard, HB
   Stankovich, J
   Strange, RC
   Sulonen, AM
   Sundqvist, E
   Syvänen, AC
   Taddeo, F
   Taylor, B
   Blackwell, JM
   Tienari, P
   Bramon, E
   Tourbah, A
   Brown, MA
   Tronczynska, E
   Casas, JP
   Tubridy, N
   Corvin, A
   Vickery, J
   Jankowski, J
   Villoslada, P
   Markus, HS
   Wang, K
   Mathew, CG
   Wason, J
   Palmer, CNA
   Wichmann, HE
   Plomin, R
   Willoughby, E
   Rautanen, A
   Winkelmann, J
   Wittig, M
   Trembath, RC
   Yaouanq, J
   Viswanathan, AC
   Zhang, HT
   Wood, NW
   Zuvich, R
   Deloukas, P
   Langford, C
   Duncanson, A
   Oksenberg, JR
   Pericak-Vance, MA
   Haines, JL
   Olsson, T
   Hillert, J
   Ivinson, AJ
   De Jager, PL
   Peltonen, L
   Stewart, GJ
   Hafler, DA
   Hauser, SL
   McVean, G
   Donnelly, P
   Compston, A
AF Sawcer, Stephen
   Hellenthal, Garrett
   Pirinen, Matti
   Spencer, Chris C. A.
   Patsopoulos, Nikolaos A.
   Moutsianas, Loukas
   Dilthey, Alexander
   Su, Zhan
   Freeman, Colin
   Hunt, Sarah E.
   Edkins, Sarah
   Gray, Emma
   Booth, David R.
   Potter, Simon C.
   Goris, An
   Band, Gavin
   Oturai, Annette Bang
   Strange, Amy
   Saarela, Janna
   Bellenguez, Celine
   Fontaine, Bertrand
   Gillman, Matthew
   Hemmer, Bernhard
   Gwilliam, Rhian
   Zipp, Frauke
   Jayakumar, Alagurevathi
   Martin, Roland
   Leslie, Stephen
   Hawkins, Stanley
   Giannoulatou, Eleni
   D'alfonso, Sandra
   Blackburn, Hannah
   Boneschi, Filippo Martinelli
   Liddle, Jennifer
   Harbo, Hanne F.
   Perez, Marc L.
   Spurkland, Anne
   Waller, Matthew J.
   Mycko, Marcin P.
   Ricketts, Michelle
   Comabella, Manuel
   Hammond, Naomi
   Kockum, Ingrid
   McCann, Owen T.
   Ban, Maria
   Whittaker, Pamela
   Kemppinen, Anu
   Weston, Paul
   Hawkins, Clive
   Widaa, Sara
   Zajicek, John
   Dronov, Serge
   Robertson, Neil
   Bumpstead, Suzannah J.
   Barcellos, Lisa F.
   Ravindrarajah, Rathi
   Abraham, Roby
   Alfredsson, Lars
   Ardlie, Kristin
   Aubin, Cristin
   Baker, Amie
   Baker, Katharine
   Baranzini, Sergio E.
   Bergamaschi, Laura
   Bergamaschi, Roberto
   Bernstein, Allan
   Berthele, Achim
   Boggild, Mike
   Bradfield, Jonathan P.
   Brassat, David
   Broadley, Simon A.
   Buck, Dorothea
   Butzkueven, Helmut
   Capra, Ruggero
   Carroll, William M.
   Cavalla, Paola
   Celius, Elisabeth G.
   Cepok, Sabine
   Chiavacci, Rosetta
   Clerget-Darpoux, Francoise
   Clysters, Katleen
   Comi, Giancarlo
   Cossburn, Mark
   Cournu-Rebeix, Isabelle
   Cox, Mathew B.
   Cozen, Wendy
   Cree, Bruce A. C.
   Cross, Anne H.
   Cusi, Daniele
   Daly, Mark J.
   Davis, Emma
   de Bakker, Paul I. W.
   Debouverie, Marc
   D'hooghe, Marie Beatrice
   Dixon, Katherine
   Dobosi, Rita
   Dubois, Benedicte
   Ellinghaus, David
   Elovaara, Irina
   Esposito, Federica
   Fontenille, Claire
   Foote, Simon
   Franke, Andre
   Galimberti, Daniela
   Ghezzi, Angelo
   Glessner, Joseph
   Gomez, Refujia
   Gout, Olivier
   Graham, Colin
   Grant, Struan F. A.
   Guerini, Franca Rosa
   Hakonarson, Hakon
   Hall, Per
   Hamsten, Anders
   Hartung, Hans-Peter
   Heard, Rob N.
   Heath, Simon
   Hobart, Jeremy
   Hoshi, Muna
   Infante-Duarte, Carmen
   Ingram, Gillian
   Ingram, Wendy
   Islam, Talat
   Jagodic, Maja
   Kabesch, Michael
   Kermode, Allan G.
   Kilpatrick, Trevor J.
   Kim, Cecilia
   Klopp, Norman
   Koivisto, Keijo
   Larsson, Malin
   Lathrop, Mark
   Lechner-Scott, Jeannette S.
   Leone, Maurizio A.
   Leppa, Virpi
   Liljedahl, Ulrika
   Bomfim, Izaura Lima
   Lincoln, Robin R.
   Link, Jenny
   Liu, Jianjun
   Lorentzen, Aslaug R.
   Lupoli, Sara
   Macciardi, Fabio
   Mack, Thomas
   Marriott, Mark
   Martinelli, Vittorio
   Mason, Deborah
   McCauley, Jacob L.
   Mentch, Frank
   Mero, Inger-Lise
   Mihalova, Tania
   Montalban, Xavier
   Mottershead, John
   Myhr, Kjell-Morten
   Naldi, Paola
   Ollier, William
   Page, Alison
   Palotie, Aarno
   Pelletier, Jean
   Piccio, Laura
   Pickersgill, Trevor
   Piehl, Fredrik
   Pobywajlo, Susan
   Quach, Hong L.
   Ramsay, Patricia P.
   Reunanen, Mauri
   Reynolds, Richard
   Rioux, Johnd.
   Rodegher, Mariaemma
   Roesner, Sabine
   Rubio, Justin P.
   Rueckert, Ina-Maria
   Salvetti, Marco
   Salvi, Erika
   Santaniello, Adam
   Schaefer, Catherine A.
   Schreiber, Stefan
   Schulze, Christian
   Scott, Rodney J.
   Sellebjerg, Finn
   Selmaj, Krzysztof W.
   Sexton, David
   Shen, Ling
   Simms-Acuna, Brigid
   Skidmore, Sheila
   Sleiman, Patrick M. A.
   Smestad, Cathrine
   Sorensen, Per Soelberg
   Sondergaard, Helle Bach
   Stankovich, Jim
   Strange, Richard C.
   Sulonen, Anna-Maija
   Sundqvist, Emilie
   Syvaenen, Ann-Christine
   Taddeo, Francesca
   Taylor, Bruce
   Blackwell, Jenefer M.
   Tienari, Pentti
   Bramon, Elvira
   Tourbah, Ayman
   Brown, Matthew A.
   Tronczynska, Ewa
   Casas, Juan P.
   Tubridy, Niall
   Corvin, Aiden
   Vickery, Jane
   Jankowski, Janusz
   Villoslada, Pablo
   Markus, Hugh S.
   Wang, Kai
   Mathew, Christopher G.
   Wason, James
   Palmer, Colin N. A.
   Wichmann, H-Erich
   Plomin, Robert
   Willoughby, Ernest
   Rautanen, Anna
   Winkelmann, Juliane
   Wittig, Michael
   Trembath, Richard C.
   Yaouanq, Jacqueline
   Viswanathan, Ananth C.
   Zhang, Haitao
   Wood, Nicholas W.
   Zuvich, Rebecca
   Deloukas, Panos
   Langford, Cordelia
   Duncanson, Audrey
   Oksenberg, Jorge R.
   Pericak-Vance, Margaret A.
   Haines, Jonathan L.
   Olsson, Tomas
   Hillert, Jan
   Ivinson, Adrian J.
   De Jager, Philip L.
   Peltonen, Leena
   Stewart, Graeme J.
   Hafler, David A.
   Hauser, Stephen L.
   McVean, Gil
   Donnelly, Peter
   Compston, Alastair
TI Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
SO NATURE
LA English
DT Article
ID genome-wide association; susceptibility loci; heterogeneity; haplotypes; variants; alleles
AB Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability(1). Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals(2,3), and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk(4). Modestly powered genome-wide association studies (GWAS)(5-10) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility(11). Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
C1 [Sawcer, Stephen; Ban, Maria; Kemppinen, Anu; Baker, Amie; Skidmore, Sheila; Compston, Alastair] Univ Cambridge, Dept Clin Neurosci, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
   [Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C. A.; Su, Zhan; Freeman, Colin; Band, Gavin; Strange, Amy; Bellenguez, Celine; Giannoulatou, Eleni; Rautanen, Anna; McVean, Gil; Donnelly, Peter] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Patsopoulos, Nikolaos A.; de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.
   [Patsopoulos, Nikolaos A.; Ardlie, Kristin; Aubin, Cristin; Daly, Mark J.; de Bakker, Paul I. W.; De Jager, Philip L.; Hafler, David A.] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Patsopoulos, Nikolaos A.; Pobywajlo, Susan; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Moutsianas, Loukas; Dilthey, Alexander; Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Potter, Simon C.; Gillman, Matthew; Gwilliam, Rhian; Jayakumar, Alagurevathi; Blackburn, Hannah; Liddle, Jennifer; Perez, Marc L.; Waller, Matthew J.; Ricketts, Michelle; Hammond, Naomi; McCann, Owen T.; Whittaker, Pamela; Weston, Paul; Widaa, Sara; Dronov, Serge; Bumpstead, Suzannah J.; Ravindrarajah, Rathi; Palotie, Aarno; Deloukas, Panos; Langford, Cordelia] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Booth, David R.; Heard, Rob N.; Stewart, Graeme J.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2145, Australia.
   [Goris, An; Clysters, Katleen; Dobosi, Rita; Dubois, Benedicte] Katholieke Univ Leuven, Sect Expt Neurol, Lab Neuroimmunol, B-3000 Louvain, Belgium.
   [Oturai, Annette Bang; Sellebjerg, Finn; Sorensen, Per Soelberg; Sondergaard, Helle Bach] Rigshosp, Copenhagen Univ Hosp, Dept Neurol, Danish Multiple Sclerosis Ctr, DK-2100 Copenhagen, Denmark.
   [Saarela, Janna; Leppa, Virpi; Palotie, Aarno; Sulonen, Anna-Maija] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland.
   [Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Fontenille, Claire] UPMC, AP HP, INSERM UMR S CRICM 975, Dept Neurol Pitie Salpetriere, F-75013 Paris, France.
   [Hemmer, Bernhard; Berthele, Achim; Buck, Dorothea; Cepok, Sabine; Hoshi, Muna; Winkelmann, Juliane] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, D-81675 Munich, Germany.
   [Zipp, Frauke] Johannes Gutenberg Univ Mainz, Univ Med Mainz, Dept Neurol, D-55131 Mainz, Germany.
   [Zipp, Frauke; Martin, Roland] Max Delbrueck Ctr Mol Med, D-13092 Berlin, Germany.
   [Roesner, Sabine] Ctr Mol Neurobiol, Inst Neuroimmunol & Clin MS Res Inims, D-20251 Hamburg, Germany.
   [Leslie, Stephen] Univ Oxford, Dept Clin Pharmacol, Oxford OX3 7DQ, England.
   [Hawkins, Stanley] Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland.
   [D'alfonso, Sandra; Bergamaschi, Laura] Univ Piemonte Orientale, Dept Med Sci, I-28100 Novara, Italy.
   [D'alfonso, Sandra; Bergamaschi, Laura] Univ Piemonte Orientale, IRCAD, I-28100 Novara, Italy.
   [Boneschi, Filippo Martinelli; Comi, Giancarlo; Esposito, Federica; Martinelli, Vittorio; Rodegher, Mariaemma] Ist Sci San Raffaele, Dept Neurol, Inst Expt Neurol INSPE, Div Neurosci, I-20132 Milan, Italy.
   [Harbo, Hanne F.; Celius, Elisabeth G.; Mero, Inger-Lise; Smestad, Cathrine] Oslo Univ Hosp, Dept Neurol, N-0407 Oslo, Norway.
   [Harbo, Hanne F.; Lorentzen, Aslaug R.] Univ Oslo, Dept Neurol, N-0318 Oslo, Norway.
   [Spurkland, Anne] Univ Oslo, Inst Basal Med Sci, N-0317 Oslo, Norway.
   [Mycko, Marcin P.; Selmaj, Krzysztof W.; Tronczynska, Ewa] Med Univ Lodz, Lab Neuroimmunol, Dept Neurol, PL-90153 Lodz, Poland.
   [Comabella, Manuel; Montalban, Xavier] Vall dHebron Univ Hosp, Multiple Sclerosis Ctr Catalonia CEM Cat, Clin Neuroinmunol Unit, Barcelona 08035, Spain.
   [Kockum, Ingrid; Jagodic, Maja; Bomfim, Izaura Lima; Link, Jenny; Piehl, Fredrik; Sundqvist, Emilie; Olsson, Tomas; Hillert, Jan] Karolinska Inst, Karolinska Univ Hosp, Ctr Mol Med CMM, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.
   [Hawkins, Clive; Abraham, Roby; Mihalova, Tania; Strange, Richard C.] Keele Univ, Sch Med, Stoke On Trent ST4 7NY, Staffs, England.
   [Zajicek, John; Hobart, Jeremy; Ingram, Wendy; Vickery, Jane] Univ Exeter, Peninsula Coll Med & Dent, Plymouth PL6 8BX, Devon, England.
   [Zajicek, John; Hobart, Jeremy; Ingram, Wendy; Vickery, Jane] Univ Plymouth, Clin Neurol Res Grp, Plymouth PL6 8BX, Devon, England.
   [Robertson, Neil; Baker, Katharine; Cossburn, Mark; Ingram, Gillian; Pickersgill, Trevor] Univ Wales Hosp, Dept Neurol, Cardiff CF14 4XW, S Glam, Wales.
   [Barcellos, Lisa F.; Quach, Hong L.; Ramsay, Patricia P.] Univ Calif Berkeley, Genet Epidemiol & Genom Lab, Div Epidemiol, Sch Publ Hlth, Berkeley, CA 94720 USA.
   [Barcellos, Lisa F.; Bernstein, Allan; Schaefer, Catherine A.; Shen, Ling; Simms-Acuna, Brigid] Kaiser Permanente No Calif Div Res, Oakland, CA 94612 USA.
   [Alfredsson, Lars] Karolinska Inst, Inst Expt Med, S-17177 Stockholm, Sweden.
   [Baranzini, Sergio E.; Cree, Bruce A. C.; Gomez, Refujia; Lincoln, Robin R.; Santaniello, Adam; Oksenberg, Jorge R.; Hauser, Stephen L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Bergamaschi, Roberto] IRCCS, Neurol Inst C Mondino, I-27100 Pavia, Italy.
   [Boggild, Mike] Walton Ctr Neurol & Neurosurg, Liverpool L7 9LJ, Merseyside, England.
   [Bradfield, Jonathan P.; Chiavacci, Rosetta; Glessner, Joseph; Grant, Struan F. A.; Hakonarson, Hakon; Kim, Cecilia; Mentch, Frank; Sleiman, Patrick M. A.; Wang, Kai; Zhang, Haitao] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Brassat, David] INSERM, U1043, F-31059 Toulouse, France.
   [Brassat, David] Hop Purpan, F-31059 Toulouse, France.
   [Broadley, Simon A.] Griffith Univ, Sch Med, Gold Coast, Qld 4222, Australia.
   [Butzkueven, Helmut; Kilpatrick, Trevor J.; Marriott, Mark; Rubio, Justin P.] Univ Melbourne, Florey Neurosci Inst, Melbourne, Vic 3010, Australia.
   [Butzkueven, Helmut; Kilpatrick, Trevor J.; Marriott, Mark; Tubridy, Niall] Royal Melbourne Hosp, Parkville, Vic 3050, Australia.
   [Butzkueven, Helmut] Monash Univ, Box Hill Hosp, Clayton, Vic 3800, Australia.
   [Butzkueven, Helmut] Univ Melbourne, Dept Med, RMH Cluster, Melbourne, Vic 3010, Australia.
   [Capra, Ruggero] Osped Civili Brescia, Dept Neurol, Multiple Sclerosis Ctr, I-25018 Brescia, Italy.
   [Carroll, William M.; Kermode, Allan G.] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, Perth, WA 6009, Australia.
   [Cavalla, Paola] Univ Turin, AOU San Giovanni Battista, Dept Neurosci, I-10126 Turin, Italy.
   [Clerget-Darpoux, Francoise] Univ Paris 11, INSERM, U669, F-94800 Villejuif, France.
   [Cox, Mathew B.; Lechner-Scott, Jeannette S.; Scott, Rodney J.] Univ Newcastle, Callaghan, NSW 2308, Australia.
   [Cozen, Wendy; Islam, Talat; Mack, Thomas] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Cross, Anne H.; Piccio, Laura] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
   [Cusi, Daniele; Lupoli, Sara; Macciardi, Fabio; Salvi, Erika] Univ Milan, Filarete Fdn, AO San Paolo, Dept Med Surg & Dent, I-20139 Milan, Italy.
   [Daly, Mark J.; Ivinson, Adrian J.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Davis, Emma; Dixon, Katherine; Ollier, William] Univ Manchester, UK DNA Banking Network, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England.
   [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Div Biomed Genet, Dept Med Genet, NL-3508 GA Utrecht, Netherlands.
   [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands.
   [Debouverie, Marc] Hop Cent, Serv Neurol, F-54035 Nancy, France.
   [D'hooghe, Marie Beatrice] Natl Multiple Sclerosis Ctr, B-1820 Melsbroek, Belgium.
   [Ellinghaus, David; Franke, Andre; Schreiber, Stefan; Wittig, Michael] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Elovaara, Irina] Tampere Univ Hosp, Dept Neurol, FIN-33014 Tampere, Finland.
   [Elovaara, Irina] Univ Tampere, Sch Med, Tampere 33014, Finland.
   [Foote, Simon; Stankovich, Jim; Taylor, Bruce] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia.
   [Galimberti, Daniela] Univ Milan, Fdn Ca Granda, Ctr Dino Ferrari, Dept Neurol Sci,Osped Maggiore Policlin, I-20122 Milan, Italy.
   [Ghezzi, Angelo] Osped Gallarate, Ctr Studi Sclerosi Multipla, I-21013 Gallarate, VA, Italy.
   [Gout, Olivier] Fdn Ophtalmol Adolphe de Rothschild, Serv Neurol, F-75019 Paris, France.
   [Graham, Colin] Belfast Hlth & Social Care Trust, City Hosp, Belfast BT9 7AB, Antrim, North Ireland.
   [Grant, Struan F. A.; Hakonarson, Hakon; Sleiman, Patrick M. A.; Wang, Kai; Zhang, Haitao] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA.
   [Grant, Struan F. A.; Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Guerini, Franca Rosa] Don C Gnocchi Fdn IRCCS, Lab Mol Med & Biotechnol, I-20148 Milan, Italy.
   [Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
   [Hamsten, Anders; Larsson, Malin] Karolinska Inst, Karolinska Univ, Dept Med Solna, Atherosclerosis Res Unit, S-17176 Stockholm, Sweden.
   [Hartung, Hans-Peter] Univ Dusseldorf, Dept Neurol, D-40225 Dusseldorf, Germany.
   [Heath, Simon; Lathrop, Mark] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France.
   [Infante-Duarte, Carmen] Univ Med Berlin, Charite, Expt & Clin Res Ctr, D-13125 Berlin, Germany.
   [Infante-Duarte, Carmen] Max Delbrueck Ctr Mol Med, D-13125 Berlin, Germany.
   [Kabesch, Michael] Hannover Med Sch, Dept Paediat Pneumol Allergy & Neonatol, D-30625 Hannover, Germany.
   [Kilpatrick, Trevor J.] Univ Melbourne, Ctr Neurosci, Melbourne, Vic 3010, Australia.
   [Klopp, Norman; Rueckert, Ina-Maria; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Munich, Germany.
   [Koivisto, Keijo] Seinajoki Cent Hosp, Seinajoki 60220, Finland.
   [Lechner-Scott, Jeannette S.] John Hunter Hosp, Hunter Med Res Inst, New Lambton, NSW 2305, Australia.
   [Leone, Maurizio A.; Naldi, Paola] Maggiore della Carita Hosp, SCDU Neurol, I-28100 Novara, Italy.
   [Leppa, Virpi; Sulonen, Anna-Maija] Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland.
   [Liljedahl, Ulrika; Syvaenen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Univ Hosp,Res Dept 2, S-75185 Uppsala, Sweden.
   [Liu, Jianjun] Genome Inst Singapore, Singapore 138672, Singapore.
   [Lorentzen, Aslaug R.; Mero, Inger-Lise] Oslo Univ Hosp, Inst Immunol, N-0027 Oslo, Norway.
   [Lupoli, Sara] Ist Sci San Raffaele, Inst Expt Neurol INSPE, I-20132 Milan, Italy.
   [Macciardi, Fabio] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA.
   [Mason, Deborah] Univ Otago, Christchurch Sch Med, Christchurch 8041, New Zealand.
   [McCauley, Jacob L.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [McCauley, Jacob L.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.
   [Mottershead, John] Hope Hosp, Greater Manchester Ctr Clin Neurosci, Salford M6 8HD, Lancs, England.
   [Mottershead, John] Dunedin Publ Hosp, Dept Neurol, Otago 9016, New Zealand.
   [Myhr, Kjell-Morten] Haukeland Hosp, Dept Neurol, Norwegian Multiple Sclerosis Competence Ctr, N-5021 Bergen, Norway.
   [Myhr, Kjell-Morten] Univ Bergen, Dept Clin Med, N-5021 Bergen, Norway.
   [Page, Alison] Derriford Hosp, Dept Neurol, Plymouth Hosp NHS Trust, Plymouth PL6 8DH, Devon, England.
   [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki 00014, Finland.
   [Palotie, Aarno] Univ Cent Hosp, Helsinki 00014, Finland.
   [Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA 02142 USA.
   [Pelletier, Jean] Hop La Timone, Serv Neurol, Pole Neurosci Clin, F-13005 Marseille, France.
   [Reunanen, Mauri] Oulu Univ Hosp, Dept Neurol, Oulu 90029, Finland.
   [Reynolds, Richard] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Wolfson Neurosci Labs, UK MS Tissue Bank, London W12 0NN, England.
   [Rioux, Johnd.] Univ Montreal, Montreal, PQ H1T 1C8, Canada.
   [Rioux, Johnd.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
   [Salvetti, Marco] Univ Roma La Sapienza, Ctr Expt Neurol Therapy CENTERS, I-00189 Rome, Italy.
   [Salvi, Erika; Taddeo, Francesca] KOS Genet Srl, I-20123 Milan, Italy.
   [Schreiber, Stefan] Univ Kiel, Univ Hosp, Dept Gen Internal Med, D-24105 Kiel, Germany.
   [Schulze, Christian] Ctr Mol Neurobiol, D-20251 Hamburg, Germany.
   [Sexton, David; Zuvich, Rebecca; Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Blackwell, Jenefer M.] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Subiaco, WA 6008, Australia.
   [Blackwell, Jenefer M.] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Tienari, Pentti] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00290 Helsinki, Finland.
   [Blackwell, Jenefer M.; Tienari, Pentti] Univ Helsinki, Biomedicum, Mol Neurol Programme, FIN-00290 Helsinki, Finland.
   [Bramon, Elvira] Kings Coll London, Inst Psychiat, Biomed Res Ctr Mental Hlth, Div Psychol Med & Psychiat, London SE5 8AF, England.
   [Bramon, Elvira] S London & Maudsley NHS Fdn Trust, London SE5 8AF, England.
   [Tourbah, Ayman] Univ Reims, Serv Neurol, F-51100 Reims, France.
   [Tourbah, Ayman] Univ Reims, Fac Med Reims, F-51100 Reims, France.
   [Brown, Matthew A.] Univ Queensland, Brisbane, Qld 4102, Australia.
   [Brown, Matthew A.] Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia.
   [Casas, Juan P.] Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England.
   [Tubridy, Niall] St Vincents Univ Hosp, Dublin 4, Ireland.
   [Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin 2, Eire, Ireland.
   [Jankowski, Janusz] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London E1 2AT, England.
   [Villoslada, Pablo] Hosp Clin Barcelona, Inst Biomed Res August Pi Sunyer IDIBAPS, Dept Neurosci, Barcelona 08036, Spain.
   [Markus, Hugh S.] St Georges Univ London, London SW17 0RE, England.
   [Mathew, Christopher G.; Trembath, Richard C.] Kings Coll London, Guys Hosp, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England.
   [Wason, James] Med Res Council Biostat Unit, Cambridge CB2 0SR, England.
   [Palmer, Colin N. A.] Univ Dundee, Inst Biomed Res, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
   [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany.
   [Wichmann, H-Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
   [Plomin, Robert] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England.
   [Willoughby, Ernest] Auckland City Hosp, Dept Neurol, Auckland 1010, New Zealand.
   [Winkelmann, Juliane] Tech Univ Munich, Inst Humangenet, D-81675 Munich, Germany.
   [Winkelmann, Juliane] Helmholtz Zentrum Munchen, Inst Humangenet, D-85764 Munich, Germany.
   [Wittig, Michael] Univ Kiel, Popgen Biobank, D-24105 Kiel, Germany.
   [Yaouanq, Jacqueline] CHU Pontchaillou, F-35033 Rennes, France.
   [Viswanathan, Ananth C.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London EC1V 2PD, England.
   [Viswanathan, Ananth C.] UCL Inst Ophthalmol, London EC1V 2PD, England.
   [Wood, Nicholas W.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
   [Duncanson, Audrey] Wellcome Trust Res Labs, London NW1 2BE, England.
   [Ivinson, Adrian J.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA.
   [Hafler, David A.] Yale Univ, Sch Med, Dept Neurol & Immunol, New Haven, CT 06520 USA.
C3 University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Oxford; Wellcome Centre for Human Genetics; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Oxford; Wellcome Trust Sanger Institute; University of Sydney; Westmead Institute for Medical Research; KU Leuven; Rigshospitalet; University of Copenhagen; Copenhagen University Hospital; University of Helsinki; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Technical University of Munich; Johannes Gutenberg University of Mainz; Helmholtz Association; Max Delbruck Center for Molecular Medicine; University of Oxford; Queens University Belfast; University of Eastern Piedmont Amedeo Avogadro; University of Eastern Piedmont Amedeo Avogadro; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Oslo; University of Oslo; University of Oslo; Medical University Lodz; Hospital Universitari Vall d'Hebron; Karolinska Institutet; Karolinska University Hospital; Keele University; University of Exeter; University of Plymouth; University of Plymouth; Cardiff University; University of California System; University of California Berkeley; Kaiser Permanente; Karolinska Institutet; University of California System; University of California San Francisco; University of Pavia; IRCCS Fondazione Casimiro Mondino; Walton Centre; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; CHU de Toulouse; Griffith University; University of Melbourne; Florey Institute of Neuroscience & Mental Health; Melbourne Health; Royal Melbourne Hospital; Eastern Health; Box Hill Hospital; Monash University; University of Melbourne; Hospital Spedali Civili Brescia; University of Western Australia; University of Turin; A.O.U. Citta della Salute e della Scienza di Torino; AOU San Giovanni Battista-Molinette; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Newcastle; University of Southern California; Washington University (WUSTL); University of Milan; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Manchester; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; CHU de Nancy; University of Kiel; Tampere University; Tampere University Hospital; Tampere University; University of Tasmania; IRCCS Ca Granda Ospedale Maggiore Policlinico; University of Milan; Belfast City Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; IRCCS Fondazione Don Carlo Gnocchi Onlus; Karolinska Institutet; Karolinska Institutet; Karolinska University Hospital; Heinrich Heine University Dusseldorf; Universite Paris Saclay; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Hannover Medical School; University of Melbourne; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Seinajoki Central Hospital; John Hunter Hospital; University of Newcastle; Hunter Medical Research Institute; Finland National Institute for Health & Welfare; Uppsala University; Uppsala University Hospital; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of Oslo; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of California System; University of California Irvine; University of Otago; University of Miami; University of Miami; University of Bergen; Haukeland University Hospital; University of Bergen; University of Plymouth; Derriford Hospital; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Aix-Marseille Universite; Assistance Publique-Hopitaux de Marseille; University of Oulu; Imperial College London; Universite de Montreal; Universite de Montreal; Sapienza University Rome; University of Kiel; Schleswig Holstein University Hospital; Vanderbilt University; University of Western Australia; The Kids Research Institute Australia; University of Cambridge; University of Helsinki; Helsinki University Central Hospital; University of Helsinki; University of London; King's College London; South London & Maudsley NHS Trust; Universite de Reims Champagne-Ardenne; Universite de Reims Champagne-Ardenne; University of Queensland; Princess Alexandra Hospital; University of Queensland; University of London; London School of Hygiene & Tropical Medicine; University College Dublin; Saint Vincent's University Hospital; Trinity College Dublin; University of London; Queen Mary University London; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; City St Georges, University of London; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; MRC Biostatistics Unit; University of Dundee; University of Munich; University of Munich; University of London; King's College London; Auckland City Hospital; Technical University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Kiel; Universite de Rennes; CHU Rennes; University of London; University College London; Moorfields Eye Hospital NHS Foundation Trust; University of London; University College London; University of London; University College London; Harvard University; Harvard Medical School; Yale University
RP Compston, A (corresponding author), Univ Cambridge, Dept Clin Neurosci, Addenbrookes Hosp, BOX 165,Hills Rd, Cambridge CB2 0QQ, England.
EM donnelly@well.ox.ac.uk; alastair.compston@medschl.cam.ac.uk
FU Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z, 075491/Z/04/Z, 068545/Z/02]; National Institutes of Health [AI076544, NS032830, NS049477, NS19142, NS049510, NS26799, NS43559, NS067305, CA104021, RR020092, RR024992, K23N/S048869]; US National Multiple Sclerosis Society [RG 4201-A-1]; Nancy Davis Foundation; Cambridge NIHR Biomedical Research Centre; UK Medical Research Council [G0700061, G0000934]; Multiple Sclerosis Society of Great Britain and Northern Ireland [898/08]; Wolfson Royal Society; Peter Doherty fellowship; Lagrange Fellowship; Harry Weaver Neuroscience Scholarships; Australian National Health and Medical Research Council (NHMRC); Australian Research Council; JHH Charitable Trust; Multiple Sclerosis Research Australia; Health Research Council New Zealand; National MS Society of New Zealand; Wetenschappelijk Onderzoek Multiple Sclerose; Bayer Chair on Fundamental Genetic Research; Biogen Idec Chair Translational Research in Multiple Sclerosis; FWO-Vlaanderen; Belgian Neurological Society; Danish Multiple Sclerosis Society; Neuropromise EU [LSHM-CT-2005-018637]; Center of Excellence for Disease Genetics of the Academy of Finland; Sigrid Juselius Foundation; Helsinki University Central Hospital Research Foundation; Bundesministerium fur Bildung und Technologie (KKNMS consortium Control MS); Deutsche Forschungsgemeinschaft; Institut National de la Sante et de la Recherche Medicale (INSERM); Association pour la Recherche sur la Sclerose En Plaques (ARSEP); Association Francaise contre les Myopathies (AFM); Italian Foundation for Multiple Sclerosis [2002/R/40, 2005/R/10, 2008/R/11, 2008/R/15]; Italian Ministry of Health [Giovani Ricercatori 2007-D.lgs 502/92]; Regione Piemonte [2003, 2004, 2008, 2009]; CRT Foundation; Turin; Moorfields/UCL Institute of Ophthalmology NIHR Biomedical Research Centre; Norwegian MS Register and Biobank; Research Council of Norway; South-Eastern and Western Norway regional Health Authories; Ulleval University Hospital Scientific Advisory Council; Haukeland University Hospital; Amici Centro Sclerosi Multipla del San Raffaele (ACESM); Association of British Neurologists; Spanish Ministry of Health [FISPI060117]; Bibbi and Niels Jensens Foundation; Montel Williams foundation; Hjarnfonden and Swedish medical research council [8691]; Stockholm County Council [562183]; Swedish Council for Working life and Social Research; Gemeinnutzige Hertie Stiftung; Northern California Kaiser Permanente members and Polpharma Foundation; Washington University Institute of Clinical and Translational Sciences-Brain, Behavioral and Performance Unit; German Ministry of Education and Research; Helmholtz Zentrum Munchen-National Research Center; German National Genome Research Network (NGFN); LMUinnovativ; Knut and Alice Wallenberg Foundation; Children's Hospital of Philadelphia; Agency for Science & Technology and Research of Singapore; Susan G. Komen Breast Cancer Foundation; Medical Research Council [G0700061, G0100594, MC_EX_G0800860, G19/2, G0801418B, G0901310, G9817803B, G0901461, G0400017] Funding Source: researchfish; National Institute for Health Research [PDA/02/06/016, NF-SI-0507-10379] Funding Source: researchfish; Parkinson&apos;s UK [J-0804, G-0909] Funding Source: researchfish; MRC [MC_EX_G0800860, G0400017, G0700061, G19/2, G0901310, G0100594, G0901461] Funding Source: UKRI
NR 26
TC 2195
Z9 2487
U1 3
U2 490
PU 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 11
PY 2011
VL 476
IS 7359
BP 214
EP 219
DI 10.1038/nature10251
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900038
PM 21833088
DA 2026-03-09
ER

PT J
AU Boothroyd, AT
   Babkevich, P
   Prabhakaran, D
   Freeman, PG
AF Boothroyd, A. T.
   Babkevich, P.
   Prabhakaran, D.
   Freeman, P. G.
TI An hour-glass magnetic spectrum in an insulating, hole-doped antiferromagnet
SO NATURE
LA English
DT Article
ID high-temperature superconductor; copper-oxide superconductors; spin dynamics; excitations; stripes; transition; state
AB Superconductivity in layered copper oxide compounds emerges when charge carriers are added to antiferromagnetically ordered CuO(2) layers(1). The carriers destroy the antiferromagnetic order, but strong spin fluctuations persist throughout the superconducting phase and are intimately linked to superconductivity(2). Neutron scattering measurements of spin fluctuations in hole-doped copper oxides have revealed an unusual 'hour-glass' feature in the momentum-resolved magnetic spectrum that is present in a wide range of superconducting and non-superconducting materials(3-15). There is no widely accepted explanation for this feature. One possibility is that it derives from a pattern of alternating spin and charge stripes(16), and this idea is supported by measurements on stripe-ordered La(1.875)Ba(0.125)CuO(4) (ref. 15). Many copper oxides without stripe order, however, also exhibit an hour-glass spectrum(3-12). Here we report the observation of an hour-glass magnetic spectrum in a hole-doped antiferromagnet from outside the family of superconducting copper oxides. Our system has stripe correlations and is an insulator, which means that its magnetic dynamics can conclusively be ascribed to stripes. The results provide compelling evidence that the hour-glass spectrum in the copper oxide superconductors arises from fluctuating stripes.
C1 [Boothroyd, A. T.; Babkevich, P.; Prabhakaran, D.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Babkevich, P.] Paul Scherrer Inst, Neutron Scattering Lab, CH-5232 Villigen, Switzerland.
   [Freeman, P. G.] Inst Max Von Laue Paul Langevin, F-38042 Grenoble 9, France.
C3 University of Oxford; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Institut Laue-Langevin (ILL)
RP Boothroyd, AT (corresponding author), Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
EM a.boothroyd@physics.ox.ac.uk
FU Engineering and Physical Sciences Research Council of Great Britain; Paul Scherrer Institut, Switzerland; EPSRC [EP/H033939/1, EP/F001266/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H033939/1, EP/F001266/1] Funding Source: researchfish
NR 29
TC 56
Z9 56
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 MAR 17
PY 2011
VL 471
IS 7338
BP 341
EP 344
DI 10.1038/nature09902
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000037
PM 21412334
DA 2026-03-09
ER

PT J
AU O'Neill, JS
   Reddy, AB
AF O'Neill, John S.
   Reddy, Akhilesh B.
TI Circadian clocks in human red blood cells
SO NATURE
LA English
DT Article
ID gene-expression; peroxiredoxins; oscillations; feedback; nadh; mechanisms; health; states; rhythm; dimer
AB Circadian (similar to 24 hour) clocks are fundamentally important for coordinated physiology in organisms as diverse as cyanobacteria and humans. All current models of the molecular circadian clockwork in eukaryotic cells are based on transcription-translation feedback loops. Non-transcriptional mechanisms in the clockwork have been difficult to study in mammalian systems. We circumvented these problems by developing novel assays using human red blood cells, which have no nucleus (or DNA) and therefore cannot perform transcription. Our results show that transcription is not required for circadian oscillations in humans, and that non-transcriptional events seem to be sufficient to sustain cellular circadian rhythms. Using red blood cells, we found that peroxiredoxins, highly conserved antioxidant proteins, undergo similar to 24-hour redox cycles, which persist for many days under constant conditions (that is, in the absence of external cues). Moreover, these rhythms are entrainable (that is, tunable by environmental stimuli) and temperature-compensated, both key features of circadian rhythms. We anticipate that our findings will facilitate more sophisticated cellular clock models, highlighting the interdependency of transcriptional and non-transcriptional oscillations in potentially all eukaryotic cells.
C1 [O'Neill, John S.; Reddy, Akhilesh B.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
C3 Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge
RP Reddy, AB (corresponding author), Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
EM areddy@cantab.net
FU Wellcome Trust [083643/Z/07/Z]; MRC Centre for Obesity and Related metabolic Disorders (MRC CORD); NIHR Cambridge Biomedical Research Centre; Wellcome Trust [083643/Z/07/Z] Funding Source: Wellcome Trust
NR 45
TC 645
Z9 750
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 JAN 27
PY 2011
VL 469
IS 7331
BP 498
EP U70
DI 10.1038/nature09702
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500025
PM 21270888
DA 2026-03-09
ER

PT J
AU Shim, W
   Braunschweig, AB
   Liao, X
   Chai, JN
   Lim, JK
   Zheng, GF
   Mirkin, CA
AF Shim, Wooyoung
   Braunschweig, Adam B.
   Liao, Xing
   Chai, Jinan
   Lim, Jong Kuk
   Zheng, Gengfeng
   Mirkin, Chad A.
TI Hard-tip, soft-spring lithography
SO NATURE
LA English
DT Article
ID dip-pen nanolithography; afm data-storage; parallel; microscope; arrays; nanofabrication; nanoplotter; polymers; density
AB Nanofabrication strategies are becoming increasingly expensive and equipment-intensive, and consequently less accessible to researchers. As an alternative, scanning probe lithography has become a popular means of preparing nanoscale structures, in part owing to its relatively low cost and high resolution, and a registration accuracy that exceeds most existing technologies(1-6). However, increasing the throughput of cantilever-based scanning probe systems while maintaining their resolution and registration advantages has from the outset been a significant challenge(7-17). Even with impressive recent advances in cantilever array design, such arrays tend to be highly specialized for a given application, expensive, and often difficult to implement. It is therefore difficult to imagine commercially viable production methods based on scanning probe systems that rely on conventional cantilevers. Here we describe a low-cost and scalable cantilever-free tip-based nanopatterning method that uses an array of hard silicon tips mounted onto an elastomeric backing. This method-which we term hard-tip, soft-spring lithography-overcomes the throughput problems of cantilever-based scanning probe systems and the resolution limits imposed by the use of elastomeric stamps and tips: it is capable of delivering materials or energy to a surface to create arbitrary patterns of features with sub-50-nm resolution over centimetre-scale areas. We argue that hard-tip, soft-spring lithography is a versatile nanolithography strategy that should be widely adopted by academic and industrial researchers for rapid prototyping applications.
C1 [Shim, Wooyoung; Liao, Xing; Mirkin, Chad A.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Shim, Wooyoung; Braunschweig, Adam B.; Liao, Xing; Chai, Jinan; Lim, Jong Kuk; Zheng, Gengfeng; Mirkin, Chad A.] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA.
   [Braunschweig, Adam B.; Chai, Jinan; Lim, Jong Kuk; Zheng, Gengfeng; Mirkin, Chad A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
C3 Northwestern University; Northwestern University; Northwestern University
RP Mirkin, CA (corresponding author), Northwestern Univ, Dept Mat Sci & Engn, 2220 Campus Dr, Evanston, IL 60208 USA.
EM chadnano@northwestern.edu
FU US Air Force Office of Scientific Research (AFOSR); US Defense Advanced Research Projects Agency (DARPA); US NSF; US Department of Defense; US NIH
NR 30
TC 159
Z9 207
U1 3
U2 239
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 516
EP 521
DI 10.1038/nature09697
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500029
PM 21270890
DA 2026-03-09
ER

PT J
AU Keane, TM
   Goodstadt, L
   Danecek, P
   White, MA
   Wong, K
   Yalcin, B
   Heger, A
   Agam, A
   Slater, G
   Goodson, M
   Furlotte, NA
   Eskin, E
   Nellåker, C
   Whitley, H
   Cleak, J
   Janowitz, D
   Hernandez-Pliego, P
   Edwards, A
   Belgard, TG
   Oliver, PL
   McIntyre, RE
   Bhomra, A
   Nicod, J
   Gan, XC
   Yuan, W
   van der Weyden, L
   Steward, CA
   Bala, S
   Stalker, J
   Mott, R
   Durbin, R
   Jackson, IJ
   Czechanski, A
   Guerra-Assunçao, JA
   Donahue, LR
   Reinholdt, LG
   Payseur, BA
   Ponting, CP
   Birney, E
   Flint, J
   Adams, DJ
AF Keane, Thomas M.
   Goodstadt, Leo
   Danecek, Petr
   White, Michael A.
   Wong, Kim
   Yalcin, Binnaz
   Heger, Andreas
   Agam, Avigail
   Slater, Guy
   Goodson, Martin
   Furlotte, Nicholas A.
   Eskin, Eleazar
   Nellaker, Christoffer
   Whitley, Helen
   Cleak, James
   Janowitz, Deborah
   Hernandez-Pliego, Polinka
   Edwards, Andrew
   Belgard, T. Grant
   Oliver, Peter L.
   McIntyre, Rebecca E.
   Bhomra, Amarjit
   Nicod, Jerome
   Gan, Xiangchao
   Yuan, Wei
   van der Weyden, Louise
   Steward, Charles A.
   Bala, Sendu
   Stalker, Jim
   Mott, Richard
   Durbin, Richard
   Jackson, Ian J.
   Czechanski, Anne
   Guerra-Assuncao, Jose Afonso
   Donahue, Leah Rae
   Reinholdt, Laura G.
   Payseur, Bret A.
   Ponting, Chris P.
   Birney, Ewan
   Flint, Jonathan
   Adams, David J.
TI Mouse genomic variation and its effect on phenotypes and gene regulation
SO NATURE
LA English
DT Article
ID complex traits; intellectual history; mice; strains; wide; association; concordance; trees; architecture; dissection
AB We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism.
C1 [Goodstadt, Leo; Yalcin, Binnaz; Agam, Avigail; Goodson, Martin; Whitley, Helen; Cleak, James; Janowitz, Deborah; Hernandez-Pliego, Polinka; Edwards, Andrew; Bhomra, Amarjit; Nicod, Jerome; Gan, Xiangchao; Yuan, Wei; Mott, Richard; Flint, Jonathan] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Keane, Thomas M.; Danecek, Petr; Wong, Kim; Slater, Guy; McIntyre, Rebecca E.; van der Weyden, Louise; Steward, Charles A.; Bala, Sendu; Stalker, Jim; Durbin, Richard; Adams, David J.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [White, Michael A.; Payseur, Bret A.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
   [Heger, Andreas; Agam, Avigail; Nellaker, Christoffer; Belgard, T. Grant; Oliver, Peter L.; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Furlotte, Nicholas A.; Eskin, Eleazar] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Janowitz, Deborah] Ernst Moritz Arndt Univ Greifswald, Greifswald Klinikum Hansestadt Stralsund, Dept Psychiat & Psychotherapy, D-18437 Stralsund, Germany.
   [Jackson, Ian J.] MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Czechanski, Anne; Donahue, Leah Rae; Reinholdt, Laura G.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Guerra-Assuncao, Jose Afonso; Birney, Ewan] European Bioinformat Inst, Cambridge CB10 1SD, England.
C3 University of Oxford; Wellcome Centre for Human Genetics; Wellcome Trust Sanger Institute; University of Wisconsin System; University of Wisconsin Madison; University of Oxford; University of California System; University of California Los Angeles; Universitat Greifswald; University of Edinburgh; Jackson Laboratory; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute
RP Flint, J (corresponding author), Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM jf@well.ox.ac.uk; da1@sanger.ac.uk
FU Medical Research Council, UK; Wellcome Trust; Cancer Research UK; Jackson Laboratory; NSF [DEB 0918000]; NLM [NLM 2T15LM007359]; Wellcome Trust [085906/Z/08/Z, 083573/Z/07/Z]; BBSRC [BB/F022697/1]; Immune Tolerance Network [AI 15416]; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; Juvenile Diabetes Research Foundation International; Direct For Biological Sciences; Division Of Environmental Biology [0918000] Funding Source: National Science Foundation; National Human Genome Research Institute [T32HG002536] Funding Source: NIH RePORTER; National Library of Medicine; National Institute of Allergy and Infectious Diseases [T15LM007359] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/F022697/1] Funding Source: researchfish; Medical Research Council [MC_EX_G0802457, MC_U137761446, G0800024, MC_U127561112] Funding Source: researchfish; Wellcome Trust [083573/Z/07/Z] Funding Source: Wellcome Trust; BBSRC [BB/F022697/1] Funding Source: UKRI; MRC [MC_EX_G0802457, MC_U127561112, MC_U137761446, G0800024] Funding Source: UKRI
NR 44
TC 1209
Z9 1413
U1 1
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 SEP 15
PY 2011
VL 477
IS 7364
BP 289
EP 294
DI 10.1038/nature10413
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400022
PM 21921910
DA 2026-03-09
ER

PT J
AU Licausi, F
   Kosmacz, M
   Weits, DA
   Giuntoli, B
   Giorgi, FM
   Voesenek, LACJ
   Perata, P
   van Dongen, JT
AF Licausi, Francesco
   Kosmacz, Monika
   Weits, Daan A.
   Giuntoli, Beatrice
   Giorgi, Federico M.
   Voesenek, Laurentius A. C. J.
   Perata, Pierdomenico
   van Dongen, Joost T.
TI Oxygen sensing in plants is mediated by an N-end rule pathway for protein destabilization
SO NATURE
LA English
DT Article
ID ethylene response factors; evolutionary conservation; arabidopsis-thaliana; gene-expression; binding protein; hypoxia; stress; localization; system; cells
AB The majority of eukaryotic organisms rely on molecular oxygen for respiratory energy production(1). When the supply of oxygen is compromised, a variety of acclimation responses are activated to reduce the detrimental effects of energy depletion(2-4). Various oxygen-sensing mechanisms have been described that are thought to trigger these responses(5-9), but they each seem to be kingdom specific and no sensing mechanism has been identified in plants until now. Here we show that one branch of the ubiquitin-dependent N-end rule pathway for protein degradation, which is active in both mammals and plants(10,11), functions as an oxygen-sensing mechanism in Arabidopsis thaliana. We identified a conserved amino-terminal amino acid sequence of the ethylene response factor (ERF)-transcription factor RAP2.12 to be dedicated to an oxygen-dependent sequence of post-translational modifications, which ultimately lead to degradation of RAP2.12 under aerobic conditions. When the oxygen concentration is low-as during flooding-RAP2.12 is released from the plasma membrane and accumulates in the nucleus to activate gene expression for hypoxia acclimation. Our discovery of an oxygen-sensing mechanism opens up new possibilities for improving flooding tolerance in crops.
C1 [Licausi, Francesco; Kosmacz, Monika; Weits, Daan A.; Giorgi, Federico M.; van Dongen, Joost T.] Max Planck Inst Mol Plant Physiol, D-14476 Potsdam, Germany.
   [Licausi, Francesco; Giuntoli, Beatrice; Perata, Pierdomenico] Scuola Super Sant Anna, Inst Life Sci, PlantLab, I-56127 Pisa, Italy.
   [Voesenek, Laurentius A. C. J.] Univ Utrecht, Inst Environm Biol, NL-3584 CH Utrecht, Netherlands.
   [Voesenek, Laurentius A. C. J.] Ctr Biosyst Genom, NL-6708 PB Wageningen, Netherlands.
C3 Max Planck Society; Scuola Superiore Sant'Anna; Utrecht University; Centre for BioSystems Genomics
RP Licausi, F (corresponding author), Max Planck Inst Mol Plant Physiol, Muehlenberg 1, D-14476 Potsdam, Germany.
EM f.licausi@sssup.it; dongen@mpimp-golm.mpg.de
FU Max Planck Institute of Molecular Plant Physiology; Scuola Superiore Sant'Anna; Deutsche Forschungsgemeinschaft (DFG) [DO 1298/2-1]
NR 35
TC 653
Z9 713
U1 12
U2 336
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 419
EP U177
DI 10.1038/nature10536
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700050
PM 22020282
DA 2026-03-09
ER

PT J
AU Langevin, F
   Crossan, GP
   Rosado, IV
   Arends, MJ
   Patel, KJ
AF Langevin, Frederic
   Crossan, Gerry P.
   Rosado, Ivan V.
   Arends, Mark J.
   Patel, Ketan J.
TI Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice
SO NATURE
LA English
DT Article
ID fetal alcohol syndrome; fanconi-anemia; dna-adducts; childhood leukemia; knockout mice; bone-marrow; acetaldehyde; ethanol; consumption; metabolism
AB Reactive aldehydes are common carcinogens. They are also by-products of several metabolic pathways and, without enzymatic catabolism, may accumulate and cause DNA damage. Ethanol, which is metabolished to acetaldehyde, is both carcinogenic and teratogenic in humans. Here we find that the Fanconi anaemia DNA repair pathway counteracts acetaldehyde-induced genotoxicity in mice. Our results show that the acetaldehyde-catabolising enzyme Aldh2 is essential for the development of Fancd2(-/-) embryos. Nevertheless, acetaldehyde-catabolism-competent mothers (Aldh2(+/-)) can support the development of double-mutant (Aldh2(-/-)Fancd2(-/-)) mice. However, these embryos are usually sensitive to ethanol exposure in utero, and ethanol consumption by postnatal double-deficient mice rapidly precipitates bone marrow failure. Lastly, Aldh2(-/-)Fancd2(-/-) mice spontaneously develop acute leukaemia. Acetaldehyde-mediated DNA damage may critically contribute to the genesis of fetal alcohol syndrome in fetuses, as well as to abnormal development, haematopoietic failure and cancer predisposition in Fanconi anaemia patients.
C1 [Langevin, Frederic; Crossan, Gerry P.; Rosado, Ivan V.; Patel, Ketan J.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Arends, Mark J.] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Cambridge CB2 2QQ, England.
   [Patel, Ketan J.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England.
C3 MRC Laboratory Molecular Biology; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital
RP Patel, KJ (corresponding author), MRC Lab Mol Biol, Hills Rd, Cambridge CB2 0QH, England.
EM kjp@mrc-lmb.cam.ac.uk
FU Children's Leukaemia Trust; Fanconi Anaemia Research Fund; MRC [MC_U105178811] Funding Source: UKRI; Medical Research Council [MC_U105178811] Funding Source: researchfish
NR 41
TC 408
Z9 477
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 JUL 7
PY 2011
VL 475
IS 7354
BP 53
EP U67
DI 10.1038/nature10192
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300043
PM 21734703
DA 2026-03-09
ER

PT J
AU Hof, C
   Araújo, MB
   Jetz, W
   Rahbek, C
AF Hof, Christian
   Araujo, Miguel B.
   Jetz, Walter
   Rahbek, Carsten
TI Additive threats from pathogens, climate and land-use change for global amphibian diversity
SO NATURE
LA English
DT Article
ID species distribution models; population declines; sample-size; conservation; disease; extinction; ecology; future; worlds; distributions
AB Amphibian population declines far exceed those of other vertebrate groups, with 30% of all species listed as threatened by the International Union for Conservation of Nature(1-3). The causes of these declines are a matter of continued research, but probably include climate change, land-use change and spread of the pathogenic fungal disease chytridiomycosis(1,4,5). Here we assess the spatial distribution and interactions of these primary threats in relation to the global distribution of amphibian species. We show that the greatest proportions of species negatively affected by climate change are projected to be found in Africa, parts of northern South America and the Andes. Regions with the highest projected impact of land-use and climate change coincide, but there is little spatial overlap with regions highly threatened by the fungal disease. Overall, the areas harbouring the richest amphibian faunas are disproportionately more affected by one or multiple threat factors than areas with low richness. Amphibian declines are likely to accelerate in the twenty-first century, because multiple drivers of extinction could jeopardize their populations more than previous, mono-causal, assessments have suggested.
C1 [Hof, Christian; Araujo, Miguel B.; Rahbek, Carsten] Univ Copenhagen, Dept Biol, Ctr Macroecol Evolut & Climate, DK-2100 Copenhagen O, Denmark.
   [Hof, Christian; Araujo, Miguel B.] CSIC, Natl Museum Nat Sci, Dept Biodivers & Evolutionary Biol, E-28006 Madrid, Spain.
   [Araujo, Miguel B.] Univ Evora, CIBIO, Rui Nabeiro Biodivers Chair, P-7000 Evora, Portugal.
   [Jetz, Walter] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
C3 University of Copenhagen; Consejo Superior de Investigaciones Cientificas (CSIC); University of Evora; Yale University
RP Hof, C (corresponding author), Univ Copenhagen, Dept Biol, Ctr Macroecol Evolut & Climate, Univ Pk 15, DK-2100 Copenhagen O, Denmark.
EM christian.hof@senckenberg.de
FU Danish National Research Foundation; Portuguese Foundation for Science and Technology [PTDC/AAC-AMB/98163/2008]; NSF [DBI 0960550, DEB 1026764]; Division Of Environmental Biology; Direct For Biological Sciences [1026764] Funding Source: National Science Foundation
NR 51
TC 526
Z9 630
U1 5
U2 494
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 516
EP U137
DI 10.1038/nature10650
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000059
PM 22089134
DA 2026-03-09
ER

PT J
AU Young, DA
   Wright, AP
   Roberts, JL
   Warner, RC
   Young, NW
   Greenbaum, JS
   Schroeder, DM
   Holt, JW
   Sugden, DE
   Blankenship, DD
   van Ommen, TD
   Siegert, MJ
AF Young, Duncan A.
   Wright, Andrew P.
   Roberts, Jason L.
   Warner, Roland C.
   Young, Neal W.
   Greenbaum, Jamin S.
   Schroeder, Dustin M.
   Holt, John W.
   Sugden, David E.
   Blankenship, Donald D.
   van Ommen, Tas D.
   Siegert, Martin J.
TI A dynamic early East Antarctic Ice Sheet suggested by ice-covered fjord landscapes
SO NATURE
LA English
DT Article
ID southern victoria land; exobiological implications; alternative origin; numerical-model; lake vostok; miocene; mountains; evolution; roughness; erosion
AB The first Cenozoic ice sheets initiated in Antarctica from the Gamburtsev Subglacial Mountains(1) and other highlands as a result of rapid global cooling similar to 34 million years ago(2). In the subsequent 20 million years, at a time of declining atmospheric carbon dioxide concentrations(2) and an evolving Antarctic circumpolar current(2), sedimentary sequence interpretation(3) and numerical modelling(4) suggest that cyclical periods of ice-sheet expansion to the continental margin, followed by retreat to the subglacial highlands, occurred up to thirty times. These fluctuations were paced by orbital changes and were a major influence on global sea levels(5). Ice-sheet models show that the nature of such oscillations is critically dependent on the pattern and extent of Antarctic topographic lowlands. Here we show that the basal topography of the Aurora Subglacial Basin of East Antarctica, at present overlain by 2-4.5 km of ice, is characterized by a series of well-defined topographic channels within a mountain block landscape. The identification of this fjord landscape, based on new data from ice-penetrating radar, provides an improved understanding of the topography of the Aurora Subglacial Basin and its surroundings, and reveals a complex surface sculpted by a succession of ice-sheet configurations substantially different from today's. At different stages during its fluctuations, the edge of the East Antarctic Ice Sheet lay pinned along the margins of the Aurora Subglacial Basin, the upland boundaries of which are currently above sea level and the deepest parts of which are more than 1 km below sea level. Although the timing of the channel incision remains uncertain, our results suggest that the fjord landscape was carved by at least two ice-flow regimes of different scales and directions, each of which would have over-deepened existing topographic depressions, reversing valley floor slopes.
C1 [Young, Duncan A.; Greenbaum, Jamin S.; Schroeder, Dustin M.; Holt, John W.; Blankenship, Donald D.] Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
   [Wright, Andrew P.; Sugden, David E.; Siegert, Martin J.] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JW, Midlothian, Scotland.
   [Roberts, Jason L.; Warner, Roland C.; Young, Neal W.; van Ommen, Tas D.] Australian Antarctic Div, Kingston, Tas 7050, Australia.
   [Roberts, Jason L.; Warner, Roland C.; Young, Neal W.; van Ommen, Tas D.] Antarctic Climate & Ecosyst Cooperat Res Ctr, Hobart, Tas 7001, Australia.
C3 University of Texas System; University of Texas Austin; University of Edinburgh; Australian Antarctic Division; Antarctic Climate & Ecosystems Cooperative Research Centre (ACE CRC)
RP Young, DA (corresponding author), Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
EM duncan@utig.ig.utexas.edu; m.j.siegert@ed.ac.uk
FU NSF [ANT-0733025]; NASA [NNX09AR52G]; NERC [NE/D003733/1]; Australian Antarctic Division [3103]; Jackson School of Geoscience; Jet Propulsion Laboratory; G. Unger Vetlesen Foundation; Antarctic Climate and Ecosystems Cooperative Research Centre; Natural Environment Research Council [NE/F016646/1, NE/E018254/1] Funding Source: researchfish; NERC [NE/E018254/1, NE/F016646/1] Funding Source: UKRI; NASA [106520, NNX09AR52G] Funding Source: Federal RePORTER; Academy of Finland (AKA) [106520] Funding Source: Academy of Finland (AKA)
NR 30
TC 149
Z9 163
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 JUN 2
PY 2011
VL 474
IS 7349
BP 72
EP 75
DI 10.1038/nature10114
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700039
PM 21637255
DA 2026-03-09
ER

PT J
AU Zaidi, MR
   Davis, S
   Noonan, FP
   Graff-Cherry, C
   Hawley, TS
   Walker, RL
   Feigenbaum, L
   Fuchs, E
   Lyakh, L
   Young, HA
   Hornyak, TJ
   Arnheiter, H
   Trinchieri, G
   Meltzer, PS
   De Fabo, EC
   Merlino, G
AF Zaidi, M. Raza
   Davis, Sean
   Noonan, Frances P.
   Graff-Cherry, Cari
   Hawley, Teresa S.
   Walker, Robert L.
   Feigenbaum, Lionel
   Fuchs, Elaine
   Lyakh, Lyudmila
   Young, Howard A.
   Hornyak, Thomas J.
   Arnheiter, Heinz
   Trinchieri, Giorgio
   Meltzer, Paul S.
   De Fabo, Edward C.
   Merlino, Glenn
TI Interferon-γ links ultraviolet radiation to melanomagenesis in mice
SO NATURE
LA English
DT Article
ID hla-g; mouse; melanocytes; expression; cells; sequence; exposure; level; niche
AB Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood(1,2). We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA(3,4). However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-gamma (IFN-gamma), but not type-I interferons. IFN-gamma was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-gamma blockade abolished macrophage-enhanced melanoma growth and survival. IFN-gamma-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-gamma in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients.
C1 [Zaidi, M. Raza; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
   [Davis, Sean; Walker, Robert L.; Meltzer, Paul S.] NCI, Genet Branch, Bethesda, MD 20892 USA.
   [Noonan, Frances P.; De Fabo, Edward C.] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Lab Photobiol & Photoimmunol, Washington, DC 20037 USA.
   [Graff-Cherry, Cari; Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Frederick, MD 21702 USA.
   [Fuchs, Elaine] Rockefeller Univ, New York, NY 10021 USA.
   [Lyakh, Lyudmila; Young, Howard A.; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
   [Hornyak, Thomas J.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
   [Arnheiter, Heinz] NINDS, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); George Washington University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Rockefeller University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RP Merlino, G (corresponding author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM drmecd@gwumc.edu; gmerlino@helix.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute; National Institutes of Health [CA53765, CA92258]; Melanoma Research Foundation; National Cancer Institute [ZIABC008756, ZIABC011091] Funding Source: NIH RePORTER
NR 43
TC 245
Z9 288
U1 1
U2 42
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 548
EP U129
DI 10.1038/nature09666
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500036
PM 21248750
DA 2026-03-09
ER

PT J
AU Graveley, BR
   Brooks, AN
   Carlson, J
   Duff, MO
   Landolin, JM
   Yang, L
   Artieri, CG
   van Baren, MJ
   Boley, N
   Booth, BW
   Brown, JB
   Cherbas, L
   Davis, CA
   Dobin, A
   Li, RH
   Lin, W
   Malone, JH
   Mattiuzzo, NR
   Miller, D
   Sturgill, D
   Tuch, BB
   Zaleski, C
   Zhang, DY
   Blanchette, M
   Dudoit, S
   Eads, B
   Green, RE
   Hammonds, A
   Jiang, LC
   Kapranov, P
   Langton, L
   Perrimon, N
   Sandler, JE
   Wan, KH
   Willingham, A
   Zhang, Y
   Zou, Y
   Andrews, J
   Bickel, PJ
   Brenner, SE
   Brent, MR
   Cherbas, P
   Gingeras, TR
   Hoskins, RA
   Kaufman, TC
   Oliver, B
   Celniker, SE
AF Graveley, Brenton R.
   Brooks, Angela N.
   Carlson, JosephW.
   Duff, Michael O.
   Landolin, Jane M.
   Yang, Li
   Artieri, Carlo G.
   van Baren, Marijke J.
   Boley, Nathan
   Booth, Benjamin W.
   Brown, James B.
   Cherbas, Lucy
   Davis, Carrie A.
   Dobin, Alex
   Li, Renhua
   Lin, Wei
   Malone, John H.
   Mattiuzzo, Nicolas R.
   Miller, David
   Sturgill, David
   Tuch, Brian B.
   Zaleski, Chris
   Zhang, Dayu
   Blanchette, Marco
   Dudoit, Sandrine
   Eads, Brian
   Green, Richard E.
   Hammonds, Ann
   Jiang, Lichun
   Kapranov, Phil
   Langton, Laura
   Perrimon, Norbert
   Sandler, Jeremy E.
   Wan, Kenneth H.
   Willingham, Aarron
   Zhang, Yu
   Zou, Yi
   Andrews, Justen
   Bickel, Peter J.
   Brenner, Steven E.
   Brent, Michael R.
   Cherbas, Peter
   Gingeras, Thomas R.
   Hoskins, Roger A.
   Kaufman, Thomas C.
   Oliver, Brian
   Celniker, Susan E.
TI The developmental transcriptome of Drosophila melanogaster
SO NATURE
LA English
DT Article
ID gene-expression; functional elements; bithorax complex; abdominal-b; identification; genm; targets
AB Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development.
C1 [Graveley, Brenton R.; Duff, Michael O.; Yang, Li] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, 263 Farmington Ave, Farmington, CT 06030 USA.
   [Brooks, Angela N.; Brenner, Steven E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Carlson, JosephW.; Landolin, Jane M.; Booth, Benjamin W.; Hammonds, Ann; Sandler, Jeremy E.; Wan, Kenneth H.; Hoskins, Roger A.; Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Dynam, Berkeley, CA 94720 USA.
   [Artieri, Carlo G.; Li, Renhua; Malone, John H.; Mattiuzzo, Nicolas R.; Sturgill, David; Jiang, Lichun; Zhang, Yu; Oliver, Brian] NIDDK, Sect Dev Genom, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [van Baren, Marijke J.; Langton, Laura; Brent, Michael R.] Washington Univ, Ctr Genome Sci, St Louis, MO 63108 USA.
   [van Baren, Marijke J.; Langton, Laura; Brent, Michael R.] Washington Univ, Dept Comp Sci, St Louis, MO 63108 USA.
   [Boley, Nathan; Brown, James B.; Bickel, Peter J.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Cherbas, Lucy; Zhang, Dayu; Cherbas, Peter] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA.
   [Davis, Carrie A.; Dobin, Alex; Lin, Wei; Zaleski, Chris; Kapranov, Phil; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Miller, David; Eads, Brian; Andrews, Justen; Cherbas, Peter; Kaufman, Thomas C.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Tuch, Brian B.] Life Technol, Res & Dev, Genet Syst Div, Foster City, CA 94404 USA.
   [Tuch, Brian B.] Amgen Inc, Genome Anal Unit, San Francisco, CA 94080 USA.
   [Blanchette, Marco] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Blanchette, Marco] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA.
   [Dudoit, Sandrine] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA.
   [Green, Richard E.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Willingham, Aarron; Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Gingeras, Thomas R.] Affymetrix, Santa Clara, CA 95051 USA.
C3 University of Connecticut; 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; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California Berkeley; Indiana University System; Indiana University Bloomington; Cold Spring Harbor Laboratory; Indiana University System; Indiana University Bloomington; Thermo Fisher Scientific; Amgen; Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center; University of California System; University of California Berkeley; University of California System; University of California Santa Cruz; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; University of California System; University of California Berkeley; Affymetrix
RP Graveley, BR (corresponding author), Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, 263 Farmington Ave, Farmington, CT 06030 USA.
EM graveley@neuron.uchc.edu; celniker@fruitfly.org
FU National Human Genome Research INstitute [U01 HB004271]; Department of Energy [DE-AC02-05CH11231]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK015600] Funding Source: NIH RePORTER
NR 49
TC 1181
Z9 1421
U1 2
U2 276
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 473
EP 479
DI 10.1038/nature09715
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200054
PM 21179090
DA 2026-03-09
ER

PT J
AU Latta, C
   Haupt, F
   Hanl, M
   Weichselbaum, A
   Claassen, M
   Wuester, W
   Fallahi, P
   Faelt, S
   Glazman, L
   von Delft, J
   Türeci, HE
   Imamoglu, A
AF Latta, C.
   Haupt, F.
   Hanl, M.
   Weichselbaum, A.
   Claassen, M.
   Wuester, W.
   Fallahi, P.
   Faelt, S.
   Glazman, L.
   von Delft, J.
   Tuereci, H. E.
   Imamoglu, A.
TI Quantum quench of Kondo correlations in optical absorption
SO NATURE
LA English
DT Article
ID states; dots
AB The interaction between a single confined spin and the spins of an electron reservoir leads to one of the most remarkable phenomena of many-body physics-the Kondo effect(1,2). Electronic transport measurements on single artificial atoms, or quantum dots, have made it possible to study the effect in great detail(3-5). Here we report optical measurements on a single semiconductor quantum dot tunnel-coupled to a degenerate electron gas which show that absorption of a single photon leads to an abrupt change in the system Hamiltonian and a quantum quench of Kondo correlations. By inferring the characteristic power-law exponents from the experimental absorption line shapes, we find a unique signature of the quench in the form of an Anderson orthogonality catastrophe(6,7), induced by a vanishing overlap between the initial and final many-body wavefunctions. We show that the power-law exponent that determines the degree of orthogonality can be tuned using an external magnetic field(8), which unequivocally demonstrates that the observed absorption line shape originates from Kondo correlations. Our experiments demonstrate that optical measurements on single artificial atoms offer new perspectives on many-body phenomena previously studied using transport spectroscopy only.
C1 [Hanl, M.; Weichselbaum, A.; von Delft, J.] Univ Munich, Arnold Sommerfeld Ctr Theoret Phys, D-80333 Munich, Germany.
   [Latta, C.; Haupt, F.; Claassen, M.; Wuester, W.; Fallahi, P.; Faelt, S.; Tuereci, H. E.; Imamoglu, A.] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
   [Glazman, L.] Yale Univ, Sloane Phys Lab, New Haven, CT 06520 USA.
   [Tuereci, H. E.] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
C3 University of Munich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Yale University; Princeton University
RP Latta, C (corresponding author), ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM clatta@phys.ethz.ch; imamoglu@phys.ethz.ch
FU Swiss NSF [200021-121757, PP00P2-123519/1]; ERC; DFG [SFB631, SFB-TR12, De730/3-2, De730/4-1]; Cluster of Excellence 'Nanosystems Initiative Munich'; NSF DMR [0906498]; Swiss National Science Foundation (SNF) [200021_121757] Funding Source: Swiss National Science Foundation (SNF)
NR 28
TC 95
Z9 104
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 627
EP 630
DI 10.1038/nature10204
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300036
PM 21720368
DA 2026-03-09
ER

PT J
AU Stuber, GD
   Sparta, DR
   Stamatakis, AM
   van Leeuwen, WA
   Hardjoprajitno, JE
   Cho, S
   Tye, KM
   Kempadoo, KA
   Zhang, F
   Deisseroth, K
   Bonci, A
AF Stuber, Garret D.
   Sparta, Dennis R.
   Stamatakis, Alice M.
   van Leeuwen, Wieke A.
   Hardjoprajitno, Juanita E.
   Cho, Saemi
   Tye, Kay M.
   Kempadoo, Kimberly A.
   Zhang, Feng
   Deisseroth, Karl
   Bonci, Antonello
TI Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking
SO NATURE
LA English
DT Article
ID midbrain dopamine neurons; basolateral amygdala; cocaine-seeking; behavior; core; release; disconnection; involvement; motivation; interface
AB The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence(1-5,21-23). The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours(4,6,7,24,25), but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.
C1 [Stuber, Garret D.; Sparta, Dennis R.; Stamatakis, Alice M.] Univ N Carolina, UNC Neurosci Ctr, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [Stuber, Garret D.; Sparta, Dennis R.; Stamatakis, Alice M.] Univ N Carolina, UNC Neurosci Ctr, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA.
   [Stuber, Garret D.; Sparta, Dennis R.; van Leeuwen, Wieke A.; Hardjoprajitno, Juanita E.; Cho, Saemi; Tye, Kay M.; Kempadoo, Kimberly A.; Bonci, Antonello] Univ Calif San Francisco, Wheeler Ctr Neurobiol Drug Addict, Dept Neurol, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94608 USA.
   [Tye, Kay M.; Zhang, Feng; Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Tye, Kay M.; Zhang, Feng; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of California System; University of California San Francisco; Ernest Gallo Clinic & Research Center; Stanford University; Stanford University; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA)
RP Stuber, GD (corresponding author), Univ N Carolina, UNC Neurosci Ctr, Dept Psychiat, Chapel Hill, NC 27599 USA.
EM gstuber@med.unc.edu
FU NARSAD; ABMRF; Foundation of Hope; NIDA [DA029325]; Psychiatry Department at UNC Chapel Hill; State of California through the University of California at San Francisco;  [F32AA018610]
NR 26
TC 681
Z9 881
U1 2
U2 116
PU 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 21
PY 2011
VL 475
IS 7356
BP 377
EP U129
DI 10.1038/nature10194
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200042
PM 21716290
DA 2026-03-09
ER

PT J
AU Brock, DA
   Douglas, TE
   Queller, DC
   Strassmann, JE
AF Brock, Debra A.
   Douglas, Tracy E.
   Queller, David C.
   Strassmann, Joan E.
TI Primitive agriculture in a social amoeba
SO NATURE
LA English
DT Article
ID evolution; bacteria; cooperation; mutualism
AB Agriculture has been a large part of the ecological success of humans(1). A handful of animals, notably the fungus-growing ants, termites and ambrosia beetles(2-4), have advanced agriculture that involves dispersal and seeding of food propagules, cultivation of the crop and sustainable harvesting(5). More primitive examples, which could be called husbandry because they involve fewer adaptations, include marine snails farming intertidal fungi(6) and damsel-fish farming algae(7). Recent work has shown that microorganisms are surprisingly like animals in having sophisticated behaviours such as cooperation, communication(8,9) and recognition(10,11), as well as many kinds of symbiosis(12-15). Here we show that the social amoeba Dictyostelium discoideum has a primitive farming symbiosis that includes dispersal and prudent harvesting of the crop. About one-third of wild-collected clones engage in husbandry of bacteria. Instead of consuming all bacteria in their patch, they stop feeding early and incorporate bacteria into their fruiting bodies. They then carry bacteria during spore dispersal and can seed a new food crop, which is a major advantage if edible bacteria are lacking at the new site. However, if they arrive at sites already containing appropriate bacteria, the costs of early feeding cessation are not compensated for, which may account for the dichotomous nature of this farming symbiosis. The striking convergent evolution between bacterial husbandry in social amoebas and fungus farming in social insects makes sense because multigenerational benefits of farming go to already established kin groups.
C1 [Brock, Debra A.; Douglas, Tracy E.; Queller, David C.; Strassmann, Joan E.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA.
C3 Rice University
RP Brock, DA (corresponding author), Rice Univ, Dept Ecol & Evolutionary Biol, 6100 Main St, Houston, TX 77005 USA.
EM dbrock@rice.edu
FU US National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1204352, 0816690] Funding Source: National Science Foundation
NR 32
TC 196
Z9 234
U1 6
U2 227
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 20
PY 2011
VL 469
IS 7330
BP 393
EP +
DI 10.1038/nature09668
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600051
PM 21248849
DA 2026-03-09
ER

PT J
AU Schönbauer, C
   Distler, J
   Jährling, N
   Radolf, M
   Dodt, HU
   Frasch, M
   Schnorrer, F
AF Schoenbauer, Cornelia
   Distler, Jutta
   Jaehrling, Nina
   Radolf, Martin
   Dodt, Hans-Ulrich
   Frasch, Manfred
   Schnorrer, Frank
TI Spalt mediates an evolutionarily conserved switch to fibrillar muscle fate in insects
SO NATURE
LA English
DT Article
ID flight-muscle; drosophila embryo; genetic-analysis; protein; expression; myogenesis; sall1; actin
AB Flying insects oscillate their wings at high frequencies of up to 1,000 Hz(1,2) and produce large mechanical forces of 80 W per kilogram of muscle(3). They utilize a pair of perpendicularly oriented indirect flight muscles that contain fibrillar, stretch-activated myofibres. In contrast, all other, more slowly contracting, insect body muscles have a tubular muscle morphology(4). Here we identify the transcription factor Spalt major (Salm) as a master regulator of fibrillar flight muscle fate in Drosophila. salm is necessary and sufficient to induce fibrillar muscle fate. salm switches the entire transcriptional program from tubular to fibrillar fate by regulating the expression and splicing of key sarcomeric components specific to each muscle type. Spalt function is conserved in insects evolutionarily separated by 280 million years. We propose that Spalt proteins switch myofibres from tubular to fibrillar fate during development, a function potentially conserved in the vertebrate heart-a stretch-activated muscle sharing features with insect flight muscle.
C1 [Schoenbauer, Cornelia; Schnorrer, Frank] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
   [Distler, Jutta; Frasch, Manfred] Univ Erlangen Nurnberg, Dept Biol, Dev Biol Div, D-91058 Erlangen, Germany.
   [Jaehrling, Nina; Dodt, Hans-Ulrich] Vienna Univ Technol, FKE, Dept Bioelect, A-1040 Vienna, Austria.
   [Jaehrling, Nina; Dodt, Hans-Ulrich] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria.
   [Radolf, Martin] IMP, A-1030 Vienna, Austria.
C3 Max Planck Society; University of Erlangen Nuremberg; Technische Universitat Wien; Medical University of Vienna; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Schnorrer, F (corresponding author), Max Planck Inst Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM schnorrer@biochem.mpg.de
FU Max-Planck-Society; Human Frontier Science Programme; Austrian Academy of Sciences; DFG
NR 37
TC 88
Z9 103
U1 2
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 406
EP U160
DI 10.1038/nature10559
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700047
PM 22094701
DA 2026-03-09
ER

PT J
AU Lepre, CJ
   Roche, H
   Kent, DV
   Harmand, S
   Quinn, RL
   Brugal, JP
   Texier, PJ
   Lenoble, A
   Feibel, CS
AF Lepre, Christopher J.
   Roche, Helene
   Kent, Dennis V.
   Harmand, Sonia
   Quinn, Rhonda L.
   Brugal, Jean-Philippe
   Texier, Pierre-Jean
   Lenoble, Arnaud
   Feibel, Craig S.
TI An earlier origin for the Acheulian
SO NATURE
LA English
DT Article
ID koobi-fora-formation; turkana-basin; early homo; pleistocene; kenya; age; magnetostratigraphy; geochronology
AB The Acheulian is one of the first defined prehistoric technocomplexes and is characterized by shaped bifacial stone tools(1-3). It probably originated in Africa, spreading to Europe and Asia perhaps as early as similar to 1 million years (Myr) ago(4-6). The origin of the Acheulian is thought to have closely coincided with major changes in human brain evolution, allowing for further technological developments(7,8). Nonetheless, the emergence of the Acheulian remains unclear because well-dated sites older than 1.4 Myr ago are scarce. Here we report on the lithic assemblage and geological context for the Kokiselei 4 archaeological site from the Nachukui formation (West Turkana, Kenya) that bears characteristic early Acheulian tools and pushes the first appearance datum for this stone-age technology back to 1.76 Myr ago. Moreover, co-occurrence of Oldowan and Acheulian artefacts at the Kokiselei site complex indicates that the two technologies are not mutually exclusive time-successive components of an evolving cultural lineage, and suggests that the Acheulian was either imported from another location yet to be identified or originated from Oldowan hominins at this vicinity. In either case, the Acheulian did not accompany the first human dispersal from Africa(9,10) despite being available at the time. This may indicate that multiple groups of hominins distinguished by separate stone-tool-making behaviours and dispersal strategies coexisted in Africa at 1.76 Myr ago.
C1 [Lepre, Christopher J.; Kent, Dennis V.] Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Lepre, Christopher J.; Kent, Dennis V.; Quinn, Rhonda L.; Feibel, Craig S.] Rutgers State Univ, Dept Earth & Planetary Sci, Piscataway, NJ 08854 USA.
   [Roche, Helene; Harmand, Sonia] Univ Paris Ouest Nanterre, UMR CNRS 7055, F-92023 Nanterre, France.
   [Quinn, Rhonda L.] Seton Hall Univ, Dept Sociol Anthropol & Social Work, S Orange, NJ 07079 USA.
   [Brugal, Jean-Philippe] Maison Mediterraneenne Sci Homme, UMR CNRS 6636, F-13094 Aix En Provence 2, France.
   [Texier, Pierre-Jean; Lenoble, Arnaud] Univ Bordeaux 1, UMR CNRS PACEA 5199, F-33405 Talence, France.
C3 Columbia University; Rutgers University System; Rutgers University New Brunswick; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Seton Hall University; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux
RP Lepre, CJ (corresponding author), Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM lepre@ldeo.columbia.edu
FU French Ministry of Foreign Affairs; National Science Foundation [BCS 02-18511]
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NR 28
TC 363
Z9 412
U1 1
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 82
EP 85
DI 10.1038/nature10372
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300035
PM 21886161
DA 2026-03-09
ER

PT J
AU Engineer, ND
   Riley, JR
   Seale, JD
   Vrana, WA
   Shetake, JA
   Sudanagunta, SP
   Borland, MS
   Kilgard, MP
AF Engineer, Navzer D.
   Riley, Jonathan R.
   Seale, Jonathan D.
   Vrana, Will A.
   Shetake, Jai A.
   Sudanagunta, Sindhu P.
   Borland, Michael S.
   Kilgard, Michael P.
TI Reversing pathological neural activity using targeted plasticity
SO NATURE
LA English
DT Article
ID vagus nerve-stimulation; cortical map reorganization; phantom-limb pain; auditory-cortex; hearing-loss; assessing tinnitus; trauma; hyperactivity; selectivity; nucleus
AB Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus(1-3). Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively(1,4). Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations(5). However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.
C1 [Engineer, Navzer D.; Riley, Jonathan R.; Seale, Jonathan D.; Vrana, Will A.; Shetake, Jai A.; Sudanagunta, Sindhu P.; Borland, Michael S.; Kilgard, Michael P.] Univ Texas Dallas, Cort Plast Lab, Richardson, TX 75080 USA.
   [Engineer, Navzer D.] MicroTransponder Inc, Austin, TX 78738 USA.
C3 University of Texas System; University of Texas Dallas
RP Engineer, ND (corresponding author), Univ Texas Dallas, Cort Plast Lab, Richardson, TX 75080 USA.
EM navzer@utdallas.edu
FU James S. McDonnell Foundation; Texas Advanced Research Program; National Institute for Deafness and other Communication Disorders; MicroTransponder Inc.
NR 34
TC 508
Z9 651
U1 1
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 101
EP U114
DI 10.1038/nature09656
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400042
PM 21228773
DA 2026-03-09
ER

PT J
AU Macheboeuf, P
   Buffalo, C
   Fu, CY
   Zinkernagel, AS
   Cole, JN
   Johnson, JE
   Nizet, V
   Ghosh, P
AF Macheboeuf, Pauline
   Buffalo, Cosmo
   Fu, Chi-yu
   Zinkernagel, Annelies S.
   Cole, Jason N.
   Johnson, John E.
   Nizet, Victor
   Ghosh, Partho
TI Streptococcal M1 protein constructs a pathological host fibrinogen network
SO NATURE
LA English
DT Article
ID heparin-binding protein; group-a streptococci; oligomerization state; crystal-structure; surface-proteins; coiled coils; fragment-d; crystallography; phagocytosis; stability
AB M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen that, unlike M1 or fibrinogen alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the complex formed between streptococcal M1 and human fibrinogen. A conformationally dynamic coiled-coil dimer of M1 was found to organize four fibrinogen molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock.
C1 [Macheboeuf, Pauline; Buffalo, Cosmo; Ghosh, Partho] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Fu, Chi-yu; Johnson, John E.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Zinkernagel, Annelies S.; Cole, Jason N.; Nizet, Victor] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [Cole, Jason N.] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia.
   [Nizet, Victor] Univ Calif San Diego, Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Scripps Research Institute; University of California System; University of California San Diego; University of Queensland; University of California System; University of California San Diego
RP Ghosh, P (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM pghosh@ucsd.edu
FU NIH [R21 AI071167, T32 GM007240, R01 AI077780, R01 GM54076]; National Health and Medical Research Council of Australia [514639]; National Health and Medical Research Council (NHMRC) [514639] Funding Source: National Health and Medical Research Council (NHMRC)
NR 41
TC 85
Z9 102
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 APR 7
PY 2011
VL 472
IS 7341
BP 64
EP 68
DI 10.1038/nature09967
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400037
PM 21475196
DA 2026-03-09
ER

PT J
AU Cao, Y
   Jin, XS
   Levin, EJ
   Huang, H
   Zong, YN
   Quick, M
   Weng, J
   Pan, YP
   Love, J
   Punta, M
   Rost, B
   Hendrickson, WA
   Javitch, JA
   Rajashankar, KR
   Zhou, M
AF Cao, Yu
   Jin, Xiangshu
   Levin, Elena J.
   Huang, Hua
   Zong, Yinong
   Quick, Matthias
   Weng, Jun
   Pan, Yaping
   Love, James
   Punta, Marco
   Rost, Burkhard
   Hendrickson, Wayne A.
   Javitch, Jonathan A.
   Rajashankar, Kanagalaghatta R.
   Zhou, Ming
TI Crystal structure of a phosphorylation-coupled saccharide transporter
SO NATURE
LA English
DT Article
ID coli mannitol permease; bacterial phosphotransferase system; escherichia-coli; membrane topology; carbohydrate transporters; chitin disaccharide; substrate-binding; phosphoenolpyruvate; protein; n,n'-diacetylchitobiose
AB Saccharides have a central role in the nutrition of all living organisms. Whereas several saccharide uptake systems are shared between the different phylogenetic kingdoms, the phosphoenolpyruvate-dependent phosphotransferase system exists almost exclusively in bacteria. This multi-component system includes an integral membrane protein EIIC that transports saccharides and assists in their phosphorylation. Here we present the crystal structure of an EIIC from Bacillus cereus that transports diacetylchitobiose. The EIIC is a homodimer, with an expansive interface formed between the amino-terminal halves of the two protomers. The carboxy-terminal half of each protomer has a large binding pocket that contains a diacetylchitobiose, which is occluded from both sides of the membrane with its site of phosphorylation near the conserved His 250 and Glu 334 residues. The structure shows the architecture of this important class of transporters, identifies the determinants of substrate binding and phosphorylation, and provides a framework for understanding the mechanism of sugar translocation.
C1 [Cao, Yu; Levin, Elena J.; Huang, Hua; Weng, Jun; Pan, Yaping; Zhou, Ming] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Jin, Xiangshu] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Zong, Yinong] Sanford Burnham Inst, La Jolla, CA 92037 USA.
   [Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Ctr Mol Recognit, New York, NY 10032 USA.
   [Quick, Matthias; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
   [Love, James; Punta, Marco; Rost, Burkhard; Hendrickson, Wayne A.] New York Struct Biol Ctr, New York Consortium Membrane Prot Struct, New York, NY 10027 USA.
   [Punta, Marco; Rost, Burkhard] Tech Univ Munich, Dept Comp Sci, D-85748 Munich, Germany.
   [Punta, Marco; Rost, Burkhard] Tech Univ Munich, Inst Adv Study, D-85748 Munich, Germany.
   [Javitch, Jonathan A.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Dept Chem & Chem Biol, NE CAT, Adv Photon Source, Argonne, IL 60439 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; Sanford Burnham Prebys Medical Discovery Institute; Columbia University; Columbia University; New York State Psychiatry Institute; Technical University of Munich; Technical University of Munich; Columbia University; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory
RP Zhou, M (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, 630 W 168th St, New York, NY 10032 USA.
EM mz2140@columbia.edu
FU US National Institutes of Health [DK088057, GM098878, GM05026-sub0007, T32HL087745];  [GM05026]
NR 51
TC 74
Z9 84
U1 0
U2 40
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 50
EP U58
DI 10.1038/nature09939
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300028
PM 21471968
DA 2026-03-09
ER

PT J
AU Jones, SB
   Simmons, B
   Mastracchio, A
   MacMillan, DWC
AF Jones, Spencer B.
   Simmons, Bryon
   Mastracchio, Anthony
   MacMillan, David W. C.
TI Collective synthesis of natural products by means of organocascade catalysis
SO NATURE
LA English
DT Article
ID indole alkaloids; aspidosperma alkaloids; cascade catalysis; (+)-aspidospermidine; (-)-strychnine; derivatives; cyclization; kopsinine; oxidation
AB Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.
C1 [Jones, Spencer B.; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W. C.] Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA.
C3 Princeton University
RP MacMillan, DWC (corresponding author), Princeton Univ, Merck Ctr Catalysis, Princeton, NJ 08544 USA.
EM dmacmill@princeton.edu
FU NIHGMS [R01 GM078201-05]; Bristol-Myers Squibb; Merck
NR 38
TC 627
Z9 688
U1 4
U2 357
PU 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 14
PY 2011
VL 475
IS 7355
BP 183
EP 188
DI 10.1038/nature10232
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500041
PM 21753848
DA 2026-03-09
ER

PT J
AU van Groenigen, KJ
   Osenberg, CW
   Hungate, BA
AF van Groenigen, Kees Jan
   Osenberg, Craig W.
   Hungate, Bruce A.
TI Increased soil emissions of potent greenhouse gases under increased atmospheric CO2
SO NATURE
LA English
DT Article
ID elevated co2; carbon-dioxide; nitrous-oxide; methane; metaanalysis; water; denitrification; questions; wetlands; europe
AB Increasing concentrations of atmospheric carbon dioxide (CO2) can affect biotic and abiotic conditions in soil, such as microbial activity and water content(1,2). In turn, these changes might be expected to alter the production and consumption of the important greenhouse gases nitrous oxide (N2O) and methane (CH4) (refs 2, 3). However, studies on fluxes of N2O and CH4 from soil under increased atmospheric CO2 have not been quantitatively synthesized. Here we show, using meta-analysis, that increased CO2 (ranging from 463 to 780 parts per million by volume) stimulates both N2O emissions from upland soils and CH4 emissions from rice paddies and natural wetlands. Because enhanced greenhouse-gas emissions add to the radiative forcing of terrestrial ecosystems, these emissions are expected to negate at least 16.6 per cent of the climate change mitigation potential previously predicted from an increase in the terrestrial carbon sink under increased atmospheric CO2 concentrations(4). Our results therefore suggest that the capacity of land ecosystems to slow climate warming has been overestimated.
C1 [van Groenigen, Kees Jan; Hungate, Bruce A.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA.
   [van Groenigen, Kees Jan; Hungate, Bruce A.] No Arizona Univ, Merriam Powell Ctr Environm Res, Flagstaff, AZ 86011 USA.
   [van Groenigen, Kees Jan] Trinity Coll Dublin, Sch Nat Sci, Dept Bot, Dublin 2, Ireland.
   [Osenberg, Craig W.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
C3 Northern Arizona University; Northern Arizona University; Trinity College Dublin; State University System of Florida; University of Florida
RP van Groenigen, KJ (corresponding author), No Arizona Univ, Dept Biol Sci, Box 5640, Flagstaff, AZ 86011 USA.
EM cjvangroenigen@nau.edu
FU DOE-NICCR; NSF [DEB-0949460]; Irish Research Council for Science, Engineering and Technology; Marie Curie Actions under FP7
NR 30
TC 455
Z9 507
U1 32
U2 871
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 214
EP U121
DI 10.1038/nature10176
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500047
PM 21753852
DA 2026-03-09
ER

PT J
AU Schoggins, JW
   Wilson, SJ
   Panis, M
   Murphy, MY
   Jones, CT
   Bieniasz, P
   Rice, CM
AF Schoggins, John W.
   Wilson, Sam J.
   Panis, Maryline
   Murphy, Mary Y.
   Jones, Christopher T.
   Bieniasz, Paul
   Rice, Charles M.
TI A diverse range of gene products are effectors of the type I interferon antiviral response
SO NATURE
LA English
DT Article
ID hepatitis-c virus; identification; proteins; reveals; rna; classification; replication; expression; resistance; disease
AB The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago(1-3), only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.
C1 [Schoggins, John W.; Panis, Maryline; Murphy, Mary Y.; Jones, Christopher T.; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, New York, NY 10065 USA.
   [Wilson, Sam J.; Bieniasz, Paul] Rockefeller Univ, Howard Hughes Med Inst, Aaron Diamond AIDS Res Ctr, Lab Retrovirol, New York, NY 10016 USA.
C3 Rockefeller University; Howard Hughes Medical Institute; Rockefeller University
RP Rice, CM (corresponding author), Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, New York, NY 10065 USA.
EM ricec@mail.rockefeller.edu
FU New York State Department of Health (NYSDOH) [C023046]; National Institutes of Health [AI057158, AI064003]; Greenberg Medical Research Institute; Starr Foundation; Ronald A. Shellow, M. D. Memorial Fund; National Institute of Diabetes and Digestive and Kidney Diseases [DK082155, DK081193]
NR 42
TC 1994
Z9 2347
U1 3
U2 252
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 481
EP U545
DI 10.1038/nature09907
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600036
PM 21478870
DA 2026-03-09
ER

PT J
AU Park, D
   Han, CZ
   Elliott, MR
   Kinchen, JM
   Trampont, PC
   Das, S
   Collins, S
   Lysiak, JJ
   Hoehn, KL
   Ravichandran, KS
AF Park, Daeho
   Han, Claudia Z.
   Elliott, Michael R.
   Kinchen, Jason M.
   Trampont, Paul C.
   Das, Soumita
   Collins, Sheila
   Lysiak, Jeffrey J.
   Hoehn, Kyle L.
   Ravichandran, Kodi S.
TI Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein
SO NATURE
LA English
DT Article
ID mitochondrial uncoupling-protein; phosphatidylserine receptor; proton leak; engulfment; obesity; gene
AB Rapid and efficient removal of apoptotic cells by phagocytes is important during development, tissue homeostasis and in immune responses(1-5). Efficient clearance depends on the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the corpse-derived cellular material(6). However, the factors that influence continued clearance by phagocytes are not known. Here we show that the mitochondrial membrane potential of the phagocyte critically controls engulfment capacity, with lower potential enhancing engulfment and vice versa. The mitochondrial membrane protein Ucp2, which acts to lower the mitochondrial membrane potential(7-9), was upregulated in phagocytes engulfing apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2 overexpression enhanced engulfment. Mutational and pharmacological studies indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice(10,11) were impaired in phagocytosis in vitro, and Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in the thymus and testes. Collectively, these data indicate that mitochondrial membrane potential and Ucp2 are key molecular determinants of apoptotic cell clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis(11,12), this newly discovered role for Ucp2 in apoptotic cell clearance has implications for the complex aetiology and pathogenesis of these diseases.
C1 [Park, Daeho; Han, Claudia Z.; Elliott, Michael R.; Kinchen, Jason M.; Trampont, Paul C.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Park, Daeho; Han, Claudia Z.; Elliott, Michael R.; Kinchen, Jason M.; Trampont, Paul C.; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Han, Claudia Z.; Kinchen, Jason M.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Das, Soumita] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
   [Collins, Sheila] Sanford Burnham Med Res Inst, Diabet & Obes Res Ctr, Orlando, FL 32827 USA.
   [Lysiak, Jeffrey J.] Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA.
   [Hoehn, Kyle L.] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA.
   [Hoehn, Kyle L.] Univ Virginia, CVRC, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia; Sanford Burnham Prebys Medical Discovery Institute; University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
EM ravi@virginia.edu
FU National Institute of General Medical Sciences; National Institute of Child Health and Development; American Heart Association; National Institute of Allergy and Infectious Diseases [T32AI055432] Funding Source: NIH RePORTER
NR 28
TC 205
Z9 245
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 220
EP U126
DI 10.1038/nature10340
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900038
PM 21857682
DA 2026-03-09
ER

PT J
AU Yizhar, O
   Fenno, LE
   Prigge, M
   Schneider, F
   Davidson, TJ
   O'Shea, DJ
   Sohal, VS
   Goshen, I
   Finkelstein, J
   Paz, JT
   Stehfest, K
   Fudim, R
   Ramakrishnan, C
   Huguenard, JR
   Hegemann, P
   Deisseroth, K
AF Yizhar, Ofer
   Fenno, Lief E.
   Prigge, Matthias
   Schneider, Franziska
   Davidson, Thomas J.
   O'Shea, Daniel J.
   Sohal, Vikaas S.
   Goshen, Inbal
   Finkelstein, Joel
   Paz, Jeanne T.
   Stehfest, Katja
   Fudim, Roman
   Ramakrishnan, Charu
   Huguenard, John R.
   Hegemann, Peter
   Deisseroth, Karl
TI Neocortical excitation/inhibition balance in information processing and social dysfunction
SO NATURE
LA English
DT Article
ID rett-syndrome; optogenetic control; prefrontal cortex; neural systems; mouse model; autism; schizophrenia; neurons; children; memory
AB Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
C1 [Yizhar, Ofer; Fenno, Lief E.; Davidson, Thomas J.; O'Shea, Daniel J.; Sohal, Vikaas S.; Goshen, Inbal; Finkelstein, Joel; Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Clark Ctr W083, Stanford, CA 94305 USA.
   [Yizhar, Ofer] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
   [Fenno, Lief E.; O'Shea, Daniel J.] Stanford Univ, Neurosci Program, Clark Ctr W083, Stanford, CA 94305 USA.
   [Prigge, Matthias; Schneider, Franziska; Stehfest, Katja; Fudim, Roman; Hegemann, Peter] Humboldt Univ, Inst Biol, D-10115 Berlin, Germany.
   [Sohal, Vikaas S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
   [Paz, Jeanne T.; Huguenard, John R.] Stanford Univ, Dept Neurol & Neurol Sci, Clark Ctr W083, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Clark Ctr W083, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Clark Ctr W083, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, CNC Program, Clark Ctr W083, Stanford, CA 94305 USA.
C3 Stanford University; Weizmann Institute of Science; Stanford University; Humboldt University of Berlin; University of California System; University of California San Francisco; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Yizhar, O (corresponding author), Stanford Univ, Dept Bioengn, Clark Ctr W083, 318 Campus Dr W, Stanford, CA 94305 USA.
EM ofer.yizhar@weizmann.ac.il; hegemape@rz.hu-berlin.de; deissero@stanford.edu
FU Human Frontier Science Program; Stanford MSTP program; DFG [HE3824/9-1, 17-1]; NIMH; NIDA; NINDS; DARPA; CIRM; Yu Foundation; Woo Foundation; Snyder Foundation; Keck Foundation; National Institute of Mental Health [R01MH086373] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS034774] Funding Source: NIH RePORTER
NR 50
TC 1896
Z9 2323
U1 7
U2 322
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 171
EP 178
DI 10.1038/nature10360
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900027
PM 21796121
DA 2026-03-09
ER

PT J
AU Solt, LA
   Kumar, N
   Nuhant, P
   Wang, YJ
   Lauer, JL
   Liu, J
   Istrate, MA
   Kamenecka, TM
   Roush, WR
   Vidovic, D
   Schürer, SC
   Xu, JH
   Wagoner, G
   Drew, PD
   Griffin, PR
   Burris, TP
AF Solt, Laura A.
   Kumar, Naresh
   Nuhant, Philippe
   Wang, Yongjun
   Lauer, Janelle L.
   Liu, Jin
   Istrate, Monica A.
   Kamenecka, Theodore M.
   Roush, William R.
   Vidovic, Dusica
   Schuerer, Stephan C.
   Xu, Jihong
   Wagoner, Gail
   Drew, Paul D.
   Griffin, Patrick R.
   Burris, Thomas P.
TI Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand
SO NATURE
LA English
DT Article
ID th17 cell-differentiation; orphan receptor-alpha; rev-erb-alpha; gamma-t; nuclear receptors; mass-spectrometry; target gene; identification; exchange; agonist
AB T-helper cells that produce interleukin-17 (T(H)17 cells) are a recently identified CD4(+) T-cell subset with characterized pathological roles in autoimmune diseases(1-3). The nuclear receptors retinoic-acid-receptor-related orphan receptors alpha and gamma t (ROR alpha and ROR gamma t, respectively) have indispensible roles in the development of this cell type(4-7). Here we present SR1001, a high-affinity synthetic ligand-the first in a new class of compound-that is specific to both ROR alpha and ROR gamma t and which inhibits T(H)17 cell differentiation and function. SR1001 binds specifically to the ligand-binding domains of ROR alpha and ROR gamma t, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. SR1001 inhibited the development of murine T(H)17 cells, as demonstrated by inhibition of interleukin-17A gene expression and protein production. Furthermore, SR1001 inhibited the expression of cytokines when added to differentiated murine or human T(H)17 cells. Finally, SR1001 effectively suppressed the clinical severity of autoimmune disease in mice. Our data demonstrate the feasibility of targeting the orphan receptors ROR alpha and ROR gamma t to inhibit specifically T(H)17 cell differentiation and function, and indicate that this novel class of compound has potential utility in the treatment of autoimmune diseases.
C1 [Solt, Laura A.; Kumar, Naresh; Wang, Yongjun; Lauer, Janelle L.; Liu, Jin; Istrate, Monica A.; Griffin, Patrick R.; Burris, Thomas P.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
   [Kumar, Naresh; Istrate, Monica A.; Vidovic, Dusica; Schuerer, Stephan C.; Griffin, Patrick R.] Scripps Res Inst, Scripps Res Inst Mol Screening Ctr, Jupiter, FL 33458 USA.
   [Nuhant, Philippe; Roush, William R.] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA.
   [Kamenecka, Theodore M.; Griffin, Patrick R.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
   [Vidovic, Dusica; Schuerer, Stephan C.] Univ Miami, Ctr Computat Sci, Miami, FL 33136 USA.
   [Xu, Jihong; Wagoner, Gail; Drew, Paul D.] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA.
C3 State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; University of Miami; University of Arkansas System; University of Arkansas Medical Sciences
RP Burris, TP (corresponding author), Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
EM tburris@scripps.edu
FU NIH [DK080201, DK089984, MH084512, DK088499, GM084041]; National Multiple Sclerosis Society [RG389A2/1]; NIH Molecular Library Screening Center Network (MLSCN) [U54MH074404]
NR 25
TC 436
Z9 527
U1 0
U2 41
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 491
EP U547
DI 10.1038/nature10075
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600038
PM 21499262
DA 2026-03-09
ER

PT J
AU Wei, W
   Hamby, AM
   Zhou, KL
   Feller, MB
AF Wei, Wei
   Hamby, Aaron M.
   Zhou, Kaili
   Feller, Marla B.
TI Development of asymmetric inhibition underlying direction selectivity in the retina
SO NATURE
LA English
DT Article
ID starburst amacrine cells; ganglion-cells; rabbit retina; mouse retina; visual experience; identification; organization; connections; mechanisms; dendrites
AB Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells(1) (SACs) onto four subtypes of ON-OFF direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions(2). It has been reported in rabbit that the SACs on the 'null' sides of DSGCs form functional GABA (c-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not(3). However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.
C1 [Wei, Wei; Hamby, Aaron M.; Zhou, Kaili; Feller, Marla B.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Feller, Marla B.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Feller, MB (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM mfeller@berkeley.edu
FU National Institutes of Health [RO1EY013528, ARRA EY019498]; National Eye Institute [R01EY019498, R01EY013528] Funding Source: NIH RePORTER
NR 30
TC 153
Z9 205
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 JAN 20
PY 2011
VL 469
IS 7330
BP 402
EP +
DI 10.1038/nature09600
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600053
PM 21131947
DA 2026-03-09
ER

PT J
AU da Fonseca, PCA
   Kong, EH
   Zhang, ZG
   Schreiber, A
   Williams, MA
   Morris, EP
   Barford, D
AF da Fonseca, Paula C. A.
   Kong, Eric H.
   Zhang, Ziguo
   Schreiber, Anne
   Williams, Mark. A.
   Morris, Edward P.
   Barford, David
TI Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor
SO NATURE
LA English
DT Article
ID anaphase-promoting complex; destruction box; crystal-structure; cyclin-b; ken box; recognition; subunit; binding; yeast; complex/cyclosome
AB The ubiquitylation of cell-cycle regulatory proteins by the large multimeric anaphase-promoting complex (APC/C) controls sister chromatid segregation and the exit from mitosis(1,2). Selection of APC/C targets is achieved through recognition of destruction motifs, predominantly the destruction (D)-box(3) and KEN (Lys-Glu-Asn)-box(4). Although this process is known to involve a coactivator protein (either Cdc20 or Cdh1) together with core APC/C subunits(1,2), the structural basis for substrate recognition and ubiquitylation is not understood. Here we investigate budding yeast APC/C using single-particle electron microscopy and determine a cryo-electron microscopy map of APC/C in complex with the Cdh1 co-activator protein (APC/C-Cdh1) bound to a D-box peptide at similar to 10 angstrom resolution. We find that a combined catalytic and substrate-recognition module is located within the central cavity of the APC/C assembled from Cdh1, Apc10-a core APC/C subunit previously implicated in substrate recognition(5-7)-and the cullin domain of Apc2. Cdh1 and Apc10, identified from difference maps, create a co-receptor for the D-box following repositioning of Cdh1 towards Apc10. Using NMR spectroscopy we demonstrate specific D-box-Apc10 interactions, consistent with a role for Apc10 in directly contributing towards D-box recognition by the APC/C-Cdh1 complex. Our results rationalize the contribution of both co-activator and core APC/C subunits to D-box recognition(8,9) and provide a structural framework for understanding mechanisms of substrate recognition and catalysis by the APC/C.
C1 [da Fonseca, Paula C. A.; Kong, Eric H.; Zhang, Ziguo; Schreiber, Anne; Morris, Edward P.; Barford, David] Chester Beatty Labs, Inst Canc Res, Sect Struct Biol, London SW3 6JB, England.
   [Williams, Mark. A.] Univ London, Dept Biol Sci, Inst Struct & Mol Biol, London WC1E 7HX, England.
C3 Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; University of London; Birkbeck University London
RP Barford, D (corresponding author), Chester Beatty Labs, Inst Canc Res, Sect Struct Biol, 237 Fulham Rd, London SW3 6JB, England.
EM david.barford@icr.ac.uk
FU Cancer Research UK
NR 38
TC 163
Z9 208
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 274
EP +
DI 10.1038/nature09625
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200047
PM 21107322
DA 2026-03-09
ER

PT J
AU Bakr, WS
   Preiss, PM
   Tai, ME
   Ma, RC
   Simon, J
   Greiner, M
AF Bakr, Waseem S.
   Preiss, Philipp M.
   Tai, M. Eric
   Ma, Ruichao
   Simon, Jonathan
   Greiner, Markus
TI Orbital excitation blockade and algorithmic cooling in quantum gases
SO NATURE
LA English
DT Article
ID mott insulator; optical lattices; rydberg blockade; atoms; transition; superfluid; physics
AB Interaction blockade occurs when strong interactions in a confined, few-body system prevent a particle from occupying an otherwise accessible quantum state. Blockade phenomena reveal the underlying granular nature of quantum systems and allow for the detection and manipulation of the constituent particles, be they electrons(1), spins(2), atoms(3-5) or photons(6). Applications include single-electron transistors based on electronic Coulomb blockade(7) and quantum logic gates in Rydberg atoms(8,9). Here we report a form of interaction blockade that occurs when transferring ultracold atoms between orbitals in an optical lattice. We call this orbital excitation blockade (OEB). In this system, atoms at the same lattice site undergo coherent collisions described by a contact interaction whose strength depends strongly on the orbital wavefunctions of the atoms. We induce coherent orbital excitations by modulating the lattice depth, and observe staircase-like excitation behaviour as we cross the interaction-split resonances by tuning the modulation frequency. As an application of OEB, we demonstrate algorithmic cooling(10,11) of quantum gases: a sequence of reversible OEB-based quantum operations isolates the entropy in one part of the system and then an irreversible step removes the entropy from the gas. This technique may make it possible to cool quantum gases to have the ultralow entropies required for quantum simulation(12,13) of strongly correlated electron systems. In addition, the close analogy between OEB and dipole blockade in Rydberg atoms provides a plan for the implementation of two-quantum-bit gates(14) in a quantum computing architecture with natural scalability.
C1 [Bakr, Waseem S.; Preiss, Philipp M.; Tai, M. Eric; Ma, Ruichao; Simon, Jonathan; Greiner, Markus] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University
RP Greiner, M (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM greiner@physics.harvard.edu
FU US Army Research Office; DARPA OLE; AFOSR MURI; US NSF; Division Of Physics; Direct For Mathematical & Physical Scien [0969772] Funding Source: National Science Foundation
NR 31
TC 81
Z9 96
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 500
EP U118
DI 10.1038/nature10668
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000055
PM 22193104
DA 2026-03-09
ER

PT J
AU Hothorn, M
   Belkhadir, Y
   Dreux, M
   Dabi, T
   Noel, JP
   Wilson, IA
   Chory, J
AF Hothorn, Michael
   Belkhadir, Youssef
   Dreux, Marlene
   Dabi, Tsegaye
   Noel, Joseph. P.
   Wilson, Ian A.
   Chory, Joanne
TI Structural basis of steroid hormone perception by the receptor kinase BRI1
SO NATURE
LA English
DT Article
ID rich repeat protein; extracellular domain; crystal-structure; brassinosteroids; complex; bak1; recognition; activation; bri1/bak1; mutant
AB Polyhydroxylated steroids are regulators of body shape and size in higher organisms. In metazoans, intracellular receptors recognize these molecules. Plants, however, perceive steroids at membranes, using the membrane-integral receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Here we report the structure of the Arabidopsis thaliana BRI1 ligand-binding domain, determined by X-ray diffraction at 2.5 angstrom resolution. We find a superhelix of 25 twisted leucine-rich repeats (LRRs), an architecture that is strikingly different from the assembly of LRRs in animal Toll-like receptors. A 70-amino-acid island domain between LRRs 21 and 22 folds back into the interior of the superhelix to create a surface pocket for binding the plant hormone brassinolide. Known loss- and gain-of-function mutations map closely to the hormone-binding site. We propose that steroid binding to BRI1 generates a docking platform for a co-receptor that is required for receptor activation. Our findings provide insight into the activation mechanism of this highly expanded family of plant receptors that have essential roles in hormone, developmental and innate immunity signalling.
C1 [Hothorn, Michael; Belkhadir, Youssef; Dabi, Tsegaye; Chory, Joanne] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Belkhadir, Youssef; Dabi, Tsegaye; Noel, Joseph. P.; Chory, Joanne] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Dreux, Marlene] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Noel, Joseph. P.] Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Prote, La Jolla, CA 92037 USA.
   [Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Salk Institute; Howard Hughes Medical Institute; Salk Institute; Scripps Research Institute; Salk Institute; Scripps Research Institute; Scripps Research Institute
RP Chory, J (corresponding author), Salk Inst Biol Studies, Plant Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM chory@salk.edu
FU Howard Hughes Medical Institute; National Science Foundation [IOS-0649389]; European Molecular Biology Organisation; International Human Frontier Science Program Organisation; Philippe Foundation; NIH [AI042266]; Skaggs Institute for Chemical Biology
NR 50
TC 327
Z9 394
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 JUN 23
PY 2011
VL 474
IS 7352
BP 467
EP U90
DI 10.1038/nature10153
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700039
PM 21666665
DA 2026-03-09
ER

PT J
AU O'Sullivan, MC
   Sprafke, JK
   Kondratuk, DV
   Rinfray, C
   Claridge, TDW
   Saywell, A
   Blunt, MO
   O'Shea, JN
   Beton, PH
   Malfois, M
   Anderson, HL
AF O'Sullivan, Melanie C.
   Sprafke, Johannes K.
   Kondratuk, Dmitry V.
   Rinfray, Corentin
   Claridge, Timothy D. W.
   Saywell, Alex
   Blunt, Matthew O.
   O'Shea, James N.
   Beton, Peter H.
   Malfois, Marc
   Anderson, Harry L.
TI Vernier templating and synthesis of a 12-porphyrin nano-ring
SO NATURE
LA English
DT Article
ID crystal-structure; energy-transfer; pi conjugation; porphyrin; giant; assembly; antenna; complex; arrays
AB Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods(1-7). Nature uses sophisticated templates such as the ribosome, whereas chemists use simple ions or small molecules. But as we tackle the synthesis of larger targets, we require larger templates-which themselves become synthetically challenging. Here we show that Vernier complexes can solve this problem: if the number of binding sites on the template, n(T), is not a multiple of the number of binding sites on the molecular building blocks, n(B), then small templates can direct the assembly of relatively large Vernier complexes where the number of binding sites in the product, n(P), is the lowest common multiple of n(B) and n(T) (refs 8, 9). We illustrate the value of this concept for the covalent synthesis of challenging targets by using a simple six-site template to direct the synthesis of a 12-porphyrin nano-ring with a diameter of 4.7 nm, thus establishing Vernier templating as a powerful new strategy for the synthesis of large monodisperse macromolecules.
C1 [O'Sullivan, Melanie C.; Sprafke, Johannes K.; Kondratuk, Dmitry V.; Rinfray, Corentin; Claridge, Timothy D. W.; Anderson, Harry L.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
   [Saywell, Alex; Blunt, Matthew O.; O'Shea, James N.; Beton, Peter H.] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Malfois, Marc] Diamond Light Source Ltd, Didcot OX11 0DE, Oxon, England.
C3 University of Oxford; University of Nottingham; Diamond Light Source
RP Anderson, HL (corresponding author), Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England.
EM harry.anderson@chem.ox.ac.uk
FU Engineering and Physical Sciences Research Council (EPSRC); Diamond Light Source; European Commission [MRTN-CT-2006-036040, THREADMILL]; Clarendon Fund; EPSRC [EP/D076552/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/D076552/1] Funding Source: researchfish
NR 22
TC 377
Z9 405
U1 3
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 JAN 6
PY 2011
VL 469
IS 7328
BP 72
EP 75
DI 10.1038/nature09683
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600033
PM 21209660
DA 2026-03-09
ER

PT J
AU Bartels, T
   Choi, JG
   Selkoe, DJ
AF Bartels, Tim
   Choi, Joanna G.
   Selkoe, Dennis J.
TI α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation
SO NATURE
LA English
DT Article
ID parkinsons-disease; binding; neurodegeneration; mutations; complexes; proteins
AB Parkinson's disease is the second most common neurodegenerative disorder(1,2). Growing evidence indicates a causative role of misfolded forms of the protein alpha-synuclein in the pathogenesis of Parkinson's disease(3,4). Intraneuronal aggregates of alpha-synuclein occur in Lewy bodies and Lewy neurites(5), the cytopathological hallmarks of Parkinson's disease and related disorders called synucleinopathies(4). alpha-Synuclein has long been defined as a 'natively unfolded' monomer of about 14 kDa (ref. 6) that is believed to acquire alpha-helical secondary structure only upon binding to lipid vesicles(7). This concept derives from the widespread use of recombinant bacterial expression protocols for in vitro studies, and of overexpression, sample heating and/or denaturing gels for cell culture and tissue studies. In contrast, we report that endogenous alpha-synuclein isolated and analysed under non-denaturing conditions from neuronal and non-neuronal cell lines, brain tissue and living human cells occurs in large part as a folded tetramer of about 58 kDa. Several methods, including analytical ultracentrifugation, scanning transmission electron microscopy and in vitro cell crosslinking confirmed the occurrence of the tetramer. Native, cell-derived alpha-synuclein showed alpha-helical structure without lipid addition and had much greater lipid-binding capacity than the recombinant alpha-synuclein studied heretofore. Whereas recombinantly expressed monomers readily aggregated intoamyloid-like fibrilsin vitro, native human tetramers underwent little or no amyloid-like aggregation. On the basis of these findings, we propose that destabilization of the helically folded tetramer precedes alpha-synuclein misfolding and aggregation in Parkinson's disease and other human synucleinopathies, and that small molecules that stabilize the physiological tetramer could reduce alpha-synuclein pathogenicity.
C1 [Bartels, Tim; Choi, Joanna G.; Selkoe, Dennis J.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Bartels, Tim; Choi, Joanna G.; Selkoe, Dennis J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Selkoe, DJ (corresponding author), Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
EM dselkoe@rics.bwh.harvard.edu
FU NIH [NS051318, NS038375]
NR 24
TC 1051
Z9 1264
U1 11
U2 369
PU 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 1
PY 2011
VL 477
IS 7362
BP 107
EP U123
DI 10.1038/nature10324
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300041
PM 21841800
DA 2026-03-09
ER

PT J
AU Gaensler, BM
   Haverkorn, M
   Burkhart, B
   Newton-McGee, KJ
   Ekers, RD
   Lazarian, A
   McClure-Griffiths, NM
   Robishaw, T
   Dickey, JM
   Green, AJ
AF Gaensler, B. M.
   Haverkorn, M.
   Burkhart, B.
   Newton-McGee, K. J.
   Ekers, R. D.
   Lazarian, A.
   McClure-Griffiths, N. M.
   Robishaw, T.
   Dickey, J. M.
   Green, A. J.
TI Low-Mach-number turbulence in interstellar gas revealed by radio polarization gradients
SO NATURE
LA English
DT Article
ID galactic plane survey; h-alpha survey; magnetohydrodynamic turbulence; depolarization canals; mhd turbulence; density; simulations; emission; ism; anisotropy
AB The interstellar medium of the Milky Way is multiphase(1), magnetized(2) and turbulent(3). Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from 100 parsecs to 1,000 kilometres (ref. 4). Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine, because observations have lacked the sensitivity and resolution to image the small-scale structure associated with turbulent motion(5-7). Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths(8-12), and whose physical significance has been unclear(13-15). Here we report that the gradient of the Stokes vector (Q, U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse, ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm, ionized medium has a relatively low sonic Mach number, M-s less than or similar to 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions.
C1 [Gaensler, B. M.; Newton-McGee, K. J.; Robishaw, T.; Green, A. J.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
   [Haverkorn, M.] ASTRON, NL-7991 PD Dwingeloo, Netherlands.
   [Haverkorn, M.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Haverkorn, M.] Radboud Univ Nijmegen, Dept Astrophys, IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Burkhart, B.; Lazarian, A.] Univ Wisconsin, Dept Astron, Madison, WI 53711 USA.
   [Newton-McGee, K. J.; Ekers, R. D.; McClure-Griffiths, N. M.] CSIRO Astron & Space Sci, Australia Telescope Natl Facil, Epping, NSW 1710, Australia.
   [Dickey, J. M.] Univ Tasmania, Sch Math & Phys, Hobart, Tas 7001, Australia.
C3 University of Sydney; Leiden University - Excl LUMC; Leiden University; Radboud University Nijmegen; University of Wisconsin System; University of Wisconsin Madison; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; Australia Telescope National Facility; University of Tasmania
RP Gaensler, BM (corresponding author), Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
EM bryan.gaensler@sydney.edu.au
FU Commonwealth of Australia; Australian Research Council [FF0561298, FL100100114, FS100100033]; National Science Foundation [AST0808118]; NASA Wisconsin Space Grant Institution; Center for Magnetic Self-Organization in Astrophysical and Laboratory Plasmas; Australian Research Council [FS100100033] Funding Source: Australian Research Council
NR 30
TC 150
Z9 159
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 13
PY 2011
VL 478
IS 7368
BP 214
EP 217
DI 10.1038/nature10446
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800043
PM 21976022
DA 2026-03-09
ER

PT J
AU Gravel, D
   Bell, T
   Barbera, C
   Bouvier, T
   Pommier, T
   Venail, P
   Mouquet, N
AF Gravel, Dominique
   Bell, Thomas
   Barbera, Claire
   Bouvier, Thierry
   Pommier, Thomas
   Venail, Patrick
   Mouquet, Nicolas
TI Experimental niche evolution alters the strength of the diversity-productivity relationship
SO NATURE
LA English
DT Article
ID pseudomonas-fluorescens; ecosystem productivity; plant diversity; biodiversity; generalists; assemblages; specialists; resource; services; model
AB The relationship between biodiversity and ecosystem functioning (BEF) has become a cornerstone of community and ecosystem ecology(1-3) and an essential criterion for making decisions in conservation biology and policy planning(4,5). It has recently been proposed that evolutionary history should influence the BEF relationship because it determines species traits and, thus, species' ability to exploit resources(6,7). Here we test this hypothesis by combining experimental evolution with a BEF experiment. We isolated 20 bacterial strains from a marine environment and evolved each to be generalists or specialists(8). We then tested the effect of evolutionary history on the strength of the BEF relationship with assemblages of 1 to 20 species constructed from the specialists, generalists and ancestors(9). Assemblages of generalists were more productive on average because of their superior ability to exploit the environmental heterogeneity(10). The slope of the BEF relationship was, however, stronger for the specialist assemblages because of enhanced niche complementarity. These results show how the BEF relationship depends critically on the legacy of past evolutionary events.
C1 [Gravel, Dominique] Univ Quebec, Dept Biol Chim & Geog, Rimouski, PQ G5L 3A1, Canada.
   [Gravel, Dominique; Barbera, Claire; Venail, Patrick; Mouquet, Nicolas] Univ Montpellier 2, CNRS, Inst Sci Evolut UMR 5554, F-34095 Montpellier 05, France.
   [Bell, Thomas] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Bouvier, Thierry; Pommier, Thomas] Univ Montpellier 2, CNRS, Ecosyst Langunaires UMR 5119, F-34095 Montpellier 05, France.
   [Pommier, Thomas] Univ Lyon 1, CNRS, INRA, UMR 5557,USC 1193,Lab Ecol Microbienne, F-69622 Villeurbanne, France.
C3 University of Quebec; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; University of Oxford; Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; VetAgro Sup; INRAE
RP Gravel, D (corresponding author), Univ Quebec, Dept Biol Chim & Geog, 300 Alee Ursulines, Rimouski, PQ G5L 3A1, Canada.
EM dominique_gravel@uqar.qc.ca; nmouquet@univ-montp2.fr
FU Natural Sciences and Engineering Research Council of Canada; Canada Research Chair Program;  [ANR-09-JCJC-0110-01]
NR 38
TC 170
Z9 194
U1 5
U2 224
PU 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 6
PY 2011
VL 469
IS 7328
BP 89
EP U1601
DI 10.1038/nature09592
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600037
PM 21131946
DA 2026-03-09
ER

PT J
AU Hibbs, RE
   Gouaux, E
AF Hibbs, Ryan E.
   Gouaux, Eric
TI Principles of activation and permeation in an anion-selective Cys-loop receptor
SO NATURE
LA English
DT Article
ID x-ray-structure; nicotinic acetylcholine-receptor; gated chloride channel; neuromuscular-junction; crystal-structure; binding protein; ligand-binding; ion channels; subunit; ivermectin
AB Fast inhibitory neurotransmission is essential for nervous system function and is mediated by binding of inhibitory neurotransmitters to receptors of the Cys-loop family embedded in the membranes of neurons. Neurotransmitter binding triggers a conformational change in the receptor, opening an intrinsic chloride channel and thereby dampening neuronal excitability. Here we present the first three-dimensional structure, to our knowledge, of an inhibitory anion-selective Cys-loop receptor, the homopentameric Caenorhabditis elegans glutamate-gated chloride channel alpha (GluCl), at 3.3 angstrom resolution. The X-ray structure of the GluCl-Fab complex was determined with the allosteric agonist ivermectin and in additional structures with the endogenous neurotransmitter L-glutamate and the open-channel blocker picrotoxin. Ivermectin, used to treat river blindness, binds in the transmembrane domain of the receptor and stabilizes an open-pore conformation. Glutamate binds in the classical agonist site at subunit interfaces, and picrotoxin directly occludes the pore near its cytosolic base. GluCl provides a framework for understanding mechanisms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors.
C1 [Hibbs, Ryan E.; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Howard Hughes Medical Institute
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU NIH [F32NS061404]
NR 78
TC 854
Z9 956
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 JUN 2
PY 2011
VL 474
IS 7349
BP 54
EP U80
DI 10.1038/nature10139
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700035
PM 21572436
DA 2026-03-09
ER

PT J
AU Sobolev, AV
   Hofmann, AW
   Jochum, KP
   Kuzmin, DV
   Stoll, B
AF Sobolev, Alexander V.
   Hofmann, Albrecht W.
   Jochum, Klaus Peter
   Kuzmin, Dmitry V.
   Stoll, Brigitte
TI A young source for the Hawaiian plume
SO NATURE
LA English
DT Article
ID melt inclusions; oceanic-crust; mantle; pb; evolution; basalts; heterogeneity; sr-87/sr-86; enrichment; olivine
AB Recycling of oceanic crust through subduction, mantle upwelling, and remelting in mantle plumes is a widely accepted mechanism to explain ocean island volcanism(1). The timescale of this recycling is important to our understanding of mantle circulation rates. Correlations of uranogenic lead isotopes in lavas from ocean islands such as Hawaii or Iceland, when interpreted as model isochrons, have yielded source differentiation ages between 1 and 2.5 billion years (Gyr)(2-5). However, if such correlations are produced by mixing of unrelated mantle components(6) they will have no direct age significance. Re-Os decay model ages take into account the mixing of sources with different histories(7,8), but they depend on the assumed initial Re/Os ratio of the subducted crust, which is poorly constrained because of the high mobility of rhenium during subduction(9). Here we report the first data on Sr-87/Sr-86 ratios for 138 melt inclusions in olivine phenocrysts from lavas of Mauna Loa shield volcano, Hawaii, indicating enormous mantle source heterogeneity. We show that highly radiogenic strontium in severely rubidium-depleted melt inclusions matches the isotopic composition of 200-650-Myr-old sea water. We infer that such sea water must have contaminated the Mauna Loa source rock, before subduction, imparting a unique 'time stamp' on this source. Small amounts of seawater-derived strontium in plume sources may be common but can be identified clearly only in ultra-depleted melts originating from generally highly (incompatible-element) depleted source components. The presence of 200-650-Myr-old oceanic crust in the source of Hawaiian lavas implies a timescale of general mantle circulation with an average rate of about 2 (+/- 1) cm yr(-1), much faster than previously thought. [GRAPHICS] .
C1 [Sobolev, Alexander V.] Univ Grenoble 1, ISTerre, F-38041 Grenoble, France.
   [Sobolev, Alexander V.] CNRS, F-38041 Grenoble, France.
   [Sobolev, Alexander V.; Hofmann, Albrecht W.; Jochum, Klaus Peter; Kuzmin, Dmitry V.; Stoll, Brigitte] Max Planck Inst Chem, D-55020 Mainz, Germany.
   [Sobolev, Alexander V.] Russian Acad Sci, VI Vernadskii Inst Geochem & Analyt Chem, Moscow 119991, Russia.
   [Hofmann, Albrecht W.] Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Kuzmin, Dmitry V.] Russian Acad Sci, Siberian Branch, VS Sobolev Inst Geol & Mineral, Novosibirsk 630090, Russia.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Gustave-Eiffel; Universite Savoie Mont Blanc; Centre National de la Recherche Scientifique (CNRS); Max Planck Society; Russian Academy of Sciences; Vernadsky Institute of Geochemistry & Analytical Chemistry; Columbia University; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Sobolev Institute of Geology & Mineralogy of the Russian Academy of Sciences
RP Sobolev, AV (corresponding author), Univ Grenoble 1, ISTerre, BP 53, F-38041 Grenoble, France.
EM alexander.sobolev@ujf-grenoble.fr
FU Agence Nationale de la Recherche, France, Chair of Excellence [ANR-09-CEXC-003-01]; Russian Foundation for Basic Research [09-05-01193a]; Russian President grant for leading Russian scientific schools [HIII-3919.2010.5]; Earth Sciences Department of Russian Academy
NR 38
TC 88
Z9 103
U1 1
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 434
EP 437
DI 10.1038/nature10321
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400032
PM 21832996
DA 2026-03-09
ER

PT J
AU Crosnier, C
   Bustamante, LY
   Bartholdson, SJ
   Bei, AK
   Theron, M
   Uchikawa, M
   Mboup, S
   Ndir, O
   Kwiatkowski, DP
   Duraisingh, MT
   Rayner, JC
   Wright, GJ
AF Crosnier, Cecile
   Bustamante, Leyla Y.
   Bartholdson, S. Josefin
   Bei, Amy K.
   Theron, Michel
   Uchikawa, Makoto
   Mboup, Souleymane
   Ndir, Omar
   Kwiatkowski, Dominic P.
   Duraisingh, Manoj T.
   Rayner, Julian C.
   Wright, Gavin J.
TI Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum
SO NATURE
LA English
DT Article
ID genome-wide; association analysis; interaction network; genetic-analysis; malaria; selection; molecule; homolog; ligand; cells
AB Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor-ligand interactions involved(1-4) are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways(5). Here, we show that we have identified a receptor-ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth(6). Erythrocyte invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Ok(a-) erythrocytes, which express a basigin variant that has a weaker binding affinity for PfRh5, had reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor-ligand pair for erythrocyte invasion by P. falciparum provides a focus for new anti-malarial therapies.
C1 [Crosnier, Cecile; Bartholdson, S. Josefin; Wright, Gavin J.] Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge CB10 1HH, England.
   [Bustamante, Leyla Y.; Theron, Michel; Kwiatkowski, Dominic P.; Rayner, Julian C.; Wright, Gavin J.] Wellcome Trust Sanger Inst, Malaria Programme, Cambridge CB10 1SA, England.
   [Bei, Amy K.; Duraisingh, Manoj T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Uchikawa, Makoto] Tokyo Red Cross Blood Ctr, Tokyo 1358639, Japan.
   [Mboup, Souleymane; Ndir, Omar] Cheikh Anta Diop Univ, La Dantec Hosp, Lab Bacteriol & Virol, Dakar, Senegal.
   [Mboup, Souleymane; Ndir, Omar] Cheikh Anta Diop Univ, Parasitol Lab, Dakar, Senegal.
   [Kwiatkowski, Dominic P.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
C3 Wellcome Trust Sanger Institute; Wellcome Trust Sanger Institute; Harvard University; Harvard T.H. Chan School of Public Health; University Cheikh Anta Diop Dakar; University Cheikh Anta Diop Dakar; University of Oxford; Wellcome Centre for Human Genetics
RP Wright, GJ (corresponding author), Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge CB10 1HH, England.
EM jr9@sanger.ac.uk; gw2@sanger.ac.uk
FU Wellcome Trust [077108, 089084]; National Institutes of Health [R01AI057919]; Center for Disease Control [R36 CK000119-01]; Epidemiology of Infectious Disease and Biodefense Training Grant [2T32 AI007535-12]; MRC [G19/9] Funding Source: UKRI; Medical Research Council [G19/9, G0600718B] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [T32AI007535] Funding Source: NIH RePORTER
NR 32
TC 509
Z9 609
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 534
EP U158
DI 10.1038/nature10606
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000063
PM 22080952
DA 2026-03-09
ER

PT J
AU Yamada, K
   Frouws, TD
   Angst, B
   Fitzgerald, DJ
   DeLuca, C
   Schimmele, K
   Sargent, DF
   Richmond, TJ
AF Yamada, Kazuhiro
   Frouws, Timothy D.
   Angst, Brigitte
   Fitzgerald, Daniel J.
   DeLuca, Carl
   Schimmele, Kyoko
   Sargent, David F.
   Richmond, Timothy J.
TI Structure and mechanism of the chromatin remodelling factor ISW1a
SO NATURE
LA English
DT Article
ID nucleosome core particle; high-resolution; crystal-structure; dna complex; organization; expression; position; protein; domain; visualization
AB Site-specific recognition of DNA in eukaryotic organisms depends on the arrangement of nucleosomes in chromatin. In the yeast Saccharomyces cerevisiae, ISW1a and related chromatin remodelling factors are implicated in establishing the nucleosome repeat during replication and altering nucleosome position to affect gene activity. Here we have solved the crystal structures of S. cerevisiae ISW1a lacking its ATPase domain both alone and with DNA bound at resolutions of 3.25 angstrom and 3.60 angstrom, respectively, and we have visualized two different nucleosome-containing remodelling complexes using cryo-electron microscopy. The composite X-ray and electron microscopy structures combined with site-directed photocrosslinking analyses of these complexes suggest that ISW1a uses a dinucleosome substrate for chromatin remodelling. Results from a remodelling assay corroborate the dinucleosome model. We show how a chromatin remodelling factor could set the spacing between two adjacent nucleosomes acting as a 'protein ruler'.
C1 [Yamada, Kazuhiro; Frouws, Timothy D.; Angst, Brigitte; Fitzgerald, Daniel J.; DeLuca, Carl; Schimmele, Kyoko; Sargent, David F.; Richmond, Timothy J.] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Richmond, TJ (corresponding author), ETH, Inst Mol Biol & Biophys, Schafmattstr 20, CH-8093 Zurich, Switzerland.
EM richmond@mol.biol.ethz.ch
NR 55
TC 142
Z9 165
U1 1
U2 28
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 448
EP U536
DI 10.1038/nature09947
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600029
PM 21525927
DA 2026-03-09
ER

PT J
AU Usherwood, JR
   Stavrou, M
   Lowe, JC
   Roskilly, K
   Wilson, AM
AF Usherwood, James R.
   Stavrou, Marinos
   Lowe, John C.
   Roskilly, Kyle
   Wilson, Alan M.
TI Flying in a flock comes at a cost in pigeons
SO NATURE
LA English
DT Article
ID vortex theory; flight; frequency; birds; drag
AB Flying birds often form flocks, with social(1), navigational(2) and antipredator(3) implications. Further, flying in a flock can result in aerodynamic benefits, thus reducing power requirements(4), as demonstrated by a reduction in heart rate and wingbeat frequency in pelicans flying in a V-formation(5). But how general is an aerodynamic power reduction due to group-flight? V-formation flocks are limited to moderately steady flight in relatively large birds, and may represent a special case. What are the aerodynamic consequences of flying in the more usual 'cluster'(6,7) flock? Here we use data from innovative back-mounted Global Positioning System (GPS) and 6-degrees-of-freedom inertial sensors to show that pigeons (1) maintain powered, banked turns like aircraft, imposing dorsal accelerations of up to 2g, effectively doubling body weight and quadrupling induced power requirements; (2) increase flap frequency with increases in all conventional aerodynamic power requirements; and (3) increase flap frequency when flying near, particularly behind, other birds. Therefore, unlike V-formation pelicans, pigeons do not gain an aerodynamic advantage from flying in a flock. Indeed, the increased flap frequency, whether due to direct aerodynamic interactions or requirements for increased stability or control, suggests a considerable energetic cost to flight in a tight cluster flock.
C1 [Usherwood, James R.; Stavrou, Marinos; Lowe, John C.; Roskilly, Kyle; Wilson, Alan M.] Univ London, Struct & Mot Lab, Royal Vet Coll, Hatfield AL9 7TA, Herts, England.
C3 University of London; University of London Royal Veterinary College
RP Usherwood, JR (corresponding author), Univ London, Struct & Mot Lab, Royal Vet Coll, Hatfield AL9 7TA, Herts, England.
EM jusherwood@rvc.ac.uk
FU Wellcome Trust; Royal Society; BBSRC; EPSRC; EPSRC [EP/H013016/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H013016/1] Funding Source: researchfish
NR 23
TC 114
Z9 127
U1 1
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 23
PY 2011
VL 474
IS 7352
BP 494
EP 497
DI 10.1038/nature10164
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700045
PM 21697946
DA 2026-03-09
ER

PT J
AU Sun, G
   Dilcher, DL
   Wang, HS
   Chen, ZD
AF Sun, Ge
   Dilcher, David L.
   Wang, Hongshan
   Chen, Zhiduan
TI A eudicot from the Early Cretaceous of China
SO NATURE
LA English
DT Article
ID jurassic angiosperm; yixian formation; fossil evidence; age; flower; nov.
AB The current molecular systematics of angiosperms(1) recognizes the basal angiosperms and five major angiosperm lineages: the Chloranthaceae, the magnoliids, the monocots, Ceratophyllum and the eudicots, which consist of the basal eudicots and the core eudicots(2). The eudicots form the majority of the angiosperms in the world today. The flowering plants are of exceptional evolutionary interest because of their diversity of over 250,000 species and their abundance as the dominant vegetation in most terrestrial ecosystems, but little is known of their very early history. In this report we document an early presence of eudicots during the Early Cretaceous Period. Diagnostic characters of the eudicot fossil Leefructus gen. nov. include simple and deeply trilobate leaves clustered at the nodes in threes or fours, basal palinactinodromous primary venation, pinnate secondary venation, and a long axillary reproductive axis terminating in a flattened receptacle bearing five long, narrow pseudo-syncarpous carpels. These morphological characters suggest that its affinities are with the Ranunculaceae, a basal eudicot family. The fossil co-occurs with Archaefructus sinensis(3) and Hyrcantha decussata(4) whereas Archaefructus liaoningensis(5) comes from more ancient sediments. Multiple radiometric dates of the Lower Cretaceous Yixian Formation place the bed yielding this fossil at 122.6-125.8 million years old(6-8). The earliest fossil records of eudicots are 127 to 125 million years old, on the basis of pollen(9,10). Thus, Leefructus gen. nov. suggests that the basal eudicots were already present and diverse by the latest Barremian and earliest Aptian.
C1 [Sun, Ge; Dilcher, David L.; Wang, Hongshan] Shenyang Normal Univ, Inst Paleontol, Shenyang 110034, Peoples R China.
   [Sun, Ge; Dilcher, David L.] Jilin Univ, Res Ctr Paleontol, Changchun 130026, Peoples R China.
   [Dilcher, David L.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Wang, Hongshan] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [Chen, Zhiduan] Chinese Acad Sci, Inst Bot, State Key Lab Systemat & Evolutionary Bot, Beijing 100093, Peoples R China.
C3 Shenyang Normal University; Jilin University; Indiana University System; Indiana University Bloomington; State University System of Florida; University of Florida; Chinese Academy of Sciences; Institute of Botany, CAS
RP Sun, G (corresponding author), Shenyang Normal Univ, Inst Paleontol, Shenyang 110034, Peoples R China.
EM sunge@synu.edu.cn; dilcher@indiana.edu
FU Key Lab of Evolution of Past Life and Environment in Northeast Asia, Ministry of Education, China; Project "111'' of China; NSFC [40842002]
NR 30
TC 107
Z9 126
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 MAR 31
PY 2011
VL 471
IS 7340
BP 625
EP 628
DI 10.1038/nature09811
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200040
PM 21455178
DA 2026-03-09
ER

PT J
AU Frezza, C
   Zheng, L
   Folger, O
   Rajagopalan, KN
   MacKenzie, ED
   Jerby, L
   Micaroni, M
   Chaneton, B
   Adam, J
   Hedley, A
   Kalna, G
   Tomlinson, IPM
   Pollard, PJ
   Watson, DG
   Deberardinis, RJ
   Shlomi, T
   Ruppin, E
   Gottlieb, E
AF Frezza, Christian
   Zheng, Liang
   Folger, Ori
   Rajagopalan, Kartik N.
   MacKenzie, Elaine D.
   Jerby, Livnat
   Micaroni, Massimo
   Chaneton, Barbara
   Adam, Julie
   Hedley, Ann
   Kalna, Gabriela
   Tomlinson, Ian P. M.
   Pollard, Patrick J.
   Watson, Dave G.
   Deberardinis, Ralph J.
   Shlomi, Tomer
   Ruppin, Eytan
   Gottlieb, Eyal
TI Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
SO NATURE
LA English
DT Article
ID renal-cancer; models; cells; reconstruction; protein; assay
AB Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC)(1). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions(2-4). However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells nonviable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.
C1 [Frezza, Christian; Zheng, Liang; MacKenzie, Elaine D.; Chaneton, Barbara; Hedley, Ann; Kalna, Gabriela; Gottlieb, Eyal] Beatson Inst Canc Res, Canc Res UK, Glasgow G61 1BD, Lanark, Scotland.
   [Folger, Ori; Jerby, Livnat; Ruppin, Eytan] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel.
   [Rajagopalan, Kartik N.; Deberardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Rajagopalan, Kartik N.; Deberardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
   [Micaroni, Massimo] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Tomlinson, Ian P. M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Mol & Populat Genet Lab, Oxford OX3 7BN, England.
   [Watson, Dave G.] Univ Strathclyde, Strathclyde Inst Pharmaceut & Biomed Sci, Glasgow G4 0NR, Lanark, Scotland.
   [Shlomi, Tomer] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
   [Ruppin, Eytan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
C3 Cancer Research UK; Beatson Institute; Tel Aviv University; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Queensland; University of Oxford; Wellcome Centre for Human Genetics; University of Strathclyde; Technion Israel Institute of Technology; Tel Aviv University; Sackler Faculty of Medicine
RP Gottlieb, E (corresponding author), Beatson Inst Canc Res, Canc Res UK, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.
EM e.gottlieb@beatson.gla.ac.uk
FU Cancer Research UK; EMBO [ALTF330]; Wellcome Trust [WT091112MA]; NIH [DK072565-05]; Cancer Prevention and Research Institute of Texas [HIRP100437-01]; Israel Science Foundation (ISF); Israel Cancer Research Foundation; Edmond J. Safra Bioinformatics program at TAU
NR 24
TC 411
Z9 460
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 SEP 8
PY 2011
VL 477
IS 7363
BP 225
EP U132
DI 10.1038/nature10363
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900039
PM 21849978
DA 2026-03-09
ER

PT J
AU Pang, ZPP
   Yang, N
   Vierbuchen, T
   Ostermeier, A
   Fuentes, DR
   Yang, TQ
   Citri, A
   Sebastiano, V
   Marro, S
   Südhof, TC
   Wernig, M
AF Pang, Zhiping P.
   Yang, Nan
   Vierbuchen, Thomas
   Ostermeier, Austin
   Fuentes, Daniel R.
   Yang, Troy Q.
   Citri, Ami
   Sebastiano, Vittorio
   Marro, Samuele
   Suedhof, Thomas C.
   Wernig, Marius
TI Induction of human neuronal cells by defined transcription factors
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; neural development; differentiation; fibroblasts; blastocyst; pax6
AB Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types(1-12). We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells(13). Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.
C1 [Yang, Nan; Vierbuchen, Thomas; Ostermeier, Austin; Fuentes, Daniel R.; Yang, Troy Q.; Sebastiano, Vittorio; Marro, Samuele; Wernig, Marius] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, Stanford, CA 94305 USA.
   [Pang, Zhiping P.; Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Vierbuchen, Thomas; Ostermeier, Austin; Wernig, Marius] Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA.
   [Citri, Ami] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Wernig, M (corresponding author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, 265 Campus Dr, Stanford, CA 94305 USA.
EM wernig@stanford.edu
FU Institute for Stem Cell Biology and Regenerative Medicine at Stanford; Ellison Medical Foundation; Stinehard-Reed Foundation; Donald E. and Delia B. Baxter Foundation; NIH [1R01MH092931, RC4NS073015]; New York Stem Cell Foundation; NARSAD Young Investigator Awards; Ruth and Robert Halperin Stanford Graduate Fellowship; AXA research fund; BioX Undergraduate Fellowship; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of Mental Health [R01MH092931] Funding Source: NIH RePORTER
NR 27
TC 992
Z9 1226
U1 3
U2 173
PU 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 11
PY 2011
VL 476
IS 7359
BP 220
EP U122
DI 10.1038/nature10202
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900039
PM 21617644
DA 2026-03-09
ER

PT J
AU Suga, H
   Kadoshima, T
   Minaguchi, M
   Ohgushi, M
   Soen, M
   Nakano, T
   Takata, N
   Wataya, T
   Muguruma, K
   Miyoshi, H
   Yonemura, S
   Oiso, Y
   Sasai, Y
AF Suga, Hidetaka
   Kadoshima, Taisuke
   Minaguchi, Maki
   Ohgushi, Masatoshi
   Soen, Mika
   Nakano, Tokushige
   Takata, Nozomu
   Wataya, Takafumi
   Muguruma, Keiko
   Miyoshi, Hiroyuki
   Yonemura, Shigenobu
   Oiso, Yutaka
   Sasai, Yoshiki
TI Self-formation of functional adenohypophysis in three-dimensional culture
SO NATURE
LA English
DT Article
ID pituitary-gland; rathkes pouch; cell lineages; differentiation; specification; induction; growth; organogenesis; mechanisms; expression
AB The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke's pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke's-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.
C1 [Suga, Hidetaka; Kadoshima, Taisuke; Minaguchi, Maki; Soen, Mika; Nakano, Tokushige; Takata, Nozomu; Wataya, Takafumi; Muguruma, Keiko; Sasai, Yoshiki] RIKEN Ctr Dev Biol, Neurogenesis & Organogenesis Grp, Kobe, Hyogo 6500047, Japan.
   [Suga, Hidetaka; Ohgushi, Masatoshi] RIKEN Ctr Dev Biol, Div Human Stem Cell Technol, Kobe, Hyogo 6500047, Japan.
   [Suga, Hidetaka; Oiso, Yutaka] Nagoya Univ, Dept Endocrinol & Diabet, Grad Sch Med, Nagoya, Aichi 4668550, Japan.
   [Miyoshi, Hiroyuki] RIKEN, Subteam Manipulat Cell Fate, BioResource Ctr, Tsukuba, Ibaraki 3050074, Japan.
   [Yonemura, Shigenobu] RIKEN Ctr Dev Biol, Electron Microscopy Lab, Kobe, Hyogo 6500047, Japan.
C3 RIKEN; RIKEN; Nagoya University; RIKEN; RIKEN
RP Sasai, Y (corresponding author), RIKEN Ctr Dev Biol, Neurogenesis & Organogenesis Grp, Kobe, Hyogo 6500047, Japan.
EM yoshikisasai@cdb.riken.jp
FU Ministry of Education, Culture, Sports, Science and Technology; Knowledge Cluster Initiative at Kobe; Leading Project for Realization of Regenerative Medicine; Grants-in-Aid for Scientific Research [23770237, 22390188] Funding Source: KAKEN
NR 33
TC 386
Z9 460
U1 2
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 57
EP U215
DI 10.1038/nature10637
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900032
PM 22080957
DA 2026-03-09
ER

PT J
AU Kang, TW
   Yevsa, T
   Woller, N
   Hoenicke, L
   Wuestefeld, T
   Dauch, D
   Hohmeyer, A
   Gereke, M
   Rudalska, R
   Potapova, A
   Iken, M
   Vucur, M
   Weiss, S
   Heikenwalder, M
   Khan, S
   Gil, J
   Bruder, D
   Manns, M
   Schirmacher, P
   Tacke, F
   Ott, M
   Luedde, T
   Longerich, T
   Kubicka, S
   Zender, L
AF Kang, Tae-Won
   Yevsa, Tetyana
   Woller, Norman
   Hoenicke, Lisa
   Wuestefeld, Torsten
   Dauch, Daniel
   Hohmeyer, Anja
   Gereke, Marcus
   Rudalska, Ramona
   Potapova, Anna
   Iken, Marcus
   Vucur, Mihael
   Weiss, Siegfried
   Heikenwalder, Mathias
   Khan, Sadaf
   Gil, Jesus
   Bruder, Dunja
   Manns, Michael
   Schirmacher, Peter
   Tacke, Frank
   Ott, Michael
   Luedde, Tom
   Longerich, Thomas
   Kubicka, Stefan
   Zender, Lars
TI Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
SO NATURE
LA English
DT Article
ID mouse; ras; fibroblasts; suppression; expression; pathway; models; mice; p53
AB Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo(1). Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this 'secretory phenotype' can have pro-as well as anti-tumorigenic effects(2-5). Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as 'senescence surveillance'), which depends on an intact CD4(+) T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of Nras(G12V). We also found that CD4(+) T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.
C1 [Kang, Tae-Won; Yevsa, Tetyana; Hoenicke, Lisa; Wuestefeld, Torsten; Dauch, Daniel; Hohmeyer, Anja; Gereke, Marcus; Rudalska, Ramona; Potapova, Anna; Weiss, Siegfried; Bruder, Dunja; Zender, Lars] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany.
   [Yevsa, Tetyana; Woller, Norman; Wuestefeld, Torsten; Hohmeyer, Anja; Manns, Michael; Zender, Lars] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany.
   [Iken, Marcus; Ott, Michael] Twincore Ctr Expt & Clin Infect Res, D-30625 Hannover, Germany.
   [Vucur, Mihael; Tacke, Frank; Luedde, Tom] Univ Hosp Aachen, Dept Internal Med 3, D-52074 Aachen, Germany.
   [Heikenwalder, Mathias] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland.
   [Heikenwalder, Mathias] Tech Univ Munich, Helmholtz Ctr Munich, Inst Virol, D-81675 Munich, Germany.
   [Khan, Sadaf; Gil, Jesus] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC Clin Sci Ctr, London W12 0NN, England.
   [Schirmacher, Peter; Longerich, Thomas] Univ Heidelberg, Inst Pathol, D-69120 Heidelberg, Germany.
   [Kubicka, Stefan] Dist Hosp Reutlingen, Clin Internal Med, D-72764 Reutlingen, Germany.
C3 Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; Helmholtz Association; Helmholtz-Center for Infection Research; RWTH Aachen University; RWTH Aachen University Hospital; University of Zurich; University Zurich Hospital; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; Imperial College London; Ruprecht Karls University Heidelberg
RP Zender, L (corresponding author), Helmholtz Ctr Infect Res, Inhoffenstr 7, D-38124 Braunschweig, Germany.
EM Lars.Zender@helmholtz-hzi.de
FU Helmholtz Association of German Research Centres [VH-NG-424]; German Research Foundation, DFG [ZE 545/2-1, SFB/TRR77]; Wilhelm Sander Stiftung; Bear Necessities Pediatric Cancer Foundation; Federal German Ministry for Education and Research (BMBF); European Commission; MRC [MC_U120085810] Funding Source: UKRI; Medical Research Council [MC_U120085810] Funding Source: researchfish
NR 21
TC 1303
Z9 1473
U1 1
U2 184
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 547
EP 551
DI 10.1038/nature10599
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600055
PM 22080947
DA 2026-03-09
ER

PT J
AU Berer, K
   Mues, M
   Koutrolos, M
   Al Rasbi, Z
   Boziki, M
   Johner, C
   Wekerle, H
   Krishnamoorthy, G
AF Berer, Kerstin
   Mues, Marsilius
   Koutrolos, Michail
   Al Rasbi, Zakeya
   Boziki, Marina
   Johner, Caroline
   Wekerle, Hartmut
   Krishnamoorthy, Gurumoorthy
TI Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
SO NATURE
LA English
DT Article
ID t-cell responses; multiple-sclerosis; b-cells; transgenic mice; autoantibody; induction; bacteria; disease; mog
AB Active multiple sclerosis lesions show inflammatory changes suggestive of a combined attack by autoreactive T and B lymphocytes against brain white matter(1). These pathogenic immune cells derive from progenitors that are normal, innocuous components of the healthy immune repertoire but become autoaggressive upon pathological activation. The stimuli triggering this autoimmune conversion have been commonly attributed to environmental factors, in particular microbial infection(2). However, using the relapsing-remitting mouse model of spontaneously developing experimental autoimmune encephalomyelitis(3), here we show that the commensal gut flora-in the absence of pathogenic agents-is essential in triggering immune processes, leading to a relapsing-remitting autoimmune disease driven by myelin-specific CD4(+) T cells. We show further that recruitment and activation of autoantibody-producing B cells from the endogenous immune repertoire depends on availability of the target autoantigen, myelin oligodendrocyte glycoprotein (MOG), and commensal microbiota. Our observations identify a sequence of events triggering organ-specific autoimmune disease and these processes may offer novel therapeutic targets.
C1 [Berer, Kerstin; Mues, Marsilius; Koutrolos, Michail; Al Rasbi, Zakeya; Boziki, Marina; Wekerle, Hartmut; Krishnamoorthy, Gurumoorthy] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany.
   [Johner, Caroline] Max Planck Inst Immunobiol & Epigenet, D-79108 Freiburg, Germany.
C3 Max Planck Society; Max Planck Society
RP Wekerle, H (corresponding author), Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany.
EM hwekerle@neuro.mpg.de; guru@neuro.mpg.de
FU German Competence Network on Multiple Sclerosis (KKNMS); ARSEP (France); Max Planck Society; Emirates Foundation; Hellenic Neurological Society;  [SFB 571]
NR 28
TC 982
Z9 1157
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 NOV 24
PY 2011
VL 479
IS 7374
BP 538
EP U266
DI 10.1038/nature10554
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600053
PM 22031325
DA 2026-03-09
ER

PT J
AU Burrows, DN
   Kennea, JA
   Ghisellini, G
   Mangano, V
   Zhang, B
   Page, KL
   Eracleous, M
   Romano, P
   Sakamoto, T
   Falcone, AD
   Osborne, JP
   Campana, S
   Beardmore, AP
   Breeveld, AA
   Chester, MM
   Corbet, R
   Covino, S
   Cummings, JR
   D'Avanzo, P
   D'Elia, V
   Esposito, P
   Evans, PA
   Fugazza, D
   Gelbord, JM
   Hiroi, K
   Holland, ST
   Huang, KY
   Im, M
   Israel, G
   Jeon, Y
   Jeon, YB
   Jun, HD
   Kawai, N
   Kim, JH
   Krimm, HA
   Marshall, FE
   Mészáros, P
   Negoro, H
   Omodei, N
   Park, WK
   Perkins, JS
   Sugizaki, M
   Sung, HI
   Tagliaferri, G
   Troja, E
   Ueda, Y
   Urata, Y
   Usui, R
   Antonelli, LA
   Barthelmy, SD
   Cusumano, G
   Giommi, P
   Melandri, A
   Perri, M
   Racusin, JL
   Sbarufatti, B
   Siegel, MH
   Gehrels, N
AF Burrows, D. N.
   Kennea, J. A.
   Ghisellini, G.
   Mangano, V.
   Zhang, B.
   Page, K. L.
   Eracleous, M.
   Romano, P.
   Sakamoto, T.
   Falcone, A. D.
   Osborne, J. P.
   Campana, S.
   Beardmore, A. P.
   Breeveld, A. A.
   Chester, M. M.
   Corbet, R.
   Covino, S.
   Cummings, J. R.
   D'Avanzo, P.
   D'Elia, V.
   Esposito, P.
   Evans, P. A.
   Fugazza, D.
   Gelbord, J. M.
   Hiroi, K.
   Holland, S. T.
   Huang, K. Y.
   Im, M.
   Israel, G.
   Jeon, Y.
   Jeon, Y. -B.
   Jun, H. D.
   Kawai, N.
   Kim, J. H.
   Krimm, H. A.
   Marshall, F. E.
   Meszaros, P.
   Negoro, H.
   Omodei, N.
   Park, W. -K.
   Perkins, J. S.
   Sugizaki, M.
   Sung, H. -I.
   Tagliaferri, G.
   Troja, E.
   Ueda, Y.
   Urata, Y.
   Usui, R.
   Antonelli, L. A.
   Barthelmy, S. D.
   Cusumano, G.
   Giommi, P.
   Melandri, A.
   Perri, M.
   Racusin, J. L.
   Sbarufatti, B.
   Siegel, M. H.
   Gehrels, N.
TI Relativistic jet activity from the tidal disruption of a star by a massive black hole
SO NATURE
LA English
DT Article
ID x-ray outbursts; flares; nucleus; events
AB Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close(1,2), producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole(3-7). The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies(8-14), but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper(15) comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.
C1 [Burrows, D. N.; Kennea, J. A.; Eracleous, M.; Falcone, A. D.; Chester, M. M.; Fugazza, D.; Meszaros, P.; Siegel, M. H.] Penn State Univ, Dept Astron & Astrophys, 525 Davey Lab, University Pk, PA 16802 USA.
   [Ghisellini, G.; Campana, S.; Covino, S.; D'Avanzo, P.; Tagliaferri, G.; Melandri, A.] INAF Osservatorio Astron Brera, I-23807 Merate, Italy.
   [Mangano, V.; Romano, P.; Cusumano, G.; Sbarufatti, B.] INAF Ist Astrofis Spaziale & Fis Cosm, I-90146 Palermo, Italy.
   [Zhang, B.] Univ Nevada, Dept Phys & Astron, Las Vegas, NV 89154 USA.
   [Page, K. L.; Osborne, J. P.; Beardmore, A. P.; Evans, P. A.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Sakamoto, T.; Corbet, R.; Cummings, J. R.; Hiroi, K.; Krimm, H. A.; Perkins, J. S.] CRESST, Greenbelt, MD 20771 USA.
   [Sakamoto, T.; Corbet, R.; Cummings, J. R.; Hiroi, K.; Krimm, H. A.; Marshall, F. E.; Perkins, J. S.; Troja, E.; Barthelmy, S. D.; Racusin, J. L.; Gehrels, N.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Sakamoto, T.; Corbet, R.; Cummings, J. R.; Perkins, J. S.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA.
   [Breeveld, A. A.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [D'Elia, V.; Antonelli, L. A.; Giommi, P.; Perri, M.] ASI Sci Data Ctr, I-00044 Frascati, Italy.
   [Esposito, P.] INAF Osservatorio Astron Cagliari, I-09012 Capoterra, Italy.
   [Ueda, Y.] Kyoto Univ, Dept Astron, Sakyo Ku, Kyoto 6068502, Japan.
   [Holland, S. T.; Krimm, H. A.] Univ Space Res Assoc, Columbia, MD 21044 USA.
   [Huang, K. Y.] Acad Sinica, Inst Astron & Astrophys, Taipei 106, Taiwan.
   [Im, M.; Jeon, Y.; Jun, H. D.; Kim, J. H.; Park, W. -K.] Seoul Natl Univ, Dept Phys & Astron, FPRD, Ctr Explorat Origin Universe, Seoul, South Korea.
   [Israel, G.; Antonelli, L. A.] INAF Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Jeon, Y.; Sung, H. -I.] Korea Astron & Space Sci Inst KASI, Taejon 305348, South Korea.
   [Kawai, N.; Usui, R.] Tokyo Inst Technol, Dept Phys, Meguro Ku, Tokyo 1528551, Japan.
   [Sugizaki, M.] RIKEN, MAXI Team, Wako, Saitama 3510198, Japan.
   [Negoro, H.] Nihon Univ, Dept Phys, Chiyoda Ku, Tokyo 1018308, Japan.
   [Omodei, N.] Stanford Univ, Dept Phys, Kavli Inst Particle Astrophys & Cosmol, WW Hansen Expt Phys Lab, Stanford, CA 94305 USA.
   [Omodei, N.] Stanford Univ, SLAC Natl Accelerator Lab, Stanford, CA 94305 USA.
   [Urata, Y.] Natl Cent Univ, Inst Astron, Chungli 32054, Taiwan.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; University of Leicester; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland Baltimore County; University of London; University College London; Agenzia Spaziale Italiana (ASI); Istituto Nazionale Astrofisica (INAF); Kyoto University; Universities Space Research Association (USRA); Academia Sinica - Taiwan; Seoul National University (SNU); Istituto Nazionale Astrofisica (INAF); Korea Astronomy & Space Science Institute (KASI); Institute of Science Tokyo; Tokyo Institute of Technology; RIKEN; Nihon University; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; National Central University
RP Burrows, DN (corresponding author), Penn State Univ, Dept Astron & Astrophys, 525 Davey Lab, University Pk, PA 16802 USA.
EM burrows@astro.psu.edu
FU NASA (US); NSF (US); DOE (US); UK Space Agency; ASI (Italy); INAF (Italy); INFN (Italy); Autonomous Region of Sardinia; MEXT (Japan); KEK (Japan); JAXA (Japan); CRI/NRF/MEST (Korea); NSC (Taiwan); Academia Sinica (Taiwan); CEA/Irfu (France); IN2P3/CNRS (France); CNES (France); K. A. Wallenberg Foundation (Sweden); Swedish Research Council (Sweden); National Space Board (Sweden); Grants-in-Aid for Scientific Research [21340043] Funding Source: KAKEN; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908362] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0757155] Funding Source: National Science Foundation; UK Space Agency [ST/J000841/1] Funding Source: researchfish
NR 29
TC 491
Z9 534
U1 2
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 AUG 25
PY 2011
VL 476
IS 7361
BP 421
EP 424
DI 10.1038/nature10374
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400029
PM 21866154
DA 2026-03-09
ER

PT J
AU Postberg, F
   Schmidt, J
   Hillier, J
   Kempf, S
   Srama, R
AF Postberg, F.
   Schmidt, J.
   Hillier, J.
   Kempf, S.
   Srama, R.
TI A salt-water reservoir as the source of a compositionally stratified plume on Enceladus
SO NATURE
LA English
DT Article
ID liquid water; vapor plumes; e-ring; dust; sodium; origin
AB The discovery of a plume of water vapour and ice particles emerging from warm fractures ('tiger stripes') in Saturn's small, icy moon Enceladus(1-6) raised the question of whether the plume emerges from a subsurface liquid source(6-8) or from the decomposition of ice(9-12). Previous compositional analyses of particles injected by the plume into Saturn's diffuse E ring have already indicated the presence of liquid water(8), but the mechanisms driving the plume emission are still debated(13). Here we report an analysis of the composition of freshly ejected particles close to the sources. Salt-rich ice particles are found to dominate the total mass flux of ejected solids (more than 99 per cent) but they are depleted in the population escaping into Saturn's E ring. Ice grains containing organic compounds are found to be more abundant in dense parts of the plume. Whereas previous Cassini observations were compatible with a variety of plume formation mechanisms, these data eliminate or severely constrain non-liquid models and strongly imply that a salt-water reservoir with a large evaporating surface(7,8) provides nearly all of the matter in the plume.
C1 [Postberg, F.] Heidelberg Univ, Inst Geowissensch, D-69120 Heidelberg, Germany.
   [Postberg, F.; Kempf, S.; Srama, R.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Schmidt, J.] Univ Potsdam, Inst Phys & Astron, D-14476 Potsdam, Germany.
   [Hillier, J.] Open Univ, Planetary & Space Sci Res Inst, Milton Keynes MK7 6AA, Bucks, England.
   [Kempf, S.] Tech Univ Carolo Wilhelmina Braunschweig, IGEP, D-38106 Braunschweig, Germany.
   [Kempf, S.] Univ Colorado, LASP, Boulder, CO 80303 USA.
   [Srama, R.] Univ Stuttgart, IRS, D-70569 Stuttgart, Germany.
C3 Ruprecht Karls University Heidelberg; Max Planck Society; University of Potsdam; Open University - UK; Braunschweig University of Technology; University of Colorado System; University of Colorado Boulder; University of Stuttgart
RP Postberg, F (corresponding author), Heidelberg Univ, Inst Geowissensch, D-69120 Heidelberg, Germany.
EM Frank.Postberg@mpi-hd.mpg.de
FU Deutsches Zentrum fur Luft und Raumfahrt (DLR); Deutsche Forschungs Gemeinschaft (DFG); UK Science and Technology Facilities Council
NR 26
TC 405
Z9 449
U1 1
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 620
EP 622
DI 10.1038/nature10175
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300034
PM 21697830
DA 2026-03-09
ER

PT J
AU Van Keymeulen, A
   Rocha, AS
   Ousset, M
   Beck, B
   Bouvencourt, G
   Rock, J
   Sharma, N
   Dekoninck, S
   Blanpain, C
AF Van Keymeulen, Alexandra
   Rocha, Ana Sofia
   Ousset, Marielle
   Beck, Benjamin
   Bouvencourt, Gaelle
   Rock, Jason
   Sharma, Neha
   Dekoninck, Sophie
   Blanpain, Cedric
TI Distinct stem cells contribute to mammary gland development and maintenance
SO NATURE
LA English
DT Article
ID breast-cancer; in-vitro; mouse; morphogenesis; progenitor; epithelium; skin; identification; population; commitment
AB The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers.
C1 [Van Keymeulen, Alexandra; Rocha, Ana Sofia; Ousset, Marielle; Beck, Benjamin; Bouvencourt, Gaelle; Sharma, Neha; Dekoninck, Sophie; Blanpain, Cedric] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
   [Rock, Jason] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
C3 Universite Libre de Bruxelles; Duke University
RP Blanpain, C (corresponding author), Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
EM Cedric.Blanpain@ulb.ac.be
FU TELEVIE; Portuguese Science Foundation (FCT); Fondation Contre le Cancer; FNRS; CIBLES of the Wallonia Region; ULB fondation; fond Gaston Ithier; European Research Council (ERC); EMBO;  [F32HL102920]
NR 37
TC 680
Z9 833
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 189
EP U58
DI 10.1038/nature10573
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800033
PM 21983963
DA 2026-03-09
ER

PT J
AU Savin, T
   Kurpios, NA
   Shyer, AE
   Florescu, P
   Liang, HY
   Mahadevan, L
   Tabin, CJ
AF Savin, Thierry
   Kurpios, Natasza A.
   Shyer, Amy E.
   Florescu, Patricia
   Liang, Haiyi
   Mahadevan, L.
   Tabin, Clifford J.
TI On the growth and form of the gut
SO NATURE
LA English
DT Article
AB The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut.
C1 [Savin, Thierry; Florescu, Patricia; Liang, Haiyi; Mahadevan, L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Kurpios, Natasza A.; Shyer, Amy E.; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Mahadevan, L.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Mahadevan, L.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Mahadevan, L.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Mahadevan, L.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
   [Mahadevan, L.] Harvard Univ, Kavli Inst Bionano Sci & Technol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University
RP Mahadevan, L (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM lm@seas.harvard.edu
FU Harvard NSF MRSEC; MacArthur Foundation; NIH [RO1 HD047360]
NR 20
TC 416
Z9 501
U1 2
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 57
EP +
DI 10.1038/nature10277
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300028
PM 21814276
DA 2026-03-09
ER

PT J
AU Ferrón, SR
   Charalambous, M
   Radford, E
   McEwen, K
   Wildner, H
   Hind, E
   Morante-Redolat, JM
   Laborda, J
   Guillemot, F
   Bauer, SR
   Fariñas, I
   Ferguson-Smith, AC
AF Ferron, Sacri R.
   Charalambous, Marika
   Radford, Elizabeth
   McEwen, Kirsten
   Wildner, Hendrik
   Hind, Eleanor
   Manuel Morante-Redolat, Jose
   Laborda, Jorge
   Guillemot, Francois
   Bauer, Steven R.
   Farinas, Isabel
   Ferguson-Smith, Anne C.
TI Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis
SO NATURE
LA English
DT Article
ID differentiation; expression; genes; zone; mouse-chromosome-12; proliferation; gtl2; glia
AB The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome(1,2). Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. Notably, we find that there is a requirement for Dlk1 to be expressed from both maternally and paternally inherited chromosomes. Selective absence of Dlk1 imprinting in both NSCs and niche astrocytes is associated with postnatal acquisition of DNA methylation at the germ-line-derived imprinting control region. The results emphasize molecular relationships between NSCs and the niche astrocyte cells of the microenvironment, identifying a signalling system encoded by a single gene that functions coordinately in both cell types. The modulation of genomic imprinting in a stem-cell environment adds a new level of epigenetic regulation to the establishment and maintenance of the niche, raising wider questions about the adaptability, function and evolution of imprinting in specific developmental contexts.
C1 [Ferron, Sacri R.; Charalambous, Marika; Radford, Elizabeth; McEwen, Kirsten; Hind, Eleanor; Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
   [Wildner, Hendrik; Guillemot, Francois] Natl Inst Med Res, MRC, Dept Mol Neurobiol, London NW7 1AA, England.
   [Manuel Morante-Redolat, Jose; Farinas, Isabel] Univ Valencia, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Dept Biol Celular, E-46100 Burjassot, Spain.
   [Laborda, Jorge] Univ Castilla La Mancha, Reg Ctr Biomed Res, Sch Med, Dept Inorgan & Organ Chem & Biochem, Albacete 02006, Spain.
   [Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
C3 University of Cambridge; MRC National Institute for Medical Research; CIBERNED; University of Valencia; Universidad de Castilla-La Mancha; US Food & Drug Administration (FDA); Center for Biologics Evaluation & Research (CBER); Center For Biologics Evaluation & Research - Cellular & Gene Therapies
RP Ferguson-Smith, AC (corresponding author), Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
EM afsmith@mole.bio.cam.ac.uk
FU Medical Research Council; Wellcome Trust; Ministerio de Ciencia e Innovacion [SAF2008-01006, CB06/05/0086, RD06/0010/0010]; Generalitat Valenciana (Prometeo); University of Cambridge; MRC [MC_U117570528, G0701196, G0800784] Funding Source: UKRI; Medical Research Council [G0701196, G0800784, G0800784B, MC_U117570528] Funding Source: researchfish
NR 30
TC 222
Z9 258
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 JUL 21
PY 2011
VL 475
IS 7356
BP 381
EP U136
DI 10.1038/nature10229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200043
PM 21776083
DA 2026-03-09
ER

PT J
AU Isogai, Y
   Si, S
   Pont-Lezica, L
   Tan, T
   Kapoor, V
   Murthy, VN
   Dulac, C
AF Isogai, Yoh
   Si, Sheng
   Pont-Lezica, Lorena
   Tan, Taralyn
   Kapoor, Vikrant
   Murthy, Venkatesh N.
   Dulac, Catherine
TI Molecular organization of vomeronasal chemoreception
SO NATURE
LA English
DT Article
ID accessory olfactory-bulb; putative pheromone receptors; genetic-analysis; sensory neurons; organ; mice; behavior; expression; family; aggression
AB The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals(1). More than 250 putative pheromone receptors have been identified in the mouse VNO(2,3), but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.
C1 [Isogai, Yoh; Dulac, Catherine] Harvard Univ, Dept Mol & Cellular Biol, Ctr Brain Sci, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Howard Hughes Medical Institute
RP Dulac, C (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Ctr Brain Sci, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM dulac@fas.harvard.edu
FU NIDCD at the National Institute of Health; Howard Hughes Medical Institute; Damon Runyon Cancer Research Foundation [DRG-1981-08]
NR 33
TC 243
Z9 297
U1 3
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 13
PY 2011
VL 478
IS 7368
BP 241
EP U130
DI 10.1038/nature10437
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800050
PM 21937988
DA 2026-03-09
ER

PT J
AU Wu, T
   Mayaffre, H
   Krämer, S
   Horvatic, M
   Berthier, C
   Hardy, WN
   Liang, RX
   Bonn, DA
   Julien, MH
AF Wu, Tao
   Mayaffre, Hadrien
   Kraemer, Steffen
   Horvatic, Mladen
   Berthier, Claude
   Hardy, W. N.
   Liang, Ruixing
   Bonn, D. A.
   Julien, Marc-Henri
TI Magnetic-field-induced charge-stripe order in the high-temperature superconductor YBa2Cu3Oy
SO NATURE
LA English
DT Article
ID quantum oscillations; fluctuating stripes; fermi-surface; pseudogap
AB Electronic charges introduced in copper-oxide (CuO2) planes generate high-transition-temperature (T-c) superconductivity but, under special circumstances, they can also order into filaments called stripes(1). Whether an underlying tendency towards charge order is present in all copper oxides and whether this has any relationship with superconductivity are, however, two highly controversial issues(2,3). To uncover underlying electronic order, magnetic fields strong enough to destabilize superconductivity can be used. Such experiments, including quantum oscillations(4-6) in YBa2Cu3Oy (an extremely clean copper oxide in which charge order has not until now been observed) have suggested that superconductivity competes with spin, rather than charge, order(7-9). Here we report nuclear magnetic resonance measurements showing that high magnetic fields actually induce charge order, without spin order, in the CuO2 planes of YBa2Cu3Oy. The observed static, unidirectional, modulation of the charge density breaks translational symmetry, thus explaining quantum oscillation results, and we argue that it is most probably the same 4a-periodic modulation as in stripe-ordered copper oxides(1). That it develops only when superconductivity fades away and near the same 1/8 hole doping as in La2-xBaxCuO4 (ref. 1) suggests that charge order, although visibly pinned by CuO chains in YBa2Cu3Oy, is an intrinsic propensity of the superconducting planes of high-T-c copper oxides.
C1 [Wu, Tao; Mayaffre, Hadrien; Kraemer, Steffen; Horvatic, Mladen; Berthier, Claude; Julien, Marc-Henri] CNRS, Lab Natl Champs Magnet Intenses, UPR 3228, UJF,UPS,INSA, F-38042 Grenoble, France.
   [Hardy, W. N.; Liang, Ruixing; Bonn, D. A.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Hardy, W. N.; Liang, Ruixing; Bonn, D. A.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); University of British Columbia; Canadian Institute for Advanced Research (CIFAR)
RP Julien, MH (corresponding author), CNRS, Lab Natl Champs Magnet Intenses, UPR 3228, UJF,UPS,INSA, F-38042 Grenoble, France.
EM marc-henri.julien@lncmi.cnrs.fr
FU Universite Joseph Fourier
NR 30
TC 679
Z9 745
U1 1
U2 254
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 191
EP 194
DI 10.1038/nature10345
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900031
PM 21901009
DA 2026-03-09
ER

PT J
AU Strother, PK
   Battison, L
   Brasier, MD
   Wellman, CH
AF Strother, Paul K.
   Battison, Leila
   Brasier, Martin D.
   Wellman, Charles H.
TI Earth's earliest non-marine eukaryotes
SO NATURE
LA English
DT Article
ID life; oxygenation; evolution; rocks; land
AB The existence of a terrestrial Precambrian (more than 542 Myr ago) biota has been largely inferred from indirect chemical and geological evidence associated with palaeosols(1,2), the weathering of clay minerals(3) and microbially induced sedimentary structures in siliciclastic sediments(4). Direct evidence of fossils within rocks of nonmarine origin in the Precambrian is exceedingly rare(5,6). The most widely cited example comprises a single report of morphologically simple mineralized tubes and spheres interpreted as cyanobacteria, obtained from 1,200-Myr-old palaeokarst in Arizona(5). Organic-walled microfossils were first described from the non-marine Torridonian (1.2-1.0 Gyr ago) sequence of northwest Scotland in 1907(7). Subsequent studies(8-10) found few distinctive taxa-a century later, the Torridonian microflora is still being characterized as primarily nondescript "leiospheres''(11). We have comprehensively sampled grey shales and phosphatic nodules throughout the Torridonian sequence. Here we report the recovery of large populations of diverse organic-walled microfossils extracted by acid maceration, complemented by studies using thin sections of phosphatic nodules that yield exceptionally detailed three-dimensional preservation. These assemblages contain multicellular structures, complex-walled cysts, asymmetric organic structures, and dorsiventral, compressed organic thalli, some approaching one millimetre in diameter. They offer direct evidence of eukaryotes living in freshwater aquatic and subaerially exposed habitats during the Proterozoic era. The apparent dominance of eukaryotes in non-marine settings by 1 Gyr ago indicates that eukaryotic evolution on land may have commenced far earlier than previously thought.
C1 [Strother, Paul K.] Boston Coll, Dept Earth & Environm Sci, Weston, MA 02493 USA.
   [Battison, Leila; Brasier, Martin D.] Univ Oxford, Dept Earth Sci, Oxford OX1 3PR, England.
   [Wellman, Charles H.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
C3 Boston College; University of Oxford; University of Sheffield
RP Strother, PK (corresponding author), Boston Coll, Dept Earth & Environm Sci, Weston, MA 02493 USA.
EM Strother@bc.edu
FU NASA [NNX07AU79G]; NERC [NE/G015716/1, NE/G524060/1]; Natural Environment Research Council [NE/G015716/1] Funding Source: researchfish; NERC [NE/G015716/1] Funding Source: UKRI
NR 30
TC 148
Z9 167
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 MAY 26
PY 2011
VL 473
IS 7348
BP 505
EP 509
DI 10.1038/nature09943
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300039
PM 21490597
DA 2026-03-09
ER

PT J
AU Jan, CH
   Friedman, RC
   Ruby, JG
   Bartel, DP
AF Jan, Calvin H.
   Friedman, Robin C.
   Ruby, J. Graham
   Bartel, David P.
TI Formation, regulation and evolution of Caenorhabditis elegans 3′UTRs
SO NATURE
LA English
DT Article
ID 3' untranslated regions; gene-expression; messenger-rnas; polyadenylation; complex; sequences; targets; switch
AB Post-transcriptional gene regulation frequently occurs through elements in mRNA 3' untranslated regions (UTRs)(1,2). Although crucial roles for 3'UTR-mediated gene regulation have been found in Caenorhabditis elegans(3-5), most C. elegans genes have lacked annotated 3'UTRs(6,7). Here we describe a high-throughput method for reliable identification of polyadenylated RNA termini, and we apply this method, called poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans 3'UTRs. Compared to standard methods also recently applied to C. elegans UTRs(8), 3P-Seq identified 8,580 additional UTRs while excluding thousands of shorter UTR isoforms that do not seem to be authentic. Analysis of this expanded and corrected data set suggested that the high A/U content of C. elegans 3'UTRs facilitated genome compaction, because the elements specifying cleavage and polyadenylation, which are A/U rich, can more readily emerge in A/U-rich regions. Indeed, 30% of the protein-coding genes have mRNAs with alternative, partially overlapping end regions that generate another 10,480 cleavage and polyadenylation sites that had gone largely unnoticed and represent potential evolutionary intermediates of progressive UTR shortening. Moreover, a third of the convergently transcribed genes use palindromic arrangements of bidirectional elements to specify UTRs with convergent overlap, which also contributes to genome compaction by eliminating regions between genes. Although nematode 3'UTRs have median length only one-sixth that of mammalian 3'UTRs, they have twice the density of conserved microRNA sites, in part because additional types of seed-complementary sites are preferentially conserved. These findings reveal the influence of cleavage and polyadenylation on the evolution of genome architecture and provide resources for studying post-transcriptional gene regulation.
C1 [Jan, Calvin H.; Friedman, Robin C.; Ruby, J. Graham; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Jan, Calvin H.; Friedman, Robin C.; Ruby, J. Graham; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Jan, Calvin H.; Friedman, Robin C.; Ruby, J. Graham; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Friedman, Robin C.] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Bartel, DP (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dbartel@wi.mit.edu
FU NIH [GM067031]; National Science Foundation; Krell Institute/Department of Energy
NR 36
TC 374
Z9 479
U1 0
U2 45
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 97
EP U114
DI 10.1038/nature09616
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600039
PM 21085120
DA 2026-03-09
ER

PT J
AU Feld, M
   Fröhlich, B
   Vogt, E
   Koschorreck, M
   Köhl, M
AF Feld, Michael
   Froehlich, Bernd
   Vogt, Enrico
   Koschorreck, Marco
   Koehl, Michael
TI Observation of a pairing pseudogap in a two-dimensional Fermi gas
SO NATURE
LA English
DT Article
ID normal-state; t-c; behavior
AB Pairing of fermions is ubiquitous in nature, underlying many phenomena. Examples include superconductivity, superfluidity of He-3, the anomalous rotation of neutron stars, and the crossover between Bose-Einstein condensation of dimers and the BCS (Bardeen, Cooper and Schrieffer) regime in strongly interacting Fermi gases. When confined to two dimensions, interacting many-body systems show even more subtle effects(1), many of which are not understood at a fundamental level. Most striking is the (as yet unexplained) phenomenon of high-temperature superconductivity in copper oxides, which is intimately related to the two-dimensional geometry of the crystal structure. In particular, it is not understood how the many-body pairing is established at high temperature, and whether it precedes superconductivity. Here we report the observation of a many-body pairing gap above the superfluid transition temperature in a harmonically trapped, two-dimensional atomic Fermi gas in the regime of strong coupling. Our measurements of the spectral function of the gas are performed using momentum-resolved photoemission spectroscopy(2,3), analogous to angle-resolved photoemission spectroscopy in the solid state(4). Our observations mark a significant step in the emulation of layered two-dimensional strongly correlated superconductors using ultracold atomic gases.
C1 [Feld, Michael; Froehlich, Bernd; Vogt, Enrico; Koschorreck, Marco; Koehl, Michael] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
C3 University of Cambridge
RP Köhl, M (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM mk540@cam.ac.uk
FU EPSRC [EP/G029547/1]; Daimler-Benz Foundation; Studienstiftung; DAAD; Engineering and Physical Sciences Research Council [EP/G029547/1] Funding Source: researchfish; EPSRC [EP/G029547/1] Funding Source: UKRI
NR 32
TC 205
Z9 216
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 1
PY 2011
VL 480
IS 7375
BP 75
EP U233
DI 10.1038/nature10627
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900036
PM 22129727
DA 2026-03-09
ER

PT J
AU Kayagaki, N
   Warming, S
   Lamkanfi, M
   Vande Walle, L
   Louie, S
   Dong, J
   Newton, K
   Qu, Y
   Liu, JF
   Heldens, S
   Zhang, J
   Lee, WP
   Roose-Girma, M
   Dixit, VM
AF Kayagaki, Nobuhiko
   Warming, Soren
   Lamkanfi, Mohamed
   Vande Walle, Lieselotte
   Louie, Salina
   Dong, Jennifer
   Newton, Kim
   Qu, Yan
   Liu, Jinfeng
   Heldens, Sherry
   Zhang, Juan
   Lee, Wyne P.
   Roose-Girma, Merone
   Dixit, Vishva M.
TI Non-canonical inflammasome activation targets caspase-11
SO NATURE
LA English
DT Article
ID interleukin-1-beta converting-enzyme; gamma-inducing factor; anthrax lethal toxin; nlrp3 inflammasome; mice deficient; recognition; il-1-beta; receptors; apoptosis; responses
AB Caspase-1 activation by inflammasome scaffolds comprised of intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and the adaptor ASC is believed to be essential for production of the pro-inflammatory cytokines interleukin (IL)-1 beta and IL-18 during the innate immune response(1-5). Here we show, with C57BL/6 Casp11 gene-targeted mice, that caspase-11 (also known as caspase-4)(6-8) is critical for caspase-1 activation and IL-1 beta production in macrophages infected with Escherichia coli, Citrobacter rodentium or Vibrio cholerae. Strain 129 mice, like Casp11(-/-) mice, exhibited defects in IL-1 beta production and harboured a mutation in the Casp11 locus that attenuated caspase-11 expression. This finding is important because published targeting of the Casp1 gene was done using strain 129 embryonic stem cells(9,10). Casp1 and Casp11 are too close in the genome to be segregated by recombination; consequently, the published Casp1(-/-) mice lack both caspase-11 and caspase-1. Interestingly, Casp11(-/-) macrophages secreted IL-1 beta normally in response to ATP and monosodium urate, indicating that caspase-11 is engaged by a non-canonical inflammasome. Casp1(-/-)Casp11(129mt/129mt) macrophages expressing caspase-11 from a C57BL/6 bacterial artificial chromosome transgene failed to secrete IL-1 beta regardless of stimulus, confirming an essential role for caspase-1 in IL-1 beta production. Caspase-11 rather than caspase-1, however, was required for non-canonical inflammasome-triggered macrophage cell death, indicating that caspase-11 orchestrates both caspase-1-dependent and -independent outputs. Caspase-1 activation by non-canonical stimuli required NLRP3 and ASC, but caspase-11 processing and cell death did not, implying that there is a distinct activator of caspase-11. Lastly, loss of caspase-11 rather than caspase-1 protected mice from a lethal dose of lipopolysaccharide. These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections.
C1 [Kayagaki, Nobuhiko; Louie, Salina; Dong, Jennifer; Newton, Kim; Qu, Yan; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
   [Warming, Soren; Heldens, Sherry; Roose-Girma, Merone] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Lamkanfi, Mohamed; Vande Walle, Lieselotte] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Lamkanfi, Mohamed; Vande Walle, Lieselotte] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Liu, Jinfeng] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
   [Zhang, Juan; Lee, Wyne P.] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Flanders Institute for Biotechnology (VIB); Ghent University; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
RP Kayagaki, N (corresponding author), Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
EM kayagaki@gene.com; dixit@gene.com
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NR 35
TC 2111
Z9 2437
U1 5
U2 264
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 117
EP U146
DI 10.1038/nature10558
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600043
PM 22002608
DA 2026-03-09
ER

PT J
AU Santander-Syro, AF
   Copie, O
   Kondo, T
   Fortuna, F
   Pailhès, S
   Weht, R
   Qiu, XG
   Bertran, F
   Nicolaou, A
   Taleb-Ibrahimi, A
   Le Fèvre, P
   Herranz, G
   Bibes, M
   Reyren, N
   Apertet, Y
   Lecoeur, P
   Barthélémy, A
   Rozenberg, MJ
AF Santander-Syro, A. F.
   Copie, O.
   Kondo, T.
   Fortuna, F.
   Pailhes, S.
   Weht, R.
   Qiu, X. G.
   Bertran, F.
   Nicolaou, A.
   Taleb-Ibrahimi, A.
   Le Fevre, P.
   Herranz, G.
   Bibes, M.
   Reyren, N.
   Apertet, Y.
   Lecoeur, P.
   Barthelemy, A.
   Rozenberg, M. J.
TI Two-dimensional electron gas with universal subbands at the surface of SrTiO3
SO NATURE
LA English
DT Article
ID strontium titanate; insulator; heterostructures; temperature; transition; interface; oxides; bands
AB As silicon is the basis of conventional electronics, so strontium titanate (SrTiO3) is the foundation of the emerging field of oxide electronics(1,2). SrTiO3 is the preferred template for the creation of exotic, two-dimensional (2D) phases of electron matter at oxide interfaces(3-5) that have metal-insulator transitions(6,7), superconductivity(8,9) or large negative magnetoresistance(10). However, the physical nature of the electronic structure underlying these 2D electron gases (2DEGs), which is crucial to understanding their remarkable properties(11,12), remains elusive. Here we show, using angle-resolved photoemission spectroscopy, that there is a highly metallic universal 2DEG at the vacuum-cleaved surface of SrTiO3 (including the non-doped insulating material) independently of bulk carrier densities over more than seven decades. This 2DEG is confined within a region of about five unit cells and has a sheet carrier density of similar to 0.33 electrons per square lattice parameter. The electronic structure consists of multiple subbands of heavy and light electrons. The similarity of this 2DEG to those reported in SrTiO3-based heterostructures(6,8,13) and field-effect transistors(9,14) suggests that different forms of electron confinement at the surface of SrTiO3 lead to essentially the same 2DEG. Our discovery provides a model system for the study of the electronic structure of 2DEGs in SrTiO3-based devices and a novel means of generating 2DEGs at the surfaces of transition-metal oxides.
C1 [Santander-Syro, A. F.; Fortuna, F.] CNRS, IN2P3, CSNSM, F-91405 Orsay, France.
   [Apertet, Y.; Lecoeur, P.] Univ Paris 11, Inst Elect Fondamentale, F-91405 Orsay, France.
   [Santander-Syro, A. F.] UPMC, CNRS, ESPCI, Lab Phys & Etud Mat,UMR 8213, F-75231 Paris 5, France.
   [Copie, O.; Bibes, M.; Reyren, N.; Barthelemy, A.] Unite Mixte Phys CNRS Thales, F-91767 Palaiseau, France.
   [Copie, O.] Univ Wurzburg, D-97074 Wurzburg, Germany.
   [Kondo, T.] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Kondo, T.] Iowa State Univ, Ames Lab, Ames, IA 50011 USA.
   [Pailhes, S.] CEA Saclay, CNRS, CEA, Lab Leon Brillouin, F-91191 Gif Sur Yvette, France.
   [Weht, R.] Univ Nacl San Martin, Inst Sabato, CNEA, RA-1650 San Martin, Argentina.
   [Qiu, X. G.] Chinese Acad Sci, Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China.
   [Qiu, X. G.] Chinese Acad Sci, Inst Phys, Beijing 100190, Peoples R China.
   [Bertran, F.; Nicolaou, A.; Taleb-Ibrahimi, A.; Le Fevre, P.] CEA, CNRS, Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France.
   [Herranz, G.] ICMAB CSIC, Inst Ciencia Mat Barcelona, Bellaterra 08193, Catalonia, Spain.
   [Rozenberg, M. J.] Univ Paris 11, Phys Solides Lab, F-91405 Orsay, France.
   [Rozenberg, M. J.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Fis, RA-1428 Buenos Aires, DF, Argentina.
C3 Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite Paris Saclay; 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); Centre National de la Recherche Scientifique (CNRS); Thales Group; University of Wurzburg; Iowa State University; Iowa State University; United States Department of Energy (DOE); Ames National Laboratory; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Comision Nacional de Energia Atomica (CNEA); Instituto Sabato; Chinese Academy of Sciences; Chinese Academy of Sciences; Institute of Physics, CAS; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; SOLEIL Synchrotron; CEA; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB); Universite Paris Saclay; University of Buenos Aires
RP Santander-Syro, AF (corresponding author), CNRS, IN2P3, CSNSM, Batiment 104 & 108, F-91405 Orsay, France.
EM andres.santander@csnsm.in2p3.fr
FU ANR OXITRONICS; CNRS-CSIC [PICS2008FR1]; National Science Foundation [DMR-0537588]; US DOE [W-7405-ENG-82]; CONICET [PIP 112-200801-00047]; ANPCyT [PICT 837/07]; MOST and NSF of China; Spanish Government [MAT2008-06761-C03, NANOSELECT CSD2007-00041]
NR 30
TC 657
Z9 712
U1 6
U2 584
PU 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 13
PY 2011
VL 469
IS 7329
BP 189
EP 193
DI 10.1038/nature09720
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400033
PM 21228872
DA 2026-03-09
ER

PT J
AU Berardi, MJ
   Shih, WM
   Harrison, SC
   Chou, JJ
AF Berardi, Marcelo J.
   Shih, William M.
   Harrison, Stephen C.
   Chou, James J.
TI Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching
SO NATURE
LA English
DT Article
ID nuclear-magnetic-resonance; dipolar couplings; induced alignment; adp/atp carrier; secretion; ucp2; adp
AB Mitochondrial uncoupling protein 2 (UCP2) is an integral membrane protein in the mitochondrial anion carrier protein family, the members of which facilitate the transport of small molecules across the mitochondrial inner membrane(1,2). When the mitochondrial respiratory complex pumps protons from the mitochondrial matrix to the intermembrane space, it builds up an electrochemical potential(2). A fraction of this electrochemical potential is dissipated as heat, in a process involving leakage of protons back to the matrix(2). This leakage, or 'uncoupling' of the proton electrochemical potential, is mediated primarily by uncoupling proteins(2). However, the mechanism of UCP-mediated proton translocation across the lipid bilayer is unknown. Here we describe a solution-NMR method for structural characterization of UCP2. The method, which overcomes some of the challenges associated with membrane-protein structure determination(3), combines orientation restraints derived from NMR residual dipolar couplings (RDCs) and semiquantitative distance restraints from paramagnetic relaxation enhancement (PRE) measurements. The local and secondary structures of the protein were determined by piecing together molecular fragments from the Protein Data Bank that best fit experimental RDCs from samples weakly aligned in a DNA nanotube liquid crystal. The RDCs also determine the relative orientation of the secondary structural segments, and the PRE restraints provide their spatial arrangement in the tertiary fold. UCP2 closely resembles the bovine ADP/ATP carrier (the only carrier protein of known structure(4)), but the relative orientations of the helical segments are different, resulting in a wider opening on the matrix side of the inner membrane. Moreover, the nitroxide-labelled GDP binds inside the channel and seems to be closer to transmembrane helices 1-4. We believe that this biophysical approach can be applied to other membrane proteins and, in particular, to other mitochondrial carriers, not only for structure determination but also to characterize various conformational states of these proteins linked to substrate transport.
C1 [Berardi, Marcelo J.; Harrison, Stephen C.; Chou, James J.] Harvard Univ, Jack & Eileen Connors Struct Biol Lab, Sch Med, Boston, MA 02115 USA.
   [Berardi, Marcelo J.; Shih, William M.; Harrison, Stephen C.; Chou, James J.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA.
   [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02138 USA.
   [Harrison, Stephen C.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Chou, JJ (corresponding author), Harvard Univ, Jack & Eileen Connors Struct Biol Lab, Sch Med, Boston, MA 02115 USA.
EM chou@cmcd.hms.harvard.edu
FU NIH [1U54GM094608, 1DP2OD004641]
NR 37
TC 331
Z9 361
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 AUG 4
PY 2011
VL 476
IS 7358
BP 109
EP 113
DI 10.1038/nature10257
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300040
PM 21785437
DA 2026-03-09
ER

PT J
AU Vasiliauskas, D
   Mazzoni, EO
   Sprecher, SG
   Brodetskiy, K
   Johnston, RJ
   Lidder, P
   Vogt, N
   Celik, A
   Desplan, C
AF Vasiliauskas, Daniel
   Mazzoni, Esteban O.
   Sprecher, Simon G.
   Brodetskiy, Konstantin
   Johnston, Robert J., Jr.
   Lidder, Preetmoninder
   Vogt, Nina
   Celik, Arzu
   Desplan, Claude
TI Feedback from rhodopsin controls rhodopsin exclusion in Drosophila photoreceptors
SO NATURE
LA English
DT Article
ID tumor-suppressor gene; expression; r7; identification; transgenesis; specificity; dissection; encodes; system; cells
AB Sensory systems with high discriminatory power use neurons that express only one of several alternative sensory receptor proteins. This exclusive receptor gene expression restricts the sensitivity spectrum of neurons and is coordinated with the choice of their synaptic targets(1-3). However, little is known about how it is maintained throughout the life of a neuron. Here we show that the green-light sensing receptor rhodopsin 6 (Rh6) acts to exclude an alternative blue-sensitive rhodopsin 5 (Rh5) from a subset of Drosophila R8 photoreceptor neurons(4). Loss of Rh6 leads to a gradual expansion of Rh5 expression into all R8 photoreceptors of the ageing adult retina. The Rh6 feedback signal results in repression of the rh5 promoter and can be mimicked by other Drosophila rhodopsins; it is partly dependent on activation of rhodopsin by light, and relies on G(alpha q) activity, but not on the subsequent steps of the phototransduction cascade(5). Our observations reveal a thus far unappreciated spectral plasticity of R8 photoreceptors, and identify rhodopsin feedback as an exclusion mechanism.
C1 [Vasiliauskas, Daniel; Mazzoni, Esteban O.; Sprecher, Simon G.; Brodetskiy, Konstantin; Johnston, Robert J., Jr.; Lidder, Preetmoninder; Vogt, Nina; Celik, Arzu; Desplan, Claude] NYU, Dept Biol, Ctr Dev Genet, New York, NY 10003 USA.
C3 New York University
RP Desplan, C (corresponding author), NYU, Dept Biol, Ctr Dev Genet, New York, NY 10003 USA.
EM cd38@nyu.edu
FU National Institutes of Health [R01EY13012, F32EY016309]; National Eye Institute [R01EY013012] Funding Source: NIH RePORTER
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NR 48
TC 37
Z9 48
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 108
EP +
DI 10.1038/nature10451
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600041
PM 21983964
DA 2026-03-09
ER

PT J
AU Lorenzen, ED
   Nogués-Bravo, D
   Orlando, L
   Weinstock, J
   Binladen, J
   Marske, KA
   Ugan, A
   Borregaard, MK
   Gilbert, MTP
   Nielsen, R
   Ho, SYW
   Goebel, T
   Graf, KE
   Byers, D
   Stenderup, JT
   Rasmussen, M
   Campos, PF
   Leonard, JA
   Koepfli, KP
   Froese, D
   Zazula, G
   Stafford, TW
   Aaris-Sorensen, K
   Batra, P
   Haywood, AM
   Singarayer, JS
   Valdes, PJ
   Boeskorov, G
   Burns, JA
   Davydov, SP
   Haile, J
   Jenkins, DL
   Kosintsev, P
   Kuznetsova, T
   Lai, XL
   Martin, LD
   McDonald, HG
   Mol, D
   Meldgaard, M
   Munch, K
   Stephan, E
   Sablin, M
   Sommer, RS
   Sipko, T
   Scott, E
   Suchard, MA
   Tikhonov, A
   Willerslev, R
   Wayne, RK
   Cooper, A
   Hofreiter, M
   Sher, A
   Shapiro, B
   Rahbek, C
   Willerslev, E
AF Lorenzen, Eline D.
   Nogues-Bravo, David
   Orlando, Ludovic
   Weinstock, Jaco
   Binladen, Jonas
   Marske, Katharine A.
   Ugan, Andrew
   Borregaard, Michael K.
   Gilbert, M. Thomas P.
   Nielsen, Rasmus
   Ho, Simon Y. W.
   Goebel, Ted
   Graf, Kelly E.
   Byers, David
   Stenderup, Jesper T.
   Rasmussen, Morten
   Campos, Paula F.
   Leonard, Jennifer A.
   Koepfli, Klaus-Peter
   Froese, Duane
   Zazula, Grant
   Stafford, Thomas W., Jr.
   Aaris-Sorensen, Kim
   Batra, Persaram
   Haywood, Alan M.
   Singarayer, Joy S.
   Valdes, Paul J.
   Boeskorov, Gennady
   Burns, James A.
   Davydov, Sergey P.
   Haile, James
   Jenkins, Dennis L.
   Kosintsev, Pavel
   Kuznetsova, Tatyana
   Lai, Xulong
   Martin, Larry D.
   McDonald, H. Gregory
   Mol, Dick
   Meldgaard, Morten
   Munch, Kasper
   Stephan, Elisabeth
   Sablin, Mikhail
   Sommer, Robert S.
   Sipko, Taras
   Scott, Eric
   Suchard, Marc A.
   Tikhonov, Alexei
   Willerslev, Rane
   Wayne, Robert K.
   Cooper, Alan
   Hofreiter, Michael
   Sher, Andrei
   Shapiro, Beth
   Rahbek, Carsten
   Willerslev, Eske
TI Species-specific responses of Late Quaternary megafauna to climate and humans
SO NATURE
LA English
DT Article
ID pleistocene; dynamics; mammoth; steppe; extinctions; inference; patterns; decline; yukon
AB Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
C1 [Lorenzen, Eline D.; Orlando, Ludovic; Weinstock, Jaco; Binladen, Jonas; Gilbert, M. Thomas P.; Stenderup, Jesper T.; Rasmussen, Morten; Campos, Paula F.; Stafford, Thomas W., Jr.; Aaris-Sorensen, Kim; Haile, James; Meldgaard, Morten; Willerslev, Eske] Univ Copenhagen, Ctr GeoGenet, DK-1350 Copenhagen K, Denmark.
   [Nogues-Bravo, David; Marske, Katharine A.; Borregaard, Michael K.; Rahbek, Carsten] Univ Copenhagen, Dept Biol, Ctr Macroecol Evolut & Climate, DK-2100 Copenhagen O, Denmark.
   [Ugan, Andrew] Smithsonian Trop Res Inst, Ancon, Punama, Panama.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Nielsen, Rasmus] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Ho, Simon Y. W.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia.
   [Goebel, Ted; Graf, Kelly E.] Texas A&M Univ, Dept Anthropol, Ctr Study Amer 1, College Stn, TX 77843 USA.
   [Byers, David] Missouri State Univ, Dept Sociol & Anthropol, Springfield, MO 65807 USA.
   [Leonard, Jennifer A.] Uppsala Univ, Dept Evolutionary Biol, S-75236 Uppsala, Sweden.
   [Leonard, Jennifer A.] EBD CSIC, Conservat & Evolutionary Genet Grp, Seville 41092, Spain.
   [Koepfli, Klaus-Peter; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Koepfli, Klaus-Peter] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
   [Froese, Duane] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Zazula, Grant] Govt Yukon, Dept Tourism & Culture, Yukon Palaeontol Program, Whitehorse, YT Y1A 2C6, Canada.
   [Stafford, Thomas W., Jr.] Stafford Res Inc, Lafayette, CO 80026 USA.
   [Batra, Persaram] Mt Holyoke Coll, Dept Earth & Environm, S Hadley, MA 01075 USA.
   [Haywood, Alan M.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Singarayer, Joy S.; Valdes, Paul J.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Boeskorov, Gennady] Russian Acad Sci, Siberian Branch, Diamond & Precious Met Geol Inst, Yakutsk 677891, Russia.
   [Burns, James A.] Royal Alberta Museum, Edmonton, AB T5N 0M6, Canada.
   [Burns, James A.] Manitoba Museum, Winnipeg, MB R3B 0N2, Canada.
   [Davydov, Sergey P.] Russian Acad Sci, Far E Branch, Pacific Inst Geog, NE Sci Stn, Chersky 678830, Russia.
   [Jenkins, Dennis L.] Univ Oregon, Museum Nat & Cultural Hist, Eugene, OR 97403 USA.
   [Kosintsev, Pavel] Russian Acad Sci, Ural Branch, Inst Plant & Anim Ecol, Ekaterinburg 620144, Russia.
   [Kuznetsova, Tatyana] Moscow MV Lomonosov State Univ, Moscow 119899, Russia.
   [Lai, Xulong] China Univ Geosci, State Key Lab Biogeol & Environm Geol, Wuhan 430074, Hubei, Peoples R China.
   [Martin, Larry D.] Univ Kansas, Museum Nat Hist, Lawrence, KS 66045 USA.
   [McDonald, H. Gregory] Natl Pk Serv, Pk Museum Management Program, Ft Collins, CO 80525 USA.
   [Mol, Dick] Nat Hist Museum, Rotterdam, Netherlands.
   [Munch, Kasper] Aarhus Univ, BiRC, DK-8000 Aarhus C, Denmark.
   [Stephan, Elisabeth] Landesamt Denkmalpflege, Regierungsprasidium Stuttgart, D-78467 Constance, Germany.
   [Sablin, Mikhail; Tikhonov, Alexei] Russian Acad Sci, Inst Zool, St Petersburg 199034, Russia.
   [Sommer, Robert S.] Univ Kiel, Inst Nat & Resource Conservat, Dept Landscape Ecol, D-24098 Kiel, Germany.
   [Sipko, Taras; Sher, Andrei] Russian Acad Sci, Inst Ecol & Evolut, Moscow 119071, Russia.
   [Scott, Eric] San Bernardino Cty Museum, Div Geol Sci, Redlands, CA 92374 USA.
   [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath Genet, Los Angeles, CA 90095 USA.
   [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
   [Willerslev, Rane] Univ Oslo, Museum Cultural Hist, N-0130 Oslo, Norway.
   [Cooper, Alan] Univ Adelaide, Australian Ctr Ancient DNA, Adelaide, SA 5005, Australia.
   [Hofreiter, Michael] Univ York, Dept Biol, Area 2, York YO10 5DD, N Yorkshire, England.
   [Shapiro, Beth] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
   [Ugan, Andrew] Univ Utah, Dept Anthropol, Salt Lake City, UT 84112 USA.
   [Ugan, Andrew] Museo Hist Nat San Rafael, Mendoza, Argentina.
C3 University of Copenhagen; University of Copenhagen; Smithsonian Institution; Smithsonian Tropical Research Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Copenhagen; University of Sydney; Texas A&M University System; Texas A&M University College Station; Missouri State University; Uppsala University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); University of California System; University of California Los Angeles; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Alberta; Mount Holyoke College; University of Leeds; University of Bristol; Russian Academy of Sciences; Diamond & Precious Metal Geology Institute Siberian Branch of Russian Academy of Sciences; Russian Academy of Sciences; Pacific Geographical Institute of the Far Eastern Branch of the Russian Academy of Sciences; University of Oregon; Russian Academy of Sciences; Institute of Plant & Animal Ecology of the Russian Academy of Sciences; Lomonosov Moscow State University; China University of Geosciences; University of Kansas; United States Department of the Interior; US National Park Service; Aarhus University; Russian Academy of Sciences; Zoological Institute of the Russian Academy of Sciences; University of Kiel; Russian Academy of Sciences; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of Oslo; Adelaide University; University of Adelaide; University of York - UK; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Utah System of Higher Education; University of Utah
RP Willerslev, E (corresponding author), Univ Copenhagen, Ctr GeoGenet, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
EM ewillerslev@snm.ku.dk
FU Leverhulme Trust [F/757/A]; McDonald Grants and Awards Fund; NSF [ARC-0909456]; Danish National Research Foundation; Lundbeck Foundation; Danish Council for Independent Research; US National Science Foundation; Directorate For Geosciences [0910272] Funding Source: National Science Foundation; Office of Polar Programs (OPP) [0910272] Funding Source: National Science Foundation; Lundbeck Foundation [R9-2007-1031, R24-2008-2527, R70-2010-6286] Funding Source: researchfish; Natural Environment Research Council [ncas10009] Funding Source: researchfish
NR 42
TC 551
Z9 612
U1 11
U2 758
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 359
EP U195
DI 10.1038/nature10574
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700037
PM 22048313
DA 2026-03-09
ER

PT J
AU Grotjohann, T
   Testa, I
   Leutenegger, M
   Bock, H
   Urban, NT
   Lavoie-Cardinal, F
   Willig, KI
   Eggeling, C
   Jakobs, S
   Hell, SW
AF Grotjohann, Tim
   Testa, Ilaria
   Leutenegger, Marcel
   Bock, Hannes
   Urban, Nicolai T.
   Lavoie-Cardinal, Flavie
   Willig, Katrin I.
   Eggeling, Christian
   Jakobs, Stefan
   Hell, Stefan W.
TI Diffraction-unlimited all-optical imaging and writing with a photochromic GFP
SO NATURE
LA English
DT Article
ID green fluorescent protein; stimulated-emission; resolution barrier; dendritic spines; structural basis; microscopy; nanoscopy; breaking; light; depletion
AB Lens-based optical microscopy failed to discern fluorescent features closer than 200 nm for decades, but the recent breaking of the diffraction resolution barrier by sequentially switching the fluorescence capability of adjacent features on and off is making nanoscale imaging routine. Reported fluorescence nanoscopy variants switch these features either with intense beams at defined positions or randomly, molecule by molecule. Here we demonstrate an optical nanoscopy that records raw data images from living cells and tissues with low levels of light. This advance has been facilitated by the generation of reversibly switchable enhanced green fluorescent protein (rsEGFP), a fluorescent protein that can be reversibly photoswitched more than a thousand times. Distributions of functional rsEGFP-fusion proteins in living bacteria and mammalian cells are imaged at <40-nanometre resolution. Dendritic spines in living brain slices are super-resolved with about a million times lower light intensities than before. The reversible switching also enables all-optical writing of features with subdiffraction size and spacings, which can be used for data storage.
C1 [Grotjohann, Tim; Testa, Ilaria; Leutenegger, Marcel; Bock, Hannes; Urban, Nicolai T.; Lavoie-Cardinal, Flavie; Willig, Katrin I.; Eggeling, Christian; Jakobs, Stefan; Hell, Stefan W.] Max Planck Inst Biophys Chem, Dept NanoBiophoton, D-37077 Gottingen, Germany.
   [Jakobs, Stefan] Univ Gottingen, Sch Med, D-37075 Gottingen, Germany.
C3 Max Planck Society; University of Gottingen
RP Jakobs, S (corresponding author), Max Planck Inst Biophys Chem, Dept NanoBiophoton, Fassberg 11, D-37077 Gottingen, Germany.
EM sjakobs@gwdg.de; shell@gwdg.de
FU Deutsche Forschungsgemeinschaft (DFG) through the DFG-Research Center for Molecular Physiology of the Brain; DFG
NR 47
TC 407
Z9 465
U1 4
U2 293
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 204
EP 208
DI 10.1038/nature10497
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800041
PM 21909116
DA 2026-03-09
ER

PT J
AU Cernilogar, FM
   Onorati, MC
   Kothe, GO
   Burroughs, AM
   Parsi, KM
   Breiling, A
   Lo Sardo, F
   Saxena, A
   Miyoshi, K
   Siomi, H
   Siomi, MC
   Carninci, P
   Gilmour, DS
   Corona, DFV
   Orlando, V
AF Cernilogar, Filippo M.
   Onorati, Maria Cristina
   Kothe, Greg O.
   Burroughs, A. Maxwell
   Parsi, Krishna Mohan
   Breiling, Achim
   Lo Sardo, Federica
   Saxena, Alka
   Miyoshi, Keita
   Siomi, Haruhiko
   Siomi, Mikiko C.
   Carninci, Piero
   Gilmour, David S.
   Corona, Davide F. V.
   Orlando, Valerio
TI Chromatin-associated RNA interference components contribute to transcriptional regulation in Drosophila
SO NATURE
LA English
DT Article
ID polymerase-ii; in-vivo; distinct roles; somatic-cells; heat-shock; pathway; polycomb; proteins; promoter; risc
AB RNA interference (RNAi) pathways have evolved as important modulators of gene expression that operate in the cytoplasm by degrading RNA target molecules through the activity of short (21-30 nucleotide) RNAs1-6. RNAi components have been reported to have a role in the nucleus, as they are involved in epigenetic regulation and heterochromatin formation(7-10). However, although RNAi-mediated post-transcriptional gene silencing is well documented, the mechanisms of RNAi-mediated transcriptional gene silencing and, in particular, the role of RNAi components in chromatin dynamics, especially in animal multicellular organisms, are elusive. Here we show that the key RNAi components Dicer 2 (DCR2) and Argonaute 2 (AGO2) associate with chromatin (with a strong preference for euchromatic, transcriptionally active, loci) and interact with the core transcription machinery. Notably, loss of function of DCR2 or AGO2 showed that transcriptional defects are accompanied by the perturbation of RNA polymerase II positioning on promoters. Furthermore, after heat shock, both Dcr2 and Ago2 null mutations, as well as missense mutations that compromise the RNAi activity, impaired the global dynamics of RNA polymerase II. Finally, the deep sequencing of the AGO2-associated small RNAs (AGO2 RIP-seq) revealed that AGO2 is strongly enriched in small RNAs that encompass the promoter regions and other regions of heat-shock and other genetic loci on both the sense and antisense DNA strands, but with a strong bias for the antisense strand, particularly after heat shock. Taken together, our results show that DCR2 and AGO2 are globally associated with transcriptionally active loci and may have a pivotal role in shaping the transcriptome by controlling the processivity of RNA polymerase II.
C1 [Cernilogar, Filippo M.; Parsi, Krishna Mohan; Lo Sardo, Federica; Orlando, Valerio] IRCCS Fdn Santa Lucia, Dulbecco Telethon Inst, Epigenet & Genome Reprogramming, I-00143 Rome, Italy.
   [Cernilogar, Filippo M.; Parsi, Krishna Mohan] IGB ABT CNR, Dulbecco Telethon Inst, I-80131 Naples, Italy.
   [Onorati, Maria Cristina; Corona, Davide F. V.] Univ Palermo, Dulbecco Telethon Inst, Dipartimento STEMBIO, Sez Biol Cellulare, I-90128 Palermo, Italy.
   [Kothe, Greg O.; Gilmour, David S.] Penn State Univ, Ctr Eukaryot Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Burroughs, A. Maxwell; Saxena, Alka; Carninci, Piero] RIKEN Yokohama Inst, RIKEN Om Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Breiling, Achim] German Canc Res Ctr, DKFZ ZMBH Alliance, Div Epigenet, D-69120 Heidelberg, Germany.
   [Miyoshi, Keita; Siomi, Haruhiko; Siomi, Mikiko C.] Keio Univ, Sch Med, Tokyo 1608582, Japan.
   [Siomi, Mikiko C.] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
C3 Fondazione Telethon; Dulbecco Telethon Institute (DTI); IRCCS Santa Lucia; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e Biofisica Adriano Buzzati-Traverso (IGB-CNR); Fondazione Telethon; Dulbecco Telethon Institute (DTI); Fondazione Telethon; Dulbecco Telethon Institute (DTI); University of Palermo; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; RIKEN; Helmholtz Association; German Cancer Research Center (DKFZ); Keio University; Japan Science & Technology Agency (JST)
RP Orlando, V (corresponding author), IRCCS Fdn Santa Lucia, Dulbecco Telethon Inst, Epigenet & Genome Reprogramming, Via Fosso di Fiorano 64, I-00143 Rome, Italy.
EM vorlando@dti.telethon.it
FU National Institutes of Health [GM47477]; Deutsche Forschungsgemeinschaft [SPP 1356]; Japan Society for the Promotion of Science (JSPS) [20241047, P09745]; Council for Science and Technology Policy; NEXT Program; Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Agency; Fondazione Telethon; Giovanni Armenise Harvard Foundation; FIRB-MIUR; Associazione Italiana Ricerca Cancro (AIRC); Human Frontier Science Program CDA; EMBO; AIRC; EU; National Institute of General Medical Sciences [R01GM047477] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [20221008, 20241047] Funding Source: KAKEN
NR 44
TC 185
Z9 216
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 DEC 15
PY 2011
VL 480
IS 7377
BP 391
EP U151
DI 10.1038/nature10492
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000057
PM 22056986
DA 2026-03-09
ER

PT J
AU Liu, YY
   Slotine, JJ
   Barabási, AL
AF Liu, Yang-Yu
   Slotine, Jean-Jacques
   Barabasi, Albert-Laszlo
TI Controllability of complex networks
SO NATURE
LA English
DT Article
ID contraction analysis; percolation
AB The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered and natural systems towards a desired state, a framework to control complex self-organized systems is lacking. Here we develop analytical tools to study the controllability of an arbitrary complex directed network, identifying the set of driver nodes with time-dependent control that can guide the system's entire dynamics. We apply these tools to several real networks, finding that the number of driver nodes is determined mainly by the network's degree distribution. We show that sparse inhomogeneous networks, which emerge in many real complex systems, are the most difficult to control, but that dense and homogeneous networks can be controlled using a few driver nodes. Counterintuitively, we find that in both model and real systems the driver nodes tend to avoid the high-degree nodes.
C1 [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
   [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci & Biol, Boston, MA 02115 USA.
   [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
   [Slotine, Jean-Jacques] MIT, Nonlinear Syst Lab, Cambridge, MA 02139 USA.
   [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
   [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
C3 Northeastern University; Northeastern University; Northeastern University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School
RP Barabási, AL (corresponding author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
EM alb@neu.edu
FU US Army Research Laboratory [W911NF-09-2-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems
NR 50
TC 2472
Z9 2806
U1 24
U2 1021
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2011
VL 473
IS 7346
BP 167
EP 173
DI 10.1038/nature10011
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200029
PM 21562557
DA 2026-03-09
ER

PT J
AU Gai, ZK
   Donoghue, PCJ
   Zhu, M
   Janvier, P
   Stampanoni, M
AF Gai, Zhikun
   Donoghue, Philip C. J.
   Zhu, Min
   Janvier, Philippe
   Stampanoni, Marco
TI Fossil jawless fish from China foreshadows early jawed vertebrate anatomy
SO NATURE
LA English
DT Article
ID tomographic microscopy; internal anatomy; neural crest; origin; evolution; agnathans; phylogeny; lamprey; head
AB Most living vertebrates are jawed vertebrates (gnathostomes), and the living jawless vertebrates (cyclostomes), hagfishes and lampreys, provide scarce information about the profound reorganization of the vertebrate skull during the evolutionary origin of jaws(1-9). The extinct bony jawless vertebrates, or 'ostracoderms', are regarded as precursors of jawed vertebrates and provide insight into this formative episode in vertebrate evolution(8-14). Here, using synchrotron radiation X-ray tomography(15,16), we describe the cranial anatomy of galeaspids, a 435-370-million-year-old 'ostracoderm' group from China and Vietnam(17). The paired nasal sacs of galeaspids are located anterolaterally in the braincase, and the hypophyseal duct opens anteriorly towards the oral cavity. These three structures (the paired nasal sacs and the hypophyseal duct) were thus already independent of each other, like in gnathostomes and unlike in cyclostomes and osteostracans (another 'ostracoderm' group), and therefore have the condition that current developmental models regard as prerequisites for the development of jaws(1-3). This indicates that the reorganization of vertebrate cranial anatomy was not driven deterministically by the evolutionary origin of jaws but occurred stepwise, ultimately allowing the rostral growth of ectomesenchyme that now characterizes gnathostome head development(1-3).
C1 [Gai, Zhikun; Donoghue, Philip C. J.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Gai, Zhikun; Zhu, Min] Chinese Acad Sci, Lab Evolutionary Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Janvier, Philippe] Museum Natl Hist Nat, CNRS, UMR 7207, F-75231 Paris 05, France.
   [Stampanoni, Marco] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Stampanoni, Marco] Univ & ETH Zurich, Inst Biomed Engn, CH-8092 Zurich, Switzerland.
C3 University of Bristol; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Donoghue, PCJ (corresponding author), Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
EM phil.donoghue@bristol.ac.uk; zhumin@ivpp.ac.cn
FU Chinese Academy of Sciences [KZCX2-YW-156]; Chinese Foundation of Natural Sciences [40872020, 40930208]; Major Basic Research Projects of MST of China [2006CB806400]; Paul Scherrer Institut; European Union; Leverhulme Trust; Natural Environmental Research Council; SYNTHESYS Project; Royal Society; NERC [NE/G016623/1] Funding Source: UKRI; Natural Environment Research Council [NE/G016623/1] Funding Source: researchfish
NR 30
TC 112
Z9 145
U1 2
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 324
EP 327
DI 10.1038/nature10276
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500036
PM 21850106
DA 2026-03-09
ER

PT J
AU Yoshida, K
   Sanada, M
   Shiraishi, Y
   Nowak, D
   Nagata, Y
   Yamamoto, R
   Sato, Y
   Sato-Otsubo, A
   Kon, A
   Nagasaki, M
   Chalkidis, G
   Suzuki, Y
   Shiosaka, M
   Kawahata, R
   Yamaguchi, T
   Otsu, M
   Obara, N
   Sakata-Yanagimoto, M
   Ishiyama, K
   Mori, H
   Nolte, F
   Hofmann, WK
   Miyawaki, S
   Sugano, S
   Haferlach, C
   Koeffler, HP
   Shih, LY
   Haferlach, T
   Chiba, S
   Nakauchi, H
   Miyano, S
   Ogawa, S
AF Yoshida, Kenichi
   Sanada, Masashi
   Shiraishi, Yuichi
   Nowak, Daniel
   Nagata, Yasunobu
   Yamamoto, Ryo
   Sato, Yusuke
   Sato-Otsubo, Aiko
   Kon, Ayana
   Nagasaki, Masao
   Chalkidis, George
   Suzuki, Yutaka
   Shiosaka, Masashi
   Kawahata, Ryoichiro
   Yamaguchi, Tomoyuki
   Otsu, Makoto
   Obara, Naoshi
   Sakata-Yanagimoto, Mamiko
   Ishiyama, Ken
   Mori, Hiraku
   Nolte, Florian
   Hofmann, Wolf-Karsten
   Miyawaki, Shuichi
   Sugano, Sumio
   Haferlach, Claudia
   Koeffler, H. Phillip
   Shih, Lee-Yung
   Haferlach, Torsten
   Chiba, Shigeru
   Nakauchi, Hiromitsu
   Miyano, Satoru
   Ogawa, Seishi
TI Frequent pathway mutations of splicing machinery in myelodysplasia
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; pre-messenger-rna; developmental disorder; somatic mutations; u4atac snrna; genome; gene; identification; spliceosome; component
AB Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (similar to 45 to similar to 85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved inhuman pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.
C1 [Yoshida, Kenichi; Sanada, Masashi; Nagata, Yasunobu; Sato, Yusuke; Sato-Otsubo, Aiko; Kon, Ayana; Shiosaka, Masashi; Kawahata, Ryoichiro; Ogawa, Seishi] Univ Tokyo, Grad Sch Med, Canc Genom Project, Bunkyo Ku, Tokyo 1138655, Japan.
   [Shiraishi, Yuichi; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab DNA Informat Anal,Minato Ku, Tokyo 1088639, Japan.
   [Nowak, Daniel; Nolte, Florian; Hofmann, Wolf-Karsten] Univ Heidelberg, Dept Hematol & Oncol, Med Fac Manheim, D-68167 Mannheim, Germany.
   [Yamamoto, Ryo; Otsu, Makoto; Nakauchi, Hiromitsu] Univ Tokyo, Div Stem Cell Therapy, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
   [Nagasaki, Masao] Univ Tokyo, Lab Funct Genom, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
   [Chalkidis, George; Miyano, Satoru] Univ Tokyo, Lab Sequence Data Anal, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan.
   [Suzuki, Yutaka; Sugano, Sumio] Univ Tokyo, Div Syst Biomed Technol, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.
   [Yamaguchi, Tomoyuki; Nakauchi, Hiromitsu] Japan Sci & Technol Agcy, Nakauchi Stem Cell & Organ Regenerat Project, Minato Ku, Tokyo 1088639, Japan.
   [Obara, Naoshi; Sakata-Yanagimoto, Mamiko; Chiba, Shigeru] Univ Tsukuba, Dept Hematol, Inst Clin Med, Tsukuba, Ibaraki 3058571, Japan.
   [Ishiyama, Ken; Miyawaki, Shuichi] Tokyo Metropolitan Otsuka Hosp, Div Hematol, Toshima Ku, Tokyo 1700005, Japan.
   [Mori, Hiraku] Showa Univ, Fujigaoka Hosp, Div Hematol, Aoba Ku, Kanagawa 2278501, Japan.
   [Haferlach, Claudia; Haferlach, Torsten] Munich Leukemia Lab, D-81377 Munich, Germany.
   [Koeffler, H. Phillip] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   [Koeffler, H. Phillip] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117456, Singapore.
   [Shih, Lee-Yung] Chang Gung Univ, Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Taipei 105, Taiwan.
C3 University of Tokyo; University of Tokyo; Ruprecht Karls University Heidelberg; University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST); University of Tsukuba; Showa Medical University; MLL Munich Leukemia Laboratory; Cedars Sinai Medical Center; National University of Singapore; Chang Gung Memorial Hospital; Chang Gung University
RP Ogawa, S (corresponding author), Univ Tokyo, Grad Sch Med, Canc Genom Project, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM sogawa-tky@umin.ac.jp
FU Ministry of Health, Labor and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology; Japan Society for the Promotion of Science (JSPS); Grants-in-Aid for Scientific Research [22130002, 22134004, 23791075, 22659058, 23659533, 23791068, 23659482, 22390191, 23390269, 22790895] Funding Source: KAKEN
NR 37
TC 1437
Z9 1696
U1 1
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 64
EP 69
DI 10.1038/nature10496
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400035
PM 21909114
DA 2026-03-09
ER

PT J
AU Lorch, JM
   Meteyer, CU
   Behr, MJ
   Boyles, JG
   Cryan, PM
   Hicks, AC
   Ballmann, AE
   Coleman, JTH
   Redell, DN
   Reeder, DM
   Blehert, DS
AF Lorch, Jeffrey M.
   Meteyer, Carol U.
   Behr, Melissa J.
   Boyles, Justin G.
   Cryan, Paul M.
   Hicks, Alan C.
   Ballmann, Anne E.
   Coleman, Jeremy T. H.
   Redell, David N.
   Reeder, DeeAnn M.
   Blehert, David S.
TI Experimental infection of bats with Geomyces destructans causes white-nose syndrome
SO NATURE
LA English
DT Article
ID myotis-lucifugus; extinction; disease; spread; update
AB White-nose syndrome(WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America(1,2). The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats(1,3). Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS4. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction(5-7). Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported(8-10), has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS11,12. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen(13). We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals(8). Demonstration of causality is an instrumental step in elucidating the pathogenesis(14) and epidemiology(15) of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease.
C1 [Lorch, Jeffrey M.; Meteyer, Carol U.; Ballmann, Anne E.; Blehert, David S.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI 53711 USA.
   [Lorch, Jeffrey M.] Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53706 USA.
   [Behr, Melissa J.] Wisconsin Vet Diagnost Lab, Madison, WI 53706 USA.
   [Boyles, Justin G.] Univ Tennessee, Dept Ecol & Evolutionary Biol, Knoxville, TN 37996 USA.
   [Cryan, Paul M.] US Geol Survey, Ft Collins Sci Ctr, Ft Collins, CO 80526 USA.
   [Hicks, Alan C.] New York Dept Environm Conservat, Albany, NY 12233 USA.
   [Coleman, Jeremy T. H.] US Fish & Wildlife Serv, Hadley, MA 01035 USA.
   [Redell, David N.] Wisconsin Dept Nat Resources, Madison, WI 53707 USA.
   [Reeder, DeeAnn M.] Bucknell Univ, Dept Biol, Lewisburg, PA 17837 USA.
C3 United States Department of the Interior; United States Geological Survey; University of Wisconsin System; University of Wisconsin Madison; University of Tennessee System; University of Tennessee Knoxville; United States Department of the Interior; United States Geological Survey; United States Department of the Interior; US Fish & Wildlife Service; Bucknell University
RP Blehert, DS (corresponding author), US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI 53711 USA.
EM dblehert@usgs.gov
FU US Geological Survey; US Fish and Wildlife Service; Bat Conservation International; Indiana State University Center for North American Bat Research and Conservation
NR 23
TC 388
Z9 482
U1 4
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 DEC 15
PY 2011
VL 480
IS 7377
BP 376
EP U129
DI 10.1038/nature10590
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000053
PM 22031324
DA 2026-03-09
ER

PT J
AU Aguilera, C
   Nakagawa, K
   Sancho, R
   Chakraborty, A
   Hendrich, B
   Behrens, A
AF Aguilera, Cristina
   Nakagawa, Kentaro
   Sancho, Rocio
   Chakraborty, Atanu
   Hendrich, Brian
   Behrens, Axel
TI c-Jun N-terminal phosphorylation antagonises recruitment of the Mbd3/NuRD repressor complex
SO NATURE
LA English
DT Article
ID binding domain; map kinases; stem-cells; mbd3; nurd; tumorigenesis; activation; component; mi-2/nurd; colon
AB AP-1 (activator protein 1) activity is strongly induced in response to numerous signals, including growth factors, cytokines and extracellular stresses(1). The proto-oncoprotein c-Jun belongs to the AP-1 group of transcription factors and it is a crucial regulator of intestinal progenitor proliferation and tumorigenesis(2-4). An important mechanism of AP-1 stimulation is phosphorylation of c-Jun by the Jun amino-terminal kinases (JNKs)(1). N-terminal phosphorylation of the c-Jun transactivation domain increases target gene transcription(5,6), but a molecular explanation was elusive. Here we show that unphosphorylated, but not N-terminally phosphorylated c-Jun, interacts with Mbd3 and thereby recruits the nucleosome remodelling and histone deacetylation (NuRD) repressor complex. Mbd3 depletion in colon cancer cells increased histone acetylation at AP-1-dependent promoters, which resulted in increased target gene expression. The intestinal stem cell marker lgr5 was identified as a novel target gene controlled by c-Jun/Mbd3. Gut-specific conditional deletion of mbd3 (mbd3(Delta G/Delta G) mice) stimulated c-Jun activity and increased progenitor cell proliferation. In response to inflammation, mdb3 deficiency resulted in colonic hyperproliferation and mbd3(Delta G/Delta G) mice showed markedly increased susceptibility to colitis-induced tumorigenesis. Notably, concomitant inactivation of a single allele of c-jun reverted physiological and pathological hyperproliferation, as well as the increased tumorigenesis in mbd3(Delta G/Delta G) mice. Thus the transactivation domain of c-Jun recruits Mbd3/NuRD to AP-1 target genes to mediate gene repression, and this repression is relieved by JNK-mediated c-Jun N-terminal phosphorylation.
C1 [Aguilera, Cristina; Nakagawa, Kentaro; Sancho, Rocio; Chakraborty, Atanu; Behrens, Axel] Canc Res UK London Res Inst, Mammalian Genet Lab, Lincolns Inn Fields Labs, London WC2A 3PX, England.
   [Nakagawa, Kentaro] Tokyo Med & Dent Univ, Grad Sch Med, Dept Med Biochem, Bunkyo Ku, Tokyo 1138519, Japan.
   [Hendrich, Brian] Univ Cambridge, Dept Biochem, MRC,Wellcome Trust Ctr Stem Cell Res, Ctr Stem Cell Biol & Regenerat Med, Cambridge CB2 1QR, England.
C3 Cancer Research UK; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); University of Cambridge
RP Behrens, A (corresponding author), Canc Res UK London Res Inst, Mammalian Genet Lab, Lincolns Inn Fields Labs, 44 Lincolns Inn Fields, London WC2A 3PX, England.
EM axel.behrens@cancer.org.uk
FU Marie Curie Intraeuropean Fellowships [PIEF-GA-2008-220566, MEIF-CT-2006-041119]; Cancer Research UK; Medical Research Council [G0800784, G0800784B] Funding Source: researchfish; MRC [G0800784] Funding Source: UKRI
NR 28
TC 109
Z9 140
U1 1
U2 21
PU 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 13
PY 2011
VL 469
IS 7329
BP 231
EP 235
DI 10.1038/nature09607
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400042
PM 21196933
DA 2026-03-09
ER

PT J
AU Antoci, V
   Handler, G
   Campante, TL
   Thygesen, AO
   Moya, A
   Kallinger, T
   Stello, D
   Grigahcène, A
   Kjeldsen, H
   Bedding, TR
   Lüftinger, T
   Christensen-Dalsgaard, J
   Catanzaro, G
   Frasca, A
   De Cat, P
   Uytterhoeven, K
   Bruntt, H
   Houdek, G
   Kurtz, DW
   Lenz, P
   Kaiser, A
   Van Cleve, J
   Allen, C
   Clarke, BD
AF Antoci, V.
   Handler, G.
   Campante, T. L.
   Thygesen, A. O.
   Moya, A.
   Kallinger, T.
   Stello, D.
   Grigahcene, A.
   Kjeldsen, H.
   Bedding, T. R.
   Lueftinger, T.
   Christensen-Dalsgaard, J.
   Catanzaro, G.
   Frasca, A.
   De Cat, P.
   Uytterhoeven, K.
   Bruntt, H.
   Houdek, G.
   Kurtz, D. W.
   Lenz, P.
   Kaiser, A.
   Van Cleve, J.
   Allen, C.
   Clarke, B. D.
TI The excitation of solar-like oscillations in a δ Sct star by efficient envelope convection
SO NATURE
LA English
DT Article
ID main-sequence; stellar oscillations; scuti; am; granulation; amplitudes; fields
AB Delta Scuti (delta Sct)(1) stars are opacity-driven pulsators with masses of 1.5-2.5 M-circle dot, their pulsations resulting from the varying ionization of helium. In less massive stars(2) such as the Sun, convection transports mass and energy through the outer 30 per cent of the star and excites a rich spectrum of resonant acoustic modes. Based on the solar example, with no firm theoretical basis, models predict that the convective envelope in delta Sct stars extends only about 1 per cent of the radius(3), but with sufficient energy to excite solar-like oscillations(4,5). This was not observed before the Kepler mission(6), so the presence of a convective envelope in the models has been questioned. Here we report the detection of solar-like oscillations in the delta Sct star HD187547, implying that surface convection operates efficiently in stars about twice as massive as the Sun, as the ad hoc models predicted.
C1 [Antoci, V.; Handler, G.; Kallinger, T.; Lueftinger, T.; Houdek, G.; Kaiser, A.] Univ Vienna, Inst Astron, A-1180 Vienna, Austria.
   [Handler, G.; Lenz, P.] Copernicus Astron Ctr, PL-00716 Warsaw, Poland.
   [Campante, T. L.; Grigahcene, A.] Univ Porto, Dept Fis Astron, Ctr Astrofis, Fac Ciencias, P-4150762 Oporto, Portugal.
   [Campante, T. L.; Kjeldsen, H.; Christensen-Dalsgaard, J.; Bruntt, H.] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Thygesen, A. O.] Nord Opt Telescope, E-38700 Santa Cruz De La Palma, Santa Cruz De T, Spain.
   [Moya, A.] CSIC, Dept Astrofis, Ctr Astrobiol, Inst Nacl Tecn Aeroesp, E-28691 Madrid, Spain.
   [Kallinger, T.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Kallinger, T.] Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Stello, D.; Bedding, T. R.] Univ Sydney, Sydney Inst Astron SIfA, Sch Phys, Sydney, NSW 2006, Australia.
   [Catanzaro, G.; Frasca, A.] Osserv Astrofis Catania, Ist Nazl Astrofis, I-95123 Catania, Italy.
   [De Cat, P.] Royal Observ Belgium, B-1180 Brussels, Belgium.
   [Uytterhoeven, K.] Univ Paris Diderot, Ctr Etud Saclay, Inst Rech Lois Fondament,Commissariat Energia Ato, Serv Astrophys,CEA DSM CNRS,Lab AIM, F-79104 Gif Sur Yvette, France.
   [Uytterhoeven, K.] Kiepenheuer Inst Sonnenphys, D-79104 Freiburg, Germany.
   [Uytterhoeven, K.] Inst Astrofis Canarias, Tenerife 38200, Spain.
   [Uytterhoeven, K.] Univ La Laguna, Dept Astrofis, Tenerife 38205, Spain.
   [Kurtz, D. W.] Univ Cent Lancashire, Jeremiah Horrocks Inst, Preston PR1 2HE, Lancs, England.
   [Van Cleve, J.; Clarke, B. D.] NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA.
   [Allen, C.] NASA, Ames Res Ctr, Orbital Sci Corp, Moffett Field, CA 94035 USA.
C3 University of Vienna; Universidade do Porto; Aarhus University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); University of British Columbia; KU Leuven; University of Sydney; Istituto Nazionale Astrofisica (INAF); CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite Paris Saclay; Kiepenheuer Institut fur Sonnenphysik; Instituto de Astrofisica de Canarias; Universidad de la Laguna; University of Lancashire; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Orbital Sciences Corporation
RP Antoci, V (corresponding author), Univ Vienna, Inst Astron, Turkenschanzstr 18, A-1180 Vienna, Austria.
EM victoria.antoci@univie.ac.at
FU Austrian Fonds zur Forderung der wissenschaftlichen Forschung; AstroMadrid; Spanish grants; Australian Research Council; Austrian Agency for International Cooperation in Education and Research; Deutsche Forschungsgemeinschaft; NASA's Science Mission Directorate; Austrian Science Fund (FWF) [P 22691, P 21830] Funding Source: researchfish
NR 30
TC 53
Z9 53
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 SEP 29
PY 2011
VL 477
IS 7366
BP 570
EP 573
DI 10.1038/nature10389
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900035
PM 21918514
DA 2026-03-09
ER

PT J
AU Garcia-Castellanos, D
   Villaseñor, A
AF Garcia-Castellanos, D.
   Villasenor, A.
TI Messinian salinity crisis regulated by competing tectonics and erosion at the Gibraltar arc
SO NATURE
LA English
DT Article
ID slab detachment; river incision; desiccation; chronology; evolution; dynamics; morocco; bedrock; events; uplift
AB The Messinian salinity crisis(1,2) (5.96 to 5.33 million years ago) was caused by reduced water inflow from the Atlantic Ocean to the Mediterranean Sea resulting in widespread salt precipitation and a decrease in Mediterranean sea level of about 1.5 kilometres due to evaporation(3). The reduced connectivity between the Atlantic and the Mediterranean at the time of the salinity crisis is thought to have resulted from tectonic uplift of the Gibraltar arc seaway and global sea-level changes, both of which control the inflow of water required to compensate for the hydrological deficit of the Mediterranean(1,4). However, the different timescales on which tectonic uplift and changes in sea level occur are difficult to reconcile with the long duration of the shallow connection between the Mediterranean and the Atlantic(5) needed to explain the large amount of salt precipitated. Here we use numerical modelling to show that seaway erosion caused by the Atlantic inflow could sustain such a shallow connection between the Atlantic and the Mediterranean by counteracting tectonic uplift. The erosion and uplift rates required are consistent with previous mountain erosion studies, with the present altitude of marine sediments in the Gibraltar arc(6,7) and with geodynamic models suggesting a lithospheric slab tear underneath the region(8-10). The moderate Mediterranean sea-level drawdown during the early stages of the Messinian salinity crisis(3,5) can be explained by an uplift of a few millimetres per year counteracted by similar rates of erosion due to Atlantic inflow. Our findings suggest that the competition between uplift and erosion can result in harmonic coupling between erosion and the Mediterranean sea level, providing an alternative mechanism for the cyclicity observed in early salt precipitation deposits and calling into question previous ideas regarding the timing of the events that occurred during the Messinian salinity crisis(1).
C1 [Garcia-Castellanos, D.; Villasenor, A.] CSIC, Inst Ciencias Tierra Jaume Almera, E-08028 Barcelona, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Geociencias Barcelona (GEO3BCN)
RP Garcia-Castellanos, D (corresponding author), CSIC, Inst Ciencias Tierra Jaume Almera, Sole & Sabaris S-N, E-08028 Barcelona, Spain.
EM danielgc@ictja.csic.es
FU Spanish government [CGL2009-09662, CGL2006-05493, CGL2008-03474-E/BTE, CSD2006-00041]
NR 45
TC 227
Z9 244
U1 4
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 359
EP U108
DI 10.1038/nature10651
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000049
PM 22170684
DA 2026-03-09
ER

PT J
AU Qian, L
   Winfree, E
   Bruck, J
AF Qian, Lulu
   Winfree, Erik
   Bruck, Jehoshua
TI Neural network computation with DNA strand displacement cascades
SO NATURE
LA English
DT Article
ID associative memory; chemical-kinetics; circuits; logic; depth
AB The impressive capabilities of the mammalian brain-ranging from perception, pattern recognition and memory formation to decision making and motor activity control-have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control(1). Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the 'intelligent' behaviour required for survival(2). However, the study of how molecules can 'think' has not produced an equal variety of computational models and applications of artificial chemical systems. Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo(3,2,4) and the synthesis of artificial chemical analogues has been proposed theoretically(5-9), experimental work(10-13) has so far fallen short of fully implementing even a single neuron. Here, building on the richness of DNA computing(14) and strand displacement circuitry(15), we show how molecular systems can exhibit autonomous brain-like behaviours. Using a simple DNA gate architecture(16) that allows experimental scale-up of multilayer digital circuits(17), we systematically transform arbitrary linear threshold circuits(18) (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks. Our approach even allows us to implement a Hopfield associative memory(19) with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern. Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment.
C1 [Qian, Lulu; Winfree, Erik; Bruck, Jehoshua] CALTECH, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Winfree, E (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM winfree@caltech.edu
FU NSF [0728703, 0832824]; HFSP award [RGY0074/2006-C]; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [0728703, 0832824] Funding Source: National Science Foundation
NR 31
TC 848
Z9 997
U1 33
U2 748
PU 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 21
PY 2011
VL 475
IS 7356
BP 368
EP 372
DI 10.1038/nature10262
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200040
PM 21776082
DA 2026-03-09
ER

PT J
AU Caiazzo, M
   Dell'Anno, MT
   Dvoretskova, E
   Lazarevic, D
   Taverna, S
   Leo, D
   Sotnikova, TD
   Menegon, A
   Roncaglia, P
   Colciago, G
   Russo, G
   Carninci, P
   Pezzoli, G
   Gainetdinov, RR
   Gustincich, S
   Dityatev, A
   Broccoli, V
AF Caiazzo, Massimiliano
   Dell'Anno, Maria Teresa
   Dvoretskova, Elena
   Lazarevic, Dejan
   Taverna, Stefano
   Leo, Damiana
   Sotnikova, Tatyana D.
   Menegon, Andrea
   Roncaglia, Paola
   Colciago, Giorgia
   Russo, Giovanni
   Carninci, Piero
   Pezzoli, Gianni
   Gainetdinov, Raul R.
   Gustincich, Stefano
   Dityatev, Alexander
   Broccoli, Vania
TI Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
SO NATURE
LA English
DT Article
ID embryonic stem-cells; expression; transplantation
AB Transplantation of dopaminergic neurons can potentially improve the clinical outcome of Parkinson's disease, a neurological disorder resulting from degeneration of mesencephalic dopaminergic neurons(1,2). In particular, transplantation of embryonic-stem-cell-derived dopaminergic neurons has been shown to be efficient in restoring motor symptoms in conditions of dopamine deficiency(3,4). However, the use of pluripotent-derived cells might lead to the development of tumours if not properly controlled(5). Here we identified a minimal set of three transcription factors-Mash1 (also known as Ascl1), Nurr1 (also known as Nr4a2) and Lmx1a-that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic (iDA) cells release dopamine and show spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The three factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson's disease patients. Direct generation of iDA cells from somatic cells might have significant implications for understanding critical processes for neuronal development, in vitro disease modelling and cell replacement therapies.
C1 [Caiazzo, Massimiliano; Dell'Anno, Maria Teresa; Colciago, Giorgia; Broccoli, Vania] Ist Sci San Raffaele, Stem Cells & Neurogenesis Unit, Div Neurosci, I-20132 Milan, Italy.
   [Dvoretskova, Elena; Taverna, Stefano; Leo, Damiana; Sotnikova, Tatyana D.; Russo, Giovanni; Pezzoli, Gianni; Gainetdinov, Raul R.; Dityatev, Alexander] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
   [Lazarevic, Dejan] CBM Srl, I-34149 Trieste, Italy.
   [Lazarevic, Dejan; Roncaglia, Paola; Gustincich, Stefano] Int Sch Adv Studies SISSA, Neurobiol Sect, I-34136 Trieste, Italy.
   [Menegon, Andrea] Ist Sci San Raffaele, Expt Imaging Ctr, Adv Light & Electron Microscopy Bioimaging Ctr, I-20132 Milan, Italy.
   [Carninci, Piero] RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, Kanagawa 2300045, Japan.
   [Pezzoli, Gianni] Ist Clin Perfezionamento, Parkinson Inst, I-20126 Milan, Italy.
   [Gustincich, Stefano] Giovanni Armenise Harvard Fdn Lab, I-34136 Trieste, Italy.
C3 Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Istituto Italiano di Tecnologia - IIT; International School for Advanced Studies (SISSA); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; RIKEN
RP Broccoli, V (corresponding author), Ist Sci San Raffaele, Stem Cells & Neurogenesis Unit, Div Neurosci, I-20132 Milan, Italy.
EM broccoli.vania@hsr.it
FU Fondazione Grigioni per il Morbo di Parkinson [FGBRCVNI10310-001-V.B.]; Eranet Neuron; Cariplo Foundation; Ministry of Health; Italian Institute of Technology; Fondazione Telethon Funding Source: Custom
NR 36
TC 804
Z9 980
U1 1
U2 205
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 224
EP U151
DI 10.1038/nature10284
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900040
PM 21725324
DA 2026-03-09
ER

PT J
AU She, J
   Han, ZF
   Kim, TW
   Wang, JJ
   Cheng, W
   Chang, JB
   Shi, SA
   Wang, JW
   Yang, MJ
   Wang, ZY
   Chai, JJ
AF She, Ji
   Han, Zhifu
   Kim, Tae-Wuk
   Wang, Jinjing
   Cheng, Wei
   Chang, Junbiao
   Shi, Shuai
   Wang, Jiawei
   Yang, Maojun
   Wang, Zhi-Yong
   Chai, Jijie
TI Structural insight into brassinosteroid perception by BRI1
SO NATURE
LA English
DT Article
ID receptor kinase bri1; signal-transduction; transcription factors; arabidopsis-thaliana; extracellular domain; plant-growth; complex; phosphorylation; activation; bri1/bak1
AB Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation.
C1 [She, Ji; Han, Zhifu; Wang, Jiawei; Yang, Maojun; Chai, Jijie] Tsinghua Univ, Key Lab Prot Sci, Minist Educ, Sch Life Sci, Beijing 100084, Peoples R China.
   [She, Ji] Peking Univ, Coll Biol Sci, Beijing 100084, Peoples R China.
   [She, Ji; Wang, Jinjing; Cheng, Wei; Chai, Jijie] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Kim, Tae-Wuk; Wang, Zhi-Yong] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA.
   [Chang, Junbiao; Shi, Shuai] Zhengzhou Univ, Dept Chem, Zhengzhou 450001, Peoples R China.
C3 Tsinghua University; Peking University; National Institute of Biological Sciences, Beijing; Carnegie Institution for Science; Zhengzhou University
RP Chai, JJ (corresponding author), Tsinghua Univ, Key Lab Prot Sci, Minist Educ, Sch Life Sci, Beijing 100084, Peoples R China.
EM chaijj@mail.tsinghua.edu.cn
FU National Outstanding Young Scholar Science Foundation of National Natural Science Foundation of China [20101331722]; NIH [R01GM066258]; National Institute of General Medical Sciences [R01GM066258] Funding Source: NIH RePORTER
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   Clouse SD, 1998, ANNU REV PLANT PHYS, V49, P427, DOI 10.1146/annurev.arplant.49.1.427
   DeLano WL, 2002, PYMOL MOL, V0, P0
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   Hink MA, 2008, BIOPHYS J, V94, P1052, DOI 10.1529/biophysj.107.112003
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   Schubert WD, 2002, CELL, V111, P825, DOI 10.1016/S0092-8674(02)01136-4
   Sheard LB, 2010, NATURE, V468, P400, DOI 10.1038/nature09430
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   Shiu SH, 2004, PLANT CELL, V16, P1220, DOI 10.1105/tpc.020834
   Sun Y, 2010, DEV CELL, V19, P765, DOI 10.1016/j.devcel.2010.10.010
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   Vert G, 2005, ANNU REV CELL DEV BI, V21, P177, DOI 10.1146/annurev.cellbio.21.090704.151241
   Wang XF, 2005, PLANT CELL, V17, P1685, DOI 10.1105/tpc.105.031393
   Wang XF, 2008, DEV CELL, V15, P220, DOI 10.1016/j.devcel.2008.06.011
   Wang XL, 2005, DEV CELL, V8, P855, DOI 10.1016/j.devcel.2005.05.001
   Wang XL, 2006, SCIENCE, V313, P1118, DOI 10.1126/science.1127593
   Whippo CW, 2005, PLANT PHYSIOL, V139, P448, DOI 10.1104/pp.105.064444
   Yun HS, 2009, MOL CELLS, V27, P183, DOI 10.1007/s10059-009-0023-1
   Zullo Marco António Teixeira, 2002, BRAZ. J. PLANT PHYSIOL., V14, P143, DOI 10.1590/S1677-04202002000300001
NR 36
TC 340
Z9 406
U1 8
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 JUN 23
PY 2011
VL 474
IS 7352
BP 472
EP U96
DI 10.1038/nature10178
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700040
PM 21666666
DA 2026-03-09
ER

PT J
AU Musset, B
   Smith, SME
   Rajan, S
   Morgan, D
   Cherny, VV
   DeCoursey, TE
AF Musset, Boris
   Smith, Susan M. E.
   Rajan, Sindhu
   Morgan, Deri
   Cherny, Vladimir V.
   DeCoursey, Thomas E.
TI Aspartate 112 is the selectivity filter of the human voltage-gated proton channel
SO NATURE
LA English
DT Article
ID influenza-a virus; alveolar epithelial-cells; human-neutrophils; nadph oxidase; ion-channel; h+ currents; transport; permeation; sensor; pore
AB The ion selectivity of pumps and channels is central to their ability to perform a multitude of functions. Here we investigate the mechanism of the extraordinary selectivity of the human voltage-gated proton channel(1), H(V)1 (also known as HVCN1). This selectivity is essential to its ability to regulate reactive oxygen species production by leukocytes(2-4), histamine secretion by basophils(5), sperm capacitation(6), and airway pH(7). The most selective ion channel known, H(V)1 shows no detectable permeability to other ions(1). Opposing classes of selectivity mechanisms postulate that (1) a titratable amino acid residue in the permeation pathway imparts proton selectivity(1,8-11), or (2) water molecules 'frozen' in a narrow pore conduct protons while excluding other ions(12). Here we identify aspartate 112 as a crucial component of the selectivity filter of H(V)1. When a neutral amino acid replaced Asp 112, the mutant channel lost proton specificity and became anion-selective or did not conduct. Only the glutamate mutant remained proton-specific. Mutation of the nearby Asp 185 did not impair proton selectivity, indicating that Asp 112 has a unique role. Although histidine shuttles protons in other proteins, when histidine or lysine replaced Asp 112, the mutant channel was still anion-permeable. Evidently, the proton specificity of H(V)1 requires an acidic group at the selectivity filter.
C1 [Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; DeCoursey, Thomas E.] Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA.
   [Smith, Susan M. E.] Emory Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
   [Rajan, Sindhu] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
C3 Rush University; Emory University; University of Chicago
RP DeCoursey, TE (corresponding author), Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA.
EM tdecours@rush.edu
FU NSF [MCB-0943362]; NIH [GM087507]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0943362] Funding Source: National Science Foundation
NR 37
TC 158
Z9 180
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 273
EP U167
DI 10.1038/nature10557
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200058
PM 22020278
DA 2026-03-09
ER

PT J
AU Sansjofre, P
   Ader, M
   Trindade, RIF
   Elie, M
   Lyons, J
   Cartigny, P
   Nogueira, ACR
AF Sansjofre, P.
   Ader, M.
   Trindade, R. I. F.
   Elie, M.
   Lyons, J.
   Cartigny, P.
   Nogueira, A. C. R.
TI A carbon isotope challenge to the snowball Earth
SO NATURE
LA English
DT Article
ID organic-carbon; cap dolostone; co2 levels; fractionation; oxygen; phytoplankton; evolution; temperature; excursions; atmosphere
AB The snowball Earth hypothesis postulates that the planet was entirely covered by ice for millions of years in the Neoproterozoic era, in a self-enhanced glaciation caused by the high albedo of the ice-covered planet. In a hard-snowball picture, the subsequent rapid unfreezing resulted from an ultra-greenhouse event attributed to the buildup of volcanic carbon dioxide (CO2) during glaciation(1). High partial pressures of atmospheric CO2 (p(CO2); from 20,000 to 90,000 p. p. m. v.) in the aftermath of the Marinoan glaciation (similar to 635 Myr ago) have been inferred from both boron and triple oxygen isotopes(2,3). These p(CO2) values are 50 to 225 times higher than present-day levels. Here, we re-evaluate these estimates using paired carbon isotopic data for carbonate layers that cap Neoproterozoic glacial deposits and are considered to record post-glacial sea level rise(1). The new data reported here for Brazilian cap carbonates, together with previous ones for time-equivalent units(4-8), provide p(CO2) estimates lower than 3,200 p. p. m. v.-and possibly as low as the current value of similar to 400 p. p. m. v. Our new constraint, and our reinterpretation of the boron and triple oxygen isotope data, provide a completely different picture of the late Neoproterozoic environment, with low atmospheric concentrations of carbon dioxide and oxygen that are inconsistent with a hard-snowball Earth.
C1 [Sansjofre, P.; Ader, M.; Cartigny, P.] Univ Paris Diderot, Equipe Geochim Isotopes Stables, Inst Phys Globe Paris, UMR CNRS 7154, F-75238 Paris 05, France.
   [Sansjofre, P.; Trindade, R. I. F.] Univ Sao Paulo, Dept Geofis, Inst Astron Geofis & Ciencias Atmosfer, BR-05508900 Sao Paulo, Brazil.
   [Elie, M.] Nancy Univ, UMR CNRS G2R 7566, CNRS, F-54506 Vandoeuvre Les Nancy, France.
   [Lyons, J.] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA.
   [Nogueira, A. C. R.] Fed Univ Para, Fac Geol, Inst Geociencias, BR-66075110 Belem, Para, Brazil.
C3 Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universidade de Sao Paulo; Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California Los Angeles; Universidade Federal do Para
RP Sansjofre, P (corresponding author), Univ Paris Diderot, Equipe Geochim Isotopes Stables, Inst Phys Globe Paris, UMR CNRS 7154, F-75238 Paris 05, France.
EM sansjofre@ipgp.fr
FU French MRT doctoral fellowship; SETSI grant; INSU (SYSTER) grants; INCT-Geociam programme; FAPESP; CNPq; NASA Astrobiology Institute [NNA09DA76]
NR 39
TC 78
Z9 88
U1 2
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 OCT 6
PY 2011
VL 478
IS 7367
BP 93
EP U103
DI 10.1038/nature10499
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400041
PM 21979050
DA 2026-03-09
ER

PT J
AU Carette, JE
   Raaben, M
   Wong, AC
   Herbert, AS
   Obernosterer, G
   Mulherkar, N
   Kuehne, AI
   Kranzusch, PJ
   Griffin, AM
   Ruthel, G
   Dal Cin, P
   Dye, JM
   Whelan, SP
   Chandran, K
   Brummelkamp, TR
AF Carette, Jan E.
   Raaben, Matthijs
   Wong, Anthony C.
   Herbert, Andrew S.
   Obernosterer, Gregor
   Mulherkar, Nirupama
   Kuehne, Ana I.
   Kranzusch, Philip J.
   Griffin, April M.
   Ruthel, Gordon
   Dal Cin, Paola
   Dye, John M.
   Whelan, Sean P.
   Chandran, Kartik
   Brummelkamp, Thijn R.
TI Ebola virus entry requires the cholesterol transporter Niemann-Pick C1
SO NATURE
LA English
DT Article
ID vesicular stomatitis-virus; hemorrhagic-fever; zaire-ebolavirus; human-cells; identification; gene; glycoprotein; mechanism; receptor; antibody
AB Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available(1). Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes(2). Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification(3-5). Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes(6), and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1)(7). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.
C1 [Carette, Jan E.; Obernosterer, Gregor; Brummelkamp, Thijn R.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
   [Raaben, Matthijs; Kranzusch, Philip J.; Griffin, April M.; Whelan, Sean P.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   [Wong, Anthony C.; Mulherkar, Nirupama; Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
   [Herbert, Andrew S.; Kuehne, Ana I.; Ruthel, Gordon; Dye, John M.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
   [Dal Cin, Paola] Ctr Adv Mol Diagnost, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard Medical School; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Brummelkamp, TR (corresponding author), Netherlands Canc Inst, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM John.M.Dye1@us.army.mil; sean_whelan@hms.harvard.edu; kartik.chandran@einstein.yu.edu; t.brummelkamp@nki.nl
FU NIH [R01 AI088027, AI081842, U54 AI057159, R21 HG004938]; DTRA Project [CBM.VAXPLAT.05.10.RD.005]; Whitehead Fellows Program; Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award; NIH at the Albert Einstein College of Medicine [T32 GM007288, T32 AI070117]; National Institute of Allergy and Infectious Diseases [T32AI070117] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007288] Funding Source: NIH RePORTER
NR 49
TC 1033
Z9 1298
U1 6
U2 282
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 340
EP U115
DI 10.1038/nature10348
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400033
PM 21866103
DA 2026-03-09
ER

PT J
AU Leung, AKW
   Nagai, K
   Li, J
AF Leung, Adelaine K. W.
   Nagai, Kiyoshi
   Li, Jade
TI Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis
SO NATURE
LA English
DT Article
ID automated structure solution; crystal-structure; sm proteins; u1 snrnp; electron-microscopy; rna-binding; complex; u5; u2; u6
AB The spliceosome is a dynamic macromolecular machine that assembles on pre-messenger RNA substrates and catalyses the excision of non-coding intervening sequences (introns)(1-3). Four of the five major components of the spliceosome, U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), contain seven Sm proteins (SmB/B9, SmD1, SmD2, SmD3, SmE, SmF and SmG) in common(4,5). Following export of the U1, U2, U4 and U5 snRNAs to the cytoplasm(6,7), the seven Sm proteins, chaperoned by the survival of motor neurons (SMN) complex, assemble around a single-stranded, U-rich sequence called the Sm site in each small nuclear RNA (snRNA), to form the core domain of the respective snRNP particle(8,9). Core domain formation is a prerequisite for re-import into the nucleus(10), where these snRNPs mature via addition of their particle-specific proteins. Here we present a crystal structure of the U4 snRNP core domain at 3.6 angstrom resolution, detailing how the Sm site heptad (AUUUUUG) binds inside the central hole of the heptameric ring of Sm proteins, interacting one-to-one with SmE-SmG-SmD3-SmB-SmD1-SmD2-SmF. An irregular backbone conformation of the Sm site sequence combined with the asymmetric structure of the heteromeric protein ring allows each base to interact in a distinct manner with four key residues at equivalent positions in the L3 and L5 loops of the Sm fold. A comparison of this structure with the U1 snRNP at 5.5 angstrom resolution(11,12) reveals snRNA-dependent structural changes outside the Sm fold, which may facilitate the binding of particle-specific proteins that are crucial to biogenesis of spliceosomal snRNPs.
C1 [Leung, Adelaine K. W.; Nagai, Kiyoshi; Li, Jade] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Nagai, K (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM kn@mrc-lmb.cam.ac.uk; jl@mrc-lmb.cam.ac.uk
FU Medical Research Council of the UK; HFSP; NSERC; Sidney Sussex College, Cambridge University; MRC [MC_U105184330] Funding Source: UKRI; Medical Research Council [MC_U105184330] Funding Source: researchfish
NR 56
TC 103
Z9 127
U1 0
U2 24
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 536
EP U285
DI 10.1038/nature09956
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300046
PM 21516107
DA 2026-03-09
ER

PT J
AU Facciabene, A
   Peng, XH
   Hagemann, IS
   Balint, K
   Barchetti, A
   Wang, LP
   Gimotty, PA
   Gilks, CB
   Lal, P
   Zhang, L
   Coukos, G
AF Facciabene, Andrea
   Peng, Xiaohui
   Hagemann, Ian S.
   Balint, Klara
   Barchetti, Andrea
   Wang, Li-Ping
   Gimotty, Phyllis A.
   Gilks, C. Blake
   Lal, Priti
   Zhang, Lin
   Coukos, George
TI Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
SO NATURE
LA English
DT Article
ID endothelial growth-factor; ovarian-cancer; suppressor-cells; dendritic cells; immune therapy; b receptor; recruitment; ccr10; vegf; expression
AB Although immune mechanisms can suppress tumour growth(1,2), tumours establish potent, overlapping mechanisms that mediate immune evasion(3-6). Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms(7-10). Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system(11). Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T-reg) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth.
C1 [Facciabene, Andrea; Peng, Xiaohui; Balint, Klara; Barchetti, Andrea; Zhang, Lin; Coukos, George] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
   [Hagemann, Ian S.; Wang, Li-Ping; Lal, Priti] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Gimotty, Phyllis A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Gilks, C. Blake] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of British Columbia
RP Coukos, G (corresponding author), Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
EM gcks@mail.med.upenn.edu
FU National Institutes of Health [R01-CA116779]; National Cancer Institute [P01-CA83638]; Ovarian Cancer Research Fund
NR 37
TC 1139
Z9 1295
U1 1
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 226
EP U141
DI 10.1038/nature10169
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500050
PM 21753853
DA 2026-03-09
ER

PT J
AU Sander, LE
   Davis, MJ
   Boekschoten, MV
   Amsen, D
   Dascher, CC
   Ryffel, B
   Swanson, JA
   Müller, M
   Blander, JM
AF Sander, Leif E.
   Davis, Michael J.
   Boekschoten, Mark V.
   Amsen, Derk
   Dascher, Christopher C.
   Ryffel, Bernard
   Swanson, Joel A.
   Mueller, Michael
   Blander, J. Magarian
TI Detection of prokaryotic mRNA signifies microbial viability and promotes immunity
SO NATURE
LA English
DT Article
ID toll-like receptors; t-cell responses; transcription factors; protective immunity; innate; inflammasome; recognition; activation; regulators; phagosome
AB Live vaccines have long been known to trigger far more vigorous immune responses than their killed counterparts(1-6). This has been attributed to the ability of live microorganisms to replicate and express specialized virulence factors that facilitate invasion and infection of their hosts(7). However, protective immunization can often be achieved with a single injection of live, but not dead, attenuated microorganisms stripped of their virulence factors. Pathogen-associated molecular patterns (PAMPs), which are detected by the immune system(8,9), are present in both live and killed vaccines, indicating that certain poorly characterized aspects of live microorganisms, not incorporated in dead vaccines, are particularly effective at inducing protective immunity. Here we show that the mammalian innate immune system can directly sense microbial viability through detection of a special class of viability-associated PAMPs (vita-PAMPs). We identify prokaryotic messenger RNA as a vita-PAMP present only in viable bacteria, the recognition of which elicits a unique innate response and a robust adaptive antibody response. Notably, the innate response evoked by viability and prokaryotic mRNA was thus far considered to be reserved for pathogenic bacteria, but we show that even non-pathogenic bacteria in sterile tissues can trigger similar responses, provided that they are alive. Thus, the immune system actively gauges the infectious risk by searching PAMPs for signatures of microbial life and thus infectivity. Detection of vita-PAMPs triggers a state of alert not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines.
C1 [Sander, Leif E.; Dascher, Christopher C.; Blander, J. Magarian] Mt Sinai Sch Med, Inst Immunol, Dept Med, New York, NY 10029 USA.
   [Davis, Michael J.; Swanson, Joel A.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Boekschoten, Mark V.; Mueller, Michael] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, NL-6703 HD Wageningen, Netherlands.
   [Amsen, Derk] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands.
   [Ryffel, Bernard] Univ Orleans, Lab Mol Immunol & Embryol, F-45071 Orleans, France.
   [Ryffel, Bernard] CNRS, F-45071 Orleans, France.
C3 Icahn School of Medicine at Mount Sinai; University of Michigan System; University of Michigan; Wageningen University & Research; University of Amsterdam; Academic Medical Center Amsterdam; Universite de Orleans; Centre National de la Recherche Scientifique (CNRS)
RP Blander, JM (corresponding author), Mt Sinai Sch Med, Inst Immunol, Dept Med, 1425 Madison Ave, New York, NY 10029 USA.
EM julie.blander@mssm.edu
FU NIAID NIH HHS [R01 AI064668, R01 AI095245, R21 AI080959, AI080959A] Funding Source: Medline; NIGMS NIH HHS [T32 GM145304] Funding Source: Medline
NR 51
TC 334
Z9 388
U1 1
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 385
EP +
DI 10.1038/nature10072
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100047
PM 21602824
DA 2026-03-09
ER

PT J
AU Safavi-Naeini, AH
   Alegre, TPM
   Chan, J
   Eichenfield, M
   Winger, M
   Lin, Q
   Hill, JT
   Chang, DE
   Painter, O
AF Safavi-Naeini, A. H.
   Alegre, T. P. Mayer
   Chan, J.
   Eichenfield, M.
   Winger, M.
   Lin, Q.
   Hill, J. T.
   Chang, D. E.
   Painter, O.
TI Electromagnetically induced transparency and slow light with optomechanics
SO NATURE
LA English
DT Article
ID resonator; state
AB Controlling the interaction between localized optical and mechanical excitations has recently become possible following advances in micro-and nanofabrication techniques(1,2). So far, most experimental studies of optomechanics have focused on measurement and control of the mechanical subsystem through its interaction with optics, and have led to the experimental demonstration of dynamical back-action cooling and optical rigidity of the mechanical system(1,3). Conversely, the optical response of these systems is also modified in the presence of mechanical interactions, leading to effects such as electromagnetically induced transparency(4) (EIT) and parametric normal-mode splitting(5). In atomic systems, studies(6,7) of slow and stopped light (applicable to modern optical networks(8) and future quantum networks(9)) have thrust EIT to the forefront of experimental study during the past two decades. Here we demonstrate EIT and tunable optical delays in a nanoscale optomechanical crystal, using the optomechanical nonlinearity to control the velocity of light by way of engineered photon-phonon interactions. Our device is fabricated by simply etching holes into a thin film of silicon. At low temperature (8.7 kelvin), we report an optically tunable delay of 50 nanoseconds with near-unity optical transparency, and superluminal light with a 1.4 microsecond signal advance. These results, while indicating significant progress towards an integrated quantum optomechanical memory(10), are also relevant to classical signal processing applications. Measurements at room temperature in the analogous regime of electromagnetically induced absorption show the utility of these chip-scale optomechanical systems for optical buffering, amplification, and filtering of microwave-over-optical signals.
C1 [Safavi-Naeini, A. H.; Alegre, T. P. Mayer; Chan, J.; Eichenfield, M.; Winger, M.; Lin, Q.; Hill, J. T.; Painter, O.] CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
   [Chang, D. E.] CALTECH, Inst Quantum Informat, Pasadena, CA 91125 USA.
   [Chang, D. E.] CALTECH, Ctr Phys Informat, Pasadena, CA 91125 USA.
C3 California Institute of Technology; California Institute of Technology; California Institute of Technology
RP Painter, O (corresponding author), CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
EM opainter@caltech.edu
FU DARPA/MTO ORCHID through AFOSR; Kavli Nanoscience Institute at Caltech; NSERC
NR 30
TC 1313
Z9 1466
U1 10
U2 522
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 69
EP 73
DI 10.1038/nature09933
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400038
PM 21412237
DA 2026-03-09
ER

PT J
AU Lee, H
   Chah, OK
   Sheen, J
AF Lee, Horim
   Chah, Ok-Kyong
   Sheen, Jen
TI Stem-cell-triggered immunity through CLV3p-FLS2 signalling
SO NATURE
LA English
DT Article
ID receptor-like kinase; bacterial elicitor flagellin; rich repeat domain; arabidopsis-thaliana; innate immunity; perception; fls2; clavata1; meristem; resistance
AB Stem cells in the shoot apical meristem (SAM) of plants are the self-renewable reservoir for leaf, stem and flower organogenesis(1,2). In nature, disease-free plants can be regenerated from SAM despite infections elsewhere, which underlies a horticultural practice for decades(3). However, the molecular basis of the SAM immunity remains unclear. Here we show that the CLAVATA3 peptide (CLV3p), expressed and secreted from stem cells and functioning as a key regulator of stem-cell homeostasis in the SAM of Arabidopsis(1,2,4), can trigger immune signalling and pathogen resistance via the flagellin receptor kinase FLS2 (refs 5, 6). CLV3p-FLS2 signalling acts independently from the stem-cell signalling pathway mediated through CLV1 and CLV2 receptors(1,2,4), and is uncoupled from FLS2-mediated growth suppression(5,6). Endogenous CLV3p perception in the SAM by a pattern recognition receptor for bacterial flagellin, FLS2, breaks the previously defined self and non-self discrimination in innate immunity(6,7). The dual perception of CLV3p illustrates co-evolution of plant peptide and receptor kinase signalling for both development and immunity. The enhanced immunity in SAM or germ lines may represent a common strategy towards immortal fate in plants and animals(1,2,8).
C1 [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Lee, Horim; Chah, Ok-Kyong; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Lee, H (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM hrlee@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu
FU NSF; NIH; MGH CCIB fund; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0843244] Funding Source: National Science Foundation
NR 40
TC 60
Z9 72
U1 1
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 376
EP U559
DI 10.1038/nature09958
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400049
PM 21499263
DA 2026-03-09
ER

PT J
AU Kai, FM
   Tyler, SC
   Randerson, JT
   Blake, DR
AF Kai, Fuu Ming
   Tyler, Stanley C.
   Randerson, James T.
   Blake, Donald R.
TI Reduced methane growth rate explained by decreased Northern Hemisphere microbial sources
SO NATURE
LA English
DT Article
ID atmospheric methane; water management; rice fields; emissions; budget; china; model; gas
AB Atmospheric methane(CH4) increased through much of the twentieth century, but this trend gradually weakened until a stable state was temporarily reached around the turn of the millennium(1,2), after which levels increased once more(3). The reasons for the slowdown are incompletely understood, with past work identifying changes in fossil fuel, wetland and agricultural sources and hydroxyl (OH) sinks as important causal factors(1,4-8). Here we show that the late-twentieth century changes in the CH4 growth rates are best explained by reduced microbial sources in the Northern Hemisphere. Our results, based on synchronous time series of atmospheric CH4 mixing and C-13/C-12 ratios and a two-box atmospheric model, indicate that the evolution of the mixing ratio requires no significant change in Southern Hemisphere sources between 1984 and 2005. Observed changes in the interhemispheric difference of C-13 effectively exclude reduced fossil fuel emissions as the primary cause of the slowdown. The C-13 observations are consistent with long-term reductions in agricultural emissions or another microbial source within the Northern Hemisphere. Approximately half (51 +/- 18%) of the decrease in Northern Hemisphere CH4 emissions can be explained by reduced emissions from rice agriculture in Asia over the past three decades associated with increases in fertilizer application(9) and reductions in water use(10,11).
C1 [Kai, Fuu Ming; Tyler, Stanley C.; Randerson, James T.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Blake, Donald R.] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
C3 University of California System; University of California Irvine; University of California System; University of California Irvine
RP Kai, FM (corresponding author), Singapore MIT Alliance Res & Technol, S16-05-08,3 Sci Dr 2, Singapore 117543, Singapore.
EM fmkai@smart.mit.edu
FU NASA [NGT5-30409, NNX08AF64G]; NSF [ATM 9871077, ATM-0628637, AGS-1021776]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [1021613] Funding Source: National Science Foundation
NR 30
TC 136
Z9 168
U1 2
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 194
EP 197
DI 10.1038/nature10259
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900033
PM 21833086
DA 2026-03-09
ER

PT J
AU Dymond, JS
   Richardson, SM
   Coombes, CE
   Babatz, T
   Muller, H
   Annaluru, N
   Blake, WJ
   Schwerzmann, JW
   Dai, JB
   Lindstrom, DL
   Boeke, AC
   Gottschling, DE
   Chandrasegaran, S
   Bader, JS
   Boeke, JD
AF Dymond, Jessica S.
   Richardson, Sarah M.
   Coombes, Candice E.
   Babatz, Timothy
   Muller, Heloise
   Annaluru, Narayana
   Blake, William J.
   Schwerzmann, Joy W.
   Dai, Junbiao
   Lindstrom, Derek L.
   Boeke, Annabel C.
   Gottschling, Daniel E.
   Chandrasegaran, Srinivasan
   Bader, Joel S.
   Boeke, Jef D.
TI Synthetic chromosome arms function in yeast and generate phenotypic diversity by design
SO NATURE
LA English
DT Article
ID dna; selection; sequence; genes; site
AB Recent advances in DNA synthesis technology have enabled the construction of novel genetic pathways and genomic elements, furthering our understanding of system-level phenomena(1-7). The ability to synthesize large segments of DNA allows the engineering of pathways and genomes according to arbitrary sets of design principles. Here we describe a synthetic yeast genome project, Sc2.0, and the first partially synthetic eukaryotic chromosomes, Saccharomyces cerevisiae chromosome synIXR, and semi-synVIL. We defined three design principles for a synthetic genome as follows: first, it should result in a (near) wild-type phenotype and fitness; second, it should lack destabilizing elements such as tRNA genes or transposons(8,9); and third, it should have genetic flexibility to facilitate future studies. The synthetic genome features several systemic modifications complying with the design principles, including an inducible evolution system, SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution). We show the utility of SCRaMbLE as a novel method of combinatorial mutagenesis, capable of generating complex genotypes and a broad variety of phenotypes. When complete, the fully synthetic genome will allow massive restructuring of the yeast genome, and may open the door to a new type of combinatorial genetics based entirely on variations in gene content and copy number.
C1 [Dymond, Jessica S.; Richardson, Sarah M.; Coombes, Candice E.; Babatz, Timothy; Dai, Junbiao; Boeke, Annabel C.; Bader, Joel S.; Boeke, Jef D.] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA.
   [Dymond, Jessica S.; Coombes, Candice E.; Dai, Junbiao; Boeke, Jef D.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
   [Richardson, Sarah M.; Babatz, Timothy] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Muller, Heloise; Annaluru, Narayana; Schwerzmann, Joy W.; Chandrasegaran, Srinivasan] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
   [Blake, William J.] Codon Devices, Cambridge, MA 02139 USA.
   [Lindstrom, Derek L.; Gottschling, Daniel E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Bader, Joel S.] Johns Hopkins Univ, Dept Biomed Engn, Whiting Sch Engn, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Fred Hutchinson Cancer Center; Johns Hopkins University
RP Boeke, JD (corresponding author), Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, 733 North Broadway, Baltimore, MD 21205 USA.
EM jboeke@jhmi.edu
FU National Science Foundation [MCB0718846]; Microsoft; Department of Energy [DE-FG02097ER25308]; National Institutes of Health [AG023779]; Fondation pour la Recherche Medicale; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1443299] Funding Source: National Science Foundation
NR 29
TC 369
Z9 471
U1 8
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 SEP 22
PY 2011
VL 477
IS 7365
BP 471
EP U124
DI 10.1038/nature10403
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500042
PM 21918511
DA 2026-03-09
ER

PT J
AU Turner, SL
   Li, N
   Guda, T
   Githure, J
   Cardé, RT
   Ray, A
AF Turner, Stephanie Lynn
   Li, Nan
   Guda, Tom
   Githure, John
   Carde, Ring T.
   Ray, Anandasankar
TI Ultra-prolonged activation of CO2-sensing neurons disorients mosquitoes
SO NATURE
LA English
DT Article
ID carbon-dioxide; aedes-aegypti; anopheles-gambiae; maxillary palp; drosophila; insect; deet; receptors; responses; diptera
AB Carbon dioxide (CO2) present in exhaled air is the most important sensory cue for female blood-feeding mosquitoes, causing activation of long-distance host-seeking flight, navigation towards the vertebrate host(1) and, in the case of Aedes aegypti, increased sensitivity to skin odours(2). The CO2 detection machinery is therefore an ideal target to disrupt host seeking. Here we use electrophysiological assays to identify a volatile odorant that causes an unusual, ultra-prolonged activation of CO2-detecting neurons in three major disease-transmitting mosquitoes: Anopheles gambiae, Culex quinquefasciatus and A. aegypti. Importantly, ultra-prolonged activation of these neurons severely compromises their ability subsequently to detect CO2 for several minutes. We also identify odours that strongly inhibit CO2-sensitive neurons as candidates for use in disruption of host-seeking behaviour, as well as an odour that evokes CO2-like activity and thus has potential use as a lure in trapping devices. Analysis of responses to panels of structurally related odours across the three mosquitoes and Drosophila, which have related CO2-receptor proteins, reveals a pattern of inhibition that is often conserved. We use video tracking in wind-tunnel experiments to demonstrate that the novel ultra-prolonged activators can completely disrupt CO2-mediated activation as well as source-finding behaviour in Aedes mosquitoes, even after the odour is no longer present. Lastly, semi-field studies demonstrate that use of ultra-prolonged activators disrupts CO2-mediated hut entry behaviour of Culex mosquitoes. The three classes of CO2-response-modifying odours offer powerful instruments for developing new generations of insect repellents and lures, which even in small quantities can interfere with the ability of mosquitoes to seek humans.
C1 [Turner, Stephanie Lynn; Ray, Anandasankar] Univ Calif Riverside, Cellular Mol & Dev Biol Program, Riverside, CA 92521 USA.
   [Li, Nan; Carde, Ring T.; Ray, Anandasankar] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
   [Guda, Tom; Githure, John] ICIPE, Human Hlth Div, Nairobi, Kenya.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside; International Centre of Insect Physiology & Ecology (ICIPE)
RP Ray, A (corresponding author), Univ Calif Riverside, Cellular Mol & Dev Biol Program, Riverside, CA 92521 USA.
EM anand.ray@ucr.edu
FU Bill & Melinda Gates Foundation through the Grand Challenges Exploration Initiative; NIAID (NIH) [R01AI087785]
NR 30
TC 127
Z9 164
U1 0
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 87
EP U114
DI 10.1038/nature10081
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700043
PM 21637258
DA 2026-03-09
ER

PT J
AU Ruediger, S
   Vittori, C
   Bednarek, E
   Genoud, C
   Strata, P
   Sacchetti, B
   Caroni, P
AF Ruediger, Sarah
   Vittori, Claudia
   Bednarek, Ewa
   Genoud, Christel
   Strata, Piergiorgio
   Sacchetti, Benedetto
   Caroni, Pico
TI Learning-related feedforward inhibitory connectivity growth required for memory precision
SO NATURE
LA English
DT Article
ID structural plasticity; synaptic plasticity; cortical circuits; hippocampus; ca3; consolidation; context; brain; cells
AB In the adult brain, new synapses are formed and pre-existing ones are lost, but the function of this structural plasticity has remained unclear(1-5). Learning of new skills is correlated with formation of new synapses(6-8). These may directly encode new memories, but they may also have more general roles in memory encoding and retrieval processes(2). Here we investigated how mossy fibre terminal complexes at the entry of hippocampal and cerebellar circuits rearrange upon learning in mice, and what is the functional role of the rearrangements. We show that one-trial and incremental learning lead to robust, circuit-specific, long-lasting and reversible increases in the numbers of filopodial synapses onto fast-spiking interneurons that trigger feedforward inhibition. The increase in feedforward inhibition connectivity involved a majority of the presynaptic terminals, restricted the numbers of c-Fos-expressing postsynaptic neurons at memory retrieval, and correlated temporally with the quality of the memory. We then show that for contextual fear conditioning and Morris water maze learning, increased feedforward inhibition connectivity by hippocampal mossy fibres has a critical role for the precision of the memory and the learned behaviour. In the absence of mossy fibre long-term potentiation in Rab3a(-/-) mice(9), c-Fos ensemble reorganization and feedforward inhibition growth were both absent in CA3 upon learning, and the memory was imprecise. By contrast, in the absence of adducin 2 (Add2; also known as beta-adducin)(10) c-Fos reorganization was normal, but feedforward inhibition growth was abolished. In parallel, c-Fos ensembles in CA3 were greatly enlarged, and the memory was imprecise. Feedforward inhibition growth and memory precision were both rescued by re-expression of Add2 specifically in hippocampal mossy fibres. These results establish a causal relationship between learning-related increases in the numbers of defined synapses and the precision of learning and memory in the adult. The results further relate plasticity and feedforward inhibition growth at hippocampal mossy fibres to the precision of hippocampus-dependent memories.
C1 [Ruediger, Sarah; Vittori, Claudia; Bednarek, Ewa; Genoud, Christel; Caroni, Pico] Friedrich Miescher Inst, CH-4058 Basel, Switzerland.
   [Vittori, Claudia; Strata, Piergiorgio; Sacchetti, Benedetto] Dept Neurosci, I-10125 Turin, Italy.
   [Vittori, Claudia; Strata, Piergiorgio; Sacchetti, Benedetto] Natl Inst Neurosci Italy, I-10125 Turin, Italy.
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
NR 30
TC 223
Z9 261
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 514
EP U258
DI 10.1038/nature09946
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300041
PM 21532590
DA 2026-03-09
ER

PT J
AU Mills, RE
   Walter, K
   Stewart, C
   Handsaker, RE
   Chen, K
   Alkan, C
   Abyzov, A
   Yoon, SC
   Ye, K
   Cheetham, RK
   Chinwalla, A
   Conrad, DF
   Fu, YT
   Grubert, F
   Hajirasouliha, I
   Hormozdiari, F
   Iakoucheva, LM
   Iqbal, Z
   Kang, SL
   Kidd, JM
   Konkel, MK
   Korn, J
   Khurana, E
   Kural, D
   Lam, HYK
   Leng, J
   Li, RQ
   Li, YR
   Lin, CY
   Luo, RB
   Mu, XJ
   Nemesh, J
   Peckham, HE
   Rausch, T
   Scally, A
   Shi, XH
   Stromberg, MP
   Stütz, AM
   Urban, AE
   Walker, JA
   Wu, JT
   Zhang, YJ
   Zhang, ZDD
   Batzer, MA
   Ding, L
   Marth, GT
   McVean, G
   Sebat, J
   Snyder, M
   Wang, J
   Ye, K
   Eichler, EE
   Gerstein, MB
   Hurles, ME
   Lee, C
   McCarroll, SA
   Korbel, JO
AF Mills, Ryan E.
   Walter, Klaudia
   Stewart, Chip
   Handsaker, Robert E.
   Chen, Ken
   Alkan, Can
   Abyzov, Alexej
   Yoon, Seungtai Chris
   Ye, Kai
   Cheetham, R. Keira
   Chinwalla, Asif
   Conrad, Donald F.
   Fu, Yutao
   Grubert, Fabian
   Hajirasouliha, Iman
   Hormozdiari, Fereydoun
   Iakoucheva, Lilia M.
   Iqbal, Zamin
   Kang, Shuli
   Kidd, Jeffrey M.
   Konkel, Miriam K.
   Korn, Joshua
   Khurana, Ekta
   Kural, Deniz
   Lam, Hugo Y. K.
   Leng, Jing
   Li, Ruiqiang
   Li, Yingrui
   Lin, Chang-Yun
   Luo, Ruibang
   Mu, Xinmeng Jasmine
   Nemesh, James
   Peckham, Heather E.
   Rausch, Tobias
   Scally, Aylwyn
   Shi, Xinghua
   Stromberg, Michael P.
   Stuetz, Adrian M.
   Urban, Alexander Eckehart
   Walker, Jerilyn A.
   Wu, Jiantao
   Zhang, Yujun
   Zhang, Zhengdong D.
   Batzer, Mark A.
   Ding, Li
   Marth, Gabor T.
   McVean, Gil
   Sebat, Jonathan
   Snyder, Michael
   Wang, Jun
   Ye, Kenny
   Eichler, Evan E.
   Gerstein, Mark B.
   Hurles, Matthew E.
   Lee, Charles
   McCarroll, Steven A.
   Korbel, Jan O.
TI Mapping copy number variation by population-scale genome sequencing
SO NATURE
LA English
DT Article
ID structural variation; segmental duplications; short-read; rearrangements; common; polymorphism; insertions; deletions; snps
AB Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.
C1 [Rausch, Tobias; Stuetz, Adrian M.; Korbel, Jan O.] European Mol Biol Lab, Genome Biol Res Unit, Heidelberg, Germany.
   [Mills, Ryan E.; Shi, Xinghua; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Mills, Ryan E.; Shi, Xinghua; Lee, Charles] Harvard Univ, Sch Med, Boston, MA USA.
   [Walter, Klaudia; Conrad, Donald F.; Scally, Aylwyn; Zhang, Yujun; Hurles, Matthew E.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Stewart, Chip; Kural, Deniz; Stromberg, Michael P.; Wu, Jiantao; Marth, Gabor T.] Boston Coll, Dept Biol, Boston, MA USA.
   [Handsaker, Robert E.; Korn, Joshua; Nemesh, James; McCarroll, Steven A.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
   [Handsaker, Robert E.; Korn, Joshua; Nemesh, James; McCarroll, Steven A.] MIT, Cambridge, MA 02139 USA.
   [Chen, Ken; Chinwalla, Asif; Ding, Li] Washington Univ, Genome Ctr, St Louis, MO USA.
   [Alkan, Can; Kidd, Jeffrey M.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
   [Alkan, Can; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Abyzov, Alexej; Khurana, Ekta; Leng, Jing; Mu, Xinmeng Jasmine; Zhang, Zhengdong D.; Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA.
   [Yoon, Seungtai Chris] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY USA.
   [Yoon, Seungtai Chris] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
   [Ye, Kai] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.
   [Ye, Kai] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands.
   [Cheetham, R. Keira] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
   [Fu, Yutao; Peckham, Heather E.] Life Technol, Beverly, MA USA.
   [Grubert, Fabian; Lam, Hugo Y. K.; Urban, Alexander Eckehart; Snyder, Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Hajirasouliha, Iman; Hormozdiari, Fereydoun] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada.
   [Iakoucheva, Lilia M.; Kang, Shuli; Sebat, Jonathan] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, Dept Psychiat, La Jolla, CA 92093 USA.
   [Iqbal, Zamin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Khurana, Ekta; Gerstein, Mark B.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA.
   [Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Lin, Chang-Yun; Ye, Kenny] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Ding, Li] Washington Univ, Dept Genet, St Louis, MO 63110 USA.
   [McVean, Gil] Univ Oxford, Dept Stat, Oxford OX3 7BN, England.
   [Wang, Jun] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
   [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
   [Urban, Alexander Eckehart] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 European Molecular Biology Laboratory (EMBL); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Wellcome Trust Sanger Institute; Boston College; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Washington University (WUSTL); University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Yale University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Illumina; Thermo Fisher Scientific; Stanford University; Simon Fraser University; University of California System; University of California San Diego; University of Oxford; Wellcome Centre for Human Genetics; Louisiana State University System; Louisiana State University; Yale University; Beijing Genomics Institute (BGI); Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Washington University (WUSTL); University of Oxford; University of Copenhagen; Yale University; Harvard University; Harvard Medical School; Stanford University
RP Korbel, JO (corresponding author), European Mol Biol Lab, Genome Biol Res Unit, Heidelberg, Germany.
EM jan.korbel@embl.de
FU National Institutes of Health [RO1 GM59290, R01 HG004719, RC2 HG005552, P01 HG004120, U01 HG005209, P41 HG004221, RO1 GM081533, UO1 HG005209]; German Research Foundation (Deutsche Forschungsgemeinschaft); National Basic Research Program of China (973 program) [2011CB809200]; National Natural Science Foundation of China [30725008, 30890032, 30811130531, 30221004]; Chinese 863 program [2006AA02Z177, 2006AA02Z334, 2006AA02A302, 2009AA022707]; Shenzhen Municipal Government of China [JC200903190767A, JC200903190772A, ZYC200903240076A, CXB200903110066A, ZYC200903240077A, ZYC200903240080A]; Danish Natural Science Research Council; Medical Research Council [G0701805, G1000758, G1000758B] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10212] Funding Source: researchfish; MRC [G0701805] Funding Source: UKRI; National Human Genome Research Institute [ZIAHG000024] Funding Source: NIH RePORTER
NR 44
TC 870
Z9 1085
U1 3
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 3
PY 2011
VL 470
IS 7332
BP 59
EP 65
DI 10.1038/nature09708
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400033
PM 21293372
DA 2026-03-09
ER

PT J
AU Bell, D
   Berchuck, A
   Birrer, M
   Chien, J
   Cramer, DW
   Dao, F
   Dhir, R
   DiSaia, P
   Gabra, H
   Glenn, P
   Godwin, AK
   Gross, J
   Hartmann, L
   Huang, M
   Huntsman, DG
   Iacocca, M
   Imielinski, M
   Kalloger, S
   Karlan, BY
   Levine, DA
   Mills, GB
   Morrison, C
   Mutch, D
   Olvera, N
   Orsulic, S
   Park, K
   Petrelli, N
   Rabeno, B
   Rader, JS
   Sikic, BI
   Smith-McCune, K
   Sood, AK
   Bowtell, D
   Penny, R
   Testa, JR
   Chang, K
   Dinh, HH
   Drummond, JA
   Fowler, G
   Gunaratne, P
   Hawes, AC
   Kovar, CL
   Lewis, LR
   Morgan, MB
   Newsham, IF
   Santibanez, J
   Reid, JG
   Trevino, LR
   Wu, YQ
   Wang, M
   Muzny, DM
   Wheeler, DA
   Gibbs, RA
   Getz, G
   Lawrence, MS
   Cibulskis, K
   Sivachenko, AY
   Sougnez, C
   Voet, D
   Wilkinson, J
   Bloom, T
   Ardlie, K
   Fennell, T
   Baldwin, J
   Gabriel, S
   Lander, ES
   Ding, L
   Fulton, RS
   Koboldt, DC
   McLellan, MD
   Wylie, T
   Walker, J
   O'Laughlin, M
   Dooling, DJ
   Fulton, L
   Abbott, R
   Dees, ND
   Zhang, Q
   Kandoth, C
   Wendl, M
   Schierding, W
   Shen, D
   Harris, CC
   Schmidt, H
   Kalicki, J
   Delehaunty, KD
   Fronick, CC
   Demeter, R
   Cook, L
   Wallis, JW
   Lin, L
   Magrini, VJ
   Hodges, JS
   Eldred, JM
   Smith, SM
   Pohl, CS
   Vandin, F
   Raphael, BJ
   Weinstock, GM
   Mardis, R
   Wilson, RK
   Meyerson, M
   Winckler, W
   Getz, G
   Verhaak, RGW
   Carter, SL
   Mermel, CH
   Saksena, G
   Nguyen, H
   Onofrio, RC
   Lawrence, MS
   Hubbard, D
   Gupta, S
   Crenshaw, A
   Ramos, AH
   Ardlie, K
   Chin, L
   Protopopov, A
   Zhang, JH
   Kim, TM
   Perna, I
   Xiao, Y
   Zhang, H
   Ren, G
   Sathiamoorthy, N
   Park, RW
   Lee, E
   Park, PJ
   Kucherlapati, R
   Absher, DM
   Waite, L
   Sherlock, G
   Brooks, JD
   Li, JZ
   Xu, J
   Myers, RM
   Laird, PW
   Cope, L
   Herman, JG
   Shen, H
   Weisenberger, DJ
   Noushmehr, H
   Pan, F
   Triche, T
   Berman, BP
   Van den Berg, DJ
   Buckley, J
   Baylin, SB
   Spellman, PT
   Purdom, E
   Neuvial, P
   Bengtsson, H
   Jakkula, LR
   Durinck, S
   Han, J
   Dorton, S
   Marr, H
   Choi, YG
   Wang, V
   Wang, NJ
   Ngai, J
   Conboy, JG
   Parvin, B
   Feiler, HS
   Speed, TP
   Gray, JW
   Levine, DA
   Socci, ND
   Liang, Y
   Taylor, BS
   Schultz, N
   Borsu, L
   Lash, AE
   Brennan, C
   Viale, A
   Sander, C
   Ladanyi, M
   Hoadley, KA
   Meng, S
   Du, Y
   Shi, Y
   Li, L
   Turman, YJ
   Zang, D
   Helms, EB
   Balu, S
   Zhou, X
   Wu, J
   Topal, MD
   Hayes, DN
   Perou, CM
   Getz, G
   Voet, D
   Saksena, G
   Zhang, JNH
   Zhang, H
   Wu, CJ
   Shukla, S
   Cibulskis, K
   Lawrence, MS
   Sivachenko, A
   Jing, R
   Park, RW
   Liu, Y
   Park, PJ
   Noble, M
   Chin, L
   Carter, H
   Kim, D
   Karchin, R
   Spellman, PT
   Purdom, E
   Neuvial, P
   Bengtsson, H
   Durinck, S
   Han, J
   Korkola, JE
   Heiser, LM
   Cho, RJ
   Hu, Z
   Parvin, B
   Speed, TP
   Gray, JW
   Schultz, N
   Cerami, E
   Taylor, BS
   Olshen, A
   Reva, B
   Antipin, Y
   Shen, R
   Mankoo, P
   Sheridan, R
   Ciriello, G
   Chang, WK
   Bernanke, JA
   Borsu, L
   Levine, DA
   Ladanyi, M
   Sander, C
   Haussler, D
   Benz, CC
   Stuart, JM
   Benz, SC
   Sanborn, JZ
   Vaske, CJ
   Zhu, J
   Szeto, C
   Scott, GK
   Yau, C
   Hoadley, KA
   Du, Y
   Balu, S
   Hayes, DN
   Perou, CM
   Wilkerson, MD
   Zhang, N
   Akbani, R
   Baggerly, KA
   Yung, WK
   Mills, GB
   Weinstein, JN
   Penny, R
   Shelton, T
   Grimm, D
   Hatfield, M
   Morris, S
   Yena, P
   Rhodes, P
   Sherman, M
   Paulauskis, J
   Millis, S
   Kahn, A
   Greene, JM
   Sfeir, R
   Jensen, MA
   Chen, J
   Whitmore, J
   Alonso, S
   Jordan, J
   Chu, A
   Zhang, JH
   Barker, A
   Compton, C
   Eley, G
   Ferguson, M
   Fielding, P
   Gerhard, DS
   Myles, R
   Schaefer, C
   Shaw, KRM
   Vaught, J
   Vockley, JB
   Good, PJ
   Guyer, MS
   Ozenberger, B
   Peterson, J
   Thomson, E
AF Bell, D.
   Berchuck, A.
   Birrer, M.
   Chien, J.
   Cramer, D. W.
   Dao, F.
   Dhir, R.
   DiSaia, P.
   Gabra, H.
   Glenn, P.
   Godwin, A. K.
   Gross, J.
   Hartmann, L.
   Huang, M.
   Huntsman, D. G.
   Iacocca, M.
   Imielinski, M.
   Kalloger, S.
   Karlan, B. Y.
   Levine, D. A.
   Mills, G. B.
   Morrison, C.
   Mutch, D.
   Olvera, N.
   Orsulic, S.
   Park, K.
   Petrelli, N.
   Rabeno, B.
   Rader, J. S.
   Sikic, B. I.
   Smith-McCune, K.
   Sood, A. K.
   Bowtell, D.
   Penny, R.
   Testa, J. R.
   Chang, K.
   Dinh, H. H.
   Drummond, J. A.
   Fowler, G.
   Gunaratne, P.
   Hawes, A. C.
   Kovar, C. L.
   Lewis, L. R.
   Morgan, M. B.
   Newsham, I. F.
   Santibanez, J.
   Reid, J. G.
   Trevino, L. R.
   Wu, Y. -Q.
   Wang, M.
   Muzny, D. M.
   Wheeler, D. A.
   Gibbs, R. A.
   Getz, G.
   Lawrence, M. S.
   Cibulskis, K.
   Sivachenko, A. Y.
   Sougnez, C.
   Voet, D.
   Wilkinson, J.
   Bloom, T.
   Ardlie, K.
   Fennell, T.
   Baldwin, J.
   Gabriel, S.
   Lander, E. S.
   Ding, L.
   Fulton, R. S.
   Koboldt, D. C.
   McLellan, M. D.
   Wylie, T.
   Walker, J.
   O'Laughlin, M.
   Dooling, D. J.
   Fulton, L.
   Abbott, R.
   Dees, N. D.
   Zhang, Q.
   Kandoth, C.
   Wendl, M.
   Schierding, W.
   Shen, D.
   Harris, C. C.
   Schmidt, H.
   Kalicki, J.
   Delehaunty, K. D.
   Fronick, C. C.
   Demeter, R.
   Cook, L.
   Wallis, J. W.
   Lin, L.
   Magrini, V. J.
   Hodges, J. S.
   Eldred, J. M.
   Smith, S. M.
   Pohl, C. S.
   Vandin, F.
   Raphael, B. J.
   Weinstock, G. M.
   Mardis, R.
   Wilson, R. K.
   Meyerson, M.
   Winckler, W.
   Getz, G.
   Verhaak, R. G. W.
   Carter, S. L.
   Mermel, C. H.
   Saksena, G.
   Nguyen, H.
   Onofrio, R. C.
   Lawrence, M. S.
   Hubbard, D.
   Gupta, S.
   Crenshaw, A.
   Ramos, A. H.
   Ardlie, K.
   Chin, L.
   Protopopov, A.
   Zhang, Juinhua
   Kim, T. M.
   Perna, I.
   Xiao, Y.
   Zhang, H.
   Ren, G.
   Sathiamoorthy, N.
   Park, R. W.
   Lee, E.
   Park, P. J.
   Kucherlapati, R.
   Absher, D. M.
   Waite, L.
   Sherlock, G.
   Brooks, J. D.
   Li, J. Z.
   Xu, J.
   Myers, R. M.
   Laird, P. W.
   Cope, L.
   Herman, J. G.
   Shen, H.
   Weisenberger, D. J.
   Noushmehr, H.
   Pan, F.
   Triche, T., Jr.
   Berman, B. P.
   Van den Berg, D. J.
   Buckley, J.
   Baylin, S. B.
   Spellman, P. T.
   Purdom, E.
   Neuvial, P.
   Bengtsson, H.
   Jakkula, L. R.
   Durinck, S.
   Han, J.
   Dorton, S.
   Marr, H.
   Choi, Y. G.
   Wang, V.
   Wang, N. J.
   Ngai, J.
   Conboy, J. G.
   Parvin, B.
   Feiler, H. S.
   Speed, T. P.
   Gray, J. W.
   Levine, D. A.
   Socci, N. D.
   Liang, Y.
   Taylor, B. S.
   Schultz, N.
   Borsu, L.
   Lash, A. E.
   Brennan, C.
   Viale, A.
   Sander, C.
   Ladanyi, M.
   Hoadley, K. A.
   Meng, S.
   Du, Y.
   Shi, Y.
   Li, L.
   Turman, Y. J.
   Zang, D.
   Helms, E. B.
   Balu, S.
   Zhou, X.
   Wu, J.
   Topal, M. D.
   Hayes, D. N.
   Perou, C. M.
   Getz, G.
   Voet, D.
   Saksena, G.
   Zhang, Junihua
   Zhang, H.
   Wu, C. J.
   Shukla, S.
   Cibulskis, K.
   Lawrence, M. S.
   Sivachenko, A.
   Jing, R.
   Park, R. W.
   Liu, Y.
   Park, P. J.
   Noble, M.
   Chin, L.
   Carter, H.
   Kim, D.
   Karchin, R.
   Spellman, P. T.
   Purdom, E.
   Neuvial, P.
   Bengtsson, H.
   Durinck, S.
   Han, J.
   Korkola, J. E.
   Heiser, L. M.
   Cho, R. J.
   Hu, Z.
   Parvin, B.
   Speed, T. P.
   Gray, J. W.
   Schultz, N.
   Cerami, E.
   Taylor, B. S.
   Olshen, A.
   Reva, B.
   Antipin, Y.
   Shen, R.
   Mankoo, P.
   Sheridan, R.
   Ciriello, G.
   Chang, W. K.
   Bernanke, J. A.
   Borsu, L.
   Levine, D. A.
   Ladanyi, M.
   Sander, C.
   Haussler, D.
   Benz, C. C.
   Stuart, J. M.
   Benz, S. C.
   Sanborn, J. Z.
   Vaske, C. J.
   Zhu, J.
   Szeto, C.
   Scott, G. K.
   Yau, C.
   Hoadley, K. A.
   Du, Y.
   Balu, S.
   Hayes, D. N.
   Perou, C. M.
   Wilkerson, M. D.
   Zhang, N.
   Akbani, R.
   Baggerly, K. A.
   Yung, W. K.
   Mills, G. B.
   Weinstein, J. N.
   Penny, R.
   Shelton, T.
   Grimm, D.
   Hatfield, M.
   Morris, S.
   Yena, P.
   Rhodes, P.
   Sherman, M.
   Paulauskis, J.
   Millis, S.
   Kahn, A.
   Greene, J. M.
   Sfeir, R.
   Jensen, M. A.
   Chen, J.
   Whitmore, J.
   Alonso, S.
   Jordan, J.
   Chu, A.
   Zhang, Jinghui
   Barker, A.
   Compton, C.
   Eley, G.
   Ferguson, M.
   Fielding, P.
   Gerhard, D. S.
   Myles, R.
   Schaefer, C.
   Shaw, K. R. Mills
   Vaught, J.
   Vockley, J. B.
   Good, P. J.
   Guyer, M. S.
   Ozenberger, B.
   Peterson, J.
   Thomson, E.
TI Integrated genomic analyses of ovarian carcinoma
SO NATURE
LA English
DT Article
ID high-throughput annotation; somatic mutations; driver mutations; hybrid selection; mutant-cells; copy-number; cancer; brca1; breast; hypermethylation
AB A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
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   [Bell, D.] Mayo Clin, Div Anat Pathol, Rochester, MN 55905 USA.
   [Berchuck, A.] Duke Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Med Ctr, Durham, NC 27708 USA.
   [Berchuck, A.] Duke Univ, Duke Inst Genome Sci & Policy, Med Ctr, Durham, NC 27708 USA.
   [Birrer, M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
   [Birrer, M.; Imielinski, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Chien, J.] Mayo Clin, Div Expt Pathol, Rochester, MN 55905 USA.
   [Cramer, D. W.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Epidemiol Ctr, Boston, MA 02115 USA.
   [Levine, D. A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Dhir, R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
   [DiSaia, P.] Univ Calif Irvine, Gynecol Oncol Grp, Irvine, CA 92697 USA.
   [Gabra, H.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Ovarian Canc Act Res Ctr, London W12 0NN, England.
   [Glenn, P.; Smith-McCune, K.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Serv, San Francisco, CA 94143 USA.
   [Godwin, A. K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA.
   [Gross, J.; Karlan, B. Y.; Orsulic, S.] Univ Calif Los Angeles, Canc Res Inst, Samuel Oschin Comprehens Canc Inst, Cedars Sinai Med Ctr,Geffen Sch Med, Los Angeles, CA 90048 USA.
   [Hartmann, L.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
   [Huang, M.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
   [Huntsman, D. G.; Kalloger, S.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 1G1, Canada.
   [Iacocca, M.; Rabeno, B.] Christiana Care Hlth Syst, Dept Pathol, Newark, DE 19718 USA.
   [Karlan, B. Y.] Univ Calif Los Angeles, Dept Obstet & Gynecol, Cedars Sinai Med Ctr, Geffen Sch Med, Los Angeles, CA 90048 USA.
   [Mills, G. B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   Univ Texas MD Anderson Canc Ctr, Kleberg Ctr Mol Markers, Houston, TX 77030 USA.
   [Morrison, C.] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Buffalo, NY 14263 USA.
   [Morrison, C.] Roswell Pk Canc Inst, Div Mol Pathol, Buffalo, NY 14263 USA.
   [Mutch, D.] Washington Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Sch Med St Louis, St Louis, MO 63110 USA.
   [Park, K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Petrelli, N.] Helen F Graham Canc Ctr Christina Care, Dept Surg, Newark, DE 19713 USA.
   [Rader, J. S.] Med Coll Wisconsin, Human & Mol Genet Ctr, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA.
   [Sikic, B. I.] Stanford Univ, Dept Med, Div Oncol, Sch Med, Palo Alto, CA 94304 USA.
   [Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77230 USA.
   [Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77230 USA.
   [Bowtell, D.] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 8006, Australia.
   [Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.] Internat Genom Consortium, Phoenix, AZ 85004 USA.
   [Testa, J. R.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA.
   [Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Gunaratne, P.; Hawes, A. C.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Santibanez, J.; Reid, J. G.; Trevino, L. R.; Wu, Y. -Q.; Wang, M.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Sougnez, C.; Winckler, W.; Getz, G.] MIT, Eli & Edythe L Broad Inst, Canc Genome Project, Cambridge, MA 02142 USA.
   [Sougnez, C.; Winckler, W.; Getz, G.] MIT, Eli & Edythe L Broad Inst, Med Resequencing Project, Cambridge, MA 02142 USA.
   [Cibulskis, K.; Sougnez, C.; Wilkinson, J.; Bloom, T.; Fennell, T.; Baldwin, J.; Gabriel, S.; Winckler, W.; Getz, G.; Crenshaw, A.] Harvard Univ, Cambridge, MA 02142 USA.
   [Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Lander, E. S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
   [Ding, L.; Fulton, R. S.; Koboldt, D. C.; McLellan, M. D.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D. J.; Fulton, L.; Abbott, R.; Dees, N. D.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C. C.; Schmidt, H.; Kalicki, J.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Cook, L.; Wallis, J. W.; Lin, L.; Magrini, V. J.; Hodges, J. S.; Eldred, J. M.; Smith, S. M.; Pohl, C. S.; Weinstock, G. M.; Mardis, R.; Wilson, R. K.] Washington Univ, Sch Med St Louis, Genome Ctr, Dept Genet, St Louis, MO 63108 USA.
   [Vandin, F.; Raphael, B. J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Vandin, F.; Raphael, B. J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
   [Mardis, R.; Wilson, R. K.] Washington Univ, Siteman Canc Ctr, Sch Med St Louis, St Louis, MO 63108 USA.
   [Meyerson, M.; Verhaak, R. G. W.; Carter, S. L.; Mermel, C. H.; Hubbard, D.; Ramos, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Meyerson, M.; Hubbard, D.; Ramos, A. H.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Chin, L.; Protopopov, A.; Zhang, Juinhua; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Zhang, Junihua; Wu, C. J.; Shukla, S.; Liu, Y.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA.
   [Chin, L.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
   [Kim, T. M.; Park, R. W.; Lee, E.; Park, P. J.; Park, R. W.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA.
   [Sathiamoorthy, N.] Partners Ctr Personalized Genet Med, Cambridge, MA 02139 USA.
   Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Kucherlapati, R.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA.
   [Absher, D. M.; Waite, L.; Myers, R. M.; Speed, T. P.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Brooks, J. D.; Sander, C.] Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA.
   [Li, J. Z.; Xu, J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Laird, P. W.; Shen, H.; Weisenberger, D. J.; Noushmehr, H.; Pan, F.; Triche, T., Jr.; Berman, B. P.; Van den Berg, D. J.; Buckley, J.] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA.
   [Cope, L.] Johns Hopkins Univ, Biometry & Clin Trials Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Herman, J. G.; Baylin, S. B.] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Purdom, E.; Neuvial, P.; Bengtsson, H.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 95720 USA.
   [Choi, Y. G.; Ngai, J.] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 95720 USA.
   [Wang, V.] Univ Houston, Dept Biol & Biochem, Houston, TX 77004 USA.
   [Speed, T. P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Lash, A. E.; Sander, C.; Cerami, E.; Reva, B.; Antipin, Y.; Mankoo, P.; Sheridan, R.; Ciriello, G.] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Borsu, L.; Ladanyi, M.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Dept Pathol, New York, NY 10065 USA.
   [Brennan, C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [Viale, A.] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA.
   Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Topal, M. D.] Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y. J.; Zang, D.; Helms, E. B.; Balu, S.; Zhou, X.; Wu, J.; Topal, M. D.; Hayes, D. N.; Wilkerson, M. D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Hayes, D. N.] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
   [Carter, H.; Kim, D.; Karchin, R.] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD 21231 USA.
   [Olshen, A.; Shen, R.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY 10065 USA.
   [Bernanke, J. A.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
   [Benz, S. C.; Sanborn, J. Z.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Benz, S. C.; Sanborn, J. Z.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Benz, C. C.; Yau, C.] Buck Inst Age Res, Novato, CA 94945 USA.
   Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Zhang, N.; Akbani, R.; Baggerly, K. A.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Yung, W. K.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
   [Kahn, A.; Greene, J. M.; Sfeir, R.; Jensen, M. A.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.] SRAInternational, Fairfax, VA 22033 USA.
   St Jude Childrens Res Hosp, Dept Biotechnol, Memphis, TN 38105 USA.
   [Compton, C.; Eley, G.; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Shaw, K. R. Mills; Vaught, J.; Vockley, J. B.] NCI, NIH, Bethesda, MD 20892 USA.
   [Ferguson, M.] MLF Consulting, Arlington, MA 02474 USA.
   [Good, P. J.; Guyer, M. S.; Ozenberger, B.; Peterson, J.; Thomson, E.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Mayo Clinic; Duke University; Duke University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Mayo Clinic; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Memorial Sloan Kettering Cancer Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Irvine; Imperial College London; University of California System; University of California San Francisco; Fox Chase Cancer Center; Cedars Sinai Medical Center; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Mayo Clinic; Fox Chase Cancer Center; British Columbia Cancer Agency; Christiana Care Health System; Cedars Sinai Medical Center; 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 Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Roswell Park Comprehensive Cancer Center; Roswell Park Comprehensive Cancer Center; Washington University (WUSTL); Saint Louis University; Memorial Sloan Kettering Cancer Center; Helen F. Graham Cancer Center & Research Institute; Medical College of Wisconsin; Stanford University; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Peter Maccallum Cancer Center; International Genomics Consortium; Fox Chase Cancer Center; Baylor College of Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Saint Louis University; Washington University (WUSTL); Brown University; Brown University; Saint Louis University; Washington University (WUSTL); Siteman Cancer Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; HudsonAlpha Institute for Biotechnology; Stanford University; University of Michigan System; University of Michigan; University of Southern California; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Houston System; University of Houston; Walter & Eliza Hall Institute; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Johns Hopkins University; Memorial Sloan Kettering Cancer Center; Cornell University; Cornell University; Weill Cornell Medicine; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; 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; SRA International; St Jude Children's Research Hospital; 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 Spellman, PT (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
EM spellmap@ohsu.edu
FU USA National Institutes of Health [U24CA143840, U24CA143882, U24CA143731, U24CA143835, U24CA143845, U24CA143858, U24CA144025, U24CA143866, U24CA143867, U24CA143848, U24CA143843, R21CA135877]; National Cancer Institute [P50CA136393] Funding Source: NIH RePORTER
NR 50
TC 6286
Z9 7073
U1 11
U2 595
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 609
EP 615
DI 10.1038/nature10166
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300032
PM 21720365
DA 2026-03-09
ER

PT J
AU Dawson, MA
   Prinjha, RK
   Dittmann, A
   Giotopoulos, G
   Bantscheff, M
   Chan, WI
   Robson, SC
   Chung, CW
   Hopf, C
   Savitski, MM
   Huthmacher, C
   Gudgin, E
   Lugo, D
   Beinke, S
   Chapman, TD
   Roberts, EJ
   Soden, PE
   Auger, KR
   Mirguet, O
   Doehner, K
   Delwel, R
   Burnett, AK
   Jeffrey, P
   Drewes, G
   Lee, K
   Huntly, BJP
   Kouzarides, T
AF Dawson, Mark A.
   Prinjha, Rab K.
   Dittmann, Antje
   Giotopoulos, George
   Bantscheff, Marcus
   Chan, Wai-In
   Robson, Samuel C.
   Chung, Chun-wa
   Hopf, Carsten
   Savitski, Mikhail M.
   Huthmacher, Carola
   Gudgin, Emma
   Lugo, Dave
   Beinke, Soren
   Chapman, Trevor D.
   Roberts, Emma J.
   Soden, Peter E.
   Auger, Kurt R.
   Mirguet, Olivier
   Doehner, Konstanze
   Delwel, Ruud
   Burnett, Alan K.
   Jeffrey, Phillip
   Drewes, Gerard
   Lee, Kevin
   Huntly, Brian J. P.
   Kouzarides, Tony
TI Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia
SO NATURE
LA English
DT Article
ID bromodomain protein brd4; p-tefb; transcription; elongation; component; target; cells
AB Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL) gene initiate aggressive forms of leukaemia, which are often refractory to conventional therapies(1). Many MLL-fusion partners are members of the super elongation complex (SEC), a critical regulator of transcriptional elongation, suggesting that aberrant control of this process has an important role in leukaemia induction(2,3). Here we use a global proteomic strategy to demonstrate that MLL fusions, as part of SEC(2,3) and the polymerase-associated factor complex (PAFc)(4,5), are associated with the BET family of acetyl-lysine recognizing, chromatin 'adaptor' proteins. These data provided the basis for therapeutic intervention in MLL-fusion leukaemia, via the displacement of the BET family of proteins from chromatin. We show that a novel small molecule inhibitor of the BET family, GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion leukaemic cell lines, through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in two human leukaemia cell lines with different MLL fusions alters the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin. In vivo studies indicate that I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukaemia. Finally, the efficacy of I-BET151 against human leukaemia stem cells is demonstrated, providing further evidence of its potent therapeutic potential. These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias.
C1 [Dawson, Mark A.; Giotopoulos, George; Chan, Wai-In; Gudgin, Emma; Huntly, Brian J. P.] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
   [Dawson, Mark A.; Giotopoulos, George; Chan, Wai-In; Gudgin, Emma; Huntly, Brian J. P.] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 0XY, England.
   [Dawson, Mark A.; Robson, Samuel C.; Kouzarides, Tony] Gurdon Inst, Cambridge CB2 1QN, England.
   [Dawson, Mark A.; Robson, Samuel C.; Kouzarides, Tony] Dept Pathol, Cambridge CB2 1QN, England.
   [Prinjha, Rab K.; Lugo, Dave; Beinke, Soren; Chapman, Trevor D.; Roberts, Emma J.; Soden, Peter E.; Jeffrey, Phillip; Lee, Kevin] GlaxoSmithKline Inc, Med Res Ctr, Immunoinflammat Ctr Excellence Drug Discovery, Epinova DPU, Stevenage SG1 2NY, Herts, England.
   [Dittmann, Antje; Bantscheff, Marcus; Hopf, Carsten; Savitski, Mikhail M.; Huthmacher, Carola; Drewes, Gerard] Cellzome AG, D-69117 Heidelberg, Germany.
   [Chung, Chun-wa] GlaxoSmithKline R&D, Mol Discovery Res, Stevenage SG1 2NY, Herts, England.
   [Auger, Kurt R.] GlaxoSmithKline Inc, Oncol R&D, Canc Epigenet DPU, Collegeville, PA 19426 USA.
   [Mirguet, Olivier] GlaxoSmithKline Res & Dev Ltd, Lipid Metab Discovery Performance Unit, F-91951 Les Ulis, France.
   [Doehner, Konstanze] Univ Hosp Ulm Internal Med 3, D-89081 Ulm, Germany.
   [Delwel, Ruud] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands.
   [Burnett, Alan K.] Cardiff Univ, Sch Med, Dept Hematol, Cardiff CF14 4XN, S Glam, Wales.
C3 University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Cellzome GmbH; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Erasmus University Rotterdam; Erasmus MC; Cardiff University
RP Huntly, BJP (corresponding author), Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
EM mafd2@cam.ac.uk; bjph2@cam.ac.uk; t.kouzarides@gurdon.cam.ac.uk
FU Wellcome-Beit Intermediate Clinical Fellowship; Medical Research Council (UK); Leukaemia Lymphoma Research (UK); Wellcome Trust; Leukemia & Lymphoma Society of America; Cancer Research UK (CRUK); NIHR Cambridge Biomedical Research Centre; MRC [G0800784, G116/187] Funding Source: UKRI; Medical Research Council [G0800784B, G116/187, G0800784] Funding Source: researchfish
NR 20
TC 1291
Z9 1619
U1 1
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 OCT 27
PY 2011
VL 478
IS 7370
BP 529
EP 533
DI 10.1038/nature10509
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200046
PM 21964340
DA 2026-03-09
ER

PT J
AU Li, FY
   Chaigne-Delalande, B
   Kanellopoulou, C
   Davis, JC
   Matthews, HF
   Douek, DC
   Cohen, JI
   Uzel, G
   Su, HC
   Lenardo, MJ
AF Li, Feng-Yen
   Chaigne-Delalande, Benjamin
   Kanellopoulou, Chrysi
   Davis, Jeremiah C.
   Matthews, Helen F.
   Douek, Daniel C.
   Cohen, Jeffrey I.
   Uzel, Gulbu
   Su, Helen C.
   Lenardo, Michael J.
TI Second messenger role for Mg2+ revealed by human T-cell immunodeficiency
SO NATURE
LA English
DT Article
ID acquired-immunodeficiency; signal-transduction; hiv-infection; magnesium; activation; calcium; lymphocytopenia; receptor; deficiency; identification
AB The magnesium ion, Mg2+, is essential for all life as a cofactor for ATP, polyphosphates such as DNA and RNA, and metabolic enzymes, but whether it plays a part in intracellular signalling (as Ca2+ does) is unknown. Here we identify mutations in the magnesium transporter gene, MAGT1, in a novel X-linked human immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. We demonstrate that a rapid transient Mg2+ influx is induced by antigen receptor stimulation in normal T cells and by growth factor stimulation in non-lymphoid cells. MAGT1 deficiency abrogates the Mg2+ influx, leading to impaired responses to antigen receptor engagement, including defective activation of phospholipase C gamma 1 and a markedly impaired Ca2+ influx in T cells but not B cells. These observations reveal a role for Mg2+ as an intracellular second messenger coupling cell-surface receptor activation to intracellular effectors and identify MAGT1 as a possible target for novel therapeutics.
C1 [Li, Feng-Yen; Chaigne-Delalande, Benjamin; Kanellopoulou, Chrysi; Matthews, Helen F.; Lenardo, Michael J.] NIAID, Mol Dev Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA.
   [Li, Feng-Yen] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA.
   [Davis, Jeremiah C.; Su, Helen C.] NIAID, Human Immunol Dis Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA.
   [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of California System; University of California San Francisco; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Li, FY (corresponding author), NIAID, Mol Dev Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health; National Institute of Allergy and Infectious Diseases [ZIAAI000913, ZIAAI000769, ZIAAI001059] Funding Source: NIH RePORTER
NR 51
TC 450
Z9 499
U1 4
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 JUL 28
PY 2011
VL 475
IS 7357
BP 471
EP U63
DI 10.1038/nature10246
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900034
PM 21796205
DA 2026-03-09
ER

PT J
AU Tsukazaki, T
   Mori, H
   Echizen, Y
   Ishitani, R
   Fukai, S
   Tanaka, T
   Perederina, A
   Vassylyev, DG
   Kohno, T
   Maturana, AD
   Ito, K
   Nureki, O
AF Tsukazaki, Tomoya
   Mori, Hiroyuki
   Echizen, Yuka
   Ishitani, Ryuichiro
   Fukai, Shuya
   Tanaka, Takeshi
   Perederina, Anna
   Vassylyev, Dmitry G.
   Kohno, Toshiyuki
   Maturana, Andres D.
   Ito, Koreaki
   Nureki, Osamu
TI Structure and function of a membrane component SecDF that enhances protein export
SO NATURE
LA English
DT Article
ID escherichia-coli; preprotein translocase; cytoplasmic membrane; channel; complex; machinery; mechanism; movement; domain
AB Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase(1-4), is enhanced by proton motive force(5,6) and membrane-integrated SecDF(7-9), which associates with SecYEG. The role of SecDF has remained unclear, although it is proposed to function in later stages of translocation as well as in membrane protein biogenesis(4,10-13). Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3 angstrom resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4. Higher-resolution analysis of the periplasmic domains suggested that P1, which binds an unfolded protein, undergoes functionally important conformational changes. In vitro analyses identified an ATP-independent step of protein translocation that requires both SecDF and proton motive force. Electrophysiological analyses revealed that SecDF conducts protons in a manner dependent on pH and the presence of an unfolded protein, with conserved Asp and Arg residues at the transmembrane interface between SecD and SecF playing essential roles in the movements of protons and preproteins. Therefore, we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation.
C1 [Tsukazaki, Tomoya; Echizen, Yuka; Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.
   [Mori, Hiroyuki] Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan.
   [Fukai, Shuya] Univ Tokyo, Synchrotron Radiat Res Org, Div Life Sci, Struct Biol Lab, Tokyo 1130032, Japan.
   [Fukai, Shuya] Univ Tokyo, Ctr Struct Biol Challenging Prot, Lab Macromol Complexes, Tokyo 1130032, Japan.
   [Tanaka, Takeshi; Kohno, Toshiyuki] Mitsubishi Kagaku Inst Life Sci, Machida, Tokyo 1948511, Japan.
   [Perederina, Anna; Vassylyev, Dmitry G.] Univ Alabama, Sch Med, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Perederina, Anna; Vassylyev, Dmitry G.] Univ Alabama, Sch Dent, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA.
   [Maturana, Andres D.] Nagaoka Univ Technol, Dept Bioengn, Niigata 9402188, Japan.
   [Ito, Koreaki] Kyoto Sangyo Univ, Kita Ku, Kyoto 6038555, Japan.
C3 University of Tokyo; Kyoto University; University of Tokyo; University of Tokyo; Mitsubishi International Corporation (MIC); Mitsubishi Kagaku Institute of Life Sciences (MITILS); University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; Nagaoka University of Technology; Kyoto Sangyo University
RP Nureki, O (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.
EM kito@cc.kyoto-su.ac.jp; nureki@ims.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); JST; NIH; Grants-in-Aid for Scientific Research [20247020, 21770135, 22370070, 22020008, 22121503, 22020035, 22117007, 20227003, 19058007, 22687007, 22121003, 22117503, 21687009, 23657128] Funding Source: KAKEN
NR 27
TC 182
Z9 231
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 JUN 9
PY 2011
VL 474
IS 7350
BP 235
EP 238
DI 10.1038/nature09980
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800055
PM 21562494
DA 2026-03-09
ER

PT J
AU Star, B
   Nederbragt, AJ
   Jentoft, S
   Grimholt, U
   Malmstrom, M
   Gregers, TF
   Rounge, TB
   Paulsen, J
   Solbakken, MH
   Sharma, A
   Wetten, OF
   Lanzén, A
   Winer, R
   Knight, J
   Vogel, JH
   Aken, B
   Andersen, O
   Lagesen, K
   Tooming-Klunderud, A
   Edvardsen, RB
   Tina, KG
   Espelund, M
   Nepal, C
   Previti, C
   Karlsen, BO
   Moum, T
   Skage, M
   Berg, PR
   Gjoen, T
   Kuhl, H
   Thorsen, J
   Malde, K
   Reinhardt, R
   Du, L
   Johansen, SD
   Searle, S
   Lien, S
   Nilsen, F
   Jonassen, I
   Omholt, SW
   Stenseth, NC
   Jakobsen, KS
AF Star, Bastiaan
   Nederbragt, Alexander J.
   Jentoft, Sissel
   Grimholt, Unni
   Malmstrom, Martin
   Gregers, Tone F.
   Rounge, Trine B.
   Paulsen, Jonas
   Solbakken, Monica H.
   Sharma, Animesh
   Wetten, Ola F.
   Lanzen, Anders
   Winer, Roger
   Knight, James
   Vogel, Jan-Hinnerk
   Aken, Bronwen
   Andersen, Oivind
   Lagesen, Karin
   Tooming-Klunderud, Ave
   Edvardsen, Rolf B.
   Tina, Kirubakaran G.
   Espelund, Mari
   Nepal, Chirag
   Previti, Christopher
   Karlsen, Bard Ove
   Moum, Truls
   Skage, Morten
   Berg, Paul R.
   Gjoen, Tor
   Kuhl, Heiner
   Thorsen, Jim
   Malde, Ketil
   Reinhardt, Richard
   Du, Lei
   Johansen, Steinar D.
   Searle, Steve
   Lien, Sigbjorn
   Nilsen, Frank
   Jonassen, Inge
   Omholt, Stig W.
   Stenseth, Nils Chr.
   Jakobsen, Kjetill S.
TI The genome sequence of Atlantic cod reveals a unique immune system
SO NATURE
LA English
DT Article
ID mhc class-i; oxygen-binding property; gadus-morhua l.; genes; polymorphism; temperature; neutrophils; expression; selection; genotypes
AB Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture(1,2). Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates(3,4), but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions(5). We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.
C1 [Star, Bastiaan; Nederbragt, Alexander J.; Jentoft, Sissel; Grimholt, Unni; Malmstrom, Martin; Rounge, Trine B.; Paulsen, Jonas; Solbakken, Monica H.; Lagesen, Karin; Tooming-Klunderud, Ave; Tina, Kirubakaran G.; Espelund, Mari; Skage, Morten; Berg, Paul R.; Omholt, Stig W.; Stenseth, Nils Chr.; Jakobsen, Kjetill S.] Univ Oslo, Dept Biol, CEES, N-0316 Oslo, Norway.
   [Gregers, Tone F.] Univ Oslo, Dept Mol Biosci, Ctr Immune Regulat, N-0316 Oslo, Norway.
   [Paulsen, Jonas] Oslo Univ Hosp, Inst Med Informat, Bioinformat Core Facil, N-0310 Oslo, Norway.
   [Sharma, Animesh; Nepal, Chirag; Jonassen, Inge] Univ Bergen, Dept Informat, N-5020 Bergen, Norway.
   [Wetten, Ola F.] Hedmark Univ Coll, Dept Nat Sci & Technol, N-2306 Bedriftsenteret, Hamar, Norway.
   [Wetten, Ola F.] Univ Life Sci, Dept Anim & Aquacultural Sci, N-1432 As, Norway.
   [Lanzen, Anders] Univ Bergen, Ctr Geobiol, Dept Biol, N-5020 Bergen, Norway.
   [Lanzen, Anders; Nepal, Chirag; Previti, Christopher; Jonassen, Inge] Uni Res AS, Uni Comp, Computat Biol Unit, N-5020 Bergen, Norway.
   [Winer, Roger; Knight, James; Du, Lei] 454 Life Sci, Branford, CT 06405 USA.
   [Vogel, Jan-Hinnerk; Aken, Bronwen; Searle, Steve] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Andersen, Oivind] Nofima Marine, N-1430 As, Norway.
   [Edvardsen, Rolf B.; Malde, Ketil] Inst Marine Res, N-5817 Bergen, Norway.
   [Tina, Kirubakaran G.; Lien, Sigbjorn; Omholt, Stig W.] Norwegian Univ Life Sci, Ctr Integrat Genet, CIGENE, Dept Anim & Aquacultural Sci, N-1432 As, Norway.
   [Karlsen, Bard Ove; Moum, Truls; Johansen, Steinar D.] Univ Nordland, Fac Biosci & Aquaculture, N-8049 Bodo, Norway.
   [Gjoen, Tor] Univ Oslo, Sch Pharm, Dept Pharmaceut Biosci, N-0316 Oslo, Norway.
   [Kuhl, Heiner; Reinhardt, Richard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Thorsen, Jim] Sch Vet Sci, Inst Basic Sci & Aquat Med, N-0033 Oslo, Norway.
   [Johansen, Steinar D.] Univ Tromso, Fac Hlth Sci, Dept Med Biol, N-9037 Tromso, Norway.
C3 University of Oslo; University of Oslo; University of Oslo; University of Bergen; Inland Norway University of Applied Sciences; Norwegian University of Life Sciences; University of Bergen; University of Bergen; Wellcome Trust Sanger Institute; Nofima; Institute of Marine Research - Norway; Norwegian University of Life Sciences; Nord University; University of Oslo; Max Planck Society; UiT The Arctic University of Tromso
RP Jakobsen, KS (corresponding author), Univ Oslo, Dept Biol, CEES, POB 1066, N-0316 Oslo, Norway.
EM k.s.jakobsen@bio.uio.no
FU Research Council of Norway
NR 30
TC 626
Z9 697
U1 8
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 SEP 8
PY 2011
VL 477
IS 7363
BP 207
EP 210
DI 10.1038/nature10342
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900035
PM 21832995
DA 2026-03-09
ER

PT J
AU Zoltowski, BD
   Vaidya, AT
   Top, D
   Widom, J
   Young, MW
   Crane, BR
AF Zoltowski, Brian D.
   Vaidya, Anand T.
   Top, Deniz
   Widom, Joanne
   Young, Michael W.
   Crane, Brian R.
TI Structure of full-length Drosophila cryptochrome
SO NATURE
LA English
DT Article
ID blue-light photoreceptor; 6-4 photolyase; crystal-structure; flavin cofactor; circadian clock; mechanism; melanogaster; degradation; terminus; timeless
AB The cryptochrome/photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to ultraviolet and blue light exposure in all kingdoms of life(1-5). Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs) and 6-4 photolesions caused by ultraviolet radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks(1-5). Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism(3,6). However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalysed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable carboxy-terminal tail that appends the conserved PL homology domain (PHD) and is important for function(7-12). Here, we report a 2.3-angstrom resolution crystal structure of Drosophila CRY with an intact C terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp 536 juts into the CRY catalytic centre to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture and photochemistry can be elaborated into a range of light-driven functions.
C1 [Zoltowski, Brian D.; Vaidya, Anand T.; Widom, Joanne; Crane, Brian R.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Top, Deniz; Young, Michael W.] Rockefeller Univ, Genet Lab, New York, NY 10065 USA.
C3 Cornell University; Rockefeller University
RP Crane, BR (corresponding author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
EM bc69@cornell.edu
FU NIH [GM079679, GM054339]
NR 31
TC 143
Z9 175
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 DEC 15
PY 2011
VL 480
IS 7377
BP 396
EP U156
DI 10.1038/nature10618
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000058
PM 22080955
DA 2026-03-09
ER

PT J
AU Alter, G
   Heckerman, D
   Schneidewind, A
   Fadda, L
   Kadie, CM
   Carlson, JM
   Oniangue-Ndza, C
   Martin, M
   Li, B
   Khakoo, SI
   Carrington, M
   Allen, TM
   Altfeld, M
AF Alter, Galit
   Heckerman, David
   Schneidewind, Arne
   Fadda, Lena
   Kadie, Carl M.
   Carlson, Jonathan M.
   Oniangue-Ndza, Cesar
   Martin, Maureen
   Li, Bin
   Khakoo, Salim I.
   Carrington, Mary
   Allen, Todd M.
   Altfeld, Marcus
TI HIV-1 adaptation to NK-cell-mediated immune pressure
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; natural-killer-cells; mhc class-i; hla-b; inhibitory receptor; viral peptides; binding-site; recognition; kir3dl1; responses
AB Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors(1-3). Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs)(4-7). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4(+) T cells, and reduce the antiviral activity of KIR-positive NK cells. These data demonstrate that KIR-positive NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK-cell-mediated immune pressure by selecting for sequence polymorphisms, as was previously described for virus-specific T cells and neutralizing antibodies(8). NK cells might therefore have a previously underappreciated role in contributing to viral evolution.
C1 [Alter, Galit; Schneidewind, Arne; Fadda, Lena; Oniangue-Ndza, Cesar; Li, Bin; Carrington, Mary; Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA.
   [Heckerman, David; Kadie, Carl M.; Carlson, Jonathan M.] Microsoft Res, Redmond, WA 98053 USA.
   [Martin, Maureen; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Khakoo, Salim I.] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1PG, England.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Massachusetts Institute of Technology (MIT); Ragon Institute; Microsoft; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Imperial College London
RP Altfeld, M (corresponding author), Harvard Univ, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA.
EM maltfeld@partners.org
FU National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases [R01 AI067031, PO1 AI074415]; Doris Duke Charitable Foundation; National Cancer Institute (NIH) [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; Wellcome Trust; Microsoft Research; Bill & Melinda Gates Foundation; Mark and Lisa Schwartz Foundation; Phillip T. and Susan M. Ragon Foundation; National Cancer Institute [ZIABC010791] Funding Source: NIH RePORTER
NR 29
TC 283
Z9 341
U1 0
U2 37
PU 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 4
PY 2011
VL 476
IS 7358
BP 96
EP +
DI 10.1038/nature10237
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300037
PM 21814282
DA 2026-03-09
ER

PT J
AU McNeil, RPG
   Kataoka, M
   Ford, CJB
   Barnes, CHW
   Anderson, D
   Jones, GAC
   Farrer, I
   Ritchie, DA
AF McNeil, R. P. G.
   Kataoka, M.
   Ford, C. J. B.
   Barnes, C. H. W.
   Anderson, D.
   Jones, G. A. C.
   Farrer, I.
   Ritchie, D. A.
TI On-demand single-electron transfer between distant quantum dots
SO NATURE
LA English
DT Article
ID spin; computation
AB Single-electron circuits of the future, consisting of a network of quantum dots, will require a mechanism to transport electrons from one functional part of the circuit to another. For example, in a quantum computer(1) decoherence and circuit complexity can be reduced by separating quantum bit (qubit) manipulation from measurement and by providing a means of transporting electrons between the corresponding parts of the circuit(2). Highly controlled tunnelling between neighbouring dots has been demonstrated(3,4), and our ability to manipulate electrons in single-and double-dot systems is improving rapidly(5-8). For distances greater than a few hundred nanometres, neither free propagation nor tunnelling is viable while maintaining confinement of single electrons. Here we show how a single electron may be captured in a surface acoustic wave minimum and transferred from one quantum dot to a second, unoccupied, dot along a long, empty channel. The transfer direction may be reversed and the same electron moved back and forth more than sixty times-a cumulative distance of 0.25 mm-without error. Such on-chip transfer extends communication between quantum dots to a range that may allow the integration of discrete quantum information processing components and devices.
C1 [McNeil, R. P. G.; Kataoka, M.; Ford, C. J. B.; Barnes, C. H. W.; Anderson, D.; Jones, G. A. C.; Farrer, I.; Ritchie, D. A.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Kataoka, M.] Natl Phys Lab, Teddington TW11 0LW, Middx, England.
C3 University of Cambridge; National Physical Laboratory - UK
RP Ford, CJB (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM cjbf@cam.ac.uk
FU UK EPSRC; Toshiba Research Europe Limited; QIPIRC
NR 18
TC 265
Z9 292
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 SEP 22
PY 2011
VL 477
IS 7365
BP 439
EP 442
DI 10.1038/nature10444
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500035
PM 21938065
DA 2026-03-09
ER

PT J
AU Wilson, CM
   Johansson, G
   Pourkabirian, A
   Simoen, M
   Johansson, JR
   Duty, T
   Nori, F
   Delsing, P
AF Wilson, C. M.
   Johansson, G.
   Pourkabirian, A.
   Simoen, M.
   Johansson, J. R.
   Duty, T.
   Nori, F.
   Delsing, P.
TI Observation of the dynamical Casimir effect in a superconducting circuit
SO NATURE
LA English
DT Article
ID electromagnetic-field; squeezed states; radiation; cavity
AB One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. Although initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences-for instance, producing the Lamb shift(1) of atomic spectra and modifying the magnetic moment of the electron(2). This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed whether it might be possible to more directly observe the virtual particles that compose the quantum vacuum. Forty years ago, it was suggested(3) that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. The phenomenon, later termed the dynamical Casimir effect(4,5), has not been demonstrated previously. Here we observe the dynamical Casimir effect in a superconducting circuit consisting of a coplanar transmission line with a tunable electrical length. The rate of change of the electrical length can be made very fast (a substantial fraction of the speed of light) by modulating the inductance of a superconducting quantum interference device at high frequencies (>10 gigahertz). In addition to observing the creation of real photons, we detect two-mode squeezing in the emitted radiation, which is a signature of the quantum character of the generation process.
C1 [Wilson, C. M.; Johansson, G.; Pourkabirian, A.; Simoen, M.; Delsing, P.] Chalmers, Dept Microtechnol & Nanosci, S-41296 Gothenburg, Sweden.
   [Johansson, J. R.; Nori, F.] RIKEN, Adv Sci Inst, Wako, Saitama 3510198, Japan.
   [Duty, T.] Univ New S Wales, Sydney, NSW 2052, Australia.
   [Nori, F.] Univ Michigan, Ann Arbor, MI 48109 USA.
C3 Chalmers University of Technology; RIKEN; University of New South Wales Sydney; University of Michigan System; University of Michigan
RP Wilson, CM (corresponding author), Chalmers, Dept Microtechnol & Nanosci, S-41296 Gothenburg, Sweden.
EM chris.wilson@chalmers.se
FU Swedish Research Council; Wallenberg Foundation; STINT; European Research Council; NSF [0726909]; MEXT Kakenhi on Quantum Cybernetics; Australian Research Council [DP0986932, FT100100025]; Grants-in-Aid for Scientific Research [22224007, 11F01501] Funding Source: KAKEN; Australian Research Council [DP0986932, FT100100025] Funding Source: Australian Research Council
NR 28
TC 785
Z9 857
U1 1
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 NOV 17
PY 2011
VL 479
IS 7373
BP 376
EP 379
DI 10.1038/nature10561
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700040
PM 22094697
DA 2026-03-09
ER

PT J
AU Janich, P
   Pascual, G
   Merlos-Suárez, A
   Batlle, E
   Ripperger, J
   Albrecht, U
   Cheng, HYM
   Obrietan, K
   Di Croce, L
   Benitah, SA
AF Janich, Peggy
   Pascual, Gloria
   Merlos-Suarez, Anna
   Batlle, Eduard
   Ripperger, Juergen
   Albrecht, Urs
   Cheng, Hai-Ying M.
   Obrietan, Karl
   Di Croce, Luciano
   Aznar Benitah, Salvador
TI The circadian molecular clock creates epidermal stem cell heterogeneity
SO NATURE
LA English
DT Article
ID hair follicle; expression; niche; differentiation; proliferation; homeostasis; population; activation; pacemaker; component
AB Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.
C1 [Janich, Peggy; Pascual, Gloria; Di Croce, Luciano; Aznar Benitah, Salvador] Ctr Genom Regulat, Barcelona 08003, Spain.
   [Janich, Peggy; Pascual, Gloria; Di Croce, Luciano; Aznar Benitah, Salvador] UPF, Barcelona 08003, Spain.
   [Merlos-Suarez, Anna; Batlle, Eduard] Inst Res Biomed, Barcelona 08028, Spain.
   [Batlle, Eduard; Di Croce, Luciano; Aznar Benitah, Salvador] ICREA, Barcelona 08010, Spain.
   [Ripperger, Juergen; Albrecht, Urs] Univ Fribourg, CH-1700 Fribourg, Switzerland.
   [Cheng, Hai-Ying M.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Obrietan, Karl] Ohio State Univ, Columbus, OH 43210 USA.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Barcelona Institute of Science & Technology; Institute for Research in Biomedicine - IRB Barcelona; ICREA; University of Fribourg; University of Toronto; University Toronto Mississauga; University System of Ohio; Ohio State University
RP Benitah, SA (corresponding author), Ctr Genom Regulat, Barcelona 08003, Spain.
EM salvador.aznar-benitah@crg.es
FU AICR (Association for International Cancer Research); Spanish Ministry of Health (FIS); AGAUR (Agencia de Gestio d'Ajuts Universitaris i de Recerca; Government of Cataluna); AGAUR; FIS; ICREA Funding Source: Custom
NR 48
TC 262
Z9 309
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 DEC 8
PY 2011
VL 480
IS 7376
BP 209
EP U89
DI 10.1038/nature10649
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200044
PM 22080954
DA 2026-03-09
ER

PT J
AU Wyithe, JSB
   Yan, HJ
   Windhorst, RA
   Mao, SD
AF Wyithe, J. Stuart B.
   Yan, Haojing
   Windhorst, Rogier A.
   Mao, Shude
TI A distortion of very-high-redshift galaxy number counts by gravitational lensing
SO NATURE
LA English
DT Article
ID digital sky survey; ultra-deep-field; luminosity function; lensed galaxy; hubble; distributions; magnification; reionization; statistics; science
AB The observed number counts of high-redshift galaxy candidates(1-8) have been used to build up a statistical description of star-forming activity at redshift z greater than or similar to 7, when galaxies reionized the Universe(1,2,9,10). Standard models(11) predict that a high incidence of gravitational lensing will probably distort measurements of flux and number of these earliest galaxies. The raw probability of this happening has been estimated to be similar to 0.5 per cent (refs 11, 12), but can be larger owing to observational biases. Here we report that gravitational lensing is likely to dominate the observed properties of galaxies with redshifts of z greater than or similar to 12, when the instrumental limiting magnitude is expected to be brighter than the characteristic magnitude of the galaxy sample. The number counts could be modified by an order of magnitude, with most galaxies being part of multiply imaged systems, located less than 1 arcsec from brighter foreground galaxies at z approximate to 2. This lens-induced association of high-redshift and foreground galaxies has perhaps already been observed among a sample of galaxy candidates identified at z approximate to 10.6. Future surveys will need to be designed to account for a significant gravitational lensing bias in high-redshift galaxy samples.
C1 [Wyithe, J. Stuart B.] Univ Melbourne, Sch Phys, Parkville, Vic 3010, Australia.
   [Yan, Haojing] Ohio State Univ, Ctr Cosmol & AstroParticle Phys, Columbus, OH 43210 USA.
   [Windhorst, Rogier A.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Mao, Shude] Univ Manchester, Ctr Astrophys, Jodrell Bank, Manchester M13 9PL, Lancs, England.
   [Mao, Shude] Chinese Acad Sci, Natl Astron Observ China, Beijing 100012, Peoples R China.
C3 University of Melbourne; University System of Ohio; Ohio State University; Arizona State University; Arizona State University-Tempe; University of Manchester; Jodrell Bank Centre for Astrophysics; Chinese Academy of Sciences; National Astronomical Observatory, CAS
RP Wyithe, JSB (corresponding author), Univ Melbourne, Sch Phys, Parkville, Vic 3010, Australia.
EM swyithe@unimelb.edu.au
FU Australian Research Council; Center for Cosmology and AstroParticle Physics (CCAPP) at The Ohio State University; Space Telescope Science Institute; NASA; QE-II fellowship
NR 30
TC 65
Z9 71
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 13
PY 2011
VL 469
IS 7329
BP 181
EP 184
DI 10.1038/nature09619
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400031
PM 21228870
DA 2026-03-09
ER

PT J
AU Greer, EL
   Maures, TJ
   Ucar, D
   Hauswirth, AG
   Mancini, E
   Lim, JP
   Benayoun, BA
   Shi, Y
   Brunet, A
AF Greer, Eric L.
   Maures, Travis J.
   Ucar, Duygu
   Hauswirth, Anna G.
   Mancini, Elena
   Lim, Jana P.
   Benayoun, Berenice A.
   Shi, Yang
   Brunet, Anne
TI Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID systematic rnai screen; life-span; c. elegans; h3k4 trimethylation; stress resistance; genes; complex; methylation; demethylation; chromatin
AB Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histone methyltransferase SET-2, regulates Caenorhabditis elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants.
C1 [Greer, Eric L.; Maures, Travis J.; Ucar, Duygu; Hauswirth, Anna G.; Mancini, Elena; Lim, Jana P.; Benayoun, Berenice A.; Brunet, Anne] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Greer, Eric L.; Shi, Yang] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Greer, Eric L.; Shi, Yang] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA.
C3 Stanford University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Brunet, A (corresponding author), Stanford Univ, Dept Genet, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM anne.brunet@stanford.edu
FU NIH [R01-AG31198, ARRA-AG31198, R01-GM058012, F32-AG037254, T32-MH020016]; NSF; Helen Hay Whitney Post-Doctoral fellowship;  [T32-CA009361]; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of General Medical Sciences; National Institute of Mental Health; National Institute on Aging [T32MH020016] Funding Source: NIH RePORTER
NR 45
TC 489
Z9 587
U1 4
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 365
EP U204
DI 10.1038/nature10572
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700038
PM 22012258
DA 2026-03-09
ER

PT J
AU Dunn, M
   Greenhill, SJ
   Levinson, SC
   Gray, RD
AF Dunn, Michael
   Greenhill, Simon J.
   Levinson, Stephen C.
   Gray, Russell D.
TI Evolved structure of language shows lineage-specific trends in word-order universals
SO NATURE
LA English
DT Article
AB Languages vary widely but not without limit. The central goal of linguistics is to describe the diversity of human languages and explain the constraints on that diversity. Generative linguists following Chomsky have claimed that linguistic diversity must be constrained by innate parameters that are set as a child learns a language(1,2). In contrast, other linguists following Greenberg have claimed that there are statistical tendencies for co-occurrence of traits reflecting universal systems biases(3-5), rather than absolute constraints or parametric variation. Here we use computational phylogenetic methods to address the nature of constraints on linguistic diversity in an evolutionary framework(6). First, contrary to the generative account of parameter setting, we show that the evolution of only a few word-order features of languages are strongly correlated. Second, contrary to the Greenbergian generalizations, we show that most observed functional dependencies between traits are lineage-specific rather than universal tendencies. These findings support the view that-at least with respect to word order-cultural evolution is the primary factor that determines linguistic structure, with the current state of a linguistic system shaping and constraining future states.
C1 [Dunn, Michael; Levinson, Stephen C.] Max Planck Inst Psycholinguist, NL-6500 AH Nijmegen, Netherlands.
   [Dunn, Michael; Levinson, Stephen C.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 EN Nijmegen, Netherlands.
   [Greenhill, Simon J.; Gray, Russell D.] Univ Auckland, Dept Psychol, Auckland 1142, New Zealand.
   [Greenhill, Simon J.] Univ Auckland, Computat Evolut Grp, Auckland 1142, New Zealand.
C3 Max Planck Society; Radboud University Nijmegen; University of Auckland; University of Auckland
RP Dunn, M (corresponding author), Max Planck Inst Psycholinguist, POB 310, NL-6500 AH Nijmegen, Netherlands.
EM michael.dunn@mpi.nl
NR 29
TC 301
Z9 334
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 MAY 5
PY 2011
VL 473
IS 7345
BP 79
EP 82
DI 10.1038/nature09923
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300034
PM 21490599
DA 2026-03-09
ER

PT J
AU Bock, DD
   Lee, WCA
   Kerlin, AM
   Andermann, ML
   Hood, G
   Wetzel, AW
   Yurgenson, S
   Soucy, ER
   Kim, HS
   Reid, RC
AF Bock, Davi D.
   Lee, Wei-Chung Allen
   Kerlin, Aaron M.
   Andermann, Mark L.
   Hood, Greg
   Wetzel, Arthur W.
   Yurgenson, Sergey
   Soucy, Edward R.
   Kim, Hyon Suk
   Reid, R. Clay
TI Network anatomy and in vivo physiology of visual cortical neurons
SO NATURE
LA English
DT Article
ID inhibitory neurons; synaptic connections; pyramidal neurons; rat; cortex; interneurons; cells; map; transmission; orientation
AB In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property-the preferred stimulus orientation-of a group of neurons in the mouse primary visual cortex. Large-scale electron microscopy of serial thin sections was then used to trace a portion of these neurons' local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.
C1 [Bock, Davi D.; Lee, Wei-Chung Allen; Kerlin, Aaron M.; Andermann, Mark L.; Yurgenson, Sergey; Kim, Hyon Suk; Reid, R. Clay] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Bock, Davi D.; Lee, Wei-Chung Allen; Soucy, Edward R.; Kim, Hyon Suk; Reid, R. Clay] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [Hood, Greg; Wetzel, Arthur W.] Carnegie Mellon Univ, Pittsburgh Supercomp Ctr, Pittsburgh, PA 15213 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Carnegie Mellon University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Reid, RC (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM clay_reid@hms.harvard.edu
FU Center for Brain Science; Center for Brain Science at Harvard University; Microsoft Research; NIH though the NEI [EY10115, EY18742]; NIH though NRBSC [P41 RR06009]; Harvard Center of Neurodegeneration and Repair; NEI [EY18532]; Pittsburgh Supercomputing Center; National Eye Institute [R01EY010115] Funding Source: NIH RePORTER
NR 57
TC 636
Z9 776
U1 3
U2 138
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 177
EP U59
DI 10.1038/nature09802
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200029
PM 21390124
DA 2026-03-09
ER

PT J
AU Gebhardt, T
   Whitney, PG
   Zaid, A
   Mackay, LK
   Brooks, AG
   Heath, WR
   Carbone, FR
   Mueller, SN
AF Gebhardt, Thomas
   Whitney, Paul G.
   Zaid, Ali
   Mackay, Laura K.
   Brooks, Andrew G.
   Heath, William R.
   Carbone, Francis R.
   Mueller, Scott N.
TI Different patterns of peripheral migration by memory CD4+ and CD8+ T cells
SO NATURE
LA English
DT Article
ID herpes-simplex-virus; dendritic cells; nonlymphoid tissue; infection; skin; effector; activation; adhesion; lymphocytes; integrin
AB Infections localized to peripheral tissues such as the skin result in the priming of T-cell responses that act to control pathogens. Activated T cells undergo migrational imprinting within the draining lymph nodes(1), resulting in memory T cells that provide local and systemic protection(2). Combinations of migrating and resident memory T cells have been implicated in long-term peripheral immunity, especially at the surfaces that form pathogen entry points into the body(3). However, T-cell immunity consists of separate CD4(+) helper T cells and CD8(+) killer T cells, with distinct effector and memory programming requirements(4). Whether these subsets also differ in their ability to form a migrating pool involved in peripheral immunosurveillance or a separate resident population responsible for local infection control has not been explored. Here, using mice, we show key differences in the migration and tissue localization of memory CD4(+) and CD8(+) T cells following infection of the skin by herpes simplex virus. On resolution of infection, the skin contained two distinct virus-specific memory subsets; a slow-moving population of sequestered CD8(+) T cells that were resident in the epidermis and confined largely to the original site of infection, and a dynamic population of CD4(+) T cells that trafficked rapidly through the dermis as part of a wider recirculation pattern. Unique homing-molecule expression by recirculating CD4(+) T effector-memory cells mirrored their preferential skin-migratory capacity. Overall, these results identify a complexity in memory T-cell migration, illuminating previously unappreciated differences between the CD4(+) and CD8(+) subsets.
C1 [Gebhardt, Thomas; Whitney, Paul G.; Zaid, Ali; Mackay, Laura K.; Brooks, Andrew G.; Heath, William R.; Carbone, Francis R.; Mueller, Scott N.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
C3 University of Melbourne
RP Gebhardt, T (corresponding author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
EM gebhardt@unimelb.edu.au; smue@unimelb.edu.au
FU Australian NHMRC; ARC
NR 25
TC 427
Z9 507
U1 2
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 216
EP U119
DI 10.1038/nature10339
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900037
PM 21841802
DA 2026-03-09
ER

PT J
AU Schefuss, E
   Kuhlmann, H
   Mollenhauer, G
   Prange, M
   Pätzold, J
AF Schefuss, Enno
   Kuhlmann, Holger
   Mollenhauer, Gesine
   Prange, Matthias
   Paetzold, Juergen
TI Forcing of wet phases in southeast Africa over the past 17,000 years
SO NATURE
LA English
DT Article
ID terrestrial; variability; climate; record; plants; proxy
AB Intense debate persists about the climatic mechanisms governing hydrologic changes in tropical and subtropical southeast Africa since the Last Glacial Maximum, about 20,000 years ago. In particular, the relative importance of atmospheric and oceanic processes is not firmly established(1-5). Southward shifts of the intertropical convergence zone (ITCZ) driven by high-latitude climate changes have been suggested as a primary forcing(2,3), whereas other studies infer a predominant influence of Indian Ocean sea surface temperatures on regional rainfall changes(4,5). To address this question, a continuous record representing an integrated signal of regional climate variability is required, but has until now been missing. Here we show that remote atmospheric forcing by cold events in the northern high latitudes appears to have been the main driver of hydro-climatology in southeast Africa during rapid climate changes over the past 17,000 years. Our results are based on a reconstruction of precipitation and river discharge changes, as recorded in a marine sediment core off the mouth of the Zambezi River, near the southern boundary of the modern seasonal ITCZ migration. Indian Ocean sea surface temperatures did not exert a primary control over southeast African hydrologic variability. Instead, phases of high precipitation and terrestrial discharge occurred when the ITCZ was forced southwards during Northern Hemisphere cold events, such as Heinrich stadial 1 (around 16,000 years ago) and the Younger Dryas (around 12,000 years ago), or when local summer insolation was high in the late Holocene, that is, during the past 4,000 years.
C1 [Schefuss, Enno; Kuhlmann, Holger; Mollenhauer, Gesine; Prange, Matthias; Paetzold, Juergen] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Schefuss, Enno; Kuhlmann, Holger; Mollenhauer, Gesine; Prange, Matthias; Paetzold, Juergen] Univ Bremen, Fac Geosci, D-28359 Bremen, Germany.
   [Mollenhauer, Gesine] Alfred Wegener Inst Polar & Marine Res, D-27568 Bremerhaven, Germany.
C3 University of Bremen; University of Bremen; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Schefuss, E (corresponding author), Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
EM schefuss@uni-bremen.de
FU DFG Research Center/Cluster of Excellence 'The Ocean in the Earth System'; DFG [Sche903/8]
NR 30
TC 226
Z9 243
U1 2
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 DEC 22
PY 2011
VL 480
IS 7378
BP 509
EP 512
DI 10.1038/nature10685
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000057
PM 22193106
DA 2026-03-09
ER

PT J
AU Kocot, KM
   Cannon, JT
   Todt, C
   Citarella, MR
   Kohn, AB
   Meyer, A
   Santos, SR
   Schander, C
   Moroz, LL
   Lieb, B
   Halanych, KM
AF Kocot, Kevin M.
   Cannon, Johanna T.
   Todt, Christiane
   Citarella, Mathew R.
   Kohn, Andrea B.
   Meyer, Achim
   Santos, Scott R.
   Schander, Christoffer
   Moroz, Leonid L.
   Lieb, Bernhard
   Halanych, Kenneth M.
TI Phylogenomics reveals deep molluscan relationships
SO NATURE
LA English
DT Article
ID ribosomal-rna sequences; aplacophora; origin; solenogastres; spicules; database; radula; model; tree; tool
AB Evolutionary relationships among the eight major lineages of Mollusca have remained unresolved despite their diversity and importance. Previous investigations of molluscan phylogeny, based primarily on nuclear ribosomal gene sequences(1-3) or morphological data(4), have been unsuccessful at elucidating these relationships. Recently, phylogenomic studies using dozens to hundreds of genes have greatly improved our understanding of deep animal relationships(5). However, limited genomic resources spanning molluscan diversity has prevented use of a phylogenomic approach. Here we use transcriptome and genome data from all major lineages (except Monoplacophora) and recover a well-supported topology for Mollusca. Our results strongly support the Aculifera hypothesis placing Polyplacophora (chitons) in a clade with a monophyletic Aplacophora (worm-like molluscs). Additionally, within Conchifera, a sister-taxon relationship between Gastropoda and Bivalvia is supported. This grouping has received little consideration and contains most (>95%) molluscan species. Thus we propose the node-based name Pleistomollusca. In light of these results, we examined the evolution of morphological characters and found support for advanced cephalization and shells as possibly having multiple origins within Mollusca.
C1 [Kocot, Kevin M.; Cannon, Johanna T.; Santos, Scott R.; Halanych, Kenneth M.] Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA.
   [Todt, Christiane; Schander, Christoffer] Univ Bergen, Dept Biol, NO-5020 Bergen, Norway.
   [Todt, Christiane; Schander, Christoffer] Univ Bergen, Ctr Geobiol, NO-5020 Bergen, Norway.
   [Citarella, Mathew R.; Kohn, Andrea B.; Moroz, Leonid L.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA.
   [Meyer, Achim; Lieb, Bernhard] Johannes Gutenberg Univ Mainz, Inst Zool, D-55099 Mainz, Germany.
   [Moroz, Leonid L.] Univ Florida, Dept Neurosci, Gainesville, FL 32611 USA.
C3 Auburn University System; Auburn University; University of Bergen; University of Bergen; State University System of Florida; University of Florida; Johannes Gutenberg University of Mainz; State University System of Florida; University of Florida
RP Kocot, KM (corresponding author), Auburn Univ, Dept Biol Sci, 101 Rouse Life Sci, Auburn, AL 36849 USA.
EM kmkocot@auburn.edu; ken@auburn.edu
FU National Science Foundation (NSF) [0744649, 0821622]; National Institute of Health (NIH) [1RO1NS06076, 1R01GM097502, R21 RR025699, R21DA030118]; McKnight Brain Research Foundation; German Science Foundation [Li 998/9-1]; University of Bergen (Norway) [226270]; Direct For Computer & Info Scie & Enginr; Division Of Computer and Network Systems [0821622] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0744649] Funding Source: National Science Foundation
NR 39
TC 408
Z9 463
U1 4
U2 227
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 452
EP U101
DI 10.1038/nature10382
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500038
PM 21892190
DA 2026-03-09
ER

PT J
AU Fujiki, R
   Hashiba, W
   Sekine, H
   Yokoyama, A
   Chikanishi, T
   Ito, S
   Imai, Y
   Kim, J
   He, HH
   Igarashi, K
   Kanno, J
   Ohtake, F
   Kitagawa, H
   Roeder, RG
   Brown, M
   Kato, S
AF Fujiki, Ryoji
   Hashiba, Waka
   Sekine, Hiroki
   Yokoyama, Atsushi
   Chikanishi, Toshihiro
   Ito, Saya
   Imai, Yuuki
   Kim, Jaehoon
   He, Housheng Hansen
   Igarashi, Katsuhide
   Kanno, Jun
   Ohtake, Fumiaki
   Kitagawa, Hirochika
   Roeder, Robert G.
   Brown, Myles
   Kato, Shigeaki
TI GlcNAcylation of histone H2B facilitates its monoubiquitination
SO NATURE
LA English
DT Article
ID o-glcnac transferase; beta-n-acetylglucosamine; chromatin; acetylation; language; genes
AB Chromatin reorganization is governed by multiple post-translational modifications of chromosomal proteins and DNA(1,2). These histone modifications are reversible, dynamic events that can regulate DNA-driven cellular processes(3,4). However, the molecular mechanisms that coordinate histone modification patterns remain largely unknown. In metazoans, reversible protein modification by O-linked N-acetylglucosamine (GlcNAc) is catalysed by two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)(5,6). However, the significance of GlcNAcylation in chromatin reorganization remains elusive. Here we report that histone H2B is GlcNAcylated at residue S112 by OGT in vitro and in living cells. Histone GlcNAcylation fluctuated in response to extracellular glucose through the hexosamine biosynthesis pathway (HBP)(5,6). H2B S112 GlcNAcylation promotes K120 monoubiquitination, in which the GlcNAc moiety can serve as an anchor for a histone H2B ubiquitin ligase. H2B S112 GlcNAc was localized to euchromatic areas on fly polytene chromosomes. In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over chromosomes including transcribed gene loci, with some sites co-localizing with H2B K120 monoubiquitination. These findings suggest that H2B S112 GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination, presumably for transcriptional activation.
C1 [Fujiki, Ryoji; Hashiba, Waka; Sekine, Hiroki; Yokoyama, Atsushi; Chikanishi, Toshihiro; Ito, Saya; Imai, Yuuki; Ohtake, Fumiaki; Kitagawa, Hirochika; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kim, Jaehoon; Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
   [He, Housheng Hansen; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [He, Housheng Hansen; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Igarashi, Katsuhide; Kanno, Jun] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Setagaya Ku, Tokyo 1588501, Japan.
   [Kato, Shigeaki] Japan Sci & Technol Agcy, ERATO, Kawaguchi, Saitama 3320012, Japan.
C3 University of Tokyo; Rockefeller University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; National Institute of Health Sciences - Japan; Japan Science & Technology Agency (JST)
RP Kato, S (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan.
EM uskato@mail.ecc.u-tokyo.ac.jp
FU Naito Foundation; Astellas foundation; Ministry of Education, Culture, Sports, Science and Technology (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research [22780086, 10J04044, 22121502, 23689066] Funding Source: KAKEN
NR 25
TC 258
Z9 319
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 22
PY 2011
VL 480
IS 7378
BP 557
EP U188
DI 10.1038/nature10656
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000068
PM 22121020
DA 2026-03-09
ER

PT J
AU Lee, X
   Goulden, ML
   Hollinger, DY
   Barr, A
   Black, TA
   Bohrer, G
   Bracho, R
   Drake, B
   Goldstein, A
   Gu, LH
   Katul, G
   Kolb, T
   Law, BE
   Margolis, H
   Meyers, T
   Monson, R
   Munger, W
   Oren, R
   Kyaw, TPU
   Richardson, AD
   Schmid, HP
   Staebler, R
   Wofsy, S
   Zhao, L
AF Lee, Xuhui
   Goulden, Michael L.
   Hollinger, David Y.
   Barr, Alan
   Black, T. Andrew
   Bohrer, Gil
   Bracho, Rosvel
   Drake, Bert
   Goldstein, Allen
   Gu, Lianhong
   Katul, Gabriel
   Kolb, Thomas
   Law, Beverly E.
   Margolis, Hank
   Meyers, Tilden
   Monson, Russell
   Munger, William
   Oren, Ram
   Kyaw Tha Paw U
   Richardson, Andrew D.
   Schmid, Hans Peter
   Staebler, Ralf
   Wofsy, Steven
   Zhao, Lei
TI Observed increase in local cooling effect of deforestation at higher latitudes
SO NATURE
LA English
DT Article
ID land-use; climate; vegetation; forest; energy; water
AB Deforestation in mid-to high latitudes is hypothesized to have the potential to cool the Earth's surface by altering biophysical processes(1-3). In climate models of continental-scale land clearing, the cooling is triggered by increases in surface albedo and is reinforced by a land albedo-sea ice feedback(4,5). This feedback is crucial in the model predictions; without it other biophysical processes may overwhelm the albedo effect to generate warming instead(5). Ongoing land-use activities, such as land management for climate mitigation, are occurring at local scales (hectares) presumably too small to generate the feedback, and it is not known whether the intrinsic biophysical mechanism on its own can change the surface temperature in a consistent manner(6,7). Nor has the effect of deforestation on climate been demonstrated over large areas from direct observations. Here we show that surface air temperature is lower in open land than in nearby forested land. The effect is 0.85 +/- 0.44 K (mean +/- one standard deviation) northwards of 45 degrees N and 0.21 +/- 0.53 K southwards. Below 35 degrees N there is weak evidence that deforestation leads to warming. Results are based on comparisons of temperature at forested eddy covariance towers in the USA and Canada and, as a proxy for small areas of cleared land, nearby surface weather stations. Night-time temperature changes unrelated to changes in surface albedo are an important contributor to the overall cooling effect. The observed latitudinal dependence is consistent with theoretical expectation of changes in energy loss from convection and radiation across latitudes in both the daytime and night-time phase of the diurnal cycle, the latter of which remains uncertain in climate models(8).
C1 [Lee, Xuhui; Zhao, Lei] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
   [Goulden, Michael L.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Hollinger, David Y.] US Forest Serv, USDA, No Res Stn, Durham, NH 03824 USA.
   [Barr, Alan] Environm Canada, Div Climate Res, Saskatoon, SK S7N 3H5, Canada.
   [Black, T. Andrew] Univ British Columbia, Fac Land & Food Syst, Vancouver, BC V6T 1Z4, Canada.
   [Bohrer, Gil] Ohio State Univ, Dept Civil & Environm Engn & Geodet Sci, Columbus, OH 43210 USA.
   [Bracho, Rosvel] Univ Florida, Sch Forest Resources & Conservat, Gainesville, FL 32611 USA.
   [Drake, Bert] Smithsonian Environm Res Ctr, Edgewater, MD 21037 USA.
   [Goldstein, Allen] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA.
   [Gu, Lianhong] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA.
   [Katul, Gabriel; Oren, Ram] Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA.
   [Kolb, Thomas] No Arizona Univ, Sch Forestry, Flagstaff, AZ 86011 USA.
   [Law, Beverly E.] Oregon State Univ, Coll Forestry, Corvallis, OR 97331 USA.
   [Margolis, Hank] Univ Laval, Fac Foresterie Geog & Geomat, Ctr Etud Foret, Quebec City, PQ G1V 0A6, Canada.
   [Meyers, Tilden] NOAA ARL ATDD, Oak Ridge, TN 37830 USA.
   [Monson, Russell] Univ Colorado, Dept Ecol & Evolutionary Biol, Boulder, CO 80309 USA.
   [Munger, William; Wofsy, Steven] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Kyaw Tha Paw U] Univ Calif Davis, Dept Land Air & Water Resources, Davis, CA 95616 USA.
   [Richardson, Andrew D.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Schmid, Hans Peter] Karlsruhe Inst Technol, Inst Meteorol & Climate Res, D-82467 Garmisch Partenkirchen, Germany.
   [Staebler, Ralf] Environm Canada, Proc Res Sect, Toronto, ON M3H 5T4, Canada.
C3 Yale University; University of California System; University of California Irvine; United States Department of Agriculture (USDA); United States Forest Service; Environment & Climate Change Canada; University of British Columbia; University System of Ohio; Ohio State University; State University System of Florida; University of Florida; Smithsonian Institution; Smithsonian Environmental Research Center; University of California System; University of California Berkeley; United States Department of Energy (DOE); Oak Ridge National Laboratory; Duke University; Northern Arizona University; Oregon State University; Laval University; National Oceanic Atmospheric Admin (NOAA) - USA; University of Colorado System; University of Colorado Boulder; Harvard University; University of California System; University of California Davis; Harvard University; Helmholtz Association; Karlsruhe Institute of Technology; Environment & Climate Change Canada
RP Lee, X (corresponding author), Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
EM xuhui.lee@yale.edu
FU US Department of Energy; Yale University Climate and Energy Institute
NR 29
TC 604
Z9 691
U1 8
U2 428
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 384
EP 387
DI 10.1038/nature10588
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700042
PM 22094699
DA 2026-03-09
ER

PT J
AU Flynn, RL
   Centore, RC
   O'Sullivan, RJ
   Rai, R
   Tse, A
   Zhou, SY
   Chang, S
   Karlseder, J
   Zou, L
AF Flynn, Rachel Litman
   Centore, Richard C.
   O'Sullivan, Roderick J.
   Rai, Rekha
   Tse, Alice
   Zhou Songyang
   Chang, Sandy
   Karlseder, Jan
   Zou, Lee
TI TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA
SO NATURE
LA English
DT Article
ID replication protein-a; repeat-containing rna; fission yeast; chromosome ends; binding protein; atr; damage; pot1; rpa; elongation
AB Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres(1,2), suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres(3). Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the reaccumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity.
C1 [Flynn, Rachel Litman; Centore, Richard C.; Tse, Alice; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
   [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [O'Sullivan, Roderick J.; Karlseder, Jan] Salk Inst Biol Studies, Mol & Cellular Lab, La Jolla, CA 92037 USA.
   [Rai, Rekha; Chang, Sandy] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
   [Zhou Songyang] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Salk Institute; Yale University; Baylor College of Medicine
RP Zou, L (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
EM zou.lee@mgh.harvard.edu
FU National Institutes of Health (NIH) [5T32CA009216-28, F32-GM089150, CA133249, CA129037, GM06525, AG025837, GM076388]; American Cancer Society [0902501]; George E. Hewitt Foundation for Medical Research; Welch Foundation [Q-1673]; ACS [RSG-08-297]; National Cancer Institute [T32CA009216] Funding Source: NIH RePORTER
NR 30
TC 281
Z9 339
U1 1
U2 37
PU 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 24
PY 2011
VL 471
IS 7339
BP 532
EP +
DI 10.1038/nature09772
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200066
PM 21399625
DA 2026-03-09
ER

PT J
AU Li, HB
   Henning, T
AF Li, Hua-bai
   Henning, Thomas
TI The alignment of molecular cloud magnetic fields with the spiral arms in M33
SO NATURE
LA English
DT Article
ID instability; herschel; gas
AB The formation of molecular clouds, which serve as stellar nurseries in galaxies, is poorly understood. A class of cloud formation models suggests that a large-scale galactic magnetic field is irrelevant at the scale of individual clouds, because the turbulence and rotation of a cloud may randomize the orientation of its magnetic field(1,2). Alternatively, galactic fields could be strong enough to impose their direction upon individual clouds(3,4), thereby regulating cloud accumulation and fragmentation(5), and affecting the rate and efficiency of star formation(6). Our location in the disk of the Galaxy makes an assessment of the situation difficult. Here we report observations of the magnetic field orientation of six giant molecular cloud complexes in the nearby, almost face-on, galaxy M33. The fields are aligned with the spiral arms, suggesting that the large-scale field in M33 anchors the clouds.
C1 [Li, Hua-bai; Henning, Thomas] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 Max Planck Society
RP Li, HB (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM li@mpia.de
FU Max-Planck-Institut fur Astronomie and Harvard-Smithsonian Center for Astrophysics; Smithsonian Institution; Academia Sinica
NR 30
TC 62
Z9 66
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 499
EP 501
DI 10.1038/nature10551
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600043
PM 22089133
DA 2026-03-09
ER

PT J
AU Russell, AB
   Hood, RD
   Bui, NK
   LeRoux, M
   Vollmer, W
   Mougous, JD
AF Russell, Alistair B.
   Hood, Rachel D.
   Bui, Nhat Khai
   LeRoux, Michele
   Vollmer, Waldemar
   Mougous, Joseph D.
TI Type VI secretion delivers bacteriolytic effectors to target cells
SO NATURE
LA English
DT Article
ID complete genome sequence; pseudomonas-aeruginosa; structural features; protein; system; gene; catalog; toxin
AB Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enzymes by the outer membrane. Here we show that the type VI secretion system of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyse peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa uses specific periplasmically localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active type VI secretion system, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit.
C1 [Russell, Alistair B.; Hood, Rachel D.; Mougous, Joseph D.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [Bui, Nhat Khai; Vollmer, Waldemar] Newcastle Univ, Inst Cell & Mol Biosci, Ctr Bacterial Cell Biol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [LeRoux, Michele] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Newcastle University - UK; 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 [RO1 AI080609]; European Commission; National Science Foundation; National Institute of Allergy and Infectious Diseases [R01AI080609] Funding Source: NIH RePORTER
NR 48
TC 571
Z9 681
U1 3
U2 184
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 343
EP U92
DI 10.1038/nature10244
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200035
PM 21776080
DA 2026-03-09
ER

PT J
AU Sobolev, SV
   Sobolev, AV
   Kuzmin, DV
   Krivolutskaya, NA
   Petrunin, AG
   Arndt, NT
   Radko, VA
   Vasiliev, YR
AF Sobolev, Stephan V.
   Sobolev, Alexander V.
   Kuzmin, Dmitry V.
   Krivolutskaya, Nadezhda A.
   Petrunin, Alexey G.
   Arndt, Nicholas T.
   Radko, Viktor A.
   Vasiliev, Yuri R.
TI Linking mantle plumes, large igneous provinces and environmental catastrophes
SO NATURE
LA English
DT Article
ID carbon-isotope fluctuations; flood-basalt events; mass extinction; permian extinction; siberian traps; melt; volcanism; constraints; eruption; hawaiian
AB Large igneous provinces (LIPs) are known for their rapid production of enormous volumes of magma (up to several million cubic kilometres in less than a million years)(1), for marked thinning of the lithosphere(2,3), often ending with a continental break-up, and for their links to global environmental catastrophes(4,5). Despite the importance of LIPs, controversy surrounds even the basic idea that they form through melting in the heads of thermal mantle plumes(2,3,6-10). The Permo-Triassic Siberian Traps(11)-the type example and the largest continental LIP1,12-is located on thick cratonic lithosphere(1,12) and was synchronous with the largest known mass-extinction event(1). However, there is no evidence of pre-magmatic uplift or of a large lithospheric stretching(7), as predicted above a plume head(2,6,9). Moreover, estimates of magmatic CO2 degassing from the Siberian Traps are considered insufficient to trigger climatic crises(13-15), leading to the hypothesis that the release of thermogenic gases from the sediment pile caused the mass extinction(15,16). Here we present petrological evidence for a large amount (15 wt%) of dense recycled oceanic crust in the head of the plume and develop a thermomechanical model that predicts no pre-magmatic uplift and requires no lithospheric extension. The model implies extensive plume melting and heterogeneous erosion of the thick cratonic lithosphere over the course of a few hundred thousand years. The model suggests that massive degassing of CO2 and HCl, mostly from the recycled crust in the plume head, could alone trigger a mass extinction and predicts it happening before the main volcanic phase, in agreement with stratigraphic and geochronological data for the Siberian Traps and other LIPs(5).
C1 [Sobolev, Stephan V.; Petrunin, Alexey G.] Deutsch GeoForschungsZentrum GFZ, D-14473 Potsdam, Germany.
   [Sobolev, Stephan V.; Petrunin, Alexey G.] Russian Acad Sci, O Yu Schmidt Inst Phys Earth, Moscow 123995, Russia.
   [Sobolev, Alexander V.; Arndt, Nicholas T.] Univ Grenoble 1, CNRS, ISTerre, F-38041 Grenoble 9, France.
   [Sobolev, Alexander V.; Kuzmin, Dmitry V.] Max Planck Inst Chem, D-55128 Mainz, Germany.
   [Sobolev, Alexander V.; Krivolutskaya, Nadezhda A.] Russian Acad Sci, VI Vernadsky Inst Geochem & Analyt Chem, Moscow 119991, Russia.
   [Kuzmin, Dmitry V.; Vasiliev, Yuri R.] Russian Acad Sci, Siberian Branch, VS Sobolev Inst Geol & Mineral, Novosibirsk 630090, Russia.
   [Radko, Viktor A.] Ltd Liabil Co Norilskgeologiya Norilsk, Norilsk 663330, Russia.
C3 Helmholtz Association; GFZ Helmholtz Centre for Geosciences; Russian Academy of Sciences; Schmidt Institute of Physics of the Earth of the Russian Academy of Sciences; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Gustave-Eiffel; Universite Savoie Mont Blanc; Max Planck Society; Russian Academy of Sciences; Vernadsky Institute of Geochemistry & Analytical Chemistry; Russian Academy of Sciences; Sobolev Institute of Geology & Mineralogy of the Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences
RP Sobolev, SV (corresponding author), Deutsch GeoForschungsZentrum GFZ, D-14473 Potsdam, Germany.
EM stephan@gfz-potsdam.de; alexander.sobolev@ujf-grenoble.fr
FU Deutsche Forschungsgemeinschaft (DFG) [SPP 1375 SAMPLE (SO 425/4)]; Agence Nationale de la Recherche, France [ANR-09-CEXC-003-01]; Gottingen University, Germany; Russian Foundation for Basic Research [09-05-01193a]; Russian President [HIII-3919.2010.5]; Earth Sciences Department of Russian Academy
NR 57
TC 483
Z9 540
U1 7
U2 322
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 312
EP 316
DI 10.1038/nature10385
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400027
PM 21921914
DA 2026-03-09
ER

PT J
AU Shin, K
   Lee, J
   Guo, N
   Kim, J
   Lim, A
   Qu, LS
   Mysorekar, IU
   Beachy, PA
AF Shin, Kunyoo
   Lee, John
   Guo, Nini
   Kim, James
   Lim, Agnes
   Qu, Lishu
   Mysorekar, Indira U.
   Beachy, Philip A.
TI Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder
SO NATURE
LA English
DT Article
ID urinary-tract-infection; escherichia-coli; cancer; differentiation; metastasis; neoplasia; patterns; autopsy; renewal; organ
AB Epithelial integrity in metazoan organs is maintained through the regulated proliferation and differentiation of organ-specific stem and progenitor cells. Although the epithelia of organs such as the intestine regenerate constantly and thus remain continuously proliferative(1), other organs, such as the mammalian urinary bladder, shift from near-quiescence to a highly proliferative state in response to epithelial injury(2-4). The cellular and molecular mechanisms underlying this injury-induced mode of regenerative response are poorly defined. Here we show in mice that the proliferative response to bacterial infection or chemical injury within the bladder is regulated by signal feedback between basal cells of the urothelium and the stromal cells that underlie them. We demonstrate that these basal cells include stem cells capable of regenerating all cell types within the urothelium, and are marked by expression of the secreted protein signal Sonic hedgehog (Shh). On injury, Shh expression in these basal cells increases and elicits increased stromal expression of Wnt protein signals, which in turn stimulate the proliferation of both urothelial and stromal cells. The heightened activity of this signal feedback circuit and the associated increase in cell proliferation appear to be required for restoration of urothelial function and, in the case of bacterial injury, may help clear and prevent further spread of infection. Our findings provide a conceptual framework for injury-induced epithelial regeneration in endodermal organs, and may provide a basis for understanding the roles of signalling pathways in cancer growth and metastasis.
C1 [Shin, Kunyoo; Lee, John; Kim, James; Lim, Agnes; Qu, Lishu; Beachy, Philip A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Inst Stem Cell Biol & Regenerat Med,Dept Dev Biol, Stanford, CA 94305 USA.
   [Guo, Nini] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
   [Mysorekar, Indira U.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
C3 Stanford University; Howard Hughes Medical Institute; Johns Hopkins University; Washington University (WUSTL)
RP Beachy, PA (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Inst Stem Cell Biol & Regenerat Med,Dept Dev Biol, Stanford, CA 94305 USA.
EM kunyoos@stanford.edu; pbeachy@stanford.edu
FU Department of Defense; National Institutes of Health; Pathway to Independence Award [K99/R00]
NR 32
TC 372
Z9 442
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 110
EP U145
DI 10.1038/nature09851
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400047
PM 21389986
DA 2026-03-09
ER

PT J
AU Wechsler, T
   Newman, S
   West, SC
AF Wechsler, Thomas
   Newman, Scott
   West, Stephen C.
TI Aberrant chromosome morphology in human cells defective for Holliday junction resolution
SO NATURE
LA English
DT Article
ID structure-specific nucleases; mus81-eme1; mechanism; blm; helicase; repair; identification; replication; resolvase; complex
AB In somatic cells, Holliday junctions can be formed between sister chromatids during the recombinational repair of DNA breaks or after replication fork demise. A variety of processes act upon Holliday junctions to remove them from DNA, in events that are critical for proper chromosome segregation. In human cells, the BLM protein, inactivated in individuals with Bloom's syndrome, acts in combination with topoisomerase III alpha, RMI1 and RMI2 (BTR complex) to promote the dissolution of double Holliday junctions(1,2). Cells defective for BLM exhibit elevated levels of sister chromatid exchanges (SCEs) and patients with Bloom's syndrome develop a broad spectrum of early-onset cancers caused by chromosome instability(3). MUS81-EME1 (refs 4-7), SLX1-SLX4 (refs 8-11) and GEN1 (refs 12, 13) also process Holliday junctions but, in contrast to the BTR complex, do so by endonucleolytic cleavage. Here we deplete these nucleases from Bloom's syndrome cells to analyse human cells compromised for the known Holliday junction dissolution/resolution pathways. We show that depletion of MUS81 and GEN1, or SLX4 and GEN1, from Bloom's syndrome cells results in severe chromosome abnormalities, such that sister chromatids remain interlinked in a side-by-side arrangement and the chromosomes are elongated and segmented. Our results indicate that normally replicating human cells require Holliday junction processing activities to prevent sister chromatid entanglements and thereby ensure accurate chromosome condensation. This phenotype was not apparent when both MUS81 and SLX4 were depleted from Bloom's syndrome cells, suggesting that GEN1 can compensate for their absence. Additionally, we show that depletion of MUS81 or SLX4 reduces the high frequency of SCEs in Bloom's syndrome cells, indicating that MUS81 and SLX4 promote SCE formation, in events that may ultimately drive the chromosome instabilities that underpin early-onset cancers associated with Bloom's syndrome.
C1 [Wechsler, Thomas; West, Stephen C.] Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK, London Res Inst, S Mimms EN6 3LD, Herts, England.
   [Newman, Scott] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
C3 Cancer Research UK; University of Cambridge
RP West, SC (corresponding author), Imperial Canc Res Fund, Clare Hall Labs, Canc Res UK, London Res Inst, S Mimms EN6 3LD, Herts, England.
EM stephen.west@cancer.org.uk
FU Cancer Research UK; Louis-Jeantet Foundation; European Research Council; Swiss Bridge Foundation; Breast Cancer Campaign; UK Medical Research Council; Cancer Research UK [11582] Funding Source: researchfish
NR 30
TC 178
Z9 217
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 MAR 31
PY 2011
VL 471
IS 7340
BP 642
EP U126
DI 10.1038/nature09790
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200044
PM 21399624
DA 2026-03-09
ER

PT J
AU Chiappini, C
   Frischknecht, U
   Meynet, G
   Hirschi, R
   Barbuy, B
   Pignatari, M
   Decressin, T
   Maeder, A
AF Chiappini, Cristina
   Frischknecht, Urs
   Meynet, Georges
   Hirschi, Raphael
   Barbuy, Beatriz
   Pignatari, Marco
   Decressin, Thibaut
   Maeder, Andre
TI Imprints of fast-rotating massive stars in the Galactic Bulge
SO NATURE
LA English
DT Article
ID metal-poor stars; low-metallicity; early galaxy; s-process; evolution; abundances; elements; universe; models; yields
AB The first stars that formed after the Big Bang were probably massive(1), and they provided the Universe with the first elements heavier than helium ('metals'), which were incorporated into low-mass stars that have survived to the present(2,3). Eight stars in the oldest globular cluster in the Galaxy, NGC 6522, were found to have surface abundances consistent with the gas from which they formed being enriched by massive stars(4) (that is, with higher alpha-element/Fe and Eu/Fe ratios than those of the Sun). However, the same stars have anomalously high abundances of Ba and La with respect to Fe-4, which usually arises through nucleosynthesis in low-mass stars(5) (via the slow-neutron-capture process, or s-process). Recent theory suggests that metal-poor fast-rotating massive stars are able to boost the s-process yields by up to four orders of magnitude(6), which might provide a solution to this contradiction. Here we report a reanalysis of the earlier spectra, which reveals that Y and Sr are also over-abundant with respect to Fe, showing a large scatter similar to that observed in extremely metal-poor stars(7), whereas C abundances are not enhanced. This pattern is best explained as originating in metal-poor fast-rotating massive stars, which might point to a common property of the first stellar generations and even of the 'first stars'.
C1 [Chiappini, Cristina] Astrophys Inst Potsdam, D-14482 Potsdam, Germany.
   [Chiappini, Cristina; Meynet, Georges; Decressin, Thibaut; Maeder, Andre] Univ Geneva, Geneva Observ, CH-1290 Sauverny, Switzerland.
   [Chiappini, Cristina] Osserv Astron Trieste, Ist Nazl Astrofis, I-34143 Trieste, Italy.
   [Frischknecht, Urs; Pignatari, Marco] Univ Basel, Dept Phys, CH-4056 Basel, Switzerland.
   [Frischknecht, Urs; Hirschi, Raphael] Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
   [Hirschi, Raphael] Univ Tokyo, IPMU, Chiba 2778582, Japan.
   [Barbuy, Beatriz] Univ Sao Paulo, IAG, BR-05508900 Sao Paulo, Brazil.
C3 University of Geneva; Istituto Nazionale Astrofisica (INAF); University of Basel; Keele University; University of Tokyo; Universidade de Sao Paulo
RP Chiappini, C (corresponding author), Astrophys Inst Potsdam, Sternwarte 16, D-14482 Potsdam, Germany.
EM cristina.chiappini@aip.de
FU Swiss National Science Foundation (SNSF); NSF [PHY 02-16783]; FAPESP; CNPq (Brazil); ESF-EuroGENESIS; World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan; Science and Technology Facilities Council [ST/G002355/1, ST/J000035/1, PP/D000955/1, PP/F000057/1] Funding Source: researchfish; STFC [ST/J000035/1, ST/G002355/1, PP/D000955/1, PP/F000057/1] Funding Source: UKRI
NR 21
TC 106
Z9 114
U1 1
U2 9
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 454
EP 457
DI 10.1038/nature10000
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600030
PM 21525928
DA 2026-03-09
ER

PT J
AU Burnworth, M
   Tang, LM
   Kumpfer, JR
   Duncan, AJ
   Beyer, FL
   Fiore, GL
   Rowan, SJ
   Weder, C
AF Burnworth, Mark
   Tang, Liming
   Kumpfer, Justin R.
   Duncan, Andrew J.
   Beyer, Frederick L.
   Fiore, Gina L.
   Rowan, Stuart J.
   Weder, Christoph
TI Optically healable supramolecular polymers
SO NATURE
LA English
DT Article
ID hydrogen-bonding interactions; poly(p-phenylene ethynylene)s; polymerization; route
AB Polymers with the ability to repair themselves after sustaining damage could extend the lifetimes of materials used in many applications(1). Most approaches to healable materials require heating the damaged area(2-4). Here we present metallosupramolecular polymers that can be mended through exposure to light. They consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding. On exposure to ultraviolet light, the metal-ligand motifs are electronically excited and the absorbed energy is converted into heat. This causes temporary disengagement of the metal-ligand motifs and a concomitant reversible decrease in the polymers' molecular mass and viscosity(5), thereby allowing quick and efficient defect healing. Light can be applied locally to a damage site, so objects can in principle be healed under load. We anticipate that this approach to healable materials, based on supramolecular polymers and a light-heat conversion step, can be applied to a wide range of supramolecular materials that use different chemistries.
C1 [Burnworth, Mark; Tang, Liming; Kumpfer, Justin R.; Rowan, Stuart J.; Weder, Christoph] Case Western Reserve Univ, Dept Macromol Sci & Engn, Cleveland, OH 44106 USA.
   [Duncan, Andrew J.; Beyer, Frederick L.] USA, Res Lab, Aberdeen Proving Ground, MD 21005 USA.
   [Fiore, Gina L.; Weder, Christoph] Univ Fribourg, Adolphe Merkle Inst, CH-1700 Fribourg, Switzerland.
   [Fiore, Gina L.; Weder, Christoph] Univ Fribourg, Fribourg Ctr Nanomat, CH-1700 Fribourg, Switzerland.
C3 University System of Ohio; Case Western Reserve University; United States Department of Defense; US Army Research, Development & Engineering Command (RDECOM); US Army Research Laboratory (ARL); University of Fribourg; University of Fribourg
RP Rowan, SJ (corresponding author), Case Western Reserve Univ, Dept Macromol Sci & Engn, 2100 Adelbert Rd, Cleveland, OH 44106 USA.
EM stuart.rowan@case.edu; christoph.weder@unifr.ch
FU US Army Research Office [W911NF-09-1-0288, W911NF-06-1-0414]; National Science Foundation [CHE-0704026, DMR-0602869, MRI-0821515]; Adolphe Merkle Foundation; US Army Research Laboratory [ORISE-1120-1120-99]; US Department of Energy [ORISE-1120-1120-99]; Direct For Mathematical & Physical Scien; Division Of Chemistry [0821515] Funding Source: National Science Foundation
NR 27
TC 1594
Z9 1773
U1 19
U2 1271
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 334
EP U230
DI 10.1038/nature09963
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600036
PM 21512571
DA 2026-03-09
ER

PT J
AU Chapman, MA
   Lawrence, MS
   Keats, JJ
   Cibulskis, K
   Sougnez, C
   Schinzel, AC
   Harview, CL
   Brunet, JP
   Ahmann, GJ
   Adli, M
   Anderson, KC
   Ardlie, KG
   Auclair, D
   Baker, A
   Bergsagel, PL
   Bernstein, BE
   Drier, Y
   Fonseca, R
   Gabriel, SB
   Hofmeister, CC
   Jagannath, S
   Jakubowiak, AJ
   Krishnan, A
   Levy, J
   Liefeld, T
   Lonial, S
   Mahan, S
   Mfuko, B
   Monti, S
   Perkins, LM
   Onofrio, R
   Pugh, TJ
   Rajkumar, SV
   Ramos, AH
   Siegel, DS
   Sivachenko, A
   Stewart, AK
   Trudel, S
   Vij, R
   Voet, D
   Winckler, W
   Zimmerman, T
   Carpten, J
   Trent, J
   Hahn, WC
   Garraway, LA
   Meyerson, M
   Lander, ES
   Getz, G
   Golub, TR
AF Chapman, Michael A.
   Lawrence, Michael S.
   Keats, Jonathan J.
   Cibulskis, Kristian
   Sougnez, Carrie
   Schinzel, Anna C.
   Harview, Christina L.
   Brunet, Jean-Philippe
   Ahmann, Gregory J.
   Adli, Mazhar
   Anderson, Kenneth C.
   Ardlie, Kristin G.
   Auclair, Daniel
   Baker, Angela
   Bergsagel, P. Leif
   Bernstein, Bradley E.
   Drier, Yotam
   Fonseca, Rafael
   Gabriel, Stacey B.
   Hofmeister, Craig C.
   Jagannath, Sundar
   Jakubowiak, Andrzej J.
   Krishnan, Amrita
   Levy, Joan
   Liefeld, Ted
   Lonial, Sagar
   Mahan, Scott
   Mfuko, Bunmi
   Monti, Stefano
   Perkins, Louise M.
   Onofrio, Robb
   Pugh, Trevor J.
   Rajkumar, S. Vincent
   Ramos, Alex H.
   Siegel, David S.
   Sivachenko, Andrey
   Stewart, A. Keith
   Trudel, Suzanne
   Vij, Ravi
   Voet, Douglas
   Winckler, Wendy
   Zimmerman, Todd
   Carpten, John
   Trent, Jeff
   Hahn, William C.
   Garraway, Levi A.
   Meyerson, Matthew
   Lander, Eric S.
   Getz, Gad
   Golub, Todd R.
TI Initial genome sequencing and analysis of multiple myeloma
SO NATURE
LA English
DT Article
ID b-cell lymphoma; human cancer; somatic mutations; stress-response; gene; pathogenesis; blimp-1; exosome; differentiation; classification
AB Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-kappa B signalling was indicated by mutations in 11 members of the NF-kappa B pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.
C1 [Chapman, Michael A.; Lawrence, Michael S.; Cibulskis, Kristian; Sougnez, Carrie; Harview, Christina L.; Brunet, Jean-Philippe; Adli, Mazhar; Ardlie, Kristin G.; Bernstein, Bradley E.; Drier, Yotam; Gabriel, Stacey B.; Liefeld, Ted; Mahan, Scott; Monti, Stefano; Onofrio, Robb; Pugh, Trevor J.; Ramos, Alex H.; Sivachenko, Andrey; Voet, Douglas; Winckler, Wendy; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Golub, Todd R.] Eli & Edythe L Broad Inst, Cambridge Ctr 7, Cambridge, MA 02412 USA.
   [Keats, Jonathan J.; Ahmann, Gregory J.; Bergsagel, P. Leif; Fonseca, Rafael; Stewart, A. Keith] Mayo Clin Arizona, Scottsdale, AZ 85259 USA.
   [Keats, Jonathan J.; Ahmann, Gregory J.; Anderson, Kenneth C.; Auclair, Daniel; Bergsagel, P. Leif; Fonseca, Rafael; Hofmeister, Craig C.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Krishnan, Amrita; Levy, Joan; Lonial, Sagar; Mfuko, Bunmi; Perkins, Louise M.; Rajkumar, S. Vincent; Siegel, David S.; Stewart, A. Keith; Trudel, Suzanne; Vij, Ravi; Zimmerman, Todd] Multiple Myeloma Res Consortium, Norwalk, CT 06581 USA.
   [Schinzel, Anna C.; Anderson, Kenneth C.; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Auclair, Daniel; Levy, Joan; Mfuko, Bunmi; Perkins, Louise M.] Multiple Myeloma Res Fdn, Norwalk, CT 06581 USA.
   [Baker, Angela; Carpten, John; Trent, Jeff] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
   [Bernstein, Bradley E.; Hahn, William C.; Meyerson, Matthew; Lander, Eric S.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Bernstein, Bradley E.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Hofmeister, Craig C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
   [Jagannath, Sundar] St Vincents Comprehens Canc Ctr, New York, NY 11001 USA.
   [Jakubowiak, Andrzej J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
   [Krishnan, Amrita] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA.
   [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Rajkumar, S. Vincent] Mayo Clin Rochester, Rochester, MN 55905 USA.
   [Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ 07601 USA.
   [Trudel, Suzanne] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada.
   [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO 63110 USA.
   [Zimmerman, Todd] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
   [Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Mayo Clinic; Mayo Clinic Phoenix; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Translational Genomics Research Institute; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Weizmann Institute of Science; University System of Ohio; Ohio State University; Saint Vincents Hospital Manhattan; University of Michigan System; University of Michigan; City of Hope; Emory University; Mayo Clinic; Hackensack University Medical Center; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Washington University (WUSTL); University of Chicago; University of Chicago Medical Center; Massachusetts Institute of Technology (MIT)
RP Golub, TR (corresponding author), Eli & Edythe L Broad Inst, Cambridge Ctr 7, Cambridge, MA 02412 USA.
EM gadgetz@broadinstitute.org; golub@broadinstitute.org
FU Multiple Myeloma Research Foundation; Leukaemia and Lymphoma Research (UK); National Cancer Institute [K12CA133250] Funding Source: NIH RePORTER
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NR 47
TC 1206
Z9 1390
U1 2
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 467
EP 472
DI 10.1038/nature09837
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200053
PM 21430775
DA 2026-03-09
ER

PT J
AU de Lau, W
   Barker, N
   Low, TY
   Koo, BK
   Li, VSW
   Teunissen, H
   Kujala, P
   Haegebarth, A
   Peters, PJ
   van de Wetering, M
   Stange, DE
   van Es, JE
   Guardavaccaro, D
   Schasfoort, RBM
   Mohri, Y
   Nishimori, K
   Mohammed, S
   Heck, AJR
   Clevers, H
AF de Lau, Wim
   Barker, Nick
   Low, Teck Y.
   Koo, Bon-Kyoung
   Li, Vivian S. W.
   Teunissen, Hans
   Kujala, Pekka
   Haegebarth, Andrea
   Peters, Peter J.
   van de Wetering, Marc
   Stange, Daniel E.
   van Es, Johan E.
   Guardavaccaro, Daniele
   Schasfoort, Richard B. M.
   Mohri, Yasuaki
   Nishimori, Katsuhiko
   Mohammed, Shabaz
   Heck, Albert J. R.
   Clevers, Hans
TI Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling
SO NATURE
LA English
DT Article
ID paneth cell-differentiation; stem-cells; small-intestine; peptide identification; hair follicle; reporter gene; null mice; in-vitro; expression; r-spondin1
AB The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.
C1 [de Lau, Wim; Barker, Nick; Koo, Bon-Kyoung; Li, Vivian S. W.; Teunissen, Hans; Haegebarth, Andrea; van de Wetering, Marc; Stange, Daniel E.; van Es, Johan E.; Guardavaccaro, Daniele; Clevers, Hans] Univ Med Ctr, NL-3584 CX Utrecht, Netherlands.
   [de Lau, Wim; Barker, Nick; Koo, Bon-Kyoung; Li, Vivian S. W.; Teunissen, Hans; Haegebarth, Andrea; van de Wetering, Marc; Stange, Daniel E.; van Es, Johan E.; Guardavaccaro, Daniele; Clevers, Hans] Hubrecht Inst, NL-3584 CX Utrecht, Netherlands.
   [Low, Teck Y.; Mohammed, Shabaz; Heck, Albert J. R.] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
   [Low, Teck Y.; Mohammed, Shabaz; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands.
   [Kujala, Pekka; Peters, Peter J.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Schasfoort, Richard B. M.] Univ Twente, Med Cell Biophys MIRA Inst, NL-7500 AE Enschede, Netherlands.
   [Mohri, Yasuaki; Nishimori, Katsuhiko] Tohoku Univ, Sendai, Miyagi 9818555, Japan.
C3 Utrecht University; Utrecht University Medical Center; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University; Netherlands Cancer Institute; University of Twente; Tohoku University
RP Clevers, H (corresponding author), Univ Med Ctr, NL-3584 CX Utrecht, Netherlands.
EM h.clevers@hubrecht.eu
FU Grants-in-Aid for Scientific Research [23240057, 23380055] Funding Source: KAKEN
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NR 42
TC 1037
Z9 1212
U1 3
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 293
EP U57
DI 10.1038/nature10337
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500030
PM 21727895
DA 2026-03-09
ER

PT J
AU Dragoi, G
   Tonegawa, S
AF Dragoi, George
   Tonegawa, Susumu
TI Preplay of future place cell sequences by hippocampal cellular assemblies
SO NATURE
LA English
DT Article
ID pyramidal cells; replay; reactivation; memory; experience
AB During spatial exploration, hippocampal neurons show a sequential firing pattern in which individual neurons fire specifically at particular locations along the animal's trajectory (place cells(1,2)). According to the dominant model of hippocampal cell assembly activity, place cell firing order is established for the first time during exploration, to encode the spatial experience, and is subsequently replayed during rest(3-6) or slow-wave sleep(7-10) for consolidation of the encoded experience(11,12). Here we report that temporal sequences of firing of place cells expressed during a novel spatial experience occurred on a significant number of occasions during the resting or sleeping period preceding the experience. This phenomenon, which is called preplay, occurred in disjunction with sequences of replay of a familiar experience. These results suggest that internal neuronal dynamics during resting or sleep organize hippocampal cellular assemblies(13-15) into temporal sequences that contribute to the encoding of a related novel experience occurring in the future.
C1 [Dragoi, George; Tonegawa, Susumu] MIT, Dept Biol, RIKEN MIT Ctr Neural Circuit Genet, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Dragoi, George; Tonegawa, Susumu] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 RIKEN; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Dragoi, G (corresponding author), MIT, Dept Biol, RIKEN MIT Ctr Neural Circuit Genet, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM gdragoi@mit.edu; tonegawa@mit.edu
FU NIH [R01-MH078821, P50-MH58880]
NR 28
TC 461
Z9 575
U1 0
U2 42
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 20
PY 2011
VL 469
IS 7330
BP 397
EP +
DI 10.1038/nature09633
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600052
PM 21179088
DA 2026-03-09
ER

PT J
AU Borg, LE
   Connelly, JN
   Boyet, M
   Carlson, RW
AF Borg, Lars E.
   Connelly, James N.
   Boyet, Maud
   Carlson, Richard W.
TI Chronological evidence that the Moon is either young or did not have a global magma ocean
SO NATURE
LA English
DT Article
ID noritic anorthosite clast; sm-nd; ferroan anorthosite-60025; lunar; age; crust; differentiation; petrology; origin; model
AB Chemical evolution of planetary bodies, ranging from asteroids to the large rocky planets, is thought to begin with differentiation through solidification of magma oceans many hundreds of kilometres in depth(1-3). The Earth's Moon is the archetypical example of this type of differentiation. Evidence for a lunar magma ocean is derived largely from the widespread distribution, compositional and mineralogical characteristics, and ancient ages inferred for the ferroan anorthosite (FAN) suite of lunar crustal rocks. The FANs are considered to be primary lunar flotation-cumulate crust that crystallized in the latter stages of magma ocean solidification. According to this theory, FANs represent the oldest lunar crustal rock type(2-4). Attempts to date this rock suite have yielded ambiguous results, however, because individual isochron measurements are typically incompatible with the geochemical make-up of the samples, and have not been confirmed by additional isotopic systems(5-9). By making improvements to the standard isotopic techniques, we report here the age of crystallization of FAN 60025 using the Pb-207-Pb-206, Sm-147-Nd-143 and Sm-146-Nd-142 isotopic systems to be 4,360 +/- 3 million years. This extraordinarily young age requires that either the Moon solidified significantly later than most previous estimates or the long-held assumption that FANs are flotation cumulates of a primordial magma ocean is incorrect. If the latter is correct, then much of the lunar crust may have been produced by non-magma-ocean processes, such as serial magmatism(10).
C1 [Borg, Lars E.] Lawrence Livermore Natl Lab, Div Chem Sci, Livermore, CA 94550 USA.
   [Connelly, James N.] Univ Copenhagen, Ctr Star & Planet Format, Copenhagen, Denmark.
   [Boyet, Maud] Univ Blaise Pascal, Clermont Univ, Lab Magmas & Volcans, UMR CNRS 6524, F-63038 Clermont Ferrand, France.
   [Carlson, Richard W.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Copenhagen; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Clermont Auvergne (UCA); Carnegie Institution for Science
RP Borg, LE (corresponding author), Lawrence Livermore Natl Lab, Div Chem Sci, 7000 East Ave L-231, Livermore, CA 94550 USA.
EM borg5@llnl.gov
FU US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; NASA [NNH08ZDA001N, NNX08AH65G]; Danish National Research Foundation; University of Copenhagen; NASA [100046, NNX08AH65G] Funding Source: Federal RePORTER
NR 33
TC 208
Z9 230
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 70
EP U150
DI 10.1038/nature10328
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300032
PM 21849974
DA 2026-03-09
ER

PT J
AU Navin, N
   Kendall, J
   Troge, J
   Andrews, P
   Rodgers, L
   McIndoo, J
   Cook, K
   Stepansky, A
   Levy, D
   Esposito, D
   Muthuswamy, L
   Krasnitz, A
   McCombie, WR
   Hicks, J
   Wigler, M
AF Navin, Nicholas
   Kendall, Jude
   Troge, Jennifer
   Andrews, Peter
   Rodgers, Linda
   McIndoo, Jeanne
   Cook, Kerry
   Stepansky, Asya
   Levy, Dan
   Esposito, Diane
   Muthuswamy, Lakshmi
   Krasnitz, Alex
   McCombie, W. Richard
   Hicks, James
   Wigler, Michael
TI Tumour evolution inferred by single-cell sequencing
SO NATURE
LA English
DT Article
ID whole genome amplification; copy-number alterations; breast-cancer; carcinomas; heterogeneity; progression; metastasis; phenotype; variants
AB Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common(1-3), very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
C1 [Navin, Nicholas; Kendall, Jude; Troge, Jennifer; Andrews, Peter; Rodgers, Linda; McIndoo, Jeanne; Cook, Kerry; Stepansky, Asya; Levy, Dan; Esposito, Diane; Krasnitz, Alex; McCombie, W. Richard; Hicks, James; Wigler, Michael] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Navin, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
   [Muthuswamy, Lakshmi] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
C3 Cold Spring Harbor Laboratory; University of Texas System; UTMD Anderson Cancer Center; Ontario Institute for Cancer Research; University of Toronto
RP Wigler, M (corresponding author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
EM wigler@cshl.edu
FU NCI; Department of the Army [W81XWH04-1-0477]; Breast Cancer Research Foundation; Simons Foundation; American Cancer Society
NR 25
TC 2027
Z9 2502
U1 4
U2 536
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 90
EP U119
DI 10.1038/nature09807
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400043
PM 21399628
DA 2026-03-09
ER

PT J
AU Lazarus, MB
   Nam, YS
   Jiang, JY
   Sliz, P
   Walker, S
AF Lazarus, Michael B.
   Nam, Yunsun
   Jiang, Jiaoyang
   Sliz, Piotr
   Walker, Suzanne
TI Structure of human O-GlcNAc transferase and its complex with a peptide substrate
SO NATURE
LA English
DT Article
ID n-acetylglucosamine; crystal-structure; protein; glycosylation; glcnacylation; nuclear; gene; replacement; promoters; mechanism
AB The essential mammalian enzyme O-linked beta-N-acetylglucosamine transferase (O-GlcNAc transferase, here OGT) couples metabolic status to the regulation of a wide variety of cellular signalling pathways by acting as a nutrient sensor(1). OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins(2,3), including numerous transcription factors(4), tumour suppressors, kinases(5), phosphatases(1) and histone-modifying proteins(6). Aberrant glycosylation by OGT has been linked to insulin resistance(7), diabetic complications(8), cancer(9) and neurodegenerative diseases including Alzheimer's(10). Despite the importance of OGT, the details of how it recognizes and glycosylates its protein substrates are largely unknown. We report here two crystal structures of human OGT, as a binary complex with UDP (2.8 angstrom resolution) and as a ternary complex with UDP and a peptide substrate (1.95 angstrom). The structures provide clues to the enzyme mechanism, show how OGT recognizes target peptide sequences, and reveal the fold of the unique domain between the two halves of the catalytic region. This information will accelerate the rational design of biological experiments to investigate OGT's functions; it will also help the design of inhibitors for use as cellular probes and help to assess its potential as a therapeutic target.
C1 [Lazarus, Michael B.; Jiang, Jiaoyang; Walker, Suzanne] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   [Lazarus, Michael B.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Nam, Yunsun; Sliz, Piotr] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Nam, Yunsun; Sliz, Piotr] Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Walker, S (corresponding author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
EM piotr_sliz@hms.harvard.edu; suzanne_walker@hms.harvard.edu
FU US National Institutes of Health; US National Science Foundation; Harvard Biomedical Accelerator Fund; National Institute of General Medical Sciences [R01GM094263] Funding Source: NIH RePORTER
NR 48
TC 393
Z9 487
U1 4
U2 186
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 564
EP U168
DI 10.1038/nature09638
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500039
PM 21240259
DA 2026-03-09
ER

PT J
AU Smagulova, F
   Gregoretti, IV
   Brick, K
   Khil, P
   Camerini-Otero, RD
   Petukhova, GV
AF Smagulova, Fatima
   Gregoretti, Ivan V.
   Brick, Kevin
   Khil, Pavel
   Camerini-Otero, R. Daniel
   Petukhova, Galina V.
TI Genome-wide analysis reveals novel molecular features of mouse recombination hotspots
SO NATURE
LA English
DT Article
ID meiotic recombination; hot-spot; prdm9; gene; map; instability
AB Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1-5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.
C1 [Smagulova, Fatima; Petukhova, Galina V.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   [Gregoretti, Ivan V.; Brick, Kevin; Khil, Pavel; Camerini-Otero, R. Daniel] NIDDKD, NIH, Bethesda, MD 20892 USA.
C3 Uniformed Services University of the Health Sciences - USA; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Petukhova, GV (corresponding author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
EM rdcamerini@mail.nih.gov; gpetukhova@usuhs.mil
FU March of Dimes Foundation [5-FY07-667]; NIGMS, NIH [1R01GM084104-01A1]; USUHS [FS71HU, R071HU, CS71HU]; NIDDK (NIH); National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK052034] Funding Source: NIH RePORTER
NR 30
TC 267
Z9 307
U1 0
U2 52
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 375
EP 378
DI 10.1038/nature09869
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600045
PM 21460839
DA 2026-03-09
ER

PT J
AU Lundeen, JS
   Sutherland, B
   Patel, A
   Stewart, C
   Bamber, C
AF Lundeen, Jeff S.
   Sutherland, Brandon
   Patel, Aabid
   Stewart, Corey
   Bamber, Charles
TI Direct measurement of the quantum wavefunction
SO NATURE
LA English
DT Article
ID linear optics; states; light; realization; spin
AB The wavefunction is the complex distribution used to completely describe a quantum system, and is central to quantum theory. But despite its fundamental role, it is typically introduced as an abstract element of the theory with no explicit definition(1,2). Rather, physicists come to a working understanding of the wavefunction through its use to calculate measurement outcome probabilities by way of the Born rule(3). At present, the wavefunction is determined through tomographic methods(4-8), which estimate the wavefunction most consistent with a diverse collection of measurements. The indirectness of these methods compounds the problem of defining the wavefunction. Here we show that the wavefunction can be measured directly by the sequential measurement of two complementary variables of the system. The crux of our method is that the first measurement is performed in a gentle way through weak measurement(9-18), so as not to invalidate the second. The result is that the real and imaginary components of the wavefunction appear directly on our measurement apparatus. We give an experimental example by directly measuring the transverse spatial wavefunction of a single photon, a task not previously realized by any method. We show that the concept is universal, being applicable to other degrees of freedom of the photon, such as polarization or frequency, and to other quantum systems-for example, electron spins, SQUIDs (superconducting quantum interference devices) and trapped ions. Consequently, this method gives the wavefunction a straightforward and general definition in terms of a specific set of experimental operations(19). We expect it to expand the range of quantum systems that can be characterized and to initiate new avenues in fundamental quantum theory.
C1 [Lundeen, Jeff S.; Sutherland, Brandon; Patel, Aabid; Stewart, Corey; Bamber, Charles] CNR, Inst Natl Measurement Stand, Ottawa, ON K1A 0R6, Canada.
C3 National Research Council Canada
RP Lundeen, JS (corresponding author), CNR, Inst Natl Measurement Stand, 1200 Montreal Rd, Ottawa, ON K1A 0R6, Canada.
EM jeff.lundeen@nrc-cnrc.gc.ca
FU Natural Sciences and Engineering Research Council; Business Development Bank of Canada
NR 30
TC 553
Z9 605
U1 3
U2 174
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 188
EP 191
DI 10.1038/nature10120
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800044
PM 21654800
DA 2026-03-09
ER

PT J
AU Köksal, M
   Jin, YH
   Coates, RM
   Croteau, R
   Christianson, DW
AF Koeksal, Mustafa
   Jin, Yinghua
   Coates, Robert M.
   Croteau, Rodney
   Christianson, David W.
TI Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis
SO NATURE
LA English
DT Article
ID ent-copalyl diphosphate; crystal-structure; taxol biosynthesis; committed step; geranylgeranyl diphosphate; diterpene cyclase; cyclization; mechanism; catalyzes; taxa-4(5),11(12)-diene
AB With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization(1) and shows remarkable efficacy in cancer chemotherapy(2). The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia)(3) is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5), 11(12) diene(4), which is catalysed by taxadiene synthase(5). The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids(6). We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82 angstrom resolution) and 2-fluorogeranylgeranyl diphosphate (2.25 angstrom resolution). The TXS structure reveals a modular assembly of three alpha-helical domains. The carboxy-terminal catalytic domain is a class I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third 'insertion' domain together adopt the fold of a vestigial class II terpenoid cyclase. A class II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.
C1 [Koeksal, Mustafa; Christianson, David W.] Univ Penn, Dept Chem, Roy & Diana Vagelos Labs, Philadelphia, PA 19104 USA.
   [Jin, Yinghua; Coates, Robert M.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Jin, Yinghua] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Croteau, Rodney] Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA.
C3 University of Pennsylvania; University of Illinois System; University of Illinois Urbana-Champaign; University of Colorado System; University of Colorado Boulder; Washington State University
RP Christianson, DW (corresponding author), Univ Penn, Dept Chem, Roy & Diana Vagelos Labs, 231 S 34th St, Philadelphia, PA 19104 USA.
EM chris@sas.upenn.edu
FU US National Institutes of Health [GM56838, GM13956, CA55254]; University of Illinois; National Institute of General Medical Sciences [R01GM056838] Funding Source: NIH RePORTER
NR 40
TC 263
Z9 320
U1 10
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 JAN 6
PY 2011
VL 469
IS 7328
BP 116
EP U138
DI 10.1038/nature09628
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600043
PM 21160477
DA 2026-03-09
ER

PT J
AU Guttman, M
   Donaghey, J
   Carey, BW
   Garber, M
   Grenier, JK
   Munson, G
   Young, G
   Lucas, AB
   Ach, R
   Bruhn, L
   Yang, XP
   Amit, I
   Meissner, A
   Regev, A
   Rinn, JL
   Root, DE
   Lander, ES
AF Guttman, Mitchell
   Donaghey, Julie
   Carey, Bryce W.
   Garber, Manuel
   Grenier, Jennifer K.
   Munson, Glen
   Young, Geneva
   Lucas, Anne Bergstrom
   Ach, Robert
   Bruhn, Laurakay
   Yang, Xiaoping
   Amit, Ido
   Meissner, Alexander
   Regev, Aviv
   Rinn, John L.
   Root, David E.
   Lander, Eric S.
TI lincRNAs act in the circuitry controlling pluripotency and differentiation
SO NATURE
LA English
DT Article
ID embryonic stem-cells; long noncoding rnas; self-renewal; gene-expression; developmental regulators; chromatin-structure; visceral endoderm; mouse embryo; xist rna; es cells
AB Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.
C1 [Guttman, Mitchell; Donaghey, Julie; Garber, Manuel; Grenier, Jennifer K.; Munson, Glen; Young, Geneva; Yang, Xiaoping; Amit, Ido; Meissner, Alexander; Regev, Aviv; Rinn, John L.; Root, David E.; Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Guttman, Mitchell; Carey, Bryce W.; Regev, Aviv; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Carey, Bryce W.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
   [Lucas, Anne Bergstrom; Ach, Robert; Bruhn, Laurakay] Agilent Technol, Genom Res & Dev, Santa Clara, CA 95051 USA.
   [Meissner, Alexander; Rinn, John L.] Harvard Univ, Cambridge, MA 02138 USA.
   [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; Agilent Technologies; Harvard University; Harvard University; Harvard Medical School
RP Guttman, M (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM mguttman@mit.edu; lander@broadinstitute.org
FU NHGRI, a Center for Excellence for Genomic Science; Merkin Foundation for Stem Cell Research; Broad Institute of MIT; Broad Institute of Harvard
NR 72
TC 1613
Z9 1914
U1 2
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 SEP 15
PY 2011
VL 477
IS 7364
BP 295
EP U60
DI 10.1038/nature10398
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400023
PM 21874018
DA 2026-03-09
ER

PT J
AU Furumoto, T
   Yamaguchi, T
   Ohshima-Ichie, Y
   Nakamura, M
   Tsuchida-Iwata, Y
   Shimamura, M
   Ohnishi, J
   Hata, S
   Gowik, U
   Westhoff, P
   Bräutigam, A
   Weber, APM
   Izui, K
AF Furumoto, Tsuyoshi
   Yamaguchi, Teppei
   Ohshima-Ichie, Yumiko
   Nakamura, Masayoshi
   Tsuchida-Iwata, Yoshiko
   Shimamura, Masaki
   Ohnishi, Junichi
   Hata, Shingo
   Gowik, Udo
   Westhoff, Peter
   Braeutigam, Andrea
   Weber, Andreas P. M.
   Izui, Katsura
TI A plastidial sodium-dependent pyruvate transporter
SO NATURE
LA English
DT Article
ID mesophyll chloroplasts; c-4 photosynthesis; maize; plant; expression; envelope; reveals; family; driven; taf10
AB Pyruvate serves as a metabolic precursor for many plastid-localized biosynthetic pathways, such as those for fatty acids(1), terpenoids(2) and branched-chainamino acids(3). In spite of the importance of pyruvate uptake into plastids (organelles within cells of plants and algae), the molecular mechanisms of this uptake have not yet been explored. This is mainly because pyruvate is a relatively small compound that is able to passively permeate lipid bilayers(4), which precludes accurate measurement of pyruvate transport activity in reconstituted liposomes. Using differential transcriptome analyses of C-3 and C-4 plants of the genera Flaveria and Cleome, here we have identified a novel gene that is abundant in C-4 species, named BASS2 (BILE ACID:SODIUM SYMPORTER FAMILY PROTEIN 2). The BASS2 protein is localized at the chloroplast envelope membrane, and is highly abundant in C-4 plants that have the sodium-dependent pyruvate transporter. Recombinant BASS2 shows sodium-dependent pyruvate uptake activity. Sodium influx is balanced by a sodium: proton antiporter (NHD1), which was mimicked in recombinant Escherichia coli cells expressing both BASS2 and NHD1. Arabidopsis thaliana bass2 mutants lack pyruvate uptake into chloroplasts, which affects plastid-localized isopentenyl diphosphate synthesis, as evidenced by increased sensitivity of such mutants to mevastatin, an inhibitor of cytosolic isopentenyl diphosphate biosynthesis. We thus provide molecular evidence for a sodium-coupled metabolite transporter in plastid envelopes. Orthologues of BASS2 can be detected in all the genomes of land plants that have been characterized so far, thus indicating the widespread importance of sodium-coupled pyruvate import into plastids.
C1 [Furumoto, Tsuyoshi; Shimamura, Masaki] Hiroshima Univ, Grad Sch Sci, Higashihiroshima 7398526, Japan.
   [Furumoto, Tsuyoshi; Yamaguchi, Teppei; Ohshima-Ichie, Yumiko; Nakamura, Masayoshi; Tsuchida-Iwata, Yoshiko; Hata, Shingo; Izui, Katsura] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan.
   [Ohnishi, Junichi] Saitama Univ, Grad Sch Sci & Engn, Sakura Ku, Saitama 3388570, Japan.
   [Hata, Shingo] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Gowik, Udo; Westhoff, Peter] Univ Dusseldorf, Inst Entwicklungs & Mol Biol Pflanzen, D-40225 Dusseldorf, Germany.
   [Braeutigam, Andrea; Weber, Andreas P. M.] Univ Dusseldorf, Inst Biochem Pflanzen, D-40225 Dusseldorf, Germany.
   [Izui, Katsura] Kinki Univ, Fac Biol Oriented Sci & Technol, Wakayama 6496493, Japan.
C3 Hiroshima University; Kyoto University; Saitama University; Nagoya University; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf; Kindai University (Kinki University)
RP Furumoto, T (corresponding author), Hiroshima Univ, Grad Sch Sci, 1-3-1 Kagamiyama, Higashihiroshima 7398526, Japan.
EM tfurumoto@hiroshima-u.ac.jp
FU Ministry of Education, Science and Culture of Japan; Japan Science Society; German Research Foundation [CRC-TR1, IRTG 1525/1, CRC 590]; Grants-in-Aid for Scientific Research [23770047, 22380182] Funding Source: KAKEN
NR 29
TC 214
Z9 239
U1 6
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 472
EP U131
DI 10.1038/nature10250
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400041
PM 21866161
DA 2026-03-09
ER

PT J
AU Sicardy, B
   Ortiz, JL
   Assafin, M
   Jehin, E
   Maury, A
   Lellouch, E
   Hutton, RG
   Braga-Ribas, F
   Colas, F
   Hestroffer, D
   Lecacheux, J
   Roques, F
   Santos-Sanz, P
   Widemann, T
   Morales, N
   Duffard, R
   Thirouin, A
   Castro-Tirado, AJ
   Jelínek, M
   Kubánek, P
   Sota, A
   Sánchez-Ramírez, R
   Andrei, AH
   Camargo, JIB
   Neto, DND
   Gomes, AR
   Martins, RV
   Gillon, M
   Manfroid, J
   Tozzi, GP
   Harlingten, C
   Saravia, S
   Behrend, R
   Mottola, S
   Melendo, EG
   Peris, V
   Fabregat, J
   Madiedo, JM
   Cuesta, L
   Eibe, MT
   Ullán, A
   Organero, F
   Pastor, S
   de los Reyes, JA
   Pedraz, S
   Castro, A
   de la Cueva, I
   Muler, G
   Steele, IA
   Cebrián, M
   Montañes-Rodríguez, P
   Oscoz, A
   Weaver, D
   Jacques, C
   Corradi, WJB
   Santos, FP
   Reis, W
   Milone, A
   Emilio, M
   Gutiérrez, L
   Vázquez, R
   Hernández-Toledo, H
AF Sicardy, B.
   Ortiz, J. L.
   Assafin, M.
   Jehin, E.
   Maury, A.
   Lellouch, E.
   Gil Hutton, R.
   Braga-Ribas, F.
   Colas, F.
   Hestroffer, D.
   Lecacheux, J.
   Roques, F.
   Santos-Sanz, P.
   Widemann, T.
   Morales, N.
   Duffard, R.
   Thirouin, A.
   Castro-Tirado, A. J.
   Jelinek, M.
   Kubanek, P.
   Sota, A.
   Sanchez-Ramirez, R.
   Andrei, A. H.
   Camargo, J. I. B.
   da Silva Neto, D. N.
   Ramos Gomes, A., Jr.
   Vieira Martins, R.
   Gillon, M.
   Manfroid, J.
   Tozzi, G. P.
   Harlingten, C.
   Saravia, S.
   Behrend, R.
   Mottola, S.
   Garcia Melendo, E.
   Peris, V.
   Fabregat, J.
   Madiedo, J. M.
   Cuesta, L.
   Eibe, M. T.
   Ullan, A.
   Organero, F.
   Pastor, S.
   de los Reyes, J. A.
   Pedraz, S.
   Castro, A.
   de la Cueva, I.
   Muler, G.
   Steele, I. A.
   Cebrian, M.
   Montanes-Rodriguez, P.
   Oscoz, A.
   Weaver, D.
   Jacques, C.
   Corradi, W. J. B.
   Santos, F. P.
   Reis, W.
   Milone, A.
   Emilio, M.
   Gutierrez, L.
   Vazquez, R.
   Hernandez-Toledo, H.
TI A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation
SO NATURE
LA English
DT Article
ID object; atmosphere; methane; ub313; size; tnos; cool; nix
AB The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto(1). It resides at present at 95.7 astronomical units (1 AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163 +/- 6 kilometres, density 2.52 +/- 0.05 grams per cm(3) and a high visible geometric albedo, p(V) = 0.96(-0.04)(+0.09). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than similar to 1 nanobar, about 10,000 times more tenuous than Pluto's present atmosphere(2-5). As Pluto's radius is estimated(3-8) to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.
C1 [Sicardy, B.; Lellouch, E.; Braga-Ribas, F.; Lecacheux, J.; Roques, F.; Santos-Sanz, P.; Widemann, T.] Univ Paris Diderot, Univ Paris 06, CNRS, LESIA Observ Paris, F-92195 Meudon, France.
   [Sicardy, B.] Univ Paris 06, F-75252 Paris 5, France.
   [Sicardy, B.] Inst Univ France, F-75005 Paris, France.
   [Ortiz, J. L.; Morales, N.; Duffard, R.; Thirouin, A.; Castro-Tirado, A. J.; Jelinek, M.; Kubanek, P.; Sota, A.; Sanchez-Ramirez, R.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [Assafin, M.; Andrei, A. H.; Camargo, J. I. B.; Ramos Gomes, A., Jr.; Vieira Martins, R.] Observ Valongo UFRJ, BR-20080090 Rio De Janeiro, Brazil.
   [Jehin, E.; Gillon, M.; Manfroid, J.] Univ Liege, Inst Astrophys, B-4000 Liege, Belgium.
   [Maury, A.; Saravia, S.] San Pedro de Atacama Celestial Explorat, San Pedro De Atacama, Chile.
   [Gil Hutton, R.] Complejo Astron El Leoncito CASLEO, San Juan, Argentina.
   [Gil Hutton, R.] San Juan Natl Univ, San Juan, Argentina.
   [Braga-Ribas, F.; Andrei, A. H.; Camargo, J. I. B.; da Silva Neto, D. N.; Vieira Martins, R.] Observ Nacl MCT, BR-20921400 Rio De Janeiro, Brazil.
   [Colas, F.; Hestroffer, D.; Vieira Martins, R.] Univ Lille 1, Univ Paris 06, CNRS, IMCCE Observ Paris, F-75014 Paris, France.
   [da Silva Neto, D. N.] Ctr Univ Estadual Zona Oeste, BR-23070200 Rio De Janeiro, Brazil.
   [Tozzi, G. P.] Osserv Astrofis Arcetri, INAF, I-50125 Florence, Italy.
   [Harlingten, C.] Caisey Harlingten Observ, Erpingham NR11 7QX, Norfolk, England.
   [Behrend, R.] Observ Geneva, CH-1290 Sauverny, Switzerland.
   [Mottola, S.] DLR German Aerosp Ctr, D-12489 Berlin, Germany.
   [Garcia Melendo, E.] Fundacio Privada Observ Esteve Duran, Seva 08553, Spain.
   [Garcia Melendo, E.] Fac Ciencies, Inst Ciencies Espai CSIC IEEC, Bellaterra 08193, Spain.
   [Peris, V.; Fabregat, J.] Univ Valencia, Astron Observ, Paterna 46980, Spain.
   [Madiedo, J. M.] Univ Huelva, Fac Ciencias Expt, Huelva 21071, Spain.
   [Cuesta, L.; Eibe, M. T.; Ullan, A.] Ctr Astrobiol CSIC INTA, Madrid 28850, Spain.
   [Organero, F.] Observ Astron La Hita, La Puebla De Almoradiel 45840, Toledo, Spain.
   [Pastor, S.; de los Reyes, J. A.] Observ Murta, Murcia 30153, Spain.
   [Pedraz, S.] Ctr Astron Hispano Aleman, Calar Alto Observ, Almeria 04004, Spain.
   [Castro, A.] Ctr Cultural Jose Maria Gutierrez Romero, Soc Malaguena Astron, Malaga 29016, Spain.
   [de la Cueva, I.] Astroimagen, Ibiza 07800, Spain.
   [Muler, G.] Observ Nazaret, Nazaret 35539, Lanzarote, Spain.
   [Steele, I. A.] Liverpool JMU, Birkenhead CH41 1LD, Merseyside, England.
   [Cebrian, M.; Montanes-Rodriguez, P.; Oscoz, A.] Inst Astrofis Canarias, Tenerife 38205, Spain.
   [Weaver, D.] Colegio Christus, Observ Astron Christus, BR-60140140 Fortaleza, Ceara, Brazil.
   [Jacques, C.] Observ CEAMIG REA, BR-31545120 Belo Horizonte, MG, Brazil.
   [Corradi, W. J. B.; Santos, F. P.; Reis, W.] Univ Fed Minas Gerais, Inst Ciencias Exatas, Dept Fis, BR-31270901 Belo Horizonte, MG, Brazil.
   [Milone, A.] Inst Nacl Pesquisas Espaciais INPE MCT, Div Astrofis, BR-12227010 Sao Jose Dos Campos, Brazil.
   [Emilio, M.] Univ Estadual Ponta Grossa, OA DEGEO, BR-84030900 Ponta Grossa, PR, Brazil.
   [Gutierrez, L.; Vazquez, R.] Univ Nacl Autonoma Mexico, Inst Astron, Ensenada 22860, Baja California, Mexico.
   [Hernandez-Toledo, H.] Univ Nacl Autonoma Mexico, Inst Astron, Mexico City 04510, DF, Mexico.
C3 Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; Sorbonne Universite; Institut Universitaire de France; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Universidade Federal do Rio de Janeiro; University of Liege; Universidad Nacional de San Juan; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; Universite de Lille; Centro Universitario Estadual da Zona Oeste; Istituto Nazionale Astrofisica (INAF); University of Geneva; Helmholtz Association; German Aerospace Centre (DLR); University of Barcelona; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); University of Valencia; Universidad de Huelva; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Liverpool John Moores University; Instituto de Astrofisica de Canarias; Universidade Federal de Minas Gerais; Instituto Nacional de Pesquisas Espaciais (INPE); Universidade Estadual de Ponta Grossa; Universidad Nacional Autonoma de Mexico; Universidad Nacional Autonoma de Mexico
RP Sicardy, B (corresponding author), Univ Paris Diderot, Univ Paris 06, CNRS, LESIA Observ Paris, 11 Rue Marcelin Berthelot, F-92195 Meudon, France.
EM bruno.sicardy@obspm.fr
FU French grant 'Beyond Neptune'; Institut Universitaire de France; Spanish AYA grants; FEDER; Belgian Fund for Scientific Research (FRS-FNRS); CNPq; FAPERJ; CDFB/CAPES, Brazil; STFC [ST/G009465/1, PP/E001149/1, ST/H002391/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E001149/1, ST/G009465/1, ST/H002391/1] Funding Source: researchfish
NR 26
TC 153
Z9 163
U1 2
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 493
EP 496
DI 10.1038/nature10550
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200038
PM 22031441
DA 2026-03-09
ER

PT J
AU Qian, BZ
   Li, JF
   Zhang, H
   Kitamura, T
   Zhang, JH
   Campion, LR
   Kaiser, EA
   Snyder, LA
   Pollard, JW
AF Qian, Bin-Zhi
   Li, Jiufeng
   Zhang, Hui
   Kitamura, Takanori
   Zhang, Jinghang
   Campion, Liam R.
   Kaiser, Elizabeth A.
   Snyder, Linda A.
   Pollard, Jeffrey W.
TI CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
SO NATURE
LA English
DT Article
ID chemoattractant protein-1; blood monocytes; expression; model; progression; survival; subsets; cells
AB Macrophages, which are abundant in the tumour microenvironment, enhance malignancy(1). At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells(2). Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer(3-6). Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.
C1 [Qian, Bin-Zhi; Li, Jiufeng; Zhang, Hui; Kitamura, Takanori; Pollard, Jeffrey W.] Albert Einstein Coll Med, Ctr Study Reprod Biol & Womens Hlth, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
   [Zhang, Jinghang] Albert Einstein Coll Med, Flow Cytometry Core Facil, Bronx, NY 10461 USA.
   [Campion, Liam R.; Kaiser, Elizabeth A.; Snyder, Linda A.] Ortho Biotech Oncol R&D, Radnor, PA 19087 USA.
C3 Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Johnson & Johnson; Johnson & Johnson USA
RP Pollard, JW (corresponding author), Albert Einstein Coll Med, Ctr Study Reprod Biol & Womens Hlth, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
EM pollard@aecom.yu.edu
FU NIH [NIH PO1 CA100324, RO1 CA131270]; Albert Einstein Cancer Center Core [P30 CA 13330]; MRC [G1002033] Funding Source: UKRI; Medical Research Council [G1002033] Funding Source: researchfish; National Cancer Institute [P30CA013330] Funding Source: NIH RePORTER
NR 26
TC 2341
Z9 2698
U1 5
U2 408
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 222
EP U129
DI 10.1038/nature10138
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500049
PM 21654748
DA 2026-03-09
ER

PT J
AU Fukuda, S
   Toh, H
   Hase, K
   Oshima, K
   Nakanishi, Y
   Yoshimura, K
   Tobe, T
   Clarke, JM
   Topping, DL
   Suzuki, T
   Taylor, TD
   Itoh, K
   Kikuchi, J
   Morita, H
   Hattori, M
   Ohno, H
AF Fukuda, Shinji
   Toh, Hidehiro
   Hase, Koji
   Oshima, Kenshiro
   Nakanishi, Yumiko
   Yoshimura, Kazutoshi
   Tobe, Toru
   Clarke, Julie M.
   Topping, David L.
   Suzuki, Tohru
   Taylor, Todd D.
   Itoh, Kikuji
   Kikuchi, Jun
   Morita, Hidetoshi
   Hattori, Masahira
   Ohno, Hiroshi
TI Bifidobacteria can protect from enteropathogenic infection through production of acetate
SO NATURE
LA English
DT Article
ID enterohemorrhagic escherichia-coli; smooth-muscle-cells; shiga-toxin; arabidopsis-thaliana; genome sequence; gene-expression; longum ncc2705; gut microbiota; ppar-alpha; mice
AB The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology(1-3). Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases(4-6). Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.
C1 [Fukuda, Shinji; Hase, Koji; Nakanishi, Yumiko; Ohno, Hiroshi] RIKEN Res Ctr Allergy & Immunol, Lab Epithelial Immunobiol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Fukuda, Shinji; Nakanishi, Yumiko; Kikuchi, Jun; Ohno, Hiroshi] Yokohama City Univ, Grad Sch Nanobiosci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Toh, Hidehiro; Taylor, Todd D.] RIKEN Adv Sci Inst, MetaSyst Res Team, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Oshima, Kenshiro; Hattori, Masahira] Univ Tokyo, Grad Sch Frontier Sci, Chiba 2778561, Japan.
   [Nakanishi, Yumiko; Kikuchi, Jun] RIKEN Plant Sci Ctr, Adv NMR Metab Res Team, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Yoshimura, Kazutoshi; Itoh, Kikuji] Univ Tokyo, Grad Sch Agr & Life Sci, Bunkyo Ku, Tokyo 1138657, Japan.
   [Tobe, Toru] Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan.
   [Clarke, Julie M.; Topping, David L.] CSIRO Food & Nutr Sci, Adelaide, SA 5000, Australia.
   [Suzuki, Tohru] Gifu Univ, United Grad Sch Agr Sci, Gifu 5011193, Japan.
   [Kikuchi, Jun] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Morita, Hidetoshi] Azabu Univ, Sch Vet Med, Kanagawa 2298501, Japan.
   [Ohno, Hiroshi] Chiba Univ, Grad Sch Med, Chuo Ku, Chiba 2608670, Japan.
C3 RIKEN; Yokohama City University; RIKEN; University of Tokyo; RIKEN; University of Tokyo; University of Osaka; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Gifu University; Nagoya University; Azabu University; Chiba University
RP Ohno, H (corresponding author), RIKEN Res Ctr Allergy & Immunol, Lab Epithelial Immunobiol, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.
EM hattori@k.u-tokyo.ac.jp; ohno@rcai.riken.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Science and Technology Agency; Danone Institute of Japan; Institute for Fermentation, Osaka; Kieikai Research Foundation; Naito Foundation; Nestle Nutrition Council, Japan; Japan Science Society; Yakult Bio-Science Foundation; Academic Frontier Project for Private Universities (Matching Fund Subsidy); Private University Scientific Foundation; Grants-in-Aid for Scientific Research [22689017] Funding Source: KAKEN
NR 47
TC 1877
Z9 2467
U1 11
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 JAN 27
PY 2011
VL 469
IS 7331
BP 543
EP U791
DI 10.1038/nature09646
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500035
PM 21270894
DA 2026-03-09
ER

PT J
AU Alavez, S
   Vantipalli, MC
   Zucker, DJS
   Klang, IM
   Lithgow, GJ
AF Alavez, Silvestre
   Vantipalli, Maithili C.
   Zucker, David J. S.
   Klang, Ida M.
   Lithgow, Gordon J.
TI Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; disease; stress; daf-16; proteostasis; inhibition; alzheimer; longevity; selection
AB Genetic studies indicate that protein homeostasis is a major contributor to metazoan longevity(1). Collapse of protein homeostasis results in protein misfolding cascades and the accumulation of insoluble protein fibrils and aggregates, such as amyloids(2). A group of small molecules, traditionally used in histopathology to stain amyloid in tissues, bind protein fibrils and slow aggregationin vitro and in cell culture(3,4). We proposed that treating animals with such compounds would promote protein homeostasis in vivo and increase longevity. Here we show that exposure of adult Caenorhabditis elegans to the amyloid-binding dye Thioflavin T (ThT) resulted in a profoundly extended lifespan and slowed ageing. ThT also suppressed pathological features of mutant metastable proteins and human beta-amyloid-associated toxicity. These beneficial effects of ThT depend on the protein homeostasis network regulator heat shock factor 1 (HSF-1), the stress resistance and longevity transcription factor SKN-1, molecular chaperones, autophagy and proteosomal functions. Our results demonstrate that pharmacological maintenance of the protein homeostatic network has a profound impact on ageing rates, prompting the development of novel therapeutic interventions against ageing and age-related diseases.
C1 [Alavez, Silvestre; Vantipalli, Maithili C.; Zucker, David J. S.; Klang, Ida M.; Lithgow, Gordon J.] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Zucker, David J. S.] Dominican Univ Calif, Dept Nat Sci & Math, San Rafael, CA 94901 USA.
   [Klang, Ida M.] Karolinska Inst, Ctr Biosci, Novum, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
C3 Buck Institute for Research on Aging; Karolinska Institutet
RP Lithgow, GJ (corresponding author), Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA.
EM salavez@buckinstitute.org; glithgow@buckinstitute.org
FU National Institutes of Health (NIH) National Center for Research Resources; Larry L. Hillblom Foundation; NIH [UL1024917, 1R01AG029631-01A1, AG21069, AG22868, AG029631-01A1, ES016655]; Larry L. Hillblom Foundation [UL1 RR024917]; Longevity Consortium [U19AGO231222]
NR 26
TC 307
Z9 352
U1 2
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 226
EP 229
DI 10.1038/nature09873
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100044
PM 21451522
DA 2026-03-09
ER

PT J
AU Chung, KY
   Rasmussen, SGF
   Liu, T
   Li, S
   DeVree, BT
   Chae, PS
   Calinski, D
   Kobilka, BK
   Woods, VL
   Sunahara, RK
AF Chung, Ka Young
   Rasmussen, Soren G. F.
   Liu, Tong
   Li, Sheng
   DeVree, Brian T.
   Chae, Pil Seok
   Calinski, Diane
   Kobilka, Brian K.
   Woods, Virgil L., Jr.
   Sunahara, Roger K.
TI Conformational changes in the G protein Gs induced by the β2 adrenergic receptor
SO NATURE
LA English
DT Article
ID heterotrimeric g-proteins; mass-spectrometry; crystal-structure; coupled receptor; mechanism; interface; dynamics; exchange; hydrogen/deuterium; activation
AB G protein-coupled receptors represent the largest family of membrane receptors(1) that instigate signalling through nucleotide exchange on heterotrimeric G proteins. Nucleotide exchange, or more precisely, GDP dissociation from the G protein alpha-subunit, is the key step towards G protein activation and initiation of downstream signalling cascades. Despite a wealth of biochemical and biophysical studies on inactive and active conformations of several heterotrimeric G proteins, the molecular underpinnings of G protein activation remain elusive. To characterize this mechanism, we applied peptide amide hydrogen-deuterium exchange mass spectrometry to probe changes in the structure of the heterotrimeric bovine G protein, Gs (the stimulatory G protein for adenylyl cyclase) on formation of a complex with agonist-bound human beta(2) adrenergic receptor (beta(2)AR). Here we report structural links between the receptor-binding surface and the nucleotide-binding pocket of Gs that undergo higher levels of hydrogen-deuterium exchange than would be predicted from the crystal structure of the beta(2)AR-Gs complex. Together with X-ray crystallographic and electron microscopic data of the beta(2)AR-Gs complex (from refs 2, 3), we provide a rationale for a mechanism of nucleotide exchange, whereby the receptor perturbs the structure of the amino-terminal region of the alpha-subunit of Gs and consequently alters the 'P-loop' that binds the beta-phosphate in GDP. As with the Ras family of small-molecular-weight G proteins, P-loop stabilization and beta-phosphate coordination are key determinants of GDP (and GTP) binding affinity.
C1 [DeVree, Brian T.; Calinski, Diane; Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Chung, Ka Young; Rasmussen, Soren G. F.; Kobilka, Brian K.] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
   [Rasmussen, Soren G. F.] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
   [Liu, Tong; Li, Sheng; Woods, Virgil L., Jr.] Univ Calif San Diego, Dept Med, Biomed Sci Grad Program, La Jolla, CA 92023 USA.
   [Liu, Tong; Li, Sheng; Woods, Virgil L., Jr.] Univ Calif San Diego, UCSD DXMS Prote Resource, La Jolla, CA 92023 USA.
   [Chae, Pil Seok] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
   [Chae, Pil Seok] Hanyang Univ, Dept Bionano Engn, Ansan 426791, South Korea.
C3 University of Michigan System; University of Michigan; Stanford University; University of Copenhagen; University of California System; University of California San Diego; University of California System; University of California San Diego; University of Wisconsin System; University of Wisconsin Madison; Hanyang University
RP Sunahara, RK (corresponding author), Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
EM kobilka@stanford.edu; vwoods@ucsd.edu; sunahara@umich.edu
FU American Lung Association [RT-166882-N]; Lundbeck Foundation; National Institute of General Medical Sciences (NIGMS) [GM008270, GM083118, GM068603]; National Institute of Neural Disorders and Stroke [NS28471]; NHLBI [HL071078]; Mather Charitable Foundation; Michigan Diabetes Research and Training Center; National Institute of Diabetes and Digestive and Kidney Diseases [P60DK-20572]; University of Michigan; NIH [AI076961, AI081982, AI2008031, CA118595, GM20501, GM066170, GM093325, RR029388]; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER; Lundbeck Foundation [R37-2009-3457] Funding Source: researchfish
NR 25
TC 316
Z9 382
U1 4
U2 189
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 611
EP U143
DI 10.1038/nature10488
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900044
PM 21956331
DA 2026-03-09
ER

PT J
AU Xiao, B
   Sanders, MJ
   Underwood, E
   Heath, R
   Mayer, FV
   Carmena, D
   Jing, C
   Walker, PA
   Eccleston, JF
   Haire, LF
   Saiu, P
   Howell, SA
   Aasland, R
   Martin, SR
   Carling, D
   Gamblin, SJ
AF Xiao, Bing
   Sanders, Matthew J.
   Underwood, Elizabeth
   Heath, Richard
   Mayer, Faith V.
   Carmena, David
   Jing, Chun
   Walker, Philip A.
   Eccleston, John F.
   Haire, Lesley F.
   Saiu, Peter
   Howell, Steven A.
   Aasland, Rein
   Martin, Stephen R.
   Carling, David
   Gamblin, Steven J.
TI Structure of mammalian AMPK and its regulation by ADP
SO NATURE
LA English
DT Article
ID activated protein-kinase; fatty-acid oxidation; lkb1-ampk pathway; skeletal-muscle; phosphorylation; binding
AB The heterotrimeric AMP-activated protein kinase (AMPK) has a key role in regulating cellular energy metabolism; in response to a fall in intracellular ATP levels it activates energy-producing pathways and inhibits energy-consuming processes(1). AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and, most recently, cancer(2-6). AMPK is converted from an inactive form to a catalytically competent form by phosphorylation of the activation loop within the kinase domain(7): AMP binding to the c-regulatory domain promotes phosphorylation by the upstream kinase(8), protects the enzyme against dephosphorylation, as well as causing allosteric activation(9). Here we show that ADP binding to just one of the two exchangeable AXP (AMP/ADP/ATP) binding sites on the regulatory domain protects the enzyme from dephosphorylation, although it does not lead to allosteric activation. Our studies show that active mammalian AMPK displays significantly tighter binding to ADP than to MgATP, explaining how the enzyme is regulated under physiological conditions where the concentration of Mg-ATP is higher than that of ADP and much higher than that of AMP. We have determined the crystal structure of an active AMPK complex. The structure shows how the activation loop of the kinase domain is stabilized by the regulatory domain and how the kinase linker region interacts with the regulatory nucleotide-binding site that mediates protection against dephosphorylation. From our biochemical and structural data we develop a model for how the energy status of a cell regulates AMPK activity.
C1 [Sanders, Matthew J.; Mayer, Faith V.; Carmena, David; Carling, David] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England.
   [Xiao, Bing; Underwood, Elizabeth; Heath, Richard; Jing, Chun; Walker, Philip A.; Eccleston, John F.; Haire, Lesley F.; Saiu, Peter; Howell, Steven A.; Aasland, Rein; Martin, Stephen R.; Gamblin, Steven J.] Natl Inst Med Res, MRC, London NW7 1AA, England.
C3 Imperial College London; MRC National Institute for Medical Research
RP Carling, D (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Hammersmith Hosp Campus,DuCane Rd, London W12 0NN, England.
EM david.carling@csc.mrc.ac.uk; sgambli@nimr.mrc.ac.uk
FU MRC; Medical Research Council [MC_U120027537, MC_U117584222] Funding Source: researchfish; MRC [MC_U117584222, MC_U120027537] Funding Source: UKRI
NR 30
TC 742
Z9 916
U1 4
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 230
EP 233
DI 10.1038/nature09932
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100045
PM 21399626
DA 2026-03-09
ER

PT J
AU Simmons, S
   Brown, RM
   Riemann, H
   Abrosimov, NV
   Becker, P
   Pohl, HJ
   Thewalt, MLW
   Itoh, KM
   Morton, JJL
AF Simmons, Stephanie
   Brown, Richard M.
   Riemann, Helge
   Abrosimov, Nikolai V.
   Becker, Peter
   Pohl, Hans-Joachim
   Thewalt, Mike L. W.
   Itoh, Kohei M.
   Morton, John J. L.
TI Entanglement in a solid-state spin ensemble
SO NATURE
LA English
DT Article
ID quantum; separability; phase
AB Entanglement is the quintessential quantum phenomenon. It is a necessary ingredient in most emerging quantum technologies, including quantum repeaters(1), quantum information processing(2) and the strongest forms of quantum cryptography(3). Spin ensembles, such as those used in liquid-state nuclear magnetic resonance(4,5), have been important for the development of quantum control methods. However, these demonstrations contain no entanglement and ultimately constitute classical simulations of quantum algorithms. Here we report the on-demand generation of entanglement between an ensemble of electron and nuclear spins in isotopically engineered, phosphorus-doped silicon. We combined high-field (3.4 T), low-temperature (2.9 K) electron spin resonance with hyperpolarization of the P-31 nuclear spin to obtain an initial state of sufficient purity to create a non-classical, inseparable state. The state was verified using density matrix tomography based on geometric phase gates, and had a fidelity of 98% relative to the ideal state at this field and temperature. The entanglement operation was performed simultaneously, with high fidelity, on 10(10) spin pairs; this fulfils one of the essential requirements for a silicon-based quantum information processor.
C1 [Simmons, Stephanie; Brown, Richard M.; Morton, John J. L.] Univ Oxford, Dept Mat, Oxford OX1 3PH, England.
   [Riemann, Helge; Abrosimov, Nikolai V.] Leibniz Inst Kristallzuchtung, D-12489 Berlin, Germany.
   [Becker, Peter] PTB Braunschweig, D-38116 Braunschweig, Germany.
   [Pohl, Hans-Joachim] VITCON Projectconsult GmbH, D-07743 Jena, Germany.
   [Thewalt, Mike L. W.] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada.
   [Itoh, Kohei M.] Keio Univ, Sch Fundamental Sci & Technol, Yokohama, Kanagawa 2238522, Japan.
   [Morton, John J. L.] Univ Oxford, Clarendon Lab, CAESR, Oxford OX1 3PU, England.
C3 University of Oxford; Leibniz Association; Leibniz Institut fur Kristallzuchtung (IKZ); Physikalisch-Technische Bundesanstalt (PTB); Simon Fraser University; Keio University; University of Oxford
RP Morton, JJL (corresponding author), Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
EM john.morton@materials.ox.ac.uk
FU EPSRC at Oxford through CAESR [EP/D048559/1]; Oxford-Keio collaboration through the JST-EPSRC SIC [EP/H025952/1]; MEXT; JSPS; Clarendon Fund; St John's College, Oxford; Royal Society; Engineering and Physical Sciences Research Council [EP/H025952/1, EP/D048559/1] Funding Source: researchfish; EPSRC [EP/H025952/1, EP/D048559/1] Funding Source: UKRI; Grants-in-Aid for Scientific Research [18001002, 22241024] Funding Source: KAKEN
NR 30
TC 122
Z9 138
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 3
PY 2011
VL 470
IS 7332
BP 69
EP 72
DI 10.1038/nature09696
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400035
PM 21248751
DA 2026-03-09
ER

PT J
AU Walker, LM
   Huber, M
   Doores, KJ
   Falkowska, E
   Pejchal, R
   Julien, JP
   Wang, SK
   Ramos, A
   Chan-Hui, PY
   Moyle, M
   Mitcham, JL
   Hammond, PW
   Olsen, OA
   Phung, P
   Fling, S
   Wong, CH
   Phogat, S
   Wrin, T
   Simek, MD
   Koff, WC
   Wilson, IA
   Burton, DR
   Poignard, P
AF Walker, Laura M.
   Huber, Michael
   Doores, Katie J.
   Falkowska, Emilia
   Pejchal, Robert
   Julien, Jean-Philippe
   Wang, Sheng-Kai
   Ramos, Alejandra
   Chan-Hui, Po-Ying
   Moyle, Matthew
   Mitcham, Jennifer L.
   Hammond, Phillip W.
   Olsen, Ole A.
   Pham Phung
   Fling, Steven
   Wong, Chi-Huey
   Phogat, Sanjay
   Wrin, Terri
   Simek, Melissa D.
   Koff, Wayne C.
   Wilson, Ian A.
   Burton, Dennis R.
   Poignard, Pascal
TI Broad neutralization coverage of HIV by multiple highly potent antibodies
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; human monoclonal-antibody; cross-clade neutralization; vaccine; protection; challenge; macaques; trial; titer; assay
AB Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies(1-3). The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.
C1 [Walker, Laura M.; Huber, Michael; Doores, Katie J.; Falkowska, Emilia; Ramos, Alejandra; Burton, Dennis R.; Poignard, Pascal] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Walker, Laura M.; Huber, Michael; Doores, Katie J.; Falkowska, Emilia; Pejchal, Robert; Julien, Jean-Philippe; Ramos, Alejandra; Wilson, Ian A.; Burton, Dennis R.; Poignard, Pascal] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Huber, Michael; Doores, Katie J.; Falkowska, Emilia; Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA.
   [Pejchal, Robert; Julien, Jean-Philippe; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Wang, Sheng-Kai; Wong, Chi-Huey] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Chan-Hui, Po-Ying; Moyle, Matthew; Mitcham, Jennifer L.; Hammond, Phillip W.; Olsen, Ole A.] Theraclone Sci Inc, Seattle, WA 98104 USA.
   [Pham Phung; Wrin, Terri] Monogram Biosci Inc, San Francisco, CA 94080 USA.
   [Fling, Steven; Phogat, Sanjay; Simek, Melissa D.; Koff, Wayne C.; Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
C3 Scripps Research Institute; International AIDS Vaccine Initiative; Scripps Research Institute; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Scripps Research Institute; Scripps Research Institute; Monogram Biosciences Inc.; International AIDS Vaccine Initiative
RP Burton, DR (corresponding author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu; poignard@scripps.edu
FU IAVI; NIAID; Ragon Institute; United States for International Development (USAID)
NR 33
TC 1261
Z9 1599
U1 3
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 SEP 22
PY 2011
VL 477
IS 7365
BP 466
EP U117
DI 10.1038/nature10373
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500041
PM 21849977
DA 2026-03-09
ER

PT J
AU Côté, M
   Misasi, J
   Ren, T
   Bruchez, A
   Lee, K
   Filone, CM
   Hensley, L
   Li, Q
   Ory, D
   Chandran, K
   Cunningham, J
AF Cote, Marceline
   Misasi, John
   Ren, Tao
   Bruchez, Anna
   Lee, Kyungae
   Filone, Claire Marie
   Hensley, Lisa
   Li, Qi
   Ory, Daniel
   Chandran, Kartik
   Cunningham, James
TI Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection
SO NATURE
LA English
DT Article
ID sterol-sensing domain; cholesterol accumulation; zaire ebolavirus; viral entry; binding; glycoprotein; protein; trafficking; events; identification
AB Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection(1) and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV(2). Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain(3-7), which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit(8). Thus, NPC1 is essential for EboV entry and a target for antiviral therapy.
C1 [Cote, Marceline; Misasi, John; Bruchez, Anna; Filone, Claire Marie; Li, Qi; Chandran, Kartik; Cunningham, James] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
   [Misasi, John] Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
   [Ren, Tao; Lee, Kyungae] Harvard Univ, Sch Med, New England Reg Ctr Excellence Biodefense & Emerg, Boston, MA 02115 USA.
   [Filone, Claire Marie; Hensley, Lisa] USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA.
   [Ory, Daniel] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
   [Cunningham, James] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Washington University (WUSTL); Harvard University; Harvard Medical School
RP Cunningham, J (corresponding author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
EM jcunningham@rics.bwh.harvard.edu
FU PIDS-Sanofi-Pasteur Fellowship [K12-HD052896, 5K08AI079381, 5-T32-HL007623]; Fonds de la Recherche en Sante du Quebec; US Army Medical Research and Material Command;  [U54 AI057159];  [R01 CA104266]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD052896] Funding Source: NIH RePORTER
NR 30
TC 567
Z9 704
U1 1
U2 178
PU 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 15
PY 2011
VL 477
IS 7364
BP 344
EP U122
DI 10.1038/nature10380
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400034
PM 21866101
DA 2026-03-09
ER

PT J
AU Prud'homme, B
   Minervino, C
   Hocine, M
   Cande, JD
   Aouane, A
   Dufour, HD
   Kassner, VA
   Gompel, N
AF Prud'homme, Benjamin
   Minervino, Caroline
   Hocine, Melanie
   Cande, Jessica D.
   Aouane, Aicha
   Dufour, Heloise D.
   Kassner, Victoria A.
   Gompel, Nicolas
TI Body plan innovation in treehoppers through the evolution of an extra wing-like appendage
SO NATURE
LA English
DT Article
ID beetle tribolium-castaneum; insect wings; gene; constraints; origin
AB Body plans, which characterize the anatomical organization of animal groups of high taxonomic rank(1), often evolve by the reduction or loss of appendages (limbs in vertebrates and legs and wings in insects, for example). In contrast, the addition of new features is extremely rare and is thought to be heavily constrained, although the nature of the constraints remains elusive(2-4). Here we show that the treehopper (Membracidae) 'helmet' is actually an appendage, a wing serial homologue on the first thoracic segment. This innovation in the insect body plan is an unprecedented situation in 250 Myr of insect evolution. We provide evidence suggesting that the helmet arose by escaping the ancestral repression of wing formation imparted by a member of the Hox gene family, which sculpts the number and pattern of appendages along the body axis(5-8). Moreover, we propose that the exceptional morphological diversification of the helmet was possible because, in contrast to the wings, it escaped the stringent functional requirements imposed by flight. This example illustrates how complex morphological structures can arise by the expression of ancestral developmental potentials and fuel the morphological diversification of an evolutionary lineage.
C1 [Prud'homme, Benjamin; Minervino, Caroline; Hocine, Melanie; Cande, Jessica D.; Aouane, Aicha; Gompel, Nicolas] CNRS, UMR 6216, Inst Biol Dev Marseille Luminy, F-13288 Marseille 9, France.
   [Dufour, Heloise D.; Kassner, Victoria A.] Univ Wisconsin, Madison, WI 53706 USA.
   [Dufour, Heloise D.; Kassner, Victoria A.] Howard Hughes Med Inst, Bock Labs, Madison, WI 53706 USA.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); University of Wisconsin System; University of Wisconsin Madison; Howard Hughes Medical Institute
RP Prud'homme, B (corresponding author), CNRS, UMR 6216, Inst Biol Dev Marseille Luminy, Case 907,Parc Sci Luminy, F-13288 Marseille 9, France.
EM benjamin.prudhomme@univmed.fr; nicolas.gompel@univmed.fr
FU EURYI award; Human Frontier Science Program; CNRS
NR 29
TC 79
Z9 95
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 83
EP 86
DI 10.1038/nature09977
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300035
PM 21544145
DA 2026-03-09
ER

PT J
AU Vivian, JP
   Duncan, RC
   Berry, R
   O'Connor, GM
   Reid, HH
   Beddoe, T
   Gras, S
   Saunders, PM
   Olshina, MA
   Widjaja, JML
   Harpur, CM
   Lin, J
   Maloveste, SM
   Price, DA
   Lafont, BAP
   McVicar, DW
   Clements, CS
   Brooks, AG
   Rossjohn, J
AF Vivian, Julian P.
   Duncan, Renee C.
   Berry, Richard
   O'Connor, Geraldine M.
   Reid, Hugh H.
   Beddoe, Travis
   Gras, Stephanie
   Saunders, Philippa M.
   Olshina, Maya A.
   Widjaja, Jacqueline M. L.
   Harpur, Christopher M.
   Lin, Jie
   Maloveste, Sebastien M.
   Price, David A.
   Lafont, Bernard A. P.
   McVicar, Daniel W.
   Clements, Craig S.
   Brooks, Andrew G.
   Rossjohn, Jamie
TI Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B
SO NATURE
LA English
DT Article
ID complex class-i; hla-b; crystal-structure; polymorphisms; progression; molecules; selection; subtypes; history; kir3ds1
AB Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses(1). Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies(1-3). Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards beta 2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLAB*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C-4,C-5 and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species.
C1 [Saunders, Philippa M.; Widjaja, Jacqueline M. L.; Harpur, Christopher M.; Lin, Jie; Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
   [Vivian, Julian P.; Duncan, Renee C.; Berry, Richard; Reid, Hugh H.; Beddoe, Travis; Gras, Stephanie; Olshina, Maya A.; Clements, Craig S.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
   [Maloveste, Sebastien M.; Lafont, Bernard A. P.] NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales.
   [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
C3 University of Melbourne; Monash University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Cardiff University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Brooks, AG (corresponding author), Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
EM agbrooks@unimelb.edu.au; jamie.rossjohn@monash.edu
FU National Health and Medical Research Council of Australia (NHMRC); Australian Research Council (ARC); National Cancer Institute, National Institutes of Health; National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health; NHMRC; Medical Research Council (UK); ARC QEII; Medical Research Council [G0501963] Funding Source: researchfish; MRC [G0501963] Funding Source: UKRI
NR 29
TC 161
Z9 189
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 NOV 17
PY 2011
VL 479
IS 7373
BP 401
EP U155
DI 10.1038/nature10517
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700046
PM 22020283
DA 2026-03-09
ER

PT J
AU Wang, M
   Gamo, NJ
   Yang, Y
   Jin, LE
   Wang, XJ
   Laubach, M
   Mazer, JA
   Lee, D
   Arnsten, AFT
AF Wang, Min
   Gamo, Nao J.
   Yang, Yang
   Jin, Lu E.
   Wang, Xiao-Jing
   Laubach, Mark
   Mazer, James A.
   Lee, Daeyeol
   Arnsten, Amy F. T.
TI Neuronal basis of age-related working memory decline
SO NATURE
LA English
DT Article
ID monkey prefrontal-cortex; cognitive decline; rhesus-monkey; executive function; impairment; dysfunction; network; macaque
AB Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction(1-4). The PFC guides behaviour and thought using working memory(5), which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation(6). This fragile process is highly dependent on the neurochemical environment(7). For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels(8,9). It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.
C1 [Wang, Min; Gamo, Nao J.; Yang, Yang; Jin, Lu E.; Wang, Xiao-Jing; Laubach, Mark; Mazer, James A.; Lee, Daeyeol; Arnsten, Amy F. T.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
   [Laubach, Mark] John B Pierce Lab, New Haven, CT 06510 USA.
C3 Yale University; Yale University; The John B Pierce Laboratory, Inc
RP Arnsten, AFT (corresponding author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06510 USA.
EM amy.arnsten@yale.edu
FU PHS, National Institute on Aging [PO1AG030004]
NR 30
TC 340
Z9 419
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 11
PY 2011
VL 476
IS 7359
BP 210
EP U110
DI 10.1038/nature10243
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900037
PM 21796118
DA 2026-03-09
ER

PT J
AU Simsek, D
   Furda, A
   Gao, Y
   Artus, J
   Brunet, E
   Hadjantonakis, AK
   Van Houten, B
   Shuman, S
   McKinnon, PJ
   Jasin, M
AF Simsek, Deniz
   Furda, Amy
   Gao, Yankun
   Artus, Jerome
   Brunet, Erika
   Hadjantonakis, Anna-Katerina
   Van Houten, Bennett
   Shuman, Stewart
   McKinnon, Peter J.
   Jasin, Maria
TI Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair
SO NATURE
LA English
DT Article
ID strand break repair; embryonic lethality; gene encodes; xrcc1; nuclear; proteins; binding; alpha; cells; cycle
AB Mammalian cells have three ATP-dependent DNA ligases, which are required for DNA replication and repair(1). Homologues of ligase I (Lig1) and ligase IV (Lig4) are ubiquitous in Eukarya, whereas ligase III (Lig3), which has nuclear and mitochondrial forms, appears to be restricted to vertebrates. Lig3 is implicated in various DNA repair pathways with its partner protein Xrcc1 (ref. 1). Deletion of Lig3 results in early embryonic lethality in mice, as well as apparent cellular lethality(2), which has precluded definitive characterization of Lig3 function. Here we used pre-emptive complementation to determine the viability requirement for Lig3 in mammalian cells and its requirement in DNA repair. Various forms of Lig3 were introduced stably into mouse embryonic stem (mES) cells containing a conditional allele of Lig3 that could be deleted with Cre recombinase. With this approach, we find that the mitochondrial, but not nuclear, Lig3 is required for cellular viability. Although the catalytic function of Lig3 is required, the zinc finger (ZnF) and BRCA1 carboxy (C)-terminal-related (BRCT) domains of Lig3 are not. Remarkably, the viability requirement for Lig3 can be circumvented by targeting Lig1 to the mitochondria or expressing Chlorella virus DNA ligase, the minimal eukaryal nick-sealing enzyme(3), or Escherichia coli LigA, an NAD(+)-dependent ligase(1). Lig3-null cells are not sensitive to several DNA-damaging agents that sensitize Xrcc1-deficient cells(4-6). Our results establish a role for Lig3 in mitochondria, but distinguish it from its interacting protein Xrcc1.
C1 [Simsek, Deniz; Artus, Jerome; Brunet, Erika; Hadjantonakis, Anna-Katerina; Jasin, Maria] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Simsek, Deniz; Hadjantonakis, Anna-Katerina; Shuman, Stewart; Jasin, Maria] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA.
   [Furda, Amy; Van Houten, Bennett] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
   [Furda, Amy; Van Houten, Bennett] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA.
   [Gao, Yankun; McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA.
   [Brunet, Erika] Museum Natl Hist Nat, F-75005 Paris, France.
   [Brunet, Erika] CNRS, UMR7196, F-75005 Paris, France.
   [Brunet, Erika] INSERM, U565, F-75005 Paris, France.
   [Shuman, Stewart] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; St Jude Children's Research Hospital; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Institut National de la Sante et de la Recherche Medicale (Inserm); Memorial Sloan Kettering Cancer Center
RP Jasin, M (corresponding author), Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
EM m-jasin@ski.mskcc.org
FU PA CURE; National Institutes of Health [ES019566, NS37956, CA21765, GM54668]; National Cancer Institute [P30CA021765, P30CA008748] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS037956] Funding Source: NIH RePORTER
NR 26
TC 193
Z9 237
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 MAR 10
PY 2011
VL 471
IS 7337
BP 245
EP U139
DI 10.1038/nature09794
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200043
PM 21390132
DA 2026-03-09
ER

PT J
AU Bollinger, AT
   Dubuis, G
   Yoon, J
   Pavuna, D
   Misewich, J
   Bozovic, I
AF Bollinger, A. T.
   Dubuis, G.
   Yoon, J.
   Pavuna, D.
   Misewich, J.
   Bozovic, I.
TI Superconductor-insulator transition in La2-xSrxCuO4 at the pair quantum resistance
SO NATURE
LA English
DT Article
ID high-temperature superconductivity; interface superconductivity; 2-dimensional limit; superfluid density; ground-state; liquid; films
AB High-temperature superconductivity in copper oxides arises when a parent insulator compound is doped beyond some critical concentration; what exactly happens at this superconductor-insulator transition is a key open question(1). The cleanest approach is to tune the carrier density using the electric field effect(2-7); for example, it was learned in this way(5) that weak electron localization transforms superconducting SrTiO3 into a Fermi-glass insulator. But in the copper oxides this has been a long-standing technical challenge(3), because perfect ultrathin films and huge local fields (>10(9) V m(-1)) are needed. Recently, such fields have been obtained using electrolytes or ionic liquids in the electric double-layer transistor configuration(8-10). Here we report synthesis of epitaxial films of La2 - xSrxCuO4 that are one unit cell thick, and fabrication of double-layer transistors. Very large fields and induced changes in surface carrier density enable shifts in the critical temperature by up to 30 K. Hundreds of resistance versus temperature and carrier density curves were recorded and shown to collapse onto a single function, as predicted for a two-dimensional superconductor-insulator transition(11-14). The observed critical resistance is precisely the quantum resistance for pairs, R-Q = h/(2e)(2) = 6.45 k Omega, suggestive of a phase transition driven by quantum phase fluctuations, and Cooper pair (de) localization.
C1 [Bollinger, A. T.; Dubuis, G.; Yoon, J.; Misewich, J.; Bozovic, I.] Brookhaven Natl Lab, Upton, NY 11973 USA.
   [Dubuis, G.; Pavuna, D.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
C3 United States Department of Energy (DOE); Brookhaven National Laboratory; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Bozovic, I (corresponding author), Brookhaven Natl Lab, Upton, NY 11973 USA.
EM bozovic@bnl.gov
FU US Department of Energy, Basic Energy Sciences, Materials Sciences and Engineering Division; US DOE, Energy Frontier Research Center; Laboratory for Physics of Complex Matter (EPFL); Swiss National Science Foundation
NR 30
TC 435
Z9 472
U1 8
U2 437
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 458
EP 460
DI 10.1038/nature09998
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600031
PM 21525929
DA 2026-03-09
ER

PT J
AU Phan, G
   Remaut, H
   Wang, T
   Allen, WJ
   Pirker, KF
   Lebedev, A
   Henderson, NS
   Geibel, S
   Volkan, E
   Yan, J
   Kunze, MBA
   Pinkner, JS
   Ford, B
   Kay, CWM
   Li, HL
   Hultgren, SJ
   Thanassi, DG
   Waksman, G
AF Phan, Gilles
   Remaut, Han
   Wang, Tao
   Allen, William J.
   Pirker, Katharina F.
   Lebedev, Andrey
   Henderson, Nadine S.
   Geibel, Sebastian
   Volkan, Ender
   Yan, Jun
   Kunze, Micha B. A.
   Pinkner, Jerome S.
   Ford, Bradley
   Kay, Christopher W. M.
   Li, Huilin
   Hultgren, Scott J.
   Thanassi, David G.
   Waksman, Gabriel
TI Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate
SO NATURE
LA English
DT Article
ID chaperone-subunit complexes; bacterial outer-membrane; pilus biogenesis; molecular replacement; adhesin; recognition; domain; site
AB Type 1 pili are the archetypal representative of a widespread class of adhesive multisubunit fibres in Gram-negative bacteria. During pilus assembly, subunits dock as chaperone-bound complexes to an usher, which catalyses their polymerization and mediates pilus translocation across the outer membrane. Here we report the crystal structure of the full-length FimD usher bound to the FimC-FimH chaperone-adhesin complex and that of the unbound form of the FimD translocation domain. The FimD-FimC-FimH structure shows FimH inserted inside the FimD 24-stranded beta-barrel translocation channel. FimC-FimH is held in place through interactions with the two carboxy-terminal periplasmic domains of FimD, a binding mode confirmed in solution by electron paramagnetic resonance spectroscopy. To accommodate FimH, the usher plug domain is displaced from the barrel lumen to the periplasm, concomitant with a marked conformational change in the beta-barrel. The amino-terminal domain of FimD is observed in an ideal position to catalyse incorporation of a newly recruited chaperone-subunit complex. The FimD-FimC-FimH structure provides unique insights into the pilus subunit incorporation cycle, and captures the first view of a protein transporter in the act of secreting its cognate substrate.
C1 [Phan, Gilles; Remaut, Han; Allen, William J.; Pirker, Katharina F.; Geibel, Sebastian; Yan, Jun; Kunze, Micha B. A.; Kay, Christopher W. M.; Waksman, Gabriel] UCL, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Phan, Gilles; Remaut, Han; Allen, William J.; Pirker, Katharina F.; Geibel, Sebastian; Yan, Jun; Kunze, Micha B. A.; Kay, Christopher W. M.; Waksman, Gabriel] Univ London Birkbeck Coll, London WC1E 7HX, England.
   [Remaut, Han] Vrije Univ Brussel VIB, B-1050 Brussels, Belgium.
   [Wang, Tao; Li, Huilin] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
   [Lebedev, Andrey] Univ York, Dept Chem, York YO10 5YW, N Yorkshire, England.
   [Henderson, Nadine S.; Thanassi, David G.] SUNY Stony Brook, Ctr Infect Dis, Stony Brook, NY 11794 USA.
   [Henderson, Nadine S.; Thanassi, David G.] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
   [Volkan, Ender; Pinkner, Jerome S.; Ford, Bradley; Hultgren, Scott J.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Volkan, Ender; Pinkner, Jerome S.; Ford, Bradley; Hultgren, Scott J.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63110 USA.
   [Ford, Bradley] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Kay, Christopher W. M.] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Kay, Christopher W. M.; Waksman, Gabriel] UCL, Res Dept Struct & Mol Biol, London WC1E 6BT, England.
   [Li, Huilin] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
C3 University of London; Birkbeck University London; University College London; University of London; Birkbeck University London; Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); United States Department of Energy (DOE); Brookhaven National Laboratory; University of York - UK; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of London; University College London; University of London; University College London; State University of New York (SUNY) System; Stony Brook University
RP Waksman, G (corresponding author), UCL, Inst Struct & Mol Biol, Malet St, London WC1E 7HX, England.
EM david.thanassi@stonybrook.edu; g.waksman@ucl.ac.uk
FU Medical Research Council [85602]; NIH [GM62987, 49950, 29549, 48689, GM74985]; BNL [10-16]; VIB; FWO-Vlaanderen; Austrian Science Fund [J 2959-N17]; BBSRC [BB/F001134/1] Funding Source: UKRI; MRC [G0800002, G0100442] Funding Source: UKRI; National Institute of General Medical Sciences [R01GM062987] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/F001134/1] Funding Source: researchfish; Medical Research Council [G0100442, G0800002] Funding Source: researchfish
NR 44
TC 146
Z9 176
U1 1
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 49
EP U71
DI 10.1038/nature10109
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700034
PM 21637253
DA 2026-03-09
ER

PT J
AU Rothberg, JM
   Hinz, W
   Rearick, TM
   Schultz, J
   Mileski, W
   Davey, M
   Leamon, JH
   Johnson, K
   Milgrew, MJ
   Edwards, M
   Hoon, J
   Simons, JF
   Marran, D
   Myers, JW
   Davidson, JF
   Branting, A
   Nobile, JR
   Puc, BP
   Light, D
   Clark, TA
   Huber, M
   Branciforte, JT
   Stoner, IB
   Cawley, SE
   Lyons, M
   Fu, YT
   Homer, N
   Sedova, M
   Miao, X
   Reed, B
   Sabina, J
   Feierstein, E
   Schorn, M
   Alanjary, M
   Dimalanta, E
   Dressman, D
   Kasinskas, R
   Sokolsky, T
   Fidanza, JA
   Namsaraev, E
   McKernan, KJ
   Williams, A
   Roth, GT
   Bustillo, J
AF Rothberg, Jonathan M.
   Hinz, Wolfgang
   Rearick, Todd M.
   Schultz, Jonathan
   Mileski, William
   Davey, Mel
   Leamon, John H.
   Johnson, Kim
   Milgrew, Mark J.
   Edwards, Matthew
   Hoon, Jeremy
   Simons, Jan F.
   Marran, David
   Myers, Jason W.
   Davidson, John F.
   Branting, Annika
   Nobile, John R.
   Puc, Bernard P.
   Light, David
   Clark, Travis A.
   Huber, Martin
   Branciforte, Jeffrey T.
   Stoner, Isaac B.
   Cawley, Simon E.
   Lyons, Michael
   Fu, Yutao
   Homer, Nils
   Sedova, Marina
   Miao, Xin
   Reed, Brian
   Sabina, Jeffrey
   Feierstein, Erika
   Schorn, Michelle
   Alanjary, Mohammad
   Dimalanta, Eileen
   Dressman, Devin
   Kasinskas, Rachel
   Sokolsky, Tanya
   Fidanza, Jacqueline A.
   Namsaraev, Eugeni
   McKernan, Kevin J.
   Williams, Alan
   Roth, G. Thomas
   Bustillo, James
TI An integrated semiconductor device enabling non-optical genome sequencing
SO NATURE
LA English
DT Article
ID sensor array chip; cmos technology; dna; charge; transistor; sea
AB The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.
C1 [Rothberg, Jonathan M.; Hinz, Wolfgang; Rearick, Todd M.; Schultz, Jonathan; Mileski, William; Davey, Mel; Leamon, John H.; Johnson, Kim; Milgrew, Mark J.; Edwards, Matthew; Hoon, Jeremy; Simons, Jan F.; Marran, David; Myers, Jason W.; Davidson, John F.; Branting, Annika; Nobile, John R.; Puc, Bernard P.; Light, David; Clark, Travis A.; Huber, Martin; Branciforte, Jeffrey T.; Stoner, Isaac B.; Cawley, Simon E.; Lyons, Michael; Fu, Yutao; Homer, Nils; Sedova, Marina; Miao, Xin; Reed, Brian; Sabina, Jeffrey; Feierstein, Erika; Schorn, Michelle; Alanjary, Mohammad; Dimalanta, Eileen; Dressman, Devin; Kasinskas, Rachel; Sokolsky, Tanya; Fidanza, Jacqueline A.; Namsaraev, Eugeni; McKernan, Kevin J.; Williams, Alan; Roth, G. Thomas; Bustillo, James] Ion Torrent Life Technol, Guilford, CT 06437 USA.
C3 Thermo Fisher Scientific
RP Rothberg, JM (corresponding author), Ion Torrent Life Technol, Suite 100,246 Goose Lane, Guilford, CT 06437 USA.
EM Jonathan.Rothberg@Lifetech.com
FU National Human Genome Research Institute (NHGRI) [RFA-HG-08-008];  [R01 HG005094]
NR 46
TC 1548
Z9 2199
U1 7
U2 530
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 348
EP 352
DI 10.1038/nature10242
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200036
PM 21776081
DA 2026-03-09
ER

PT J
AU Williams, K
   Christensen, J
   Pedersen, MT
   Johansen, JV
   Cloos, PAC
   Rappsilber, J
   Helin, K
AF Williams, Kristine
   Christensen, Jesper
   Pedersen, Marianne Terndrup
   Johansen, Jens V.
   Cloos, Paul A. C.
   Rappsilber, Juri
   Helin, Kristian
TI TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
SO NATURE
LA English
DT Article
ID embryonic stem-cells; self-renewal; 5-hydroxymethylcytosine; wide; pluripotent; conversion; complex; genes; maps
AB Enzymes catalysing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression and maintaining cellular identity. Recently, TET1 was found to hydroxylate the methyl group of mC, converting it to 5-hydroxymethyl cytosine (hmC). Here we show that TET1 binds throughout the genome of embryonic stem cells, with the majority of binding sites located at transcription start sites (TSSs) of CpG-rich promoters and within genes. The hmC modification is found in gene bodies and in contrast to mC is also enriched at CpG-rich TSSs. We provide evidence further that TET1 has a role in transcriptional repression. TET1 binds a significant proportion of Polycomb group target genes. Furthermore, TET1 associates and colocalizes with the SIN3A co-repressor complex. We propose that TET1 fine-tunes transcription, opposes aberrant DNA methylation at CpG-rich sequences and thereby contributes to the regulation of DNA methylation fidelity.
C1 [Williams, Kristine; Christensen, Jesper; Pedersen, Marianne Terndrup; Johansen, Jens V.; Cloos, Paul A. C.; Helin, Kristian] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark.
   [Williams, Kristine; Christensen, Jesper; Pedersen, Marianne Terndrup; Cloos, Paul A. C.; Helin, Kristian] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark.
   [Johansen, Jens V.] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
   [Rappsilber, Juri] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
C3 University of Copenhagen; University of Copenhagen; University of Copenhagen; University of Edinburgh
RP Helin, K (corresponding author), Univ Copenhagen, BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark.
EM kristian.helin@bric.ku.dk
FU Danish Cancer Society; University of Copenhagen; Danish National Research Foundation; Lundbeck foundation; Novo Nordisk Foundation; Danish Medical Research Council
NR 29
TC 842
Z9 1001
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 MAY 19
PY 2011
VL 473
IS 7347
BP 343
EP U472
DI 10.1038/nature10066
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400041
PM 21490601
DA 2026-03-09
ER

PT J
AU Najmabadi, H
   Hu, H
   Garshasbi, M
   Zemojtel, T
   Abedini, SS
   Chen, W
   Hosseini, M
   Behjati, F
   Haas, S
   Jamali, P
   Zecha, A
   Mohseni, M
   Püttmann, L
   Vahid, LN
   Jensen, C
   Moheb, LA
   Bienek, M
   Larti, F
   Mueller, I
   Weissmann, R
   Darvish, H
   Wrogemann, K
   Hadavi, V
   Lipkowitz, B
   Esmaeeli-Nieh, S
   Wieczorek, D
   Kariminejad, R
   Firouzabadi, SG
   Cohen, M
   Fattahi, Z
   Rost, I
   Mojahedi, F
   Hertzberg, C
   Dehghan, A
   Rajab, A
   Banavandi, MJS
   Hoffer, J
   Falah, M
   Musante, L
   Kalscheuer, V
   Ullmann, R
   Kuss, AW
   Tzschach, A
   Kahrizi, K
   Ropers, HH
AF Najmabadi, Hossein
   Hu, Hao
   Garshasbi, Masoud
   Zemojtel, Tomasz
   Abedini, Seyedeh Sedigheh
   Chen, Wei
   Hosseini, Masoumeh
   Behjati, Farkhondeh
   Haas, Stefan
   Jamali, Payman
   Zecha, Agnes
   Mohseni, Marzieh
   Puettmann, Lucia
   Vahid, Leyla Nouri
   Jensen, Corinna
   Moheb, Lia Abbasi
   Bienek, Melanie
   Larti, Farzaneh
   Mueller, Ines
   Weissmann, Robert
   Darvish, Hossein
   Wrogemann, Klaus
   Hadavi, Valeh
   Lipkowitz, Bettina
   Esmaeeli-Nieh, Sahar
   Wieczorek, Dagmar
   Kariminejad, Roxana
   Firouzabadi, Saghar Ghasemi
   Cohen, Monika
   Fattahi, Zohreh
   Rost, Imma
   Mojahedi, Faezeh
   Hertzberg, Christoph
   Dehghan, Atefeh
   Rajab, Anna
   Banavandi, Mohammad Javad Soltani
   Hoffer, Julia
   Falah, Masoumeh
   Musante, Luciana
   Kalscheuer, Vera
   Ullmann, Reinhard
   Kuss, Andreas Walter
   Tzschach, Andreas
   Kahrizi, Kimia
   Ropers, H. Hilger
TI Deep sequencing reveals 50 novel genes for recessive cognitive disorders
SO NATURE
LA English
DT Article
ID linked mental-retardation; intellectual disability; binding-protein; frameshift mutation; identification; family; disruption; encodes; srd5a3; screen
AB Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function.
C1 [Hu, Hao; Garshasbi, Masoud; Chen, Wei; Zecha, Agnes; Puettmann, Lucia; Jensen, Corinna; Moheb, Lia Abbasi; Bienek, Melanie; Mueller, Ines; Weissmann, Robert; Wrogemann, Klaus; Lipkowitz, Bettina; Esmaeeli-Nieh, Sahar; Hoffer, Julia; Musante, Luciana; Kalscheuer, Vera; Ullmann, Reinhard; Kuss, Andreas Walter; Tzschach, Andreas; Ropers, H. Hilger] Max Planck Inst Mol Genet, Dept Human Mol Genet, D-14195 Berlin, Germany.
   [Najmabadi, Hossein; Garshasbi, Masoud; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Behjati, Farkhondeh; Mohseni, Marzieh; Vahid, Leyla Nouri; Moheb, Lia Abbasi; Larti, Farzaneh; Darvish, Hossein; Firouzabadi, Saghar Ghasemi; Fattahi, Zohreh; Banavandi, Mohammad Javad Soltani; Falah, Masoumeh; Kahrizi, Kimia] Univ Social Welf & Rehabil Sci, Genet Res Ctr, Tehran 19857, Iran.
   [Najmabadi, Hossein; Hadavi, Valeh; Kariminejad, Roxana] Kariminejad Najmabadi Pathol & Genet Ctr, Tehran 14667, Iran.
   [Zemojtel, Tomasz; Haas, Stefan] Max Planck Inst Mol Genet, Dept Computat Mol Biol, D-14195 Berlin, Germany.
   [Chen, Wei] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
   [Jamali, Payman] Shahroud Welf Org, Semnan 36156, Iran.
   [Wrogemann, Klaus] Univ Manitoba, Dept Biochem & Mol Genet, Winnipeg, MB R3E0J9, Canada.
   [Wieczorek, Dagmar] Univ Klinikum Essen, Inst Humangenet, D-45122 Essen, Germany.
   [Cohen, Monika] Kinderzentrum Muenchen, D-81377 Munich, Germany.
   [Rost, Imma] Zentrum Humangenet & Lab Med Dr Klein & Dr Rost, D-82152 Martinsried, Germany.
   [Mojahedi, Faezeh] Mashhad Med Genet Counseling Ctr, Mashhad 91767, Iran.
   [Hertzberg, Christoph] Vivantes Klinikum Neukolln, D-12351 Berlin, Germany.
   [Dehghan, Atefeh] Yazd Welf Org, Yazd 89178, Iran.
   [Rajab, Anna] Royal Hosp, Genet Unit, Minist Hlth, Directorate Gen Hlth Affairs, Muscat 113, Oman.
C3 Max Planck Society; Max Planck Society; Helmholtz Association; Max Delbruck Center for Molecular Medicine; University of Manitoba; University of Duisburg Essen; VIivantes Klinikum Neukolln; The Royal Hospital, Sultanate of Oman
RP Ropers, HH (corresponding author), Max Planck Inst Mol Genet, Dept Human Mol Genet, Ihnestr 73, D-14195 Berlin, Germany.
EM kkahrizi@uswr.ac.ir; ropers@molgen.mpg.de
FU Max Planck Innovation Funds; German Federal Ministry of Education and Research through the MRNET [01GS08161]; Iranian National Science Foundation; EU
NR 43
TC 791
Z9 891
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 6
PY 2011
VL 478
IS 7367
BP 57
EP 63
DI 10.1038/nature10423
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400034
PM 21937992
DA 2026-03-09
ER

PT J
AU Goodridge, HS
   Reyes, CN
   Becker, CA
   Katsumoto, TR
   Ma, J
   Wolf, AJ
   Bose, N
   Chan, ASH
   Magee, AS
   Danielson, ME
   Weiss, A
   Vasilakos, JP
   Underhill, DM
AF Goodridge, Helen S.
   Reyes, Christopher N.
   Becker, Courtney A.
   Katsumoto, Tamiko R.
   Ma, Jun
   Wolf, Andrea J.
   Bose, Nandita
   Chan, Anissa S. H.
   Magee, Andrew S.
   Danielson, Michael E.
   Weiss, Arthur
   Vasilakos, John P.
   Underhill, David M.
TI Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'
SO NATURE
LA English
DT Article
ID beta-glucan recognition; candida-albicans; lectin receptors; dendritic cells; macrophages; kinase; cd148; clec-2; cd45
AB Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects beta-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS)(1,2). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.
C1 [Goodridge, Helen S.; Reyes, Christopher N.; Becker, Courtney A.; Ma, Jun; Wolf, Andrea J.; Underhill, David M.] Cedars Sinai Med Ctr, IBD & Immunobiol Res Inst, Los Angeles, CA 90048 USA.
   [Goodridge, Helen S.] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
   [Goodridge, Helen S.; Underhill, David M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Katsumoto, Tamiko R.; Weiss, Arthur] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA.
   [Bose, Nandita; Chan, Anissa S. H.; Magee, Andrew S.; Danielson, Michael E.; Vasilakos, John P.] Biothera, Eagan, MN 55121 USA.
   [Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
C3 Cedars Sinai Medical Center; Cedars Sinai Medical Center; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Underhill, DM (corresponding author), Cedars Sinai Med Ctr, IBD & Immunobiol Res Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM david.underhill@csmc.edu
FU NIH [AI071116, AI066120]; American Heart Association; Crohn's and Colitis Foundation of America; National Institute of Allergy and Infectious Diseases [R01AI071116] Funding Source: NIH RePORTER
NR 24
TC 685
Z9 796
U1 4
U2 182
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 471
EP U541
DI 10.1038/nature10071
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600034
PM 21525931
DA 2026-03-09
ER

PT J
AU Gao, YK
   Katyal, S
   Lee, YS
   Zhao, JF
   Rehg, JE
   Russell, HR
   McKinnon, PJ
AF Gao, Yankun
   Katyal, Sachin
   Lee, Youngsoo
   Zhao, Jingfeng
   Rehg, Jerold E.
   Russell, Helen R.
   McKinnon, Peter J.
TI DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair
SO NATURE
LA English
DT Article
ID base excision-repair; strand break repair; mitochondrial-dna; mouse cells; disease; xrcc1; damage; inactivation; polymerase; expression
AB DNA replication and repair in mammalian cells involves three distinct DNA ligases: ligase I (Lig1), ligase III (Lig3) and ligase IV (Lig4)(1). Lig3 is considered a key ligase during base excision repair because its stability depends upon its nuclear binding partner Xrcc1, a critical factor for this DNA repair pathway(2,3). Lig3 is also present in the mitochondria, where its role in mitochondrial DNA (mtDNA) maintenance is independent of Xrcc1 (ref. 4). However, the biological role of Lig3 is unclear as inactivation of murine Lig3 results in early embryonic lethality(5). Here we report that Lig3 is essential for mtDNA integrity but dispensable for nuclear DNA repair. Inactivation of Lig3 in the mouse nervous system resulted in mtDNA loss leading to profound mitochondrial dysfunction, disruption of cellular homeostasis and incapacitating ataxia. Similarly, inactivation of Lig3 in cardiac muscle resulted in mitochondrial dysfunction and defective heart-pump function leading to heart failure. However, Lig3 inactivation did not result in nuclear DNA repair deficiency, indicating essential DNA repair functions of Xrcc1 can occur in the absence of Lig3. Instead, we found that Lig1 was critical for DNA repair, but acted in a cooperative manner with Lig3. Additionally, Lig3 deficiency did not recapitulate the hallmark features of neural Xrcc1 inactivation such as DNA damage-induced cerebellar interneuron loss(6), further underscoring functional separation of these DNA repair factors. Therefore, our data reveal that the critical biological role of Lig3 is to maintain mtDNA integrity and not Xrcc1-dependent DNA repair.
C1 [Gao, Yankun; Katyal, Sachin; Lee, Youngsoo; Zhao, Jingfeng; Russell, Helen R.; McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA.
   [Rehg, Jerold E.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital
RP McKinnon, PJ (corresponding author), St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA.
EM peter.mckinnon@stjude.org
FU National Institutes of Health [NS-37956, CA-21765]; Cancer Center [P30 CA21765]; American Lebanese and Syrian Associated Charities of St Jude Children's Research Hospital; National Cancer Institute [P30CA021765, P01CA096832] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS037956] Funding Source: NIH RePORTER
NR 30
TC 155
Z9 181
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 MAR 10
PY 2011
VL 471
IS 7337
BP 240
EP U134
DI 10.1038/nature09773
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200042
PM 21390131
DA 2026-03-09
ER

PT J
AU Ding, ZH
   Wu, CJ
   Chu, GC
   Xiao, YH
   Ho, D
   Zhang, JF
   Perry, SR
   Labrot, ES
   Wu, XQ
   Lis, R
   Hoshida, Y
   Hiller, D
   Hu, BL
   Jiang, S
   Zheng, HW
   Stegh, AH
   Scott, KL
   Signoretti, S
   Bardeesy, N
   Wang, YA
   Hill, DE
   Golub, TR
   Stampfer, MJ
   Wong, WH
   Loda, M
   Mucci, L
   Chin, L
   DePinho, RA
AF Ding, Zhihu
   Wu, Chang-Jiun
   Chu, Gerald C.
   Xiao, Yonghong
   Ho, Dennis
   Zhang, Jingfang
   Perry, Samuel R.
   Labrot, Emma S.
   Wu, Xiaoqiu
   Lis, Rosina
   Hoshida, Yujin
   Hiller, David
   Hu, Baoli
   Jiang, Shan
   Zheng, Hongwu
   Stegh, Alexander H.
   Scott, Kenneth L.
   Signoretti, Sabina
   Bardeesy, Nabeel
   Wang, Y. Alan
   Hill, David E.
   Golub, Todd R.
   Stampfer, Meir J.
   Wong, Wing H.
   Loda, Massimo
   Mucci, Lorelei
   Chin, Lynda
   DePinho, Ronald A.
TI SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
SO NATURE
LA English
DT Article
ID tgf-beta; expression; pten; smad4; inactivation; osteopontin; promoter; roles; model; leads
AB Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression(1). Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGF beta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.
C1 [Ding, Zhihu; Wu, Chang-Jiun; Chu, Gerald C.; Xiao, Yonghong; Ho, Dennis; Perry, Samuel R.; Labrot, Emma S.; Hu, Baoli; Jiang, Shan; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Ding, Zhihu; Wu, Chang-Jiun; Chu, Gerald C.; Xiao, Yonghong; Ho, Dennis; Perry, Samuel R.; Labrot, Emma S.; Wu, Xiaoqiu; Lis, Rosina; Hu, Baoli; Jiang, Shan; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Wang, Y. Alan; Loda, Massimo; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Ding, Zhihu; Wu, Chang-Jiun; Ho, Dennis; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Hill, David E.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Ding, Zhihu; Wu, Chang-Jiun; Ho, Dennis; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Chu, Gerald C.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Zhang, Jingfang] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA.
   [Wu, Xiaoqiu; Lis, Rosina; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
   [Hoshida, Yujin; Golub, Todd R.] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
   [Hoshida, Yujin; Golub, Todd R.] Harvard Univ, Cambridge, MA 02142 USA.
   [Hiller, David; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
   [Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Renal Canc Program, Boston, MA 02115 USA.
   [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
   [Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
   [Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Chin, Lynda] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Stampfer, Meir J.; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Stampfer, Meir J.; Mucci, Lorelei] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Wisconsin System; University of Wisconsin Madison; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Stanford University; 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; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP DePinho, RA (corresponding author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu; ron_depinho@dfci.harvard.edu
FU Damon Runyon Cancer Research Foundation; National Science Foundation; Helen Hay Whitney Foundation; Multiple Myeloma Research Foundation; Belfer Institute for Applied Cancer Science (NCI) [U01-CA84313]; DF/HCC SPORE in Prostate Cancer [P50 CA090381-08]; National Cancer Institute [RO1CA131945, P50 CA90381, RO1 5R01CA136578, R01CA141298]; Linda and Arthur Gelb Center for Translational Research; Prostate Cancer Foundation
NR 33
TC 414
Z9 480
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 FEB 10
PY 2011
VL 470
IS 7333
BP 269
EP +
DI 10.1038/nature09677
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200046
PM 21289624
DA 2026-03-09
ER

PT J
AU Gibbs, DJ
   Lee, SC
   Isa, NM
   Gramuglia, S
   Fukao, T
   Bassel, GW
   Correia, CS
   Corbineau, F
   Theodoulou, FL
   Bailey-Serres, J
   Holdsworth, MJ
AF Gibbs, Daniel J.
   Lee, Seung Cho
   Isa, Nurulhikma Md
   Gramuglia, Silvia
   Fukao, Takeshi
   Bassel, George W.
   Correia, Cristina Sousa
   Corbineau, Francoise
   Theodoulou, Frederica L.
   Bailey-Serres, Julia
   Holdsworth, Michael J.
TI Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants
SO NATURE
LA English
DT Article
ID submergence tolerance; arabidopsis-thaliana; protein; oxygen; rice; sensitivity; stress; degradation; adjustments; sensor
AB Plants and animals are obligate aerobes, requiring oxygen for mitochondrial respiration and energy production. In plants, an unanticipated decline in oxygen availability (hypoxia), as caused by roots becoming waterlogged or foliage submergence, triggers changes in gene transcription and messenger RNA translation that promote anaerobic metabolism and thus sustain substrate-level ATP production(1). In contrast to animals(2), oxygen sensing has not been ascribed to a mechanism of gene regulation in response to oxygen deprivation in plants. Here we show that the N-end rule pathway of targeted proteolysis acts as a homeostatic sensor of severe low oxygen levels in Arabidopsis, through its regulation of key hypoxia-response transcription factors. We found that plants lacking components of the N-end rule pathway constitutively express core hypoxia-response genes and are more tolerant of hypoxic stress. We identify the hypoxia-associated ethylene response factor group VII transcription factors of Arabidopsis as substrates of this pathway. Regulation of these proteins by the N-end rule pathway occurs through a characteristic conserved motif at the amino terminus initiating with Met-Cys. Enhanced stability of one of these proteins, HRE2, under low oxygen conditions improves hypoxia survival and reveals a molecular mechanism for oxygen sensing in plants via the evolutionarily conserved N-end rule pathway. SUB1A-1, a major determinant of submergence tolerance in rice(3), was shown not to be a substrate for the N-end rule pathway despite containing the N-terminal motif, indicating that it is uncoupled from N-end rule pathway regulation, and that enhanced stability may relate to the superior tolerance of Sub1 rice varieties to multiple abiotic stresses(4).
C1 [Gibbs, Daniel J.; Isa, Nurulhikma Md; Gramuglia, Silvia; Bassel, George W.; Correia, Cristina Sousa; Holdsworth, Michael J.] Univ Nottingham, Sch Biosci, Div Plant & Crop Sci, Loughborough LE12 5RD, Leics, England.
   [Gibbs, Daniel J.; Isa, Nurulhikma Md; Gramuglia, Silvia; Bassel, George W.; Correia, Cristina Sousa; Holdsworth, Michael J.] Univ Nottingham, Ctr Plant Integrat Biol, Loughborough LE12 5RD, Leics, England.
   [Lee, Seung Cho; Fukao, Takeshi; Bailey-Serres, Julia] Univ Calif Riverside, Ctr Plant Cell Biol, Riverside, CA 92521 USA.
   [Lee, Seung Cho; Fukao, Takeshi; Bailey-Serres, Julia] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Corbineau, Francoise] Univ Paris 06, CNRS, UPMC, EAC 7180 UR5, F-75005 Paris, France.
   [Theodoulou, Frederica L.] Rothamsted Res, Dept Biol Chem, Harpenden AL5 2JQ, Herts, England.
C3 University of Nottingham; University of Nottingham; University of California System; University of California Riverside; University of California System; University of California Riverside; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research
RP Holdsworth, MJ (corresponding author), Univ Nottingham, Sch Biosci, Div Plant & Crop Sci, Loughborough LE12 5RD, Leics, England.
EM serres@ucr.edu; michael.holdsworth@nottingham.ac.uk
FU BBSRC [BB/G010595/1]; Marie Curie International Incoming Fellowship; Malaysian government;  [NSF IOS-0750811];  [NIFA 2008-35100-04528]; BBSRC [BBS/E/C/00004948, BB/G010595/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/C/00004948, BB/G010595/1] Funding Source: researchfish
NR 38
TC 618
Z9 666
U1 6
U2 318
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 415
EP U172
DI 10.1038/nature10534
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700049
PM 22020279
DA 2026-03-09
ER

PT J
AU Saglamyurek, E
   Sinclair, N
   Jin, J
   Slater, JA
   Oblak, D
   Bussières, F
   George, M
   Ricken, R
   Sohler, W
   Tittel, W
AF Saglamyurek, Erhan
   Sinclair, Neil
   Jin, Jeongwan
   Slater, Joshua A.
   Oblak, Daniel
   Bussieres, Felix
   George, Mathew
   Ricken, Raimund
   Sohler, Wolfgang
   Tittel, Wolfgang
TI Broadband waveguide quantum memory for entangled photons
SO NATURE
LA English
DT Article
AB The reversible transfer of quantum states of light into and out of matter constitutes an important building block for future applications of quantum communication: it will allow the synchronization of quantum information(1), and the construction of quantum repeaters(2) and quantum networks(3). Much effort has been devoted to the development of such quantum memories(1), the key property of which is the preservation of entanglement during storage. Here we report the reversible transfer of photon-photon entanglement into entanglement between a photon and a collective atomic excitation in a solid-state device. Towards this end, we employ a thulium-doped lithium niobate waveguide in conjunction with a photon-echo quantum memory protocol(4), and increase the spectral acceptance from the current maximum(5) of 100 megahertz to 5 gigahertz. We assess the entanglement-preserving nature of our storage device through Bell inequality violations(6) and by comparing the amount of entanglement contained in the detected photon pairs before and after the reversible transfer. These measurements show, within statistical error, a perfect mapping process. Our broadband quantum memory complements the family of robust, integrated lithium niobate devices(7). It simplifies frequency-matching of light with matter interfaces in advanced applications of quantum communication, bringing fully quantum-enabled networks a step closer.
C1 [Saglamyurek, Erhan; Sinclair, Neil; Jin, Jeongwan; Slater, Joshua A.; Oblak, Daniel; Bussieres, Felix; Tittel, Wolfgang] Univ Calgary, Inst Quantum Informat Sci, Calgary, AB T2N 1N4, Canada.
   [Saglamyurek, Erhan; Sinclair, Neil; Jin, Jeongwan; Slater, Joshua A.; Oblak, Daniel; Bussieres, Felix; Tittel, Wolfgang] Univ Calgary, Dept Phys & Astron, Calgary, AB T2N 1N4, Canada.
   [George, Mathew; Ricken, Raimund; Sohler, Wolfgang] Univ Paderborn, Dept Phys Appl Phys, D-33095 Paderborn, Germany.
C3 University of Calgary; University of Calgary; University of Paderborn
RP Tittel, W (corresponding author), Univ Calgary, Inst Quantum Informat Sci, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.
EM wtittel@ucalgary.ca
FU NSERC; QuantumWorks; General Dynamics Canada; iCORE (now part of Alberta Innovates); CFI; AAET; FQRNT
NR 28
TC 500
Z9 540
U1 1
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 27
PY 2011
VL 469
IS 7331
BP 512
EP 515
DI 10.1038/nature09719
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500028
PM 21228775
DA 2026-03-09
ER

PT J
AU Cardinale, BJ
AF Cardinale, Bradley J.
TI Biodiversity improves water quality through niche partitioning
SO NATURE
LA English
DT Article
ID plant diversity; stream periphyton; patch dynamics; nitrogen; eutrophication; productivity; disturbance; ecology; nitrate; responses
AB Excessive nutrient loading of water bodies is a leading cause of water pollution worldwide(1,2), and controlling nutrient levels in watersheds is a primary objective of most environmental policy(3). Over the past two decades, much research has shown that ecosystems with more species are more efficient at removing nutrients from soil and water than are ecosystems with fewer species(4-7). This has led some to suggest that conservation of biodiversity might be a useful tool for managing nutrient uptake and storage(7-10), but this suggestion has been controversial, in part because the specific biological mechanisms by which species diversity influences nutrient uptake have not been identified(10-12). Here I use a model system of stream biofilms to show that niche partitioning among species of algae can increase the uptake and storage of nitrate, a nutrient pollutant of global concern. I manipulated the number of species of algae growing in the biofilms of 150 stream mesocosms that had been set up to mimic the variety of flow habitats and disturbance regimes that are typical of natural streams. Nitrogen uptake rates, as measured by using N-15-labelled nitrate, increased linearly with species richness and were driven by niche differences among species. As different forms of algae came to dominate each unique habitat in a stream, the more diverse communities achieved a higher biomass and greater N-15 uptake. When these niche opportunities were experimentally removed by making all of the habitats in a stream uniform, diversity did not influence nitrogen uptake, and biofilms collapsed to a single dominant species. These results provide direct evidence that communities with more species take greater advantage of the niche opportunities in an environment, and this allows diverse systems to capture a greater proportion of biologically available resources such as nitrogen. One implication is that biodiversity may help to buffer natural ecosystems against the ecological impacts of nutrient pollution.
C1 Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Cardinale, BJ (corresponding author), Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA.
EM bradcard@umich.edu
FU US National Science Foundation [DEB 0614428, DEB 1046121]; Direct For Biological Sciences [1046121, 1157992] Funding Source: National Science Foundation; Division Of Environmental Biology [1046121, 1157992] Funding Source: National Science Foundation
NR 49
TC 569
Z9 685
U1 15
U2 1048
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 86
EP U113
DI 10.1038/nature09904
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400042
PM 21475199
DA 2026-03-09
ER

PT J
AU Dellomonaco, C
   Clomburg, JM
   Miller, EN
   Gonzalez, R
AF Dellomonaco, Clementina
   Clomburg, James M.
   Miller, Elliot N.
   Gonzalez, Ramon
TI Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals
SO NATURE
LA English
DT Article
ID escherichia-coli; fatty-acids; clostridium-acetobutylicum; molecular characterization; glycolytic flux; metabolism; enzyme; genes; thiolase; growth
AB Advanced (long-chain) fuels and chemicals are generated from short-chain metabolic intermediates through pathways that require carbon-chain elongation. The condensation reactions mediating this carbon-carbon bond formation can be catalysed by enzymes from the thiolase superfamily, including beta-ketoacyl-acyl-carrier protein (ACP) synthases, polyketide synthases, 3-hydroxy-3-methylglutaryl-CoA synthases, and biosynthetic thiolases(1). Pathways involving these enzymes have been exploited for fuel and chemical production, with fatty-acid biosynthesis (beta-ketoacyl-ACP synthases) attracting the most attention in recent years(2-4). Degradative thiolases, which are part of the thiolase superfamily and naturally function in the beta-oxidation of fatty acids(5,6), can also operate in the synthetic direction and thus enable carbon-chain elongation. Here we demonstrate that a functional reversal of the beta-oxidation cycle can be used as a metabolic platform for the synthesis of alcohols and carboxylic acids with various chain lengths and functionalities. This pathway operates with coenzyme A (CoA) thioester intermediates and directly uses acetylCoA for acyl-chain elongation (rather than first requiring ATP-dependent activation to malonyl-CoA), characteristics that enable product synthesis at maximum carbon and energy efficiency. The reversal of the beta-oxidation cycle was engineered in Escherichia coli and used in combination with endogenous dehydrogenases and thioesterases to synthesize n-alcohols, fatty acids and 3-hydroxy-, 3-keto- and trans-Delta(2)-carboxylic acids. The superior nature of the engineered pathway was demonstrated by producing higher-chain linear n-alcohols (C >= 4) and extracellular long-chain fatty acids (C > 10) at higher efficiency than previously reported(2,4,7-9). The ubiquitous nature of beta-oxidation, aldehyde/alcohol dehydrogenase and thioesterase enzymes has the potential to enable the efficient synthesis of these products in other industrial organisms.
C1 [Dellomonaco, Clementina; Clomburg, James M.; Miller, Elliot N.; Gonzalez, Ramon] Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77005 USA.
   [Gonzalez, Ramon] Rice Univ, Dept Bioengn, Houston, TX 77005 USA.
C3 Rice University; Rice University
RP Gonzalez, R (corresponding author), Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77005 USA.
EM Ramon.Gonzalez@rice.edu
NR 40
TC 491
Z9 693
U1 8
U2 327
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 355
EP U131
DI 10.1038/nature10333
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500043
PM 21832992
DA 2026-03-09
ER

PT J
AU Kamiya, D
   Banno, S
   Sasai, N
   Ohgushi, M
   Inomata, H
   Watanabe, K
   Kawada, M
   Yakura, R
   Kiyonari, H
   Nakao, K
   Jakt, LM
   Nishikawa, S
   Sasai, Y
AF Kamiya, Daisuke
   Banno, Satoe
   Sasai, Noriaki
   Ohgushi, Masatoshi
   Inomata, Hidehiko
   Watanabe, Kiichi
   Kawada, Masako
   Yakura, Rieko
   Kiyonari, Hiroshi
   Nakao, Kazuki
   Jakt, Lars Martin
   Nishikawa, Shin-ichi
   Sasai, Yoshiki
TI Intrinsic transition of embryonic stem-cell differentiation into neural progenitors
SO NATURE
LA English
DT Article
ID zinc-finger protein; in-vitro; directed differentiation; nervous-system; motor-neurons; mouse embryo; es cells; induction; expression; signals
AB The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.
C1 [Kamiya, Daisuke; Banno, Satoe; Sasai, Noriaki; Ohgushi, Masatoshi; Inomata, Hidehiko; Watanabe, Kiichi; Kawada, Masako; Yakura, Rieko; Sasai, Yoshiki] RIKEN Ctr Dev Biol, Organogenesis & Neurogenesis Grp, Kobe, Hyogo 6500047, Japan.
   [Kamiya, Daisuke; Sasai, Yoshiki] Kyoto Univ, Grad Sch Med, Dept Med Embryol, Kyoto 6068501, Japan.
   [Kiyonari, Hiroshi; Nakao, Kazuki] RIKEN Ctr Dev Biol, Lab Anim Resource & Genet Engn, Kobe, Hyogo 6500047, Japan.
   [Jakt, Lars Martin; Nishikawa, Shin-ichi] RIKEN Ctr Dev Biol, Lab Stem Cell Res, Kobe, Hyogo 6500047, Japan.
C3 RIKEN; Kyoto University; RIKEN; RIKEN
RP Sasai, Y (corresponding author), RIKEN Ctr Dev Biol, Organogenesis & Neurogenesis Grp, Kobe, Hyogo 6500047, Japan.
EM yoshikisasai@cdb.riken.jp
FU MEXT; Kobe Cluster Project; Leading Project
NR 38
TC 177
Z9 212
U1 1
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 503
EP U92
DI 10.1038/nature09726
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900035
PM 21326203
DA 2026-03-09
ER

PT J
AU Li, WD
   Bloom, JS
   Podsiadlowski, P
   Miller, AA
   Cenko, SB
   Jha, SW
   Sullivan, M
   Howell, DA
   Nugent, PE
   Butler, NR
   Ofek, EO
   Kasliwal, MM
   Richards, JW
   Stockton, A
   Shih, HY
   Bildsten, L
   Shara, MM
   Bibby, J
   Filippenko, AV
   Ganeshalingam, M
   Silverman, JM
   Kulkarni, SR
   Law, NM
   Poznanski, D
   Quimby, RM
   McCully, C
   Patel, B
   Maguire, K
   Shen, KJ
AF Li, Weidong
   Bloom, Joshua S.
   Podsiadlowski, Philipp
   Miller, Adam A.
   Cenko, S. Bradley
   Jha, Saurabh W.
   Sullivan, Mark
   Howell, D. Andrew
   Nugent, Peter E.
   Butler, Nathaniel R.
   Ofek, Eran O.
   Kasliwal, Mansi M.
   Richards, Joseph W.
   Stockton, Alan
   Shih, Hsin-Yi
   Bildsten, Lars
   Shara, Michael M.
   Bibby, Joanne
   Filippenko, Alexei V.
   Ganeshalingam, Mohan
   Silverman, Jeffrey M.
   Kulkarni, S. R.
   Law, Nicholas M.
   Poznanski, Dovi
   Quimby, Robert M.
   McCully, Curtis
   Patel, Brandon
   Maguire, Kate
   Shen, Ken J.
TI Exclusion of a luminous red giant as a companion star to the progenitor of supernova SN 2011fe
SO NATURE
LA English
DT Article
ID white-dwarf models; ia supernovae; x-ray; recurrent novae; evolution; mass; binary; channel; distance; system
AB Type Ia supernovae are thought to result from a thermonuclear explosion of an accreting white dwarf in a binary system(1,2), but little is known of the precise nature of the companion star and the physical properties of the progenitor system. There are two classes of models(1,3): double-degenerate (involving two white dwarfs in a close binary system(2,4)) and single-degenerate models(5,6). In the latter, the primary white dwarf accretes material from a secondary companion until conditions are such that carbon ignites, at a mass of 1.38 times the mass of the Sun. The type Ia supernova SN 2011fe was recently detected in a nearby galaxy(7). Here we report an analysis of archival images of the location of SN 2011fe. The luminosity of the progenitor system (especially the companion star) is 10-100 times fainter than previous limits on other type Ia supernova progenitor systems(8-10), allowing us to rule out luminous red giants and almost all helium stars as the mass-donating companion to the exploding white dwarf.
C1 [Li, Weidong; Bloom, Joshua S.; Miller, Adam A.; Cenko, S. Bradley; Nugent, Peter E.; Richards, Joseph W.; Filippenko, Alexei V.; Ganeshalingam, Mohan; Silverman, Jeffrey M.; Shen, Ken J.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Podsiadlowski, Philipp; Sullivan, Mark; Maguire, Kate] Univ Oxford, Dept Phys Astrophys, Oxford OX1 3RH, England.
   [Jha, Saurabh W.; McCully, Curtis; Patel, Brandon] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Howell, D. Andrew] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Howell, D. Andrew; Bildsten, Lars] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Nugent, Peter E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Computat Cosmol Ctr, Berkeley, CA 94720 USA.
   [Butler, Nathaniel R.] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Ofek, Eran O.; Kulkarni, S. R.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Ofek, Eran O.] Weizmann Inst Sci, Fac Phys, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Kasliwal, Mansi M.] Carnegie Inst Sci, Pasadena, CA 91101 USA.
   [Richards, Joseph W.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Stockton, Alan; Shih, Hsin-Yi] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Bildsten, Lars] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Shara, Michael M.; Bibby, Joanne] Amer Museum Nat Hist, Dept Astrophys, New York, NY 10024 USA.
   [Law, Nicholas M.] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Quimby, Robert M.] Univ Tokyo, IPMU, Kashiwa, Chiba, Japan.
   [Poznanski, Dovi] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
C3 University of California System; University of California Berkeley; University of Oxford; Rutgers University System; Rutgers University New Brunswick; 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; Arizona State University; Arizona State University-Tempe; California Institute of Technology; Weizmann Institute of Science; Carnegie Institution for Science; University of California System; University of California Berkeley; University of Hawaii System; University of California System; University of California Santa Barbara; American Museum of Natural History (AMNH); University of Toronto; University of Tokyo; Tel Aviv University
RP Li, WD (corresponding author), Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
EM weidong@berkeley.edu
FU NASA; Carnegie-Princeton Fellowship; US National Science Foundation; Richard & Rhoda Goldman Fund; Sylvia and Jim Katzman Foundation; Gary and Cynthia Bengier; TABASGO Foundation; Hilary Lipsitz; American Museum of Natural History; Royal Society; W. M. Keck Foundation; STFC [ST/H002456/1] Funding Source: UKRI; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109174, 1009991] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009987] Funding Source: National Science Foundation; Office of Integrative Activities; Office Of The Director [0941742] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/H002456/1] Funding Source: researchfish
CR Di Stefano R, 2010, ASTROPHYS J, V719, P474, DOI 10.1088/0004-637X/719/1/474
   Di Stefano R, 2010, ASTROPHYS J, V712, P728, DOI 10.1088/0004-637X/712/1/728
   Fryer CL, 2010, ASTROPHYS J, V725, P296, DOI 10.1088/0004-637X/725/1/296
   Greiner J, 2000, NEW ASTRON, V5, P137, DOI 10.1016/S1384-1076(00)00018-X
   Hachisu I, 2001, ASTROPHYS J, V558, P323, DOI 10.1086/321601
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   IBEN I, 1984, ASTROPHYS J SUPPL S, V54, P335, DOI 10.1086/190932
   Kasen D, 2010, ASTROPHYS J, V708, P1025, DOI 10.1088/0004-637X/708/2/1025
   Liu WM, 2010, ASTRON ASTROPHYS, V523, P0, DOI 10.1051/0004-6361/201014180
   Maoz D, 2008, MON NOT R ASTRON SOC, V388, P421, DOI 10.1111/j.1365-2966.2008.13403.x
   MUNARI U, 1992, ASTROPHYS J, V397, PL87, DOI 10.1086/186551
   Nelemans G, 2008, MON NOT R ASTRON SOC, V388, P487, DOI 10.1111/j.1365-2966.2008.13416.x
   NOMOTO K, 1982, ASTROPHYS J, V253, P798, DOI 10.1086/159682
   Nomoto K, 1997, SCIENCE, V276, P1378, DOI 10.1126/science.276.5317.1378
   Podsiadlowski P, 2008, NEW ASTRON REV, V52, P381, DOI 10.1016/j.newar.2008.06.020
   Schaefer BE, 2010, ASTROPHYS J SUPPL S, V187, P275, DOI 10.1088/0067-0049/187/2/275
   Shappee BJ, 2011, ASTROPHYS J, V733, P0, DOI 10.1088/0004-637X/733/2/124
   Shen KJ, 2011, LONG TERM EVOLUTION, V0, P0
   Stetson PB, 1998, ASTROPHYS J, V508, P491, DOI 10.1086/306443
   Thoroughgood TD, 2001, MON NOT R ASTRON SOC, V327, P1323, DOI 10.1046/j.1365-8711.2001.04828.x
   Torres G, 2010, ASTRON J, V140, P1158, DOI 10.1088/0004-6256/140/5/1158
   VANDENHEUVEL EPJ, 1992, ASTRON ASTROPHYS, V262, P97
   Voss R, 2008, NATURE, V451, P802
   WEBBINK RF, 1984, ASTROPHYS J, V277, P355, DOI 10.1086/161701
   WHELAN J, 1973, ASTROPHYS J, V186, P1007, DOI 10.1086/152565
   Wizinowich PL, 2006, PUBL ASTRON SOC PAC, V118, P297, DOI 10.1086/499290
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   Yoon SC, 2007, MON NOT R ASTRON SOC, V380, P933, DOI 10.1111/j.1365-2966.2007.12161.x
   Yoon SC, 2003, ASTRON ASTROPHYS, V412, PL53, DOI 10.1051/0004-6361:20034607
NR 29
TC 270
Z9 304
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 348
EP 350
DI 10.1038/nature10646
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000046
PM 22170681
DA 2026-03-09
ER

PT J
AU Kamakura, M
AF Kamakura, Masaki
TI Royalactin induces queen differentiation in honeybees
SO NATURE
LA English
DT Article
ID cultured rat hepatocytes; apis-mellifera; enhances proliferation; caste differentiation; prothoracic gland; regulates growth; body-size; drosophila; proteins; family
AB The honeybee (Apis mellifera) forms two female castes: the queen and the worker. This dimorphism depends not on genetic differences, but on ingestion of royal jelly, although the mechanism through which royal jelly regulates caste differentiation has long remained unknown. Here I show that a 57-kDa protein in royal jelly, previously designated as royalactin, induces the differentiation of honeybee larvae into queens. Royalactin increased body size and ovary development and shortened developmental time in honeybees. Surprisingly, it also showed similar effects in the fruitfly (Drosophila melanogaster). Mechanistic studies revealed that royalactin activated p70 S6 kinase, which was responsible for the increase of body size, increased the activity of mitogen-activated protein kinase, which was involved in the decreased developmental time, and increased the titre of juvenile hormone, an essential hormone for ovary development. Knockdown of epidermal growth factor receptor (Egfr) expression in the fat body of honeybees and fruitflies resulted in a defect of all phenotypes induced by royalactin, showing that Egfr mediates these actions. These findings indicate that a specific factor in royal jelly, royalactin, drives queen development through an Egfr-mediated signalling pathway.
C1 Toyama Prefectural Univ, Biotechnol Res Ctr, Toyama 9390398, Japan.
C3 Toyama Prefectural University
RP Kamakura, M (corresponding author), Toyama Prefectural Univ, Biotechnol Res Ctr, Toyama 9390398, Japan.
EM kamakura@pu-toyama.ac.jp
NR 37
TC 486
Z9 611
U1 7
U2 337
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 478
EP 483
DI 10.1038/nature10093
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300033
PM 21516106
DA 2026-03-09
ER

PT J
AU Su, CC
   Long, F
   Zimmermann, MT
   Rajashankar, KR
   Jernigan, RL
   Yu, EW
AF Su, Chih-Chia
   Long, Feng
   Zimmermann, Michael T.
   Rajashankar, Kanagalaghatta R.
   Jernigan, Robert L.
   Yu, Edward W.
TI Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli
SO NATURE
LA English
DT Article
ID membrane-fusion protein; multidrug efflux; pseudomonas-aeruginosa; periplasmic component; pump; acrb; system; transporter; software; crystallography
AB Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals through tripartite efflux pumps that span both the inner and outer membrane. The three parts are an inner membrane, substrate-binding transporter; a membrane fusion protein; and an outer-membrane-anchored channel. The fusion protein connects the transporter to the channel within the periplasmic space. A crystallographic model of this tripartite efflux complex has been unavailable because co-crystallization of the various components of the system has proven to be extremely difficult. We previously described the crystal structures of both the inner membrane transporter CusA(1) and the membrane fusion protein CusB(2) of the CusCBA efflux system(3,4) of E. coli. Here we report the co-crystal structure of the CusBA efflux complex, showing that the transporter (or pump) CusA, which is present as a trimer, interacts with six CusB protomers and that the periplasmic domain of CusA is involved in these interactions. The six CusB molecules seem to form a continuous channel. The affinity of the CusA and CusB interaction was found to be in the micromolar range. Finally, we have predicted a three-dimensional structure for the trimeric CusC outer membrane channel and developed a model of the tripartite efflux assemblage. This CusC(3)-CusB(6)-CusA(3) model shows a 750-kilodalton efflux complex that spans the entire bacterial cell envelope and exports Cu I and Ag I ions.
C1 [Su, Chih-Chia; Long, Feng; Yu, Edward W.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
   [Zimmermann, Michael T.; Jernigan, Robert L.; Yu, Edward W.] Iowa State Univ, Bioinformat & Computat Biol Interdept Grad Progra, Ames, IA 50011 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Argonne Natl Lab, Dept Chem & Chem Biol, Argonne, IL 60439 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Argonne Natl Lab, NE CAT, Argonne, IL 60439 USA.
   [Jernigan, Robert L.; Yu, Edward W.] Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA.
   [Yu, Edward W.] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
C3 Iowa State University; Iowa State University; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Iowa State University; Iowa State University
RP Yu, EW (corresponding author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
EM ewyu@iastate.edu
FU National Institutes of Health [R01GM074027, R01GM086431, R01GM081680, R01GM072014]; National Center for Research Resources at the National Institutes of Health [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]
NR 33
TC 183
Z9 212
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 FEB 24
PY 2011
VL 470
IS 7335
BP 558
EP U153
DI 10.1038/nature09743
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900047
PM 21350490
DA 2026-03-09
ER

PT J
AU Kinnard, C
   Zdanowicz, CM
   Fisher, DA
   Isaksson, E
   de Vernal, A
   Thompson, LG
AF Kinnard, Christophe
   Zdanowicz, Christian M.
   Fisher, David A.
   Isaksson, Elisabeth
   de Vernal, Anne
   Thompson, Lonnie G.
TI Reconstructed changes in Arctic sea ice over the past 1,450 years
SO NATURE
LA English
DT Article
ID last millennium; climate; variability; regression; extent; bay
AB Arctic sea ice extent is now more than two million square kilometres less than it was in the late twentieth century, with important consequences for the climate, the ocean and traditional lifestyles in the Arctic(1,2). Although observations show a more or less continuous decline for the past four or five decades(3,4), there are few long-term records with which to assess natural sea ice variability. Until now, the question of whether or not current trends are potentially anomalous(5) has therefore remained unanswerable. Here we use a network of high-resolution terrestrial proxies from the circum-Arctic region to reconstruct past extents of summer sea ice, and show that-although extensive uncertainties remain, especially before the sixteenth century-both the duration and magnitude of the current decline in sea ice seem to be unprecedented for the past 1,450 years. Enhanced advection of warm Atlantic water to the Arctic(6) seems to be the main factor driving the decline of sea ice extent on multidecadal timescales, and may result from nonlinear feedbacks between sea ice and the Atlantic meridional overturning circulation. These results reinforce the assertion that sea ice is an active component of Arctic climate variability and that the recent decrease in summer Arctic sea ice is consistent with anthropogenically forced warming.
C1 [Kinnard, Christophe] Ctr Estudios Avanzados Zonas Aridas, La Serena 1720170, Chile.
   [Zdanowicz, Christian M.; Fisher, David A.] Geol Survey Canada, NRCAN, Ottawa, ON K1A 0E8, Canada.
   [Isaksson, Elisabeth] FRAM High N Res Ctr Climate & Environm, Norwegian Polar Res Inst, NO-9296 Tromso, Norway.
   [de Vernal, Anne] Univ Quebec, GEOTOP, Montreal, PQ H3C 3P8, Canada.
   [Thompson, Lonnie G.] Ohio State Univ, Byrd Polar Res Ctr, Columbus, OH 43210 USA.
C3 Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; Norwegian Polar Institute; University of Quebec; University of Quebec Montreal; University System of Ohio; Ohio State University
RP Kinnard, C (corresponding author), Ctr Estudios Avanzados Zonas Aridas, Benavente 980,Casilla 554, La Serena 1720170, Chile.
EM christophe.kinnard@ceaza.cl
FU Canadian Foundation for Climate and Atmospheric Sciences (Polar Climate Stability Network); Natural Sciences and Engineering Research Council of Canada
NR 38
TC 262
Z9 312
U1 0
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 509
EP U231
DI 10.1038/nature10581
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600046
PM 22113692
DA 2026-03-09
ER

PT J
AU Smith, SA
   Wilson, NG
   Goetz, FE
   Feehery, C
   Andrade, SCS
   Rouse, GW
   Giribet, G
   Dunn, CW
AF Smith, Stephen A.
   Wilson, Nerida G.
   Goetz, Freya E.
   Feehery, Caitlin
   Andrade, Sonia C. S.
   Rouse, Greg W.
   Giribet, Gonzalo
   Dunn, Casey W.
TI Resolving the evolutionary relationships of molluscs with phylogenomic tools
SO NATURE
LA English
DT Article
ID cephalopoda; monoplacophoran; reconstruction; aplacophora; algorithms; alignment; genm; chitons; radula; fossil
AB Molluscs (snails, octopuses, clams and their relatives) have a great disparity of body plans and, among the animals, only arthropods surpass them in species number. This diversity has made Mollusca one of the best-studied groups of animals, yet their evolutionary relationships remain poorly resolved(1). Open questions have important implications for the origin of Mollusca and for morphological evolution within the group. These questions include whether the shell-less, vermiform aplacophoran molluscs diverged before the origin of the shelled molluscs (Conchifera)(2-4) or lost their shells secondarily. Monoplacophorans were not included in molecular studies until recently(5,6), when it was proposed that they constitute a clade named Serialia together with Polyplacophora (chitons), reflecting the serial repetition of body organs in both groups(5). Attempts to understand the early evolution of molluscs become even more complex when considering the large diversity of Cambrian fossils. These can have multiple dorsal shell plates and sclerites(7-10) or can be shell-less but with a typical molluscan radula and serially repeated gills(11). To better resolve the relationships among molluscs, we generated transcriptome data for 15 species that, in combination with existing data, represent for the first time all major molluscan groups. We analysed multiple data sets containing up to 216,402 sites and 1,185 gene regions using multiple models and methods. Our results support the clade Aculifera, containing the three molluscan groups with spicules but without true shells, and they support the monophyly of Conchifera. Monoplacophora is not the sister group to other Conchifera but to Cephalopoda. Strong support is found for a clade that comprises Scaphopoda (tusk shells), Gastropoda and Bivalvia, with most analyses placing Scaphopoda and Gastropoda as sister groups. This well-resolved tree will constitute a framework for further studies of mollusc evolution, development and anatomy.
C1 [Wilson, Nerida G.] Australian Museum, Sydney, NSW 2010, Australia.
   [Smith, Stephen A.; Goetz, Freya E.; Feehery, Caitlin; Dunn, Casey W.] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02912 USA.
   [Smith, Stephen A.] Heidelberg Inst Theoret Studies, D-69118 Heidelberg, Germany.
   [Wilson, Nerida G.; Feehery, Caitlin; Rouse, Greg W.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Andrade, Sonia C. S.; Giribet, Gonzalo] Harvard Univ, Dept Organism & Evolutionary Biol, Museum Comparat Zool, Cambridge, MA 02138 USA.
C3 Australian Museum; Brown University; Heidelberg Institute for Theoretical Studies; University of California System; University of California San Diego; Scripps Institution of Oceanography; Harvard University
RP Wilson, NG (corresponding author), Australian Museum, Sydney, NSW 2010, Australia.
EM nerida.wilson@austmus.gov.au; ggiribet@oeb.harvard.edu; casey_dunn@brown.edu
FU US National Science Foundation [0844596, 0844881, 0844652]; AToL Program [EF-0531757]; EPSCoR (Infrastructure to Advance Life Sciences in the Ocean State) [1004057]; iPlant Collaborative [0735191]; Scripps Institution of Oceanography; University of California Ship Funds; Museum of Comparative Zoology; Carlsberg Foundation; Direct For Biological Sciences; Division Of Environmental Biology [0844652] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0735191] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0844596, 0844881] Funding Source: National Science Foundation; Office of Integrative Activities; Office Of The Director [1004057] Funding Source: National Science Foundation
NR 45
TC 357
Z9 408
U1 2
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 364
EP U114
DI 10.1038/nature10526
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000050
PM 22031330
DA 2026-03-09
ER

PT J
AU Shukla, S
   Kavak, E
   Gregory, M
   Imashimizu, M
   Shutinoski, B
   Kashlev, M
   Oberdoerffer, P
   Sandberg, R
   Oberdoerffer, S
AF Shukla, Sanjeev
   Kavak, Ersen
   Gregory, Melissa
   Imashimizu, Masahiko
   Shutinoski, Bojan
   Kashlev, Mikhail
   Oberdoerffer, Philipp
   Sandberg, Rickard
   Oberdoerffer, Shalini
TI CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing
SO NATURE
LA English
DT Article
ID insulator protein ctcf; binding-sites; zinc fingers; cd45; transcription; identification; elongation; expression; repressor; sequences
AB Alternative splicing of pre-messenger RNA is a key feature of transcriptome expansion in eukaryotic cells, yet its regulation is poorly understood. Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may directly influence alternative splicing. Supporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns. Moreover, the rate of transcription elongation has been linked to alternative splicing. Here we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide. We further show that CTCF binding to CD45 exon 5 is inhibited by DNA methylation, leading to reciprocal effects on exon 5 inclusion. These findings provide a mechanistic basis for developmental regulation of splicing outcome through heritable epigenetic marks.
C1 [Shukla, Sanjeev; Gregory, Melissa; Shutinoski, Bojan; Oberdoerffer, Philipp; Oberdoerffer, Shalini] Natl Canc Inst Frederick, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
   [Kavak, Ersen; Sandberg, Rickard] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
   [Kavak, Ersen; Sandberg, Rickard] Ludwig Inst Canc Res, SE-17177 Stockholm, Sweden.
   [Imashimizu, Masahiko; Kashlev, Mikhail] Natl Canc Inst Frederick, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Karolinska Institutet; Ludwig Institute for Cancer Research; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Oberdoerffer, S (corresponding author), Natl Canc Inst Frederick, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
EM shalini.oberdoerffer@nih.gov
FU NIH, the National Cancer Institute, The Center for Cancer Research; Swedish Research Council Foundation; Foundation for Strategic Research; National Cancer Institute [ZIABC010795] Funding Source: NIH RePORTER
NR 54
TC 763
Z9 962
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 74
EP U99
DI 10.1038/nature10442
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600034
PM 21964334
DA 2026-03-09
ER

PT J
AU Becken, M
   Ritter, O
   Bedrosian, PA
   Weckmann, U
AF Becken, Michael
   Ritter, Oliver
   Bedrosian, Paul A.
   Weckmann, Ute
TI Correlation between deep fluids, tremor and creep along the central San Andreas fault
SO NATURE
LA English
DT Article
ID magnetotelluric data; electrical-resistivity; internal structure; new-zealand; california; beneath; parkfield; crust; permeability; serpentinite
AB The seismicity pattern along the San Andreas fault near Parkfield and Cholame, California, varies distinctly over a length of only fifty kilometres. Within the brittle crust, the presence of frictionally weak minerals, fault-weakening high fluid pressures and chemical weakening are considered possible causes of an anomalously weak fault northwest of Parkfield(1-4). Non-volcanic tremor from lower-crustal and upper-mantle depths(5-7) is most pronounced about thirty kilometres southeast of Parkfield and is thought to be associated with high pore-fluid pressures at depth(8). Here we present geophysical evidence of fluids migrating into the creeping section of the San Andreas fault that seem to originate in the region of the uppermost mantle that also stimulates tremor, and evidence that along-strike variations in tremor activity and amplitude are related to strength variations in the lower crust and upper mantle. Interconnected fluids can explain a deep zone of anomalously low electrical resistivity that has been imaged by magnetotelluric data southwest of the Parkfield-Cholame segment. Near Cholame, where fluids seem to be trapped below a high-resistivity cap, tremor concentrates adjacent to the inferred fluids within a mechanically strong zone of high resistivity. By contrast, sub-vertical zones of low resistivity breach the entire crust near the drill hole of the San Andreas Fault Observatory at Depth, northwest of Parkfield, and imply pathways for deep fluids into the eastern fault block, coincident with a mechanically weak crust and the lower tremor amplitudes in the lower crust. Fluid influx to the fault system is consistent with hypotheses of fault-weakening high fluid pressures in the brittle crust.
C1 [Becken, Michael; Weckmann, Ute] Univ Potsdam, Inst Geosci, D-14476 Potsdam, Germany.
   [Bedrosian, Paul A.] US Geol Survey, Denver, CO 80225 USA.
   [Becken, Michael; Ritter, Oliver; Weckmann, Ute] GFZ German Res Ctr Geosci, D-14473 Potsdam, Germany.
C3 University of Potsdam; United States Department of the Interior; United States Geological Survey; Helmholtz Association; GFZ Helmholtz Centre for Geosciences
RP Becken, M (corresponding author), Univ Munster, Inst Geophys, D-48149 Munster, Germany.
EM michael.becken@uni-muenster.de
FU German Science Foundation (DFG); Helmholtz Centre Potsdam GFZ German Research Centre for Geosciences
NR 44
TC 198
Z9 219
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 DEC 1
PY 2011
VL 480
IS 7375
BP 87
EP U248
DI 10.1038/nature10609
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900039
PM 22129729
DA 2026-03-09
ER

PT J
AU Connors, M
   Wiegert, P
   Veillet, C
AF Connors, Martin
   Wiegert, Paul
   Veillet, Christian
TI Earth's Trojan asteroid
SO NATURE
LA English
DT Article
ID infrared-survey-explorer; co-orbitals
AB It was realized in 1772 that small bodies can stably share the same orbit as a planet if they remain near 'triangular points' 60 degrees ahead of or behind it in the orbit(1). Such 'Trojan asteroids' have been found co-orbiting with Jupiter(2), Mars(3) and Neptune(4). They have not hitherto been found associated with Earth, where the viewing geometry poses difficulties for their detection(5), although other kinds of co-orbital asteroid (horseshoe orbiters(6) and quasi-satellites(7)) have been observed(8). Here we report an archival search of infrared data for possible Earth Trojans, producing the candidate 2010 TK7. We subsequently made optical observations which established that 2010 TK7 is a Trojan companion of Earth, librating around the leading Lagrange triangular point, L-4. Its orbit is stable over at least ten thousand years.
C1 [Connors, Martin] Athabasca Univ, Athabasca, AB T9S 3A3, Canada.
   [Connors, Martin] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Wiegert, Paul] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
   [Veillet, Christian] Canada France Hawaii Telescope Corp, Kamuela, HI 96743 USA.
C3 Athabasca University; University of California System; University of California Los Angeles; Western University (University of Western Ontario); Canada France Hawaii Telescope
RP Connors, M (corresponding author), Athabasca Univ, 1 Univ Dr, Athabasca, AB T9S 3A3, Canada.
EM martinc@athabascau.ca
FU Canada's Natural Sciences and Engineering Research Council; Canada's Research Chairs
NR 27
TC 119
Z9 135
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 481
EP 483
DI 10.1038/nature10233
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900036
PM 21796207
DA 2026-03-09
ER

PT J
AU Kormendy, J
   Bender, R
AF Kormendy, John
   Bender, Ralf
TI Supermassive black holes do not correlate with dark matter haloes of galaxies
SO NATURE
LA English
DT Article
ID spiral galaxy; fundamental relation; velocity dispersion; star-clusters; quasars; mass; spectroscopy; evolution; nuclei; origin
AB Supermassive black holes have been detected in all galaxies that contain bulge components when the galaxies observed were close enough that the searches were feasible. Together with the observation that bigger black holes live in bigger bulges(1-4), this has led to the belief that black-hole growth and bulge formation regulate each other(5). That is, black holes and bulges coevolve. Therefore, reports(6,7) of a similar correlation between black holes and the dark matter haloes in which visible galaxies are embedded have profound implications. Dark matter is likely to be non-baryonic, so these reports suggest that unknown, exotic physics controls black-hole growth. Here we show, in part on the basis of recent measurements(8) of bulgeless galaxies, that there is almost no correlation between dark matter and parameters that measure black holes unless the galaxy also contains a bulge. We conclude that black holes do not correlate directly with dark matter. They do not correlate with galaxy disks, either(9,10). Therefore, black holes coevolve only with bulges. This simplifies the puzzle of their coevolution by focusing attention on purely baryonic processes in the galaxy mergers that make bulges(11).
C1 [Kormendy, John] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Kormendy, John; Bender, Ralf] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Kormendy, John; Bender, Ralf] Univ Sternwarte, D-81679 Munich, Germany.
C3 University of Texas System; University of Texas Austin; Max Planck Society; University of Munich
RP Kormendy, J (corresponding author), Univ Texas Austin, Dept Astron, 1 Univ Stn, Austin, TX 78712 USA.
EM kormendy@astro.as.utexas.edu
FU National Science Foundation
NR 31
TC 116
Z9 128
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 JAN 20
PY 2011
VL 469
IS 7330
BP 377
EP 380
DI 10.1038/nature09695
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600047
PM 21248846
DA 2026-03-09
ER

PT J
AU Bos, KI
   Schuenemann, VJ
   Golding, GB
   Burbano, HA
   Waglechner, N
   Coombes, BK
   McPhee, JB
   DeWitte, SN
   Meyer, M
   Schmedes, S
   Wood, J
   Earn, DJD
   Herring, DA
   Bauer, P
   Poinar, HN
   Krause, J
AF Bos, Kirsten I.
   Schuenemann, Verena J.
   Golding, G. Brian
   Burbano, Hernan A.
   Waglechner, Nicholas
   Coombes, Brian K.
   McPhee, Joseph B.
   DeWitte, Sharon N.
   Meyer, Matthias
   Schmedes, Sarah
   Wood, James
   Earn, David J. D.
   Herring, D. Ann
   Bauer, Peter
   Poinar, Hendrik N.
   Krause, Johannes
TI A draft genome of Yersinia pestis from victims of the Black Death
SO NATURE
LA English
DT Article
ID evolution; sequence; dynamics; patterns; lost
AB Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard(1). This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organismis ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.
C1 [Schuenemann, Verena J.; Krause, Johannes] Univ Tubingen, Inst Archaeol Sci, D-72070 Tubingen, Germany.
   [Bos, Kirsten I.; Poinar, Hendrik N.] McMaster Univ, Dept Anthropol, McMaster Ancient DNA Ctr, Hamilton, ON L8S 4L8, Canada.
   [Golding, G. Brian; Poinar, Hendrik N.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4L8, Canada.
   [Burbano, Hernan A.; Meyer, Matthias] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Waglechner, Nicholas; Coombes, Brian K.; McPhee, Joseph B.; Earn, David J. D.; Poinar, Hendrik N.] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4L8, Canada.
   [DeWitte, Sharon N.] Univ S Carolina, Dept Anthropol, Columbia, SC 29208 USA.
   [DeWitte, Sharon N.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
   [Schmedes, Sarah] Univ N Texas, Hlth Sci Ctr, Inst Appl Genet, Ft Worth, TX 76107 USA.
   [Wood, James] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA.
   [Wood, James] Penn State Univ, Populat Res Inst, University Pk, PA 16802 USA.
   [Earn, David J. D.] McMaster Univ, Dept Math & Stat, Hamilton, ON L8S 4K1, Canada.
   [Bauer, Peter; Krause, Johannes] Univ Tubingen, Fac Med, Dept Human Genet, D-72070 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; McMaster University; McMaster University; Max Planck Society; McMaster University; University of South Carolina System; University of South Carolina Columbia; University of South Carolina System; University of South Carolina Columbia; University of North Texas System; University of North Texas Health Science Center; 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; McMaster University; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital
RP Krause, J (corresponding author), Univ Tubingen, Inst Archaeol Sci, Rumelinstr 23, D-72070 Tubingen, Germany.
EM poinarh@mcmaster.ca; johannes.krause@uni-tuebingen.de
FU McMaster Ancient DNA Centre; Carl Zeiss Foundation; Human Genetics department of the Medical faculty in Tubingen; Canada Research Chairs program; Canadian Institute for Health Research; Social Science and Humanities Research Council of Canada; Michael G. DeGroote Institute for Infectious Disease Research; Ontario Ministry of Research and Education; Natural Sciences and Engineering Research Council of Canada; James S. McDonnell Foundation; University at Albany Research Foundation and Center for Social and Demographic Analysis; Wenner-Gren Foundation
NR 28
TC 522
Z9 589
U1 3
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 OCT 27
PY 2011
VL 478
IS 7370
BP 506
EP 510
DI 10.1038/nature10549
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200041
PM 21993626
DA 2026-03-09
ER

PT J
AU Notta, F
   Mullighan, CG
   Wang, JCY
   Poeppl, A
   Doulatov, S
   Phillips, LA
   Ma, J
   Minden, MD
   Downing, JR
   Dick, JE
AF Notta, Faiyaz
   Mullighan, Charles G.
   Wang, Jean C. Y.
   Poeppl, Armando
   Doulatov, Sergei
   Phillips, Letha A.
   Ma, Jing
   Minden, Mark D.
   Downing, James R.
   Dick, John E.
TI Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; intrafemoral transplantation; pancreatic-cancer; clonal evolution; number; genome; heterogeneity; deletion; engraftment; metastasis
AB Many tumours are composed of genetically diverse cells; however, little is known about how diversity evolves or the impact that diversity has on functional properties. Here, using xenografting and DNA copy number alteration (CNA) profiling of human BCR-ABL1 lymphoblastic leukaemia, we demonstrate that genetic diversity occurs in functionally defined leukaemia-initiating cells and that many diagnostic patient samples contain multiple genetically distinct leukaemia-initiating cell subclones. Reconstructing the subclonal genetic ancestry of several samples by CNA profiling demonstrated a branching multi-clonal evolution model of leukaemogenesis, rather than linear succession. For some patient samples, the predominant diagnostic clone repopulated xenografts, whereas in others it was outcompeted by minor subclones. Reconstitution with the predominant diagnosis clone was associated with more aggressive growth properties in xenografts, deletion of CDKN2A and CDKN2B, and a trend towards poorer patient outcome. Our findings link clonal diversity with leukaemia-initiating-cell function and underscore the importance of developing therapies that eradicate all intratumoral subclones.
C1 [Notta, Faiyaz; Wang, Jean C. Y.; Poeppl, Armando; Doulatov, Sergei; Dick, John E.] Ontario Canc Inst, Campbell Family Inst Canc Res, Div Stem Cell & Dev Biol, Toronto, ON M5G 1L7, Canada.
   [Notta, Faiyaz; Doulatov, Sergei; Dick, John E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada.
   [Mullighan, Charles G.; Phillips, Letha A.; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Wang, Jean C. Y.; Minden, Mark D.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada.
   [Wang, Jean C. Y.; Minden, Mark D.] Univ Toronto, Dept Med, Toronto, ON M5G 2M9, Canada.
   [Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
C3 University of Toronto; University Health Network Toronto; University of Toronto; St Jude Children's Research Hospital; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; St Jude Children's Research Hospital
RP Dick, JE (corresponding author), Ontario Canc Inst, Campbell Family Inst Canc Res, Div Stem Cell & Dev Biol, Toronto, ON M5G 1L7, Canada.
EM jdick@uhnres.utoronto.ca
FU Canadian Institutes for Health Research (CIHR); Pew Charitable Trusts; Stem Cell Network of Canadian National Centres of Excellence; Canadian Cancer Society; Terry Fox Foundation, Genome Canada through the Ontario Genomics Institute; Ontario Institute for Cancer Research; province of Ontario; Leukemia and Lymphoma Society; Canadian Institutes for Health Research; Canada Research Chair; American and Lebanese Syrian Associated Charities of St Jude Children's Research Hospital; Ontario Ministry of Health and Long Term Care (OMOHLTC)
NR 34
TC 379
Z9 435
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 20
PY 2011
VL 469
IS 7330
BP 362
EP +
DI 10.1038/nature09733
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600044
PM 21248843
DA 2026-03-09
ER

PT J
AU Lissauer, JJ
   Fabrycky, DC
   Ford, EB
   Borucki, WJ
   Fressin, F
   Marcy, GW
   Orosz, JA
   Rowe, JF
   Torres, G
   Welsh, WF
   Batalha, NM
   Bryson, ST
   Buchhave, LA
   Caldwell, DA
   Carter, JA
   Charbonneau, D
   Christiansen, JL
   Cochran, W
   Desert, JM
   Dunham, EW
   Fanelli, MN
   Fortney, JJ
   Gautier, TN
   Geary, JC
   Gilliland, RL
   Haas, MR
   Hall, JR
   Holman, MJ
   Koch, DG
   Latham, DW
   Lopez, E
   McCauliff, S
   Miller, N
   Morehead, RC
   Quintana, EV
   Ragozzine, D
   Sasselov, D
   Short, DR
   Steffen, JH
AF Lissauer, Jack J.
   Fabrycky, Daniel C.
   Ford, Eric B.
   Borucki, William J.
   Fressin, Francois
   Marcy, Geoffrey W.
   Orosz, Jerome A.
   Rowe, Jason F.
   Torres, Guillermo
   Welsh, William F.
   Batalha, Natalie M.
   Bryson, Stephen T.
   Buchhave, Lars A.
   Caldwell, Douglas A.
   Carter, Joshua A.
   Charbonneau, David
   Christiansen, Jessie L.
   Cochran, WilliamD.
   Desert, Jean-Michel
   Dunham, Edward W.
   Fanelli, Michael N.
   Fortney, Jonathan J.
   Gautier, Thomas N., III
   Geary, John C.
   Gilliland, Ronald L.
   Haas, Michael R.
   Hall, Jennifer R.
   Holman, Matthew J.
   Koch, David G.
   Latham, David W.
   Lopez, Eric
   McCauliff, Sean
   Miller, Neil
   Morehead, Robert C.
   Quintana, Elisa V.
   Ragozzine, Darin
   Sasselov, Dimitar
   Short, Donald R.
   Steffen, Jason H.
TI A closely packed system of low-mass, low-density planets transiting Kepler-11
SO NATURE
LA English
DT Article
ID extrasolar planets; super-earths; stars; performance; evaporation; isochrones; dynamics; neptunes; jupiters; science
AB When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47 days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation.
C1 [Lissauer, Jack J.; Rowe, Jason F.; Caldwell, Douglas A.; Christiansen, Jessie L.; Quintana, Elisa V.] NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA.
   [Fabrycky, Daniel C.; Fortney, Jonathan J.; Lopez, Eric; Miller, Neil] Univ Calif Santa Cruz, Univ Calif Observ, Lick Observ, Santa Cruz, CA 95064 USA.
   [Ford, Eric B.; Morehead, Robert C.] Univ Florida, Bryant Space Sci Ctr 211, Gainesville, FL 32611 USA.
   [Fressin, Francois; Torres, Guillermo; Carter, Joshua A.; Charbonneau, David; Desert, Jean-Michel; Geary, John C.; Holman, Matthew J.; Latham, David W.; Ragozzine, Darin; Sasselov, Dimitar] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Marcy, Geoffrey W.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Orosz, Jerome A.; Welsh, William F.; Short, Donald R.] San Diego State Univ, San Diego, CA 92182 USA.
   [Batalha, Natalie M.] San Jose State Univ, Dept Phys & Astron, San Jose, CA 95192 USA.
   [Buchhave, Lars A.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Cochran, WilliamD.] Univ Texas Austin, McDonald Observ, Austin, TX 78712 USA.
   [Dunham, Edward W.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [Fanelli, Michael N.] NASA, Ames Res Ctr, Bay Area Environm Res Inst, Moffett Field, CA 94035 USA.
   [Gautier, Thomas N., III] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Gilliland, Ronald L.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Hall, Jennifer R.; McCauliff, Sean] NASA, Ames Res Ctr, Orbital Sci Corp, Moffett Field, CA 94035 USA.
   [Steffen, Jason H.] Fermilab Ctr Particle Astrophys, Batavia, IL 60510 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Ames Research Center; SETI Institute; University of California System; University of California Santa Cruz; State University System of Florida; University of Florida; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; University of California System; University of California Berkeley; California State University System; San Diego State University; California State University System; San Jose State University; University of Copenhagen; Niels Bohr Institute; University of Texas System; University of Texas Austin; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Space Telescope Science Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Orbital Sciences Corporation
RP Lissauer, JJ (corresponding author), NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA.
EM jack.lissauer@nasa.gov; fabrycky@ucolick.org
FU NASA [HF-51272.01-A, HF-51267.01-A]; STScl [NAS 5-26555]
NR 35
TC 525
Z9 595
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 53
EP 58
DI 10.1038/nature09760
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400032
PM 21293371
DA 2026-03-09
ER

PT J
AU Sato, T
   van Es, JH
   Snippert, HJ
   Stange, DE
   Vries, RG
   van den Born, M
   Barker, N
   Shroyer, NF
   van de Wetering, M
   Clevers, H
AF Sato, Toshiro
   van Es, Johan H.
   Snippert, Hugo J.
   Stange, Daniel E.
   Vries, Robert G.
   van den Born, Maaike
   Barker, Nick
   Shroyer, Noah F.
   van de Wetering, Marc
   Clevers, Hans
TI Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
SO NATURE
LA English
DT Article
ID beta-catenin; adult-mouse; epithelium; differentiation; gene; expression; cancer; math1; colon; sox9
AB Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms(1,2). Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins(3). Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells(4). Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24(+) Paneth cells express EGF, TGF-alpha, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell.
C1 [Sato, Toshiro; van Es, Johan H.; Snippert, Hugo J.; Stange, Daniel E.; Vries, Robert G.; van den Born, Maaike; Barker, Nick; van de Wetering, Marc; Clevers, Hans] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [Sato, Toshiro; van Es, Johan H.; Snippert, Hugo J.; Stange, Daniel E.; Vries, Robert G.; van den Born, Maaike; Barker, Nick; van de Wetering, Marc; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Shroyer, Noah F.] Cincinnati Childrens Hosp, Div Gastroenterol, Med Ctr, MLC 2010, Cincinnati, OH 45229 USA.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Cincinnati Children's Hospital Medical Center
RP Clevers, H (corresponding author), KNAW, Hubrecht Inst, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM h.clevers@hubrecht.eu
FU NCI NIH HHS [R01 CA142826] Funding Source: Medline; NIDDK NIH HHS [R03 DK084167] Funding Source: Medline
NR 29
TC 2018
Z9 2469
U1 15
U2 505
PU NATURE PUBLISHING 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 20
PY 2011
VL 469
IS 7330
BP 415
EP +
DI 10.1038/nature09637
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600056
PM 21113151
DA 2026-03-09
ER

PT J
AU Yeretssian, G
   Correa, RG
   Doiron, K
   Fitzgerald, P
   Dillon, CP
   Green, DR
   Reed, JC
   Saleh, M
AF Yeretssian, Garabet
   Correa, Ricardo G.
   Doiron, Karine
   Fitzgerald, Patrick
   Dillon, Christopher P.
   Green, Douglas R.
   Reed, John C.
   Saleh, Maya
TI Non-apoptotic role of BID in inflammation and innate immunity
SO NATURE
LA English
DT Article
ID family-member; cell-death; kappa-b; protein; activation; nod1; bcl-2; recognition; mechanism; binding
AB Innate immunity is a fundamental defence response that depends on evolutionarily conserved pattern recognition receptors for sensing infections or danger signals(1,2). Nucleotide-binding and oligomerization domain (NOD) proteins are cytosolic pattern-recognition receptors of paramount importance in the intestine, and their dysregulation is associated with inflammatory bowel disease(3,4). They sense peptidoglycans from commensal microorganisms and pathogens and coordinate signalling events that culminate in the induction of inflammation and anti-microbial responses(2). However, the signalling mechanisms involved in this process are not fully understood. Here, using genome-wide RNA interference, we identify candidate genes that modulate the NOD1 inflammatory response in intestinal epithelial cells. Our results reveal a significant crosstalk between innate immunity and apoptosis and identify BID, a BCL2 family protein, as a critical component of the inflammatory response. Colonocytes depleted of BID or macrophages from Bid(-/-) mice are markedly defective in cytokine production in response to NOD activation. Furthermore, Bid(-/-) mice are unresponsive to local or systemic exposure to NOD agonists or their protective effect in experimental colitis. Mechanistically, BID interacts with NOD1, NOD2 and the I kappa B kinase (IKK) complex, impacting NF-kappa B and extracellular signal-regulated kinase (ERK) signalling. Our results define a novel role of BID in inflammation and immunity independent of its apoptotic function, furthering the mounting evidence of evolutionary conservation between the mechanisms of apoptosis and immunity.
C1 [Yeretssian, Garabet; Doiron, Karine; Saleh, Maya] McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada.
   [Correa, Ricardo G.; Reed, John C.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Fitzgerald, Patrick; Dillon, Christopher P.; Green, Douglas R.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
C3 McGill University; Sanford Burnham Prebys Medical Discovery Institute; St Jude Children's Research Hospital
RP Saleh, M (corresponding author), McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada.
EM maya.saleh@mcgill.ca
FU Canadian Institutes for Health Research [CIHR-MOP 82801]; Burroughs Wellcome Fund; McGill University Health Center; SASS Foundation for Medical Research
NR 36
TC 95
Z9 107
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 JUN 2
PY 2011
VL 474
IS 7349
BP 96
EP U126
DI 10.1038/nature09982
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700045
PM 21552281
DA 2026-03-09
ER

PT J
AU Wang, K
   Diskin, SJ
   Zhang, HT
   Attiyeh, EF
   Winter, C
   Hou, CP
   Schnepp, RW
   Diamond, M
   Bosse, K
   Mayes, PA
   Glessner, J
   Kim, C
   Frackelton, E
   Garris, M
   Wang, Q
   Glaberson, W
   Chiavacci, R
   Nguyen, L
   Jagannathan, J
   Saeki, N
   Sasaki, H
   Grant, SFA
   Iolascon, A
   Mosse, YP
   Cole, KA
   Li, HZ
   Devoto, M
   McGrady, PW
   London, WB
   Capasso, M
   Rahman, N
   Hakonarson, H
   Maris, JM
AF Wang, Kai
   Diskin, Sharon J.
   Zhang, Haitao
   Attiyeh, Edward F.
   Winter, Cynthia
   Hou, Cuiping
   Schnepp, Robert W.
   Diamond, Maura
   Bosse, Kristopher
   Mayes, Patrick A.
   Glessner, Joseph
   Kim, Cecilia
   Frackelton, Edward
   Garris, Maria
   Wang, Qun
   Glaberson, Wendy
   Chiavacci, Rosetta
   Nguyen, Le
   Jagannathan, Jayanti
   Saeki, Norihisa
   Sasaki, Hiroki
   Grant, Struan F. A.
   Iolascon, Achille
   Mosse, Yael P.
   Cole, Kristina A.
   Li, Hongzhe
   Devoto, Marcella
   McGrady, Patrick W.
   London, Wendy B.
   Capasso, Mario
   Rahman, Nazneen
   Hakonarson, Hakon
   Maris, John M.
TI Integrative genomics identifies LMO1 as a neuroblastoma oncogene
SO NATURE
LA English
DT Article
ID copy number; chromosomal translocations; activating mutations; alk kinase; gene; transcription; cancer; interacts; target; cells
AB Neuroblastoma is a childhood cancer of the sympathetic nervous system that accounts for approximately 10% of all paediatric oncology deaths(1,2). To identify genetic risk factors for neuroblastoma, we performed a genome-wide association study (GWAS) on 2,251 patients and 6,097 control subjects of European ancestry from four case series. Here we report a significant association within LIM domain only 1 (LMO1) at 11p15.4 (rs110419, combined P = 5.2 x 10(-16), odds ratio of risk allele = 1.34 (95% confidence interval 1.25-1.44)). The signal was enriched in the subset of patients with the most aggressive form of the disease. LMO1 encodes a cysteine-rich transcriptional regulator, and its paralogues (LMO2, LMO3 and LMO4) have each been previously implicated in cancer. In parallel, we analysed genome-wide DNA copy number alterations in 701 primary tumours. We found that the LMO1 locus was aberrant in 12.4% through a duplication event, and that this event was associated with more advanced disease (P < 0.0001) and survival (P = 0.041). The germline single nucleotide polymorphism (SNP) risk alleles and somatic copy number gains were associated with increased LMO1 expression in neuroblastoma cell lines and primary tumours, consistent with a gain-of-function role in tumorigenesis. Short hairpin RNA (shRNA)-mediated depletion of LMO1 inhibited growth of neuroblastoma cells with high LMO1 expression, whereas forced expression of LMO1 in neuroblastoma cells with low LMO1 expression enhanced proliferation. These data show that common polymorphisms at the LMO1 locus are strongly associated with susceptibility to developing neuroblastoma, but also may influence the likelihood of further somatic alterations at this locus, leading to malignant progression.
C1 [Wang, Kai; Zhang, Haitao; Hou, Cuiping; Glessner, Joseph; Kim, Cecilia; Frackelton, Edward; Glaberson, Wendy; Chiavacci, Rosetta; Grant, Struan F. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Diskin, Sharon J.; Attiyeh, Edward F.; Winter, Cynthia; Schnepp, Robert W.; Diamond, Maura; Bosse, Kristopher; Mayes, Patrick A.; Garris, Maria; Wang, Qun; Nguyen, Le; Jagannathan, Jayanti; Mosse, Yael P.; Cole, Kristina A.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
   [Diskin, Sharon J.; Attiyeh, Edward F.; Winter, Cynthia; Schnepp, Robert W.; Diamond, Maura; Bosse, Kristopher; Mayes, Patrick A.; Garris, Maria; Wang, Qun; Nguyen, Le; Jagannathan, Jayanti; Mosse, Yael P.; Cole, Kristina A.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
   [Nguyen, Le; Li, Hongzhe; Devoto, Marcella] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Saeki, Norihisa; Sasaki, Hiroki] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 1040045, Japan.
   [Nguyen, Le; Grant, Struan F. A.; Mosse, Yael P.; Cole, Kristina A.; Devoto, Marcella; Hakonarson, Hakon; Maris, John M.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Grant, Struan F. A.; Devoto, Marcella; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.
   [Iolascon, Achille; Capasso, Mario] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
   [Devoto, Marcella] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
   [McGrady, Patrick W.] Univ Florida, Dept Stat, Gainesville, FL 32603 USA.
   [McGrady, Patrick W.] Childrens Oncol Grp, Gainesville, FL 32603 USA.
   [London, Wendy B.] Dana Farber Childrens Hosp, Ctr Canc, Boston, MA 02115 USA.
   [London, Wendy B.] Childrens Oncol Grp, Boston, MA 02115 USA.
   [Iolascon, Achille; Capasso, Mario] Univ Naples Federico 2, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy.
   [Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; National Cancer Center - Japan; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; CEINGE Biotecnologie Avanzate; Sapienza University Rome; State University System of Florida; University of Florida; Children's Oncology Group (COG); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Boston Children's Hospital; Children's Oncology Group (COG); University of Naples Federico II; University of London; Institute of Cancer Research - UK
RP Hakonarson, H (corresponding author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
EM hakonarson@chop.edu; maris@chop.edu
FU National Institutes of Health [R01-CA124709]; Giulio D'Angio Endowed Chair; Alex's Lemonade Stand Foundation; Evan Dunbar Foundation; Rally Foundation; Andrew's Army Foundation; Abramson Family Cancer Research Institute; Howard Hughes Medical Institute; Associazione Oncologia Pediatrica e Neuroblastoma; Cotswold Foundation; Children's Hospital of Philadelphia;  [UL1-RR024134-03]
NR 22
TC 246
Z9 278
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 JAN 13
PY 2011
VL 469
IS 7329
BP 216
EP 220
DI 10.1038/nature09609
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400039
PM 21124317
DA 2026-03-09
ER

PT J
AU Hussein, SM
   Batada, NN
   Vuoristo, S
   Ching, RW
   Autio, R
   Närvä, E
   Ng, S
   Sourour, M
   Hämäläinen, R
   Olsson, C
   Lundin, K
   Mikkola, M
   Trokovic, R
   Peitz, M
   Brüstle, O
   Bazett-Jones, DP
   Alitalo, K
   Lahesmaa, R
   Nagy, A
   Otonkoski, T
AF Hussein, Samer M.
   Batada, Nizar N.
   Vuoristo, Sanna
   Ching, Reagan W.
   Autio, Reija
   Narva, Elisa
   Ng, Siemon
   Sourour, Michel
   Hamalainen, Riikka
   Olsson, Cia
   Lundin, Karolina
   Mikkola, Milla
   Trokovic, Ras
   Peitz, Michael
   Bruestle, Oliver
   Bazett-Jones, David P.
   Alitalo, Kari
   Lahesmaa, Riitta
   Nagy, Andras
   Otonkoski, Timo
TI Copy number variation and selection during reprogramming to pluripotency
SO NATURE
LA English
DT Article
ID embryonic stem-cells; dna-damage response; self-renewal; fragile sites; differentiation; fibroblasts; suppression; activation; induction; culture
AB The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood. There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment. Using a high-resolution single nucleotide polymorphism array, we compared copy number variations (CNVs) of different passages of human iPS cells with their fibroblast cell origins and with human embryonic stem (ES) cells. Here we show that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells. Most CNVs are formed de novo and generate genetic mosaicism in early-passage human iPS cells. Most of these novel CNVs rendered the affected cells at a selective disadvantage. Remarkably, expansion of human iPS cells in culture selects rapidly against mutated cells, driving the lines towards a genetic state resembling human ES cells.
C1 [Hussein, Samer M.; Vuoristo, Sanna; Hamalainen, Riikka; Olsson, Cia; Lundin, Karolina; Mikkola, Milla; Trokovic, Ras; Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, Res Program Unit, FI-00014 Helsinki, Finland.
   [Hussein, Samer M.; Sourour, Michel; Hamalainen, Riikka; Nagy, Andras] Samuel Lunenfeld Res Inst, Toronto, ON M5T 3H7, Canada.
   [Batada, Nizar N.; Ng, Siemon] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Ching, Reagan W.; Bazett-Jones, David P.] Hosp Sick Children, Dept Genet & Genome Biol, Toronto, ON M5G 1L7, Canada.
   [Autio, Reija; Narva, Elisa; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku, Finland.
   [Autio, Reija; Narva, Elisa; Lahesmaa, Riitta] Abo Akad Univ, FIN-20520 Turku, Finland.
   [Autio, Reija] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland.
   [Peitz, Michael; Bruestle, Oliver] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany.
   [Peitz, Michael; Bruestle, Oliver] Hertie Fdn, D-53127 Bonn, Germany.
   [Alitalo, Kari] Univ Helsinki, Lab Mol Canc Biol, FI-00014 Helsinki, Finland.
   [Alitalo, Kari] Univ Helsinki, Cent Hosp, FI-00014 Helsinki, Finland.
   [Nagy, Andras] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Otonkoski, Timo] Univ Helsinki, Childrens Hosp, FI-00029 Helsinki, Finland.
C3 University of Helsinki; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Ontario Institute for Cancer Research; University of Toronto; Hospital for Sick Children (SickKids); University of Turku; Abo Akademi University; Tampere University; University of Bonn; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; University of Toronto; University of Helsinki
RP Otonkoski, T (corresponding author), Univ Helsinki, Biomedicum Stem Cell Ctr, Res Program Unit, FI-00014 Helsinki, Finland.
EM nagy@lunenfeld.ca; timo.otonkoski@helsinki.fi
FU EU; Academy of Finland; Finnish Cancer Organizations; Helsinki University Hospital; Sigrid Juselius Foundation; Stem Cell Network Canada; GL2; CIHR; McEwen Centre for Regenerative Medicine; Ontario Institute for Cancer Research through the Ontario Ministry of Research and Innovation
NR 49
TC 737
Z9 860
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 MAR 3
PY 2011
VL 471
IS 7336
BP 58
EP U67
DI 10.1038/nature09871
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100033
PM 21368824
DA 2026-03-09
ER

PT J
AU Efremov, RG
   Sazanov, LA
AF Efremov, Rouslan G.
   Sazanov, Leonid A.
TI Structure of the membrane domain of respiratory complex I
SO NATURE
LA English
DT Article
ID nadh-quinone oxidoreductase; escherichia-coli ndh-1; ubiquinone oxidoreductase; proton translocation; crystal-structure; subunit; model; residues; sensitivity; antiporter
AB Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 angstrom resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.
C1 [Efremov, Rouslan G.; Sazanov, Leonid A.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
RP Sazanov, LA (corresponding author), MRC, Mitochondrial Biol Unit, Wellcome Trust 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 60
TC 313
Z9 351
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 AUG 25
PY 2011
VL 476
IS 7361
BP 414
EP U62
DI 10.1038/nature10330
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400028
PM 21822288
DA 2026-03-09
ER

PT J
AU Guarani, V
   Deflorian, G
   Franco, CA
   Krüger, M
   Phng, LK
   Bentley, K
   Toussaint, L
   Dequiedt, F
   Mostoslavsky, R
   Schmidt, MHH
   Zimmermann, B
   Brandes, RP
   Mione, M
   Westphal, CH
   Braun, T
   Zeiher, AM
   Gerhardt, H
   Dimmeler, S
   Potente, M
AF Guarani, Virginia
   Deflorian, Gianluca
   Franco, Claudio A.
   Krueger, Marcus
   Phng, Li-Kun
   Bentley, Katie
   Toussaint, Louise
   Dequiedt, Franck
   Mostoslavsky, Raul
   Schmidt, Mirko H. H.
   Zimmermann, Barbara
   Brandes, Ralf P.
   Mione, Marina
   Westphal, Christoph H.
   Braun, Thomas
   Zeiher, Andreas M.
   Gerhardt, Holger
   Dimmeler, Stefanie
   Potente, Michael
TI Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase
SO NATURE
LA English
DT Article
ID negative regulator; angiogenesis; cells; dll4; differentiation; zebrafish; growth; acts
AB Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth(1-3). Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation(2,3), little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD1-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.
C1 [Guarani, Virginia; Zimmermann, Barbara; Dimmeler, Stefanie] Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany.
   [Deflorian, Gianluca; Mione, Marina] FIRC Inst Mol Oncol, IFOM, I-20139 Milan, Italy.
   [Franco, Claudio A.; Phng, Li-Kun; Bentley, Katie; Gerhardt, Holger] London Res Inst Canc Res UK, Vasc Biol Lab, London WC2A 3LY, England.
   [Krueger, Marcus; Braun, Thomas] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, D-61231 Bad Nauheim, Germany.
   [Toussaint, Louise; Dequiedt, Franck] GxABT, Lab Prot Signaling & Interact, B-5030 Gembloux, Belgium.
   [Toussaint, Louise; Dequiedt, Franck] Univ Liege, Interdisciplinary Cluster Appl Genoprote GIGA R, B-4000 Sart Tilman Par Liege, Belgium.
   [Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Schmidt, Mirko H. H.] Goethe Univ Frankfurt, Edinger Inst, Inst Neurol, D-60590 Frankfurt, Germany.
   [Brandes, Ralf P.] Goethe Univ Frankfurt, Inst Cardiovasc Physiol, Vasc Res Ctr, D-60590 Frankfurt, Germany.
   [Westphal, Christoph H.] Sirtris, Cambridge, MA 02139 USA.
   [Zeiher, Andreas M.; Potente, Michael] Goethe Univ Frankfurt, Dept Cardiol, D-60590 Frankfurt, Germany.
   [Gerhardt, Holger] VIB, Vesalius Res Ctr, Vasc Patterning Lab, Consultant Grp, B-3000 Louvain, Belgium.
C3 Goethe University Frankfurt; IFOM - FIRC Institute of Molecular Oncology; University of London; Institute of Cancer Research - UK; Max Planck Society; University of Liege; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Goethe University Frankfurt; Goethe University Frankfurt; Goethe University Frankfurt; Flanders Institute for Biotechnology (VIB)
RP Potente, M (corresponding author), Goethe Univ Frankfurt, Ctr Mol Med, Inst Cardiovasc Regenerat, D-60590 Frankfurt, Germany.
EM potente@em.uni-frankfurt.de
FU DFG [PO1306/1-1, SFB 834/A6, Exc 147/1]; Interuniversity Attraction Poles Program-Belgian Science Policy [IUAP-BELSPO PVI/28]; Sidney Kimmel Cancer Research Foundation; Massachusetts Life Sciences Center; NIH [R01DK088190-01A1, R01GM093072-01]; Cancer Research UK; European Molecular Biology Organisation; Lister Institute of Preventive Medicine; Fondation Leducq Transatlantic Network of Excellence ARTEMIS; Marie Curie FP7 People initiative; AIRC (Associazione Italiana per la Ricerca sul Cancro)
NR 36
TC 321
Z9 356
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 MAY 12
PY 2011
VL 473
IS 7346
BP 234
EP +
DI 10.1038/nature09917
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200043
PM 21499261
DA 2026-03-09
ER

PT J
AU Karijolich, J
   Yu, YT
AF Karijolich, John
   Yu, Yi-Tao
TI Converting nonsense codons into sense codons by targeted pseudouridylation
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; u2 snrna; rna; site; gene; recognition; termination; turnover
AB All three translation termination codons, or nonsense codons, contain a uridine residue at the first position of the codon(1-3). Here, we demonstrate that pseudouridylation (conversion of uridine into pseudouridine (Psi), ref. 4) of nonsense codons suppresses translation termination both in vitro and in vivo. In vivo targeting of nonsense codons is accomplished by the expression of an H/ACA RNA capable of directing the isomerization of uridine to Psi within the nonsense codon. Thus, targeted pseudouridylation represents a novel approach for promoting nonsense suppression in vivo. Remarkably, we also show that pseudouridylated nonsense codons code for amino acids with similar properties. Specifically, Psi AA and Psi AG code for serine and threonine, whereas Psi GA codes for tyrosine and phenylalanine, thus suggesting a new mode of decoding. Our results also suggest that RNA modification, as a naturally occurring mechanism, may offer a new way to expand the genetic code.
C1 [Karijolich, John; Yu, Yi-Tao] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA.
C3 University of Rochester
RP Yu, YT (corresponding author), Univ Rochester, Med Ctr, Dept Biochem & Biophys, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM yitao_yu@urmc.rochester.edu
FU NIGMS NIH HHS [R21 GM078223, R01 GM062937] Funding Source: Medline
NR 27
TC 314
Z9 409
U1 3
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 395
EP +
DI 10.1038/nature10165
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100049
PM 21677757
DA 2026-03-09
ER

PT J
AU Armstrong, JB
   Schindler, DE
AF Armstrong, Jonathan B.
   Schindler, Daniel E.
TI Excess digestive capacity in predators reflects a life of feast and famine
SO NATURE
LA English
DT Article
ID bioenergetics model; fishes; run
AB A central challenge for predators is achieving positive energy balance when prey are spatially and temporally heterogeneous. Ecological heterogeneity produces evolutionary trade-offs in the physiological design of predators; this is because the ability to capitalize on pulses of food abundance requires high capacity for food-processing, yet maintaining such capacity imposes energetic costs that are taxing during periods of food scarcity(1,2). Recent advances in physiology show that when variation in foraging opportunities is predictable, animals may adjust energetic tradeoffs by rapidly modulating their digestive system to track variation in foraging opportunities(1). However, it is increasingly recognized that foraging opportunities for animals are unpredictable(3), which should favour animals that maintain a capacity for food-processing that exceeds average levels of consumption (loads)(2,4). Despite this basic principle of quantitative evolutionary design, estimates of digestive load: capacity ratios in wild animals are virtually nonexistent(1). Here we provide an extensive assessment of load: capacity ratios for the digestive systems of predators in the wild, compiling 639 estimates across 38 species of fish. We found that piscine predators typically maintain the physiological capacity to feed at daily rates 2-3 times higher than what they experience on average. A numerical simulation of the trade-off between food-processing capacity and metabolic cost suggests that the observed level of physiological opportunism is profitable only if predator-prey encounters, and thus predator energy budgets, are far more variable in nature than currently assumed.
C1 [Armstrong, Jonathan B.; Schindler, Daniel E.] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Armstrong, JB (corresponding author), Univ Washington, Sch Aquat & Fishery Sci, Box 355020, Seattle, WA 98195 USA.
EM Jonny99@uw.edu
FU Gordon and Betty Moore Foundation; US National Science Foundation; University of Washington School of Aquatic and Fishery Sciences; Directorate For Geosciences [1114918] Funding Source: National Science Foundation
NR 36
TC 138
Z9 163
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 4
PY 2011
VL 476
IS 7358
BP 84
EP +
DI 10.1038/nature10240
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300034
PM 21734659
DA 2026-03-09
ER

PT J
AU Wicks, C
   de la Llera, JC
   Lara, LE
   Lowenstern, J
AF Wicks, Charles
   Carlos de la Llera, Juan
   Lara, Luis E.
   Lowenstern, Jacob
TI The role of dyking and fault control in the rapid onset of eruption at Chaiten volcano, Chile
SO NATURE
LA English
DT Article
ID satellite radar interferometry; 7.1 hector mine; surface deformation; slip distribution; earthquake; magma; gps; california; insar; andes
AB Rhyolite is the most viscous of liquid magmas, so it was surprising that on 2 May 2008 at Chaiten Volcano, located in Chile's southern Andean volcanic zone, rhyolitic magma migrated from more than 5 km depth in less than 4 hours (ref. 1) and erupted explosively with only two days of detected precursory seismic activity(2). The last major rhyolite eruption before that at Chaiten was the largest volcanic eruption in the twentieth century, at Novarupta volcano, Alaska, in 1912. Because of the historically rare and explosive nature of rhyolite eruptions and because of the surprisingly short warning before the eruption of the Chaiten volcano, any information about the workings of the magmatic system at Chaiten, and rhyolitic systems in general, is important from both the scientific and hazard perspectives. Here we present surface deformation data related to the Chaiten eruption based on radar interferometry observations from the Japan Aerospace Exploration Agency (JAXA) DAICHI (ALOS) satellite. The data on this explosive rhyolite eruption indicate that the rapid ascent of rhyolite occurred through dyking and that melt segregation and magma storage were controlled by existing faults.
C1 [Wicks, Charles; Lowenstern, Jacob] US Geol Survey, Menlo Pk, CA 94025 USA.
   [Carlos de la Llera, Juan] Pontificia Univ Catolica Chile, Escuela Ingn, Santiago 7820436, Chile.
   [Lara, Luis E.] Volcano Hazards Program, Serv Nacl Geol & Mineria, Santiago 8320119, Chile.
C3 United States Department of the Interior; United States Geological Survey; Pontificia Universidad Catolica de Chile
RP Wicks, C (corresponding author), US Geol Survey, 345 Middlefield Rd, Menlo Pk, CA 94025 USA.
EM cwicks@usgs.gov
FU NASA; National Science Foundation; US Geological Survey; US Government
CR Alfano F, 2011, B VOLCANOL, V73, P613, DOI 10.1007/s00445-010-0428-x
   BARRIENTOS SE, 1990, GEOPHYS J INT, V103, P589, DOI 10.1111/j.1365-246X.1990.tb05673.x
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   Brodtkorb PA, 2000, PROC 10 TH INT OFFSH, V3, P343
   Carn S, 2009, EOS T AM GEOPHYS UN, V90, P205, DOI 10.1029/2009EO240001
   Castro JM, 2009, NATURE, V461, P780, DOI 10.1038/nature08458
   Cembrano J, 2002, TECTONOPHYSICS, V354, P289, DOI 10.1016/S0040-1951(02)00388-8
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   Cembrano J, 2009, TECTONOPHYSICS, V471, P96, DOI 10.1016/j.tecto.2009.02.038
   Cisternas M, 2005, NATURE, V437, P404, DOI 10.1038/nature03943
   Fournier TJ, 2010, GEOCHEM GEOPHY GEOSY, V11, P0, DOI 10.1029/2009GC002558
   HILDRETH W, 1981, J GEOPHYS RES, V86, P153, DOI 10.1029/JB086iB11p10153
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   Jonsson S, 2002, MODELING VOLCANO AND EARTHQUAKE DEFORMATION FROM SATELLITE RADAR INTERFEROMETRIC OBSERVATIONS, V0, P0
   KANAMORI H, 1993, J GEOPHYS RES-SOL EA, V98, P6511, DOI 10.1029/92JB02867
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   Lange D, 2008, TECTONOPHYSICS, V455, P14, DOI 10.1016/j.tecto.2008.04.014
   LARA L, 2008, EOS S, V89, P0
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   Lohman RB, 2002, J GEOPHYS RES-SOL EA, V107, P0, DOI 10.1029/2001JB000627
   Mastin LG, 2008, A VOLCANO REKINDLED: THE RENEWED ERUPTION OF MOUNT ST. HELENS, V0, PP461, DOI 10.3133/PP175022
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   Simons M, 2002, B SEISMOL SOC AM, V92, P1390, DOI 10.1785/0120000933
   Thomson SN, 2002, GEOL SOC AM BULL, V114, P1159
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NR 33
TC 66
Z9 77
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 20
PY 2011
VL 478
IS 7369
BP 374
EP +
DI 10.1038/nature10541
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100043
PM 22012396
DA 2026-03-09
ER

PT J
AU Liu, Y
   Jiang, YA
   Si, YX
   Kim, JY
   Chen, ZF
   Rao, Y
AF Liu, Yan
   Jiang, Yun'ai
   Si, Yunxia
   Kim, Ji-Young
   Chen, Zhou-Feng
   Rao, Yi
TI Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice
SO NATURE
LA English
DT Article
ID para-chlorophenylalanine; copulatory-behavior; serotonin; lacking; innate; rats
AB Although the question of to whom a male directs his mating attempts(1,2) is a critical one in social interactions, little is known about the molecular and cellular mechanisms controlling mammalian sexual preference. Here we report that the neurotransmitter 5-hydroxytryptamine (5-HT) is required for male sexual preference. Wild-type male mice preferred females over males, but males lacking central serotonergic neurons lost sexual preference although they were not generally defective in olfaction or in pheromone sensing. A role for 5-HT was demonstrated by the phenotype of mice lacking tryptophan hydroxylase 2 (Tph2), which is required for the first step of 5-HT synthesis in the brain. Thirty-five minutes after the injection of the intermediate 5-hydroxytryptophan (5-HTP), which circumvented Tph2 to restore 5-HT to the wildtype level, adult Tph2 knockout mice also preferred females over males. These results indicate that 5-HT and serotonergic neurons in the adult brain regulate mammalian sexual preference.
C1 [Liu, Yan; Jiang, Yun'ai; Si, Yunxia; Rao, Yi] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Liu, Yan] Chinese Acad Med Sci, Grad Sch, Beijing 100730, Peoples R China.
   [Liu, Yan] Peking Union Med Coll, Beijing 100730, Peoples R China.
   [Jiang, Yun'ai] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Beijing 100864, Peoples R China.
   [Jiang, Yun'ai] Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China.
   [Kim, Ji-Young; Chen, Zhou-Feng] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA.
   [Kim, Ji-Young; Chen, Zhou-Feng] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Kim, Ji-Young; Chen, Zhou-Feng] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
   [Rao, Yi] Peking Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing 100871, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Peking University
RP Rao, Y (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM yrao@pku.edu.cn
FU Ministry of Science and Technology [2010CB833901]; Beijing Municipal Commission on Science and Technology; NIH
NR 30
TC 116
Z9 132
U1 2
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 APR 7
PY 2011
VL 472
IS 7341
BP 95
EP U125
DI 10.1038/nature09822
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400044
PM 21441904
DA 2026-03-09
ER

PT J
AU Zhou, Y
   Cashman, TJ
   Nevis, KR
   Obregon, P
   Carney, SA
   Liu, Y
   Gu, AH
   Mosimann, C
   Sondalle, S
   Peterson, RE
   Heideman, W
   Burns, CE
   Burns, CG
AF Zhou, Yong
   Cashman, Timothy J.
   Nevis, Kathleen R.
   Obregon, Pablo
   Carney, Sara A.
   Liu, Yan
   Gu, Aihua
   Mosimann, Christian
   Sondalle, Samuel
   Peterson, Richard E.
   Heideman, Warren
   Burns, Caroline E.
   Burns, C. Geoffrey
TI Latent TGF-β binding protein 3 identifies a second heart field in zebrafish
SO NATURE
LA English
DT Article
ID arterial pole; outflow tract; growth; cells; differentiation; origin
AB The four-chambered mammalian heart develops from two fields of cardiac progenitor cells distinguished by their spatiotemporal patterns of differentiation and contributions to the definitive heart(1-3). The first heart field differentiates earlier in lateral plate mesoderm, generates the linear heart tube and ultimately gives rise to the left ventricle. The second heart field (SHF) differentiates later in pharyngeal mesoderm, elongates the heart tube, and gives rise to the outflow tract and much of the right ventricle. Because hearts in lower vertebrates contain a rudimentary outflow tract but not a right ventricle(4), the existence and function of SHF-like cells in these species has remained a topic of speculation(4-10). Here we provide direct evidence from Cre/Lox-mediated lineage tracing and loss-of-function studies in zebrafish, a lower vertebrate with a single ventricle, that latent TGF-beta binding protein 3 (ltbp3) transcripts mark a field of cardiac progenitor cells with defining characteristics of the anterior SHF in mammals. Specifically, ltbp3(+) cells differentiate in pharyngeal mesoderm after formation of the heart tube, elongate the heart tube at the outflow pole, and give rise to three cardiovascular lineages in the outflow tract and myocardium in the distal ventricle. In addition to expressing Ltbp3, a protein that regulates the bioavailability of TGF-beta ligands(11), zebrafish SHF cells co-express nkx2.5, an evolutionarily conserved marker of cardiac progenitor cells in both fields(4). Embryos devoid of ltbp3 lack the same cardiac structures derived from ltbp3(+) cells due to compromised progenitor proliferation. Furthermore, small-molecule inhibition of TGF-beta signalling phenocopies the ltbp3-morphant phenotype whereas expression of a constitutively active TGF-beta type I receptor rescues it. Taken together, our findings uncover a requirement for ltbp3-TGF-beta signalling during zebrafish SHF development, a process that serves to enlarge the single ventricular chamber in this species.
C1 [Zhou, Yong; Cashman, Timothy J.; Nevis, Kathleen R.; Obregon, Pablo; Gu, Aihua; Sondalle, Samuel; Burns, Caroline E.; Burns, C. Geoffrey] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
   [Zhou, Yong; Cashman, Timothy J.; Nevis, Kathleen R.; Obregon, Pablo; Liu, Yan; Gu, Aihua; Mosimann, Christian; Sondalle, Samuel; Burns, Caroline E.; Burns, C. Geoffrey] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Carney, Sara A.; Peterson, Richard E.; Heideman, Warren] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA.
   [Liu, Yan] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA.
   [Gu, Aihua] Nanjing Med Univ, Sch Publ Hlth, Nanjing 210029, Peoples R China.
   [Mosimann, Christian] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
   [Mosimann, Christian] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   [Sondalle, Samuel; Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Wisconsin System; University of Wisconsin Madison; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Nanjing Medical University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University
RP Burns, CE (corresponding author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
EM cburns6@partners.org; gburns@cvrc.mgh.harvard.edu
FU NIH, National Institute of Environmental Health Sciences [R01 ES012716]; EMBO long-term fellowship; HFSP long-term fellowship; Cardiovascular Research Center at Massachusetts General Hospital; Claflin Distinguished Scholar Award; Harvard Stem Cell Institute; National Heart Lung and Blood Institute [5R01HL096816]; American Heart Association [10GRNT4270021]; American Heart Association (AHA) [10GRNT4270021] Funding Source: American Heart Association (AHA)
NR 24
TC 199
Z9 246
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 645
EP 648
DI 10.1038/nature10094
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300040
PM 21623370
DA 2026-03-09
ER

PT J
AU Schooler, SS
   Salau, B
   Julien, MH
   Ives, AR
AF Schooler, Shon S.
   Salau, Buck
   Julien, Mic H.
   Ives, Anthony R.
TI Alternative stable states explain unpredictable biological control of Salvinia molesta in Kakadu
SO NATURE
LA English
DT Article
ID regime shifts; ecosystems; restoration; ecology; community; thresholds; transients; nitrogen; growth; field
AB Suppression of the invasive plant Salvinia molesta by the salvinia weevil is an iconic example of successful biological control. However, in the billabongs (oxbow lakes) of Kakadu National Park, Australia, control is fitful and incomplete. By fitting a process-based nonlinear model to thirteen-year data sets from four billabongs, here we show that incomplete control can be explained by alternative stable states(1-4)-one state in which salvinia is suppressed and the other in which salvinia escapes weevil control. The shifts between states are associated with annual flooding events. In some years, high water flow reduces weevil populations, allowing the shift from a controlled to an uncontrolled state; in other years, benign conditions for weevils promote the return shift to the controlled state. In most described ecological examples, transitions between alternative stable states are relatively rare, facilitated by slow-moving environmental changes, such as accumulated nutrient loading or climate change(5,6). The billabongs of Kakadu give a different manifestation of alternative stable states that generate complex and seemingly unpredictable dynamics. Because shifts between alternative stable states are stochastic, they present a potential management strategy to maximize effective biological control: when the domain of attraction to the state of salvinia control is approached, augmentation of the weevil population or reduction of the salvinia biomass may allow the lower state to trap the system.
C1 [Ives, Anthony R.] Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
   [Schooler, Shon S.; Julien, Mic H.] CSIRO Ecosyst Sci, Long Pocket Labs, Indooroopilly, Qld 4068, Australia.
   [Salau, Buck] Dept Environm Water Heritage & Arts, Jabiru, NT 0886, Australia.
C3 University of Wisconsin System; University of Wisconsin Madison; Commonwealth Scientific & Industrial Research Organisation (CSIRO)
RP Ives, AR (corresponding author), Univ Wisconsin, Dept Zool, Madison, WI 53706 USA.
EM arives@wisc.edu
FU Australian Department of Agriculture, Fisheries and Forestry; CSIRO; United States National Science Foundation through the North Temperate Lakes Long Term Ecological Research Network; Direct For Biological Sciences; Division Of Environmental Biology [0822700] Funding Source: National Science Foundation
NR 28
TC 75
Z9 87
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 FEB 3
PY 2011
VL 470
IS 7332
BP 86
EP 89
DI 10.1038/nature09735
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400039
PM 21293376
DA 2026-03-09
ER

PT J
AU Rohrbach, A
   Schmidt, MW
AF Rohrbach, Arno
   Schmidt, Max W.
TI Redox freezing and melting in the Earth's deep mantle resulting from carbon-iron redox coupling
SO NATURE
LA English
DT Article
ID phase-transformations; oxygen fugacity; ferric iron; metal; peridotite; magnesiowustite; beneath; garnet; thermodynamics; solubility
AB Very low seismic velocity anomalies in the Earth's mantle(1,2) may reflect small amounts of melt present in the peridotite matrix, and the onset of melting in the Earth's upper mantle is likely to be triggered by the presence of small amounts of carbonate(3). Such carbonates stem from subducted oceanic lithosphere in part buried to depths below the 660-kilometre discontinuity and remixed into the mantle. Here we demonstrate that carbonate-induced melting may occur in deeply subducted lithosphere at near-adiabatic temperatures in the Earth's transition zone and lower mantle. We show experimentally that these carbonatite melts are unstable when infiltrating ambient mantle and are reduced to immobile diamond when recycled at depths greater than similar to 250 kilometres, where mantle redox conditions are determined by the presence of an (Fe,Ni) metal phase(4-6). This 'redox freezing' process leads to diamond-enriched mantle domains in which the Fe-0, resulting from Fe2+ disproportionation in perovskites and garnet, is consumed but the Fe3+ preserved. When such carbon-enriched mantle heterogeneities become part of the upwelling mantle, diamond will inevitably react with the Fe3+ leading to true carbonatite redox melting at similar to 660 and similar to 250 kilometres depth to form deep-seated melts in the Earth's mantle.
C1 [Rohrbach, Arno; Schmidt, Max W.] ETH, Inst Geochem & Petrol, CH-8092 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Rohrbach, A (corresponding author), ETH, Inst Geochem & Petrol, Sonneggstr 5, CH-8092 Zurich, Switzerland.
EM arno.rohrbach@gmail.com
FU Swiss National Science Foundation (SNSF) [2-777-86-06]
NR 53
TC 415
Z9 474
U1 8
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 APR 14
PY 2011
VL 472
IS 7342
BP 209
EP 212
DI 10.1038/nature09899
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100040
PM 21441908
DA 2026-03-09
ER

PT J
AU Lizak, C
   Gerber, S
   Numao, S
   Aebi, M
   Locher, KP
AF Lizak, Christian
   Gerber, Sabina
   Numao, Shin
   Aebi, Markus
   Locher, Kaspar P.
TI X-ray structure of a bacterial oligosaccharyltransferase
SO NATURE
LA English
DT Article
ID n-linked glycosylation; hydroxy amino-acid; protein glycosylation; complex; transferase; glycoprotein; peptide; specificity; biology; system
AB Asparagine-linked glycosylation is a post-translational modification of proteins containing the conserved sequence motif Asn-X-Ser/Thr. The attachment of oligosaccharides is implicated in diverse processes such as protein folding and quality control, organism development or host-pathogen interactions. The reaction is catalysed by oligosaccharyltransferase (OST), a membrane protein complex located in the endoplasmic reticulum. The central, catalytic enzyme of OST is the STT3 subunit, which has homologues in bacteria and archaea. Here we report the X-ray structure of a bacterial OST, the PglB protein of Campylobacter lari, in complex with an acceptor peptide. The structure defines the fold of STT3 proteins and provides insight into glycosylation sequon recognition and amide nitrogen activation, both of which are prerequisites for the formation of the N-glycosidic linkage. We also identified and validated catalytically important, acidic amino acid residues. Our results provide the molecular basis for understanding the mechanism of N-linked glycosylation.
C1 [Lizak, Christian; Gerber, Sabina; Locher, Kaspar P.] ETH, Dept Biol, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
   [Lizak, Christian; Numao, Shin; Aebi, Markus] ETH, Dept Biol, Inst Microbiol, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Locher, KP (corresponding author), ETH, Dept Biol, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
EM locher@mol.biol.ethz.ch
FU NCCR Structural Biology Zurich; Swiss National Science Foundation [SNF 31003A-127098/1, SNF 31003A-131075/1]
NR 53
TC 309
Z9 371
U1 2
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 350
EP U377
DI 10.1038/nature10151
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100039
PM 21677752
DA 2026-03-09
ER

PT J
AU Sexton, PF
   Norris, RD
   Wilson, PA
   Pälike, H
   Westerhold, T
   Röhl, U
   Bolton, CT
   Gibbs, S
AF Sexton, Philip F.
   Norris, Richard D.
   Wilson, Paul A.
   Paelike, Heiko
   Westerhold, Thomas
   Roehl, Ursula
   Bolton, Clara T.
   Gibbs, Samantha
TI Eocene global warming events driven by ventilation of oceanic dissolved organic carbon
SO NATURE
LA English
DT Article
ID late paleocene; atmospheric co2; hydrate; cycle; time
AB 'Hyperthermals' are intervals of rapid, pronounced global warming known from six episodes within the Palaeocene and Eocene epochs (similar to 65-34 million years (Myr) ago)(1-13). The most extreme hyperthermal was the 170 thousand year (kyr) interval(2) of 5-7 degrees C global warming(3) during the Palaeocene-Eocene Thermal Maximum (PETM, 56 Myr ago). The PETM is widely attributed to massive release of greenhouse gases from buried sedimentary carbon reservoirs(1,3,6,11,14-17), and other, comparatively modest, hyperthermals have also been linked to the release of sedimentary carbon(3,6,11,16,17). Here we show, using new 2.4-Myr-long Eocene deep ocean records, that the comparatively modest hyperthermals are much more numerous than previously documented, paced by the eccentricity of Earth's orbit and have shorter durations (40 kyr) and more rapid recovery phases than the PETM. These findings point to the operation of fundamentally different forcing and feedback mechanisms than for the PETM, involving redistribution of carbon among Earth's readily exchangeable surface reservoirs rather than carbon exhumation from, and subsequent burial back into, the sedimentary reservoir. Specifically, we interpret our records to indicate repeated, large-scale releases of dissolved organic carbon (at least 1,600 giga-tonnes) from the ocean by ventilation (strengthened oxidation) of the ocean interior. The rapid recovery of the carbon cycle following each Eocene hyperthermal strongly suggests that carbon was re-sequestered by the ocean, rather than the much slower process of silicate rock weathering proposed for the PETM1,3. Our findings suggest that these pronounced climate warming events were driven not by repeated releases of carbon from buried sedimentary sources(3,6,11,16,17), but, rather, by patterns of surficial carbon redistribution familiar from younger intervals of Earth history.
C1 [Sexton, Philip F.; Norris, Richard D.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Sexton, Philip F.; Wilson, Paul A.; Paelike, Heiko; Bolton, Clara T.; Gibbs, Samantha] Univ Southampton, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Westerhold, Thomas; Roehl, Ursula] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Southampton; NERC National Oceanography Centre; University of Bremen
RP Sexton, PF (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
EM P.F.Sexton@open.ac.uk
FU US NSF and; European Commission; Leverhulme Trust; Natural Environment Research Council UK; Philip Leverhulme Prize; DFG-Leibniz Center for Surface Process and Climate Studies at the University of Potsdam; DFG; NERC [NE/G009376/1] Funding Source: UKRI; STFC [PP/D002176/1] Funding Source: UKRI; Natural Environment Research Council [NE/G009376/1] Funding Source: researchfish; Science and Technology Facilities Council [PP/D002176/1] Funding Source: researchfish
NR 45
TC 248
Z9 290
U1 6
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 MAR 17
PY 2011
VL 471
IS 7338
BP 349
EP +
DI 10.1038/nature09826
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000039
PM 21412336
DA 2026-03-09
ER

PT J
AU Nagib, DA
   MacMillan, DWC
AF Nagib, David A.
   MacMillan, David W. C.
TI Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis
SO NATURE
LA English
DT Article
ID fluorine; electrochemistry; complexes
AB Modern drug discovery relies on the continual development of synthetic methodology to address the many challenges associated with the design of new pharmaceutical agents(1). One such challenge arises from the enzymatic metabolism of drugs in vivo by cytochrome P450 oxidases, which use single-electron oxidative mechanisms to rapidly modify small molecules to facilitate their excretion(2). A commonly used synthetic strategy to protect against in vivo metabolism involves the incorporation of electron-withdrawing functionality, such as the trifluoromethyl (CF3) group, into drug candidates(3). The CF3 group enjoys a privileged role in the realm of medicinal chemistry because its incorporation into small molecules often enhances efficacy by promoting electrostatic interactions with targets, improving cellular membrane permeability, and increasing robustness towards oxidative metabolism of the drug(4-6). Although common pharmacophores often bear CF3 motifs in an aromatic system, access to such analogues typically requires the incorporation of the CF3 group, or a surrogate moiety, at the start of a multi-step synthetic sequence. Here we report a mild, operationally simple strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes through a radical-mediated mechanism using commercial photocatalysts and a household light bulb. We demonstrate the broad utility of this transformation through addition of CF3 to a number of heteroaromatic and aromatic systems. The benefit to medicinal chemistry and applicability to late-stage drug development is also shown through examples of the direct trifluoromethylation of widely prescribed pharmaceutical agents.
C1 [Nagib, David A.; MacMillan, David W. C.] Princeton Univ, Dept Chem, Merck Ctr Catalysis, Frick Lab 192, Princeton, NJ 08540 USA.
C3 Princeton University
RP MacMillan, DWC (corresponding author), Princeton Univ, Dept Chem, Merck Ctr Catalysis, Frick Lab 192, Princeton, NJ 08540 USA.
EM dmacmill@princeton.edu
FU NIH General Medical Sciences [R01 01 GM093213-01]
NR 30
TC 1185
Z9 1310
U1 9
U2 723
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 224
EP 228
DI 10.1038/nature10647
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200047
PM 22158245
DA 2026-03-09
ER

PT J
AU Gutiérrez, NL
   Hilborn, R
   Defeo, O
AF Gutierrez, Nicolas L.
   Hilborn, Ray
   Defeo, Omar
TI Leadership, social capital and incentives promote successful fisheries
SO NATURE
LA English
DT Article
ID management; comanagement; principles; governance; quotas
AB One billion people depend on seafood as their primary source of protein and 25% of the world's total animal protein comes from fisheries(1). Yet a third of fish stocks worldwide are overexploited or depleted(1,2). Using individual case studies, many have argued that community-based co-management(3) should prevent the tragedy of the commons(4) because cooperative management by fishers, managers and scientists often results in sustainable fisheries(3,5,6). However, general and multidisciplinary evaluations of co-management regimes and the conditions for social, economic and ecological success within such regimes are lacking. Here we examine 130 co-managed fisheries in a wide range of countries with different degrees of development, ecosystems, fishing sectors and type of resources. We identified strong leadership as the most important attribute contributing to success, followed by individual or community quotas, social cohesion and protected areas. Less important conditions included enforcement mechanisms, long-term management policies and life history of the resources. Fisheries were most successful when at least eight co-management attributes were present, showing a strong positive relationship between the number of these attributes and success, owing to redundancy in management regulations. Our results demonstrate the critical importance of prominent community leaders and robust social capital(7), combined with clear incentives through catch shares and conservation benefits derived from protected areas, for successfully managing aquatic resources and securing the livelihoods of communities depending on them. Our study offers hope that co-management, the only realistic solution for the majority of the world's fisheries, can solve many of the problems facing global fisheries.
C1 [Gutierrez, Nicolas L.; Hilborn, Ray] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
   [Defeo, Omar] Fac Ciencias, UNDECIMAR, Montevideo 11400, Uruguay.
C3 University of Washington; University of Washington Seattle; Universidad de la Republica, Uruguay
RP Gutiérrez, NL (corresponding author), Univ Washington, Sch Aquat & Fishery Sci, Box 355020, Seattle, WA 98195 USA.
EM nicolasg@uw.edu
FU National Science Foundation [0308440]; Fulbright-OAS Initiative in Ecology; Pew Charitable Trusts; Division Of Ocean Sciences; Directorate For Geosciences [0308440] Funding Source: National Science Foundation
NR 30
TC 983
Z9 1164
U1 13
U2 652
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 386
EP 389
DI 10.1038/nature09689
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100040
PM 21209616
DA 2026-03-09
ER

PT J
AU Hua, YM
   Sahashi, K
   Rigo, F
   Hung, G
   Horev, G
   Bennett, CF
   Krainer, AR
AF Hua, Yimin
   Sahashi, Kentaro
   Rigo, Frank
   Hung, Gene
   Horev, Guy
   Bennett, C. Frank
   Krainer, Adrian R.
TI Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model
SO NATURE
LA English
DT Article
ID igf-i; cardiac defects; mice; delivery; phenotype; growth; survival; diseases
AB Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality; it results from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene(1). Humans have a paralogue, SMN2, whose exon 7 is predominantly skipped(2), but the limited amount of functional, full-length SMN protein expressed from SMN2 cannot fully compensate for a lack of SMN1. SMN is important for the biogenesis of spliceosomal small nuclear ribonucleoprotein particles(3), but downstream splicing targets involved in pathogenesis remain elusive. There is no effective SMA treatment, but SMN restoration in spinal cord motor neurons is thought to be necessary and sufficient(4). Non-central nervous system (CNS) pathologies, including cardiovascular defects, were recently reported in severe SMA mouse models and patients(5-8), reflecting autonomic dysfunction or direct effects in cardiac tissues. Here we compared systemic versus CNS restoration of SMN in a severe mouse model(9,10). We used an antisense oligonucleotide (ASO), ASO-10-27, that effectively corrects SMN2 splicing and restores SMN expression in motor neurons after intracerebroventricular injection(11,12). Systemic administration of ASO-10-27 to neonates robustly rescued severe SMA mice, much more effectively than intracerebroventricular administration; subcutaneous injections extended the median lifespan by 25 fold. Furthermore, neonatal SMA mice had decreased hepatic Igfals expression, leading to a pronounced reduction in circulating insulin-like growth factor 1 (IGF1), and ASO-10-27 treatment restored IGF1 to normal levels. These results suggest that the liver is important in SMA pathogenesis, underscoring the importance of SMN in peripheral tissues, and demonstrate the efficacy of a promising drug candidate.
C1 [Hua, Yimin; Sahashi, Kentaro; Horev, Guy; Krainer, Adrian R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Rigo, Frank; Hung, Gene; Bennett, C. Frank] ISIS Pharmaceut, Carlsbad, CA 92010 USA.
C3 Cold Spring Harbor Laboratory; Ionis Pharmaceuticals, Inc.
RP Krainer, AR (corresponding author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
EM Krainer@cshl.edu
FU Muscular Dystrophy Association; National Institute of General Medical Sciences; St. Giles Foundation; National Institute of General Medical Sciences [R37GM042699, R01GM042699] Funding Source: NIH RePORTER
NR 30
TC 592
Z9 712
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 OCT 6
PY 2011
VL 478
IS 7367
BP 123
EP 126
DI 10.1038/nature10485
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400047
PM 21979052
DA 2026-03-09
ER

PT J
AU Zauderer, BA
   Berger, E
   Soderberg, AM
   Loeb, A
   Narayan, R
   Frail, DA
   Petitpas, GR
   Brunthaler, A
   Chornock, R
   Carpenter, JM
   Pooley, GG
   Mooley, K
   Kulkarni, SR
   Margutti, R
   Fox, DB
   Nakar, E
   Patel, NA
   Volgenau, NH
   Culverhouse, TL
   Bietenholz, MF
   Rupen, MP
   Max-Moerbeck, W
   Readhead, ACS
   Richards, J
   Shepherd, M
   Storm, S
   Hull, CLH
AF Zauderer, B. A.
   Berger, E.
   Soderberg, A. M.
   Loeb, A.
   Narayan, R.
   Frail, D. A.
   Petitpas, G. R.
   Brunthaler, A.
   Chornock, R.
   Carpenter, J. M.
   Pooley, G. G.
   Mooley, K.
   Kulkarni, S. R.
   Margutti, R.
   Fox, D. B.
   Nakar, E.
   Patel, N. A.
   Volgenau, N. H.
   Culverhouse, T. L.
   Bietenholz, M. F.
   Rupen, M. P.
   Max-Moerbeck, W.
   Readhead, A. C. S.
   Richards, J.
   Shepherd, M.
   Storm, S.
   Hull, C. L. H.
TI Birth of a relativistic outflow in the unusual γ-ray transient Swift J164449.3+573451
SO NATURE
LA English
DT Article
ID tidal disruption; black-holes; radio-sources; galaxy; outburst; stars
AB Active galactic nuclei, which are powered by long-term accretion onto central supermassive black holes, produce(1) relativistic jets with lifetimes of at least one million years, and the observation of the birth of such a jet is therefore unlikely. Transient accretion onto a supermassive black hole, for example through the tidal disruption(2,3) of a stray star, thus offers a rare opportunity to study the birth of a relativistic jet. On 25 March 2011, an unusual transient source (Swift J164449.3+573451) was found(4), potentially representing(5,6) such an accretion event. Here we report observations spanning centimetre to millimetre wavelengths and covering the first month of evolution of a luminous radio transient associated with Swift J164449.3+573451. The radio transient coincides(7) with the nucleus of an inactive galaxy. We conclude that we are seeing a newly formed relativistic outflow, launched by transient accretion onto a million-solar-mass black hole. A relativistic outflow is not predicted in this situation, but we show that the tidal disruption of a star naturally explains the observed high-energy properties and radio luminosity and the inferred rate of such events. The weaker beaming in the radio-frequency spectrum relative to c-rays or X-rays suggests that radio searches may uncover similar events out to redshifts of z approximate to 6.
C1 [Zauderer, B. A.; Berger, E.; Soderberg, A. M.; Loeb, A.; Narayan, R.; Petitpas, G. R.; Chornock, R.; Patel, N. A.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Frail, D. A.; Rupen, M. P.] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Brunthaler, A.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Carpenter, J. M.; Mooley, K.; Kulkarni, S. R.; Max-Moerbeck, W.; Readhead, A. C. S.; Richards, J.; Shepherd, M.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Pooley, G. G.] Univ Cambridge, Cavendish Lab, Mullard Radio Observ, Cambridge CB3 0HE, England.
   [Margutti, R.] INAF Osservatorio Astron Brera, I-23807 Merate, Italy.
   [Fox, D. B.] Penn State Univ, Dept Astron, University Pk, PA 16802 USA.
   [Nakar, E.] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Volgenau, N. H.; Culverhouse, T. L.] CALTECH, Owens Valley Radio Observ, Big Pine, CA 93513 USA.
   [Bietenholz, M. F.] Hartebeesthoek Radio Astron Observ, ZA-1740 Krugersdorp, South Africa.
   [Bietenholz, M. F.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Storm, S.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Hull, C. L. H.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
C3 Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; National Radio Astronomy Observatory (NRAO); Max Planck Society; California Institute of Technology; University of Cambridge; Istituto Nazionale Astrofisica (INAF); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Tel Aviv University; California Institute of Technology; National Research Foundation - South Africa; Hartebeesthoek Radio Astronomy Observatory; York University - Canada; University System of Maryland; University of Maryland College Park; University of California System; University of California Berkeley
RP Zauderer, BA (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM bzauderer@cfa.harvard.edu; eberger@cfa.harvard.edu
FU NASA; NSF; Ministry of Universities and Research of Italy; IRG; ISF; Smithsonian Institution; Academia Sinica; California Institute of Technology; University of Chicago; states of California, Illinois and Maryland; University of Cambridge; STFC; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1107973] Funding Source: National Science Foundation
NR 21
TC 382
Z9 419
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 425
EP 428
DI 10.1038/nature10366
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400030
PM 21866155
DA 2026-03-09
ER

PT J
AU Dorner, M
   Horwitz, JA
   Robbins, JB
   Barry, WT
   Feng, Q
   Mu, K
   Jones, CT
   Schoggins, JW
   Catanese, MT
   Burton, DR
   Law, M
   Rice, CM
   Ploss, A
AF Dorner, Marcus
   Horwitz, Joshua A.
   Robbins, Justin B.
   Barry, Walter T.
   Feng, Qian
   Mu, Kathy
   Jones, Christopher T.
   Schoggins, John W.
   Catanese, Maria Teresa
   Burton, Dennis R.
   Law, Mansun
   Rice, Charles M.
   Ploss, Alexander
TI A genetically humanized mouse model for hepatitis C virus infection
SO NATURE
LA English
DT Article
ID b type-i; human liver; replication; receptor; antibody; fibroblasts; reveals; vitro; mice; cd81
AB Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro(4), we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo.
C1 [Dorner, Marcus; Horwitz, Joshua A.; Barry, Walter T.; Feng, Qian; Mu, Kathy; Jones, Christopher T.; Schoggins, John W.; Catanese, Maria Teresa; Rice, Charles M.; Ploss, Alexander] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA.
   [Robbins, Justin B.; Burton, Dennis R.; Law, Mansun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA.
C3 Rockefeller University; Scripps Research Institute; Scripps Research Institute; International AIDS Vaccine Initiative; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute
RP Ploss, A (corresponding author), Rockefeller Univ, Ctr Study Hepatitis C, 1230 York Ave, New York, NY 10021 USA.
EM aploss@rockefeller.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [RC1DK087193]; National Institute for Allergy and Infectious Disease [R01AI072613, R01AI079031, R01AI071084]; Starr Foundation; Greenberg Medical Institute; German Research Foundation (Deutsche Forschungsgesellschaft); Rockefeller University; National Institute of Health [F32DK082155, F32DK081193]
NR 35
TC 290
Z9 356
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 208
EP U246
DI 10.1038/nature10168
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800049
PM 21654804
DA 2026-03-09
ER

PT J
AU Tan, W
   Zhang, WZ
   Strasner, A
   Grivennikov, S
   Cheng, JQ
   Hoffman, RM
   Karin, M
AF Tan, Wei
   Zhang, Weizhou
   Strasner, Amy
   Grivennikov, Sergei
   Cheng, Jin Q.
   Hoffman, Robert M.
   Karin, Michael
TI Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling
SO NATURE
LA English
DT Article
ID breast-cancer; osteoclast differentiation; osteoprotegerin-ligand; gland development; bone metastases; prostate-cancer; expression; activation; denosumab; receptor
AB Inflammatory mechanisms influence tumorigenesis and metastatic progression even in cancers whose aetiology does not involve pre-existing inflammation or infection, such as breast and prostate cancers(1). For instance, prostate cancer metastasis is associated with the infiltration of lymphocytes into advanced tumours and the upregulation of two tumour-necrosis-factor family members: receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) and lymphotoxin(2). But the source of RANKL and its role in metastasis have not been established. RANKL and its receptor RANK control the proliferation of mammary lobuloalveolar cells during pregnancy(3) through inhibitor of nuclear factor-kappa B (I kappa B) kinase-alpha (IKK-alpha)(4), a protein kinase that is needed for the self-renewal of mammary cancer progenitors(5) and for prostate cancer metastasis(2). We therefore examined whether RANKL, RANK and IKK-alpha are also involved in mammary/breast cancer metastasis. Indeed, RANK signalling in mammary carcinoma cells that overexpress the proto-oncogene Erbb2 (also known as Neu)(6), which is frequently amplified in metastatic human breast cancers(7,8), was important for pulmonary metastasis. Metastatic spread of Erbb2-transformed carcinoma cells also required CD4(+)CD25(+) T cells, whose major pro-metastatic function was RANKL production. Most RANKL-producing T cells expressed forkhead box P3 (FOXP3), a transcription factor produced by regulatory T cells, and were located next to smooth muscle actin (SMA)(+) stromal cells in mouse and human breast cancers. The dependence of pulmonary metastasis on T cells was replaceable by exogenous RANKL, which also stimulated pulmonary metastasis of RANK(+) human breast cancer cells. These results are consistent with the adverse impact of tumour-infiltrating CD4(+) or FOXP3(+) T cells on human breast cancer prognosis(9,10) and suggest that the targeting of RANKL-RANK can be used in conjunction with the therapeutic elimination of primary breast tumours to prevent recurrent metastatic disease.
C1 [Tan, Wei; Zhang, Weizhou; Strasner, Amy; Grivennikov, Sergei; Karin, Michael] Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Tan, Wei; Zhang, Weizhou; Strasner, Amy; Grivennikov, Sergei; Karin, Michael] Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Dept Pathol, La Jolla, CA 92093 USA.
   [Cheng, Jin Q.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA.
   [Hoffman, Robert M.] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA.
   [Hoffman, Robert M.] AntiCancer Inc, San Diego, CA 92111 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; H Lee Moffitt Cancer Center & Research Institute; University of California System; University of California San Diego; AntiCancer, Inc.
RP Karin, M (corresponding author), Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, 9500 Gilman Dr,Mail Code 0723, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU National Institutes of Health (NIH); Susan G. Komen for the Cure; Crohn's and Colitis Foundation of America; National Cancer Institute [T32CA121938] Funding Source: NIH RePORTER
NR 27
TC 542
Z9 604
U1 2
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 FEB 24
PY 2011
VL 470
IS 7335
BP 548
EP 553
DI 10.1038/nature09707
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900045
PM 21326202
DA 2026-03-09
ER

PT J
AU Vyazovskiy, VV
   Olcese, U
   Hanlon, EC
   Nir, Y
   Cirelli, C
   Tononi, G
AF Vyazovskiy, Vladyslav V.
   Olcese, Umberto
   Hanlon, Erin C.
   Nir, Yuval
   Cirelli, Chiara
   Tononi, Giulio
TI Local sleep in awake rats
SO NATURE
LA English
DT Article
ID slow-wave activity; cortical synchronization; visual-stimulation; theta activity; homeostasis; eeg; neurons; waking; states; brain
AB In an awake state, neurons in the cerebral cortex fire irregularly and electroencephalogram (EEG) recordings display low-amplitude, high-frequency fluctuations. During sleep, neurons oscillate between 'on' periods, when they fire as in an awake brain, and 'off' periods, when they stop firing altogether and the EEG displays high-amplitude slowwaves. However, what happens to neuronal firing after a long period of being awake is not known. Here we show that in freely behaving rats after a long period in an awake state, cortical neurons can go briefly 'offline' as in sleep, accompanied by slow waves in the local EEG. Neurons often go offline in one cortical area but not in another, and during these periods of 'local sleep', the incidence of which increases with the duration of the awake state, rats are active and display an 'awake' EEG. However, they are progressively impaired in a sugar pellet reaching task. Thus, although both the EEG and behaviour indicate wakefulness, local populations of neurons in the cortex may be falling asleep, with negative consequences for performance.
C1 [Vyazovskiy, Vladyslav V.; Olcese, Umberto; Hanlon, Erin C.; Nir, Yuval; Cirelli, Chiara; Tononi, Giulio] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA.
   [Olcese, Umberto] Scuola Super Sant Anna, PERCRO Lab, I-56217 Pisa, Italy.
C3 University of Wisconsin System; University of Wisconsin Madison; Scuola Superiore Sant'Anna
RP Tononi, G (corresponding author), Univ Wisconsin, Dept Psychiat, 6001 Res Pk Blvd, Madison, WI 53719 USA.
EM gtononi@wisc.edu
FU NIMH [P20 MH077967]; NIH; AFOSR [FA9550-08-1-0244]
NR 40
TC 645
Z9 740
U1 2
U2 119
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 443
EP 447
DI 10.1038/nature10009
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600028
PM 21525926
DA 2026-03-09
ER

PT J
AU Welz, PS
   Wullaert, A
   Vlantis, K
   Kondylis, V
   Fernández-Majada, V
   Ermolaeva, M
   Kirsch, P
   Sterner-Kock, A
   van Loo, G
   Pasparakis, M
AF Welz, Patrick-Simon
   Wullaert, Andy
   Vlantis, Katerina
   Kondylis, Vangelis
   Fernandez-Majada, Vanesa
   Ermolaeva, Maria
   Kirsch, Petra
   Sterner-Kock, Anja
   van Loo, Geert
   Pasparakis, Manolis
TI FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
SO NATURE
LA English
DT Article
ID nemo/ikk-gamma; deficient mice; tnf-alpha; b-cell; death; regulator; apoptosis; deletion; immunity; rip3
AB Intestinal immune homeostasis depends on a tightly regulated cross talk between commensal bacteria, mucosal immune cells and intestinal epithelial cells (IECs)(1-4). Epithelial barrier disruption is considered to be a potential cause of inflammatory bowel disease; however, the mechanisms regulating intestinal epithelial integrity are poorly understood(1,5). Here we show that mice with IEC-specific knockout of FADD (FADD(IEC-KO)), an adaptor protein required for death-receptor-induced apoptosis(6), spontaneously developed epithelial cell necrosis, loss of Paneth cells, enteritis and severe erosive colitis. Genetic deficiency in RIP3, a critical regulator of programmed necrosis(7-9), prevented the development of spontaneous pathology in both the small intestine and colon of FADD(IEC-KO) mice, demonstrating that intestinal inflammation is triggered by RIP3-dependent death of FADD-deficient IECs. Epithelial-specific inhibition of CYLD, a deubiquitinase that regulates cellular necrosis(10), prevented colitis development in FADD(IEC-KO) but not in NEMOIEC-KO mice(11), showing that different mechanisms mediated death of colonic epithelial cells in these two models. In FADD(IEC-KO) mice, TNF deficiency ameliorated colon inflammation, whereas MYD88 deficiency and also elimination of the microbiota prevented colon inflammation, indicating that bacteria-mediated Toll-like-receptor signalling drives colitis by inducing the expression of TNF and other cytokines. However, neither CYLD, TNF or MYD88 deficiency nor elimination of the microbiota could prevent Paneth cell loss and enteritis in FADD(IEC-KO) mice, showing that different mechanisms drive RIP3-dependent necrosis of FADD-deficient IECs in the small and large bowel. Therefore, by inhibiting RIP3-mediated IEC necrosis, FADD preserves epithelial barrier integrity and antibacterial defence, maintains homeostasis and prevents chronic intestinal inflammation. Collectively, these results show that mechanisms preventing RIP3-mediated epithelial cell death are critical for the maintenance of intestinal homeostasis and indicate that programmed necrosis of IECs might be implicated in the pathogenesis of inflammatory bowel disease, in which Paneth cell and barrier defects are thought to contribute to intestinal inflammation.
C1 [Welz, Patrick-Simon; Wullaert, Andy; Vlantis, Katerina; Kondylis, Vangelis; Fernandez-Majada, Vanesa; Ermolaeva, Maria; Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50674 Cologne, Germany.
   [Kirsch, Petra] Univ Ulm, Tierforschungszentrum, D-89081 Ulm, Germany.
   [Sterner-Kock, Anja] Univ Cologne, Uniklin Koln, Ctr Med Expt, D-50931 Cologne, Germany.
   [van Loo, Geert] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium.
   [van Loo, Geert] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium.
C3 University of Cologne; Ulm University; University of Cologne; Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University
RP Pasparakis, M (corresponding author), Univ Cologne, Ctr Mol Med CMMC, Inst Genet, Zulpicher Str 47A, D-50674 Cologne, Germany.
EM Pasparakis@uni-koeln.de
FU Deutsche Forschungsgemeinschaft [SFB670, SFB829]; European Commission (EC) [223151, 223404]; EMBO; 'Group-IDMRP' of Ghent University; International Graduate School in Genetics and Functional Genomics at the University of Cologne
NR 36
TC 520
Z9 593
U1 3
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 15
PY 2011
VL 477
IS 7364
BP 330
EP U102
DI 10.1038/nature10273
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400031
PM 21804564
DA 2026-03-09
ER

PT J
AU Yazawa, M
   Hsueh, B
   Jia, XL
   Pasca, AM
   Bernstein, JA
   Hallmayer, J
   Dolmetsch, RE
AF Yazawa, Masayuki
   Hsueh, Brian
   Jia, Xiaolin
   Pasca, Anca M.
   Bernstein, Jonathan A.
   Hallmayer, Joachim
   Dolmetsch, Ricardo E.
TI Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome
SO NATURE
LA English
DT Article
ID gating mechanisms; syndrome mutation; sudden-death; channels; cardiomyocytes; roscovitine; arrhythmia; inhibitor; myocytes
AB Individuals with congenital or acquired prolongation of the QT interval, or long QT syndrome (LQTS), are at risk of life-threatening ventricular arrhythmia(1,2). LQTS is commonly genetic in origin but can also be caused or exacerbated by environmental factors(1,3). A missense mutation in the L-type calcium channel Ca(V)1.2 leads to LQTS in patients with Timothy syndrome(4,5). To explore the effect of the Timothy syndrome mutation on the electrical activity and contraction of human cardiomyocytes, we reprogrammed human skin cells from Timothy syndrome patients to generate induced pluripotent stem cells, and differentiated these cells into cardiomyocytes. Electrophysiological recording and calcium (Ca2+) imaging studies of these cells revealed irregular contraction, excess Ca2+ influx, prolonged action potentials, irregular electrical activity and abnormal calcium transients in ventricular-like cells. We found that roscovitine, a compound that increases the voltage-dependent inactivation of Ca(V)1.2 (refs 6-8), restored the electrical and Ca2+ signalling properties of cardiomyocytes from Timothy syndrome patients. This study provides new opportunities for studying the molecular and cellular mechanisms of cardiac arrhythmias in humans, and provides a robust assay for developing new drugs to treat these diseases.
C1 [Yazawa, Masayuki; Hsueh, Brian; Jia, Xiaolin; Pasca, Anca M.; Dolmetsch, Ricardo E.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
   [Bernstein, Jonathan A.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University
RP Dolmetsch, RE (corresponding author), Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
EM ricardo.dolmetsch@stanford.edu
FU Japan Society for the Promotion for Science; American Heart Association Western States; National Institutes of Health; Simons Foundation
NR 27
TC 518
Z9 637
U1 1
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 230
EP U120
DI 10.1038/nature09855
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200040
PM 21307850
DA 2026-03-09
ER

PT J
AU Sekiya, S
   Suzuki, A
AF Sekiya, Sayaka
   Suzuki, Atsushi
TI Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors
SO NATURE
LA English
DT Article
ID hepatic progenitor cells; clonal identification; stem-cells; in-vivo; liver; differentiation; cardiomyocytes; normalization; expression; neurons
AB The location and timing of cellular differentiation must be stringently controlled for proper organ formation. Normally, hepatocytes differentiate from hepatic progenitor cells to form the liver during development(1,2). However, previous studies have shown that the hepatic program can also be activated in non-hepatic lineage cells after exposure to particular stimuli or fusion with hepatocytes(3-9). These unexpected findings suggest that factors critical to hepatocyte differentiation exist and become activated to induce hepatocyte-specific properties in different cell types. Here, by screening the effects of twelve candidate factors, we identify three specific combinations of two transcription factors, comprising Hnf4 alpha plus Foxa1, Foxa2 or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells that closely resemble hepatocytes in vitro. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific features and reconstitute damaged hepatic tissues after transplantation. The generation of iHep cells may provide insights into the molecular nature of hepatocyte differentiation and potential therapies for liver diseases.
C1 [Sekiya, Sayaka; Suzuki, Atsushi] Kyushu Univ, Div Organogenesis & Regenerat, Med Inst Bioregulat, Higashi Ku, Fukuoka 8128582, Japan.
   [Suzuki, Atsushi] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
C3 Kyushu University; Japan Science & Technology Agency (JST)
RP Suzuki, A (corresponding author), Kyushu Univ, Div Organogenesis & Regenerat, Med Inst Bioregulat, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM suzukicks@bioreg.kyushu-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Japan Science and Technology Agency; Grants-in-Aid for Scientific Research [22390054] Funding Source: KAKEN
NR 31
TC 673
Z9 832
U1 0
U2 116
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 390
EP U148
DI 10.1038/nature10263
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200045
PM 21716291
DA 2026-03-09
ER

PT J
AU McIntosh, SW
   De Pontieu, B
   Carlsson, M
   Hansteen, V
   Boerner, P
   Goossens, M
AF McIntosh, Scott W.
   De Pontieu, Bart
   Carlsson, Mats
   Hansteen, Viggo
   Boerner, Paul
   Goossens, Marcel
TI Alfvenic waves with sufficient energy to power the quiet solar corona and fast solar wind
SO NATURE
LA English
DT Article
ID magnetohydrodynamic turbulence; driven; acceleration; chromosphere; model; holes; temperatures
AB Energy is required to heat the outer solar atmosphere to millions of degrees (refs 1, 2) and to accelerate the solar wind to hundreds of kilometres per second (refs 2-6). Alfven waves (travelling oscillations of ions and magnetic field) have been invoked as a possible mechanism to transport magneto-convective energy upwards along the Sun's magnetic field lines into the corona. Previous observations(7) of Alfvenic waves in the corona revealed amplitudes far too small (0.5 km s(-1)) to supply the energy flux (100-200 W m(-2)) required to drive the fast solar wind(8) or balance the radiative losses of the quiet corona(9). Here we report observations of the transition region (between the chromosphere and the corona) and of the corona that reveal how Alfvenic motions permeate the dynamic and finely structured outer solar atmosphere. The ubiquitous outward-propagating Alfvenic motions observed have amplitudes of the order of 20 km s(-1) and periods of the order of 100-500 s throughout the quiescent atmosphere (compatible with recent investigations(7,10)), and are energetic enough to accelerate the fast solar wind and heat the quiet corona.
C1 [McIntosh, Scott W.] Natl Ctr Atmospher Res, High Altitude Observ, Boulder, CO 80307 USA.
   [De Pontieu, Bart; Hansteen, Viggo; Boerner, Paul] Lockheed Martin Solar & Astrophys Lab, Palo Alto, CA 94304 USA.
   [Carlsson, Mats; Hansteen, Viggo] Univ Oslo, Inst Theoret Astrophys, N-0315 Oslo, Norway.
   [Goossens, Marcel] Katholieke Univ Leuven, Dept Math, Ctr Plasma Astrophys, B-3001 Heverlee, Belgium.
C3 National Center Atmospheric Research (NCAR) - USA; Lockheed Martin; University of Oslo; KU Leuven
RP McIntosh, SW (corresponding author), Natl Ctr Atmospher Res, High Altitude Observ, POB 3000, Boulder, CO 80307 USA.
EM mscott@ucar.edu
FU NSF
NR 23
TC 509
Z9 543
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 28
PY 2011
VL 475
IS 7357
BP 477
EP 480
DI 10.1038/nature10235
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900035
PM 21796206
DA 2026-03-09
ER

PT J
AU Reines, AE
   Sivakoff, GR
   Johnson, KE
   Brogan, CL
AF Reines, Amy E.
   Sivakoff, Gregory R.
   Johnson, Kelsey E.
   Brogan, Crystal L.
TI An actively accreting massive black hole in the dwarf starburst galaxy Henize 2-10
SO NATURE
LA English
DT Article
ID large-magellanic-cloud; super-star-clusters; radio; luminosity; emission; diffuse
AB Supermassive black holes are now thought to lie at the heart of every giant galaxy with a spheroidal component, including our own Milky Way(1,2). The birth and growth of the first 'seed' black holes in the earlier Universe, however, is observationally unconstrained(3) and we are only beginning to piece together a scenario for their subsequent evolution(4). Here we report that the nearby dwarf starburst galaxy Henize 2-10 (refs 5 and 6) contains a compact radio source at the dynamical centre of the galaxy that is spatially coincident with a hard X-ray source. From these observations, we conclude that Henize 2-10 harbours an actively accreting central black hole with a mass of approximately one million solar masses. This nearby dwarf galaxy, simultaneously hosting a massive black hole and an extreme burst of star formation, is analogous in many ways to galaxies in the infant Universe during the early stages of black-hole growth and galaxy mass assembly. Our results confirm that nearby star-forming dwarf galaxies can indeed form massive black holes, and that by implication so can their primordial counterparts. Moreover, the lack of a substantial spheroidal component in Henize 2-10 indicates that supermassive black-hole growth may precede the build-up of galaxy spheroids.
C1 [Reines, Amy E.; Sivakoff, Gregory R.; Johnson, Kelsey E.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Johnson, Kelsey E.; Brogan, Crystal L.] Natl Radio Astron Observ, Charlottesville, VA 22904 USA.
C3 University of Virginia; National Radio Astronomy Observatory (NRAO)
RP Reines, AE (corresponding author), Univ Virginia, Dept Astron, 530 McCormick Rd, Charlottesville, VA 22904 USA.
EM areines@virginia.edu
FU NASA; University of Virginia; NASA through the Chandra X-ray Observatory Center; NSF; David and Lucile Packard Foundation; NASA through Space Telescope Science Institute
NR 30
TC 205
Z9 228
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 66
EP 68
DI 10.1038/nature09724
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400034
PM 21217688
DA 2026-03-09
ER

PT J
AU Matson, CK
   Murphy, MW
   Sarver, AL
   Griswold, MD
   Bardwell, VJ
   Zarkower, D
AF Matson, Clinton K.
   Murphy, Mark W.
   Sarver, Aaron L.
   Griswold, Michael D.
   Bardwell, Vivian J.
   Zarkower, David
TI DMRT1 prevents female reprogramming in the postnatal mammalian testis
SO NATURE
LA English
DT Article
ID dm-domain gene; sex determination; ovarian failure; foxl2; differentiation; expression; mouse; sox9
AB Sex in mammals is determined in the fetal gonad by the presence or absence of the Y chromosome gene Sry, which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells(1). This pivotal decision in a single gonadal cell type ultimately controls sexual differentiation throughout the body. Sex determination can be viewed as a battle for primacy in the fetal gonad between a male regulatory gene network in which Sry activates Sox9 and a female network involving WNT/beta-catenin signalling(2). In females the primary sex-determining decision is not final: loss of the FOXL2 transcription factor in adult granulosa cells can reprogram granulosa cells into Sertoli cells(2). Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor(3) in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced and germ cells appear feminized. Thus Dmrt1 is essential to maintain mammalian testis determination, and competing regulatory networks maintain gonadal sex long after the fetal choice between male and female. Dmrt1 and Foxl2 are conserved throughout vertebrates(4,5) and Dmrt1-related sexual regulators are conserved throughout metazoans(3). Antagonism between Dmrt1 and Foxl2 for control of gonadal sex may therefore extend beyond mammals. Reprogramming due to loss of Dmrt1 also may help explain the aetiology of human syndromes linked to DMRT1, including disorders of sexual differentiation(6) and testicular cancer(7).
C1 [Matson, Clinton K.; Murphy, Mark W.; Bardwell, Vivian J.; Zarkower, David] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA.
   [Matson, Clinton K.; Murphy, Mark W.; Bardwell, Vivian J.; Zarkower, David] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Matson, Clinton K.; Bardwell, Vivian J.; Zarkower, David] Univ Minnesota, Mol Cellular Dev Biol & Genet Grad Program, Minneapolis, MN 55455 USA.
   [Sarver, Aaron L.; Bardwell, Vivian J.; Zarkower, David] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Griswold, Michael D.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 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; Washington State University
RP Zarkower, D (corresponding author), Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA.
EM bardw001@umn.edu; zarko001@umn.edu
FU NIH [GM59152]; Minnesota Medical Foundation; NSF; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD010808] Funding Source: NIH RePORTER
NR 31
TC 489
Z9 572
U1 4
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 101
EP +
DI 10.1038/nature10239
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300038
PM 21775990
DA 2026-03-09
ER

PT J
AU Evan, AT
   Kossin, JP
   Chung, C
   Ramanathan, V
AF Evan, Amato T.
   Kossin, James P.
   Chung, Chul 'Eddy'
   Ramanathan, V.
TI Arabian Sea tropical cyclones intensified by emissions of black carbon and other aerosols
SO NATURE
LA English
DT Article
ID vertical wind shear; indian-ocean; climate; impacts
AB Throughout the year, average sea surface temperatures in the Arabian Sea are warm enough to support the development of tropical cyclones(1), but the atmospheric monsoon circulation and associated strong vertical wind shear limits cyclone development and intensification, only permitting a pre-monsoon and post-monsoon period for cyclogenesis(1-4). Thus a recent increase in the intensity of tropical cyclones over the northern Indian Ocean(5) is thought to be related to the weakening of the climatological vertical wind shear(3,4). At the same time, anthropogenic emissions of aerosols have increased sixfold since the 1930s, leading to a weakening of the southwesterly lower-level and easterly upper-level winds that define the monsoonal circulation over the Arabian Sea(6-9). In principle, this aerosol-driven circulation modification could affect tropical cyclone intensity over the Arabian Sea, but so far no such linkage has been shown. Here we report an increase in the intensity of pre-monsoon Arabian Sea tropical cyclones during the period 1979-2010, and show that this change in storm strength is a consequence of a simultaneous upward trend in anthropogenic black carbon and sulphate emissions. We use a combination of observational, reanalysis and model data to demonstrate that the anomalous circulation, which is radiatively forced by these anthropogenic aerosols, reduces the basin-wide vertical wind shear, creating an environment more favourable for tropical cyclone intensification. Because most Arabian Sea tropical cyclones make landfall(1), our results suggest an additional impact on human health from regional air pollution.
C1 [Evan, Amato T.] Univ Virginia, Charlottesville, VA 22904 USA.
   [Kossin, James P.] NOAA, Natl Climat Data Ctr, Asheville, NC 28801 USA.
   [Kossin, James P.] NOAA, Cooperat Inst Meteorol Satellite Studies, Madison, WI 53706 USA.
   [Chung, Chul 'Eddy'] Gwangju Inst Sci & Technol, Kwangju 500712, South Korea.
   [Ramanathan, V.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
C3 University of Virginia; National Oceanic Atmospheric Admin (NOAA) - USA; National Center Atmospheric Research (NCAR) - USA; National Oceanic Atmospheric Admin (NOAA) - USA; Gwangju Institute of Science & Technology (GIST); University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Evan, AT (corresponding author), Univ Virginia, Charlottesville, VA 22904 USA.
EM ate9c@virginia.edu
FU National Oceanic & Atmospheric Administration (NOAA)/Climate Program Office [NA10OAR4310136]; Korea's Research Agency for Climate Science [RACS 2010-2603]; National Science Foundation [ATM-0721142]
NR 28
TC 160
Z9 179
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 NOV 3
PY 2011
VL 479
IS 7371
BP 94
EP U119
DI 10.1038/nature10552
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600038
PM 22051678
DA 2026-03-09
ER

PT J
AU Lu, FR
   Li, S
   Jiang, Y
   Jiang, J
   Fan, H
   Lu, GF
   Deng, D
   Dang, SY
   Zhang, X
   Wang, JW
   Yan, NE
AF Lu, Feiran
   Li, Shuo
   Jiang, Yang
   Jiang, Jing
   Fan, He
   Lu, Guifeng
   Deng, Dong
   Dang, Shangyu
   Zhang, Xu
   Wang, Jiawei
   Yan, Nieng
TI Structure and mechanism of the uracil transporter UraA
SO NATURE
LA English
DT Article
ID signature motif; functional-characterization; substrate recognition; xanthine permease; crystal-structure; escherichia-coli; molecular-basis; family; cloning; proteins
AB The nucleobase/ascorbate transporter (NAT) proteins, also known as nucleobase/cation symporter 2 (NCS2) proteins, are responsible for the uptake of nucleobases in all kingdoms of life and for the transport of vitamin C in mammals(1,2). Despite functional characterization of the NAT family members in bacteria, fungi and mammals, detailed structural information remains unavailable. Here we report the crystal structure of a representative NAT protein, the Escherichia coli uracil/H+ symporter UraA, in complex with uracil at a resolution of 2.8 angstrom. UraA has a novel structural fold, with 14 transmembrane segments (TMs) divided into two inverted repeats. A pair of antiparallel beta-strands is located between TM3 and TM10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analysis suggests that alternating access of the substrate may be achieved through conformational changes of the gate domain.
C1 [Lu, Feiran; Li, Shuo; Jiang, Yang; Jiang, Jing; Fan, He; Lu, Guifeng; Deng, Dong; Dang, Shangyu; Zhang, Xu; Wang, Jiawei; Yan, Nieng] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Lu, Feiran; Li, Shuo; Jiang, Yang; Jiang, Jing; Fan, He; Lu, Guifeng; Deng, Dong; Dang, Shangyu; Zhang, Xu; Wang, Jiawei; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University
RP Yan, NE (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918802, 2011CB910501]; Tsinghua University; National Natural Science Foundation of China [91017011]; Yuyuan Foundation; Li Foundation
NR 35
TC 173
Z9 181
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 243
EP 246
DI 10.1038/nature09885
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100048
PM 21423164
DA 2026-03-09
ER

PT J
AU He, FL
   Hubbell, SP
AF He, Fangliang
   Hubbell, Stephen P.
TI Species-area relationships always overestimate extinction rates from habitat loss
SO NATURE
LA English
DT Article
ID deforestation; patterns
AB Extinction from habitat loss is the signature conservation problem of the twenty-first century(1). Despite its importance, estimating extinction rates is still highly uncertain because no proven direct methods or reliable data exist for verifying extinctions. The most widely used indirect method is to estimate extinction rates by reversing the species-area accumulation curve, extrapolating backwards to smaller areas to calculate expected species loss. Estimates of extinction rates based on this method are almost always much higher than those actually observed(2-5). This discrepancy gave rise to the concept of an 'extinction debt', referring to species 'committed to extinction' owing to habitat loss and reduced population size but not yet extinct during a non-equilibrium period(6,7). Here we show that the extinction debt as currently defined is largely a sampling artefact due to an unrecognized difference between the underlying sampling problems when constructing a species-area relationship (SAR) and when extrapolating species extinction from habitat loss. The key mathematical result is that the area required to remove the last individual of a species (extinction) is larger, almost always much larger, than the sample area needed to encounter the first individual of a species, irrespective of species distribution and spatial scale. We illustrate these results with data from a global network of large, mapped forest plots and ranges of passerine bird species in the continental USA; and we show that overestimation can be greater than 160%. Although we conclude that extinctions caused by habitat loss require greater loss of habitat than previously thought, our results must not lead to complacency about extinction due to habitat loss, which is a real and growing threat.
C1 [He, Fangliang] Sun Yat Sen Univ, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China.
   [He, Fangliang] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China.
   [He, Fangliang] Univ Alberta, Dept Renewable Resources, Edmonton, AB T6G 2H1, Canada.
   [Hubbell, Stephen P.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Hubbell, Stephen P.] Smithsonian Trop Res Inst, Ctr Trop Forest Sci, Unit 0948, APO, AA 34002 USA.
C3 Sun Yat Sen University; Sun Yat Sen University; University of Alberta; University of California System; University of California Los Angeles; Smithsonian Institution; Smithsonian Tropical Research Institute
RP He, FL (corresponding author), Sun Yat Sen Univ, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China.
EM fhe@mail.sysu.edu.cn; shubbell@eeb.ucla.edu
FU Sun Yat-sen University; Natural Sciences and Engineering Research Council (Canada); NASA (National Aeronautics and Space Administration); US National Science Foundation
NR 30
TC 325
Z9 382
U1 9
U2 491
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 368
EP 371
DI 10.1038/nature09985
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400047
PM 21593870
DA 2026-03-09
ER

PT J
AU Choe, HW
   Kim, YJ
   Park, JH
   Morizumi, T
   Pai, EF
   Krauss, N
   Hofmann, KP
   Scheerer, P
   Ernst, OP
AF Choe, Hui-Woog
   Kim, Yong Ju
   Park, Jung Hee
   Morizumi, Takefumi
   Pai, Emil F.
   Krauss, Norbert
   Hofmann, Klaus Peter
   Scheerer, Patrick
   Ernst, Oliver P.
TI Crystal structure of metarhodopsin II
SO NATURE
LA English
DT Article
ID helix movement; rhodopsin; activation; transducin; ligand; displacement; conformation; spectroscopy; opsin; light
AB G-protein-coupled receptors (GPCRs) are seven transmembrane helix (TM) proteins that transduce signals into living cells by binding extracellular ligands and coupling to intracellular heterotrimeric Gproteins (G alpha beta gamma)(1). The photoreceptor rhodopsin couples to transducin and bears its ligand 11-cis-retinal covalently bound via a protonated Schiff base to the opsin apoprotein(2). Absorption of a photon causes retinal cis/trans isomerization and generates the agonist all-trans-retinal in situ. After early photoproducts, the active G-protein-binding intermediate metarhodopsin II (Meta II) is formed, in which the retinal Schiff base is still intact but deprotonated. Dissociation of the proton from the Schiff base breaks a major constraint in the protein and enables further activating steps, including an outward tilt of TM6 and formation of a large cytoplasmic crevice for uptake of the interacting C terminus of the G alpha subunit(3-5). Owing to Schiff base hydrolysis, Meta II is short-lived and notoriously difficult to crystallize. We therefore soaked opsin crystals with all-trans-retinal to form Meta II, presuming that the crystal's high concentration of opsin in an active conformation (Ops*)(6,7) may facilitate all-trans-retinal uptake and Schiff base formation. Here we present the 3.0 angstrom and 2.85 angstrom crystal structures, respectively, of Meta II alone or in complex with an 11-amino-acid C-terminal fragment derived from G alpha (G alpha CT2). G alpha CT2 binds in a large crevice at the cytoplasmic side, akin to the binding of a similar G alpha-derived peptide to Ops* (ref. 7). In the Meta II structures, the electron density from the retinal ligand seamlessly continues into the Lys 296 side chain, reflecting proper formation of the Schiff base linkage. The retinal is in a relaxed conformation and almost undistorted compared with pure crystalline all-trans-retinal. By comparison with early photoproducts we propose how retinal translocation and rotation induce the gross conformational changes characteristic for Meta II. The structures can now serve as models for the large GPCR family.
C1 [Choe, Hui-Woog; Kim, Yong Ju; Park, Jung Hee; Morizumi, Takefumi; Hofmann, Klaus Peter; Scheerer, Patrick; Ernst, Oliver P.] Charite, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Choe, Hui-Woog] Chonbuk Natl Univ, Coll Nat Sci, Dept Chem, Chonju 561756, South Korea.
   [Pai, Emil F.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Pai, Emil F.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Pai, Emil F.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada.
   [Krauss, Norbert] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Hofmann, Klaus Peter] Humboldt Univ, Zentrum Biophys & Bioinformat, D-10115 Berlin, Germany.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Jeonbuk National University; University of Toronto; University of Toronto; University of Toronto; University of London; Queen Mary University London; Humboldt University of Berlin
RP Choe, HW (corresponding author), Charite, Inst Med Phys & Biophys CC2, Charite Pl 1, D-10117 Berlin, Germany.
EM hwchoe@jbnu.ac.kr; klaus_peter.hofmann@charite.de; oliver.ernst@utoronto.ca
FU DFG [Sfb449, Sfb740]; ERC; Canada Research Chairs Program; Ministry of Education, Science and Technology [2010-0002738]; CBNU; Leibniz Graduate School of Molecular Biophysics, Berlin
NR 43
TC 572
Z9 681
U1 0
U2 150
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 651
EP U137
DI 10.1038/nature09789
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200046
PM 21389988
DA 2026-03-09
ER

PT J
AU Eiraku, M
   Takata, N
   Ishibashi, H
   Kawada, M
   Sakakura, E
   Okuda, S
   Sekiguchi, K
   Adachi, T
   Sasai, Y
AF Eiraku, Mototsugu
   Takata, Nozomu
   Ishibashi, Hiroki
   Kawada, Masako
   Sakakura, Eriko
   Okuda, Satoru
   Sekiguchi, Kiyotoshi
   Adachi, Taiji
   Sasai, Yoshiki
TI Self-organizing optic-cup morphogenesis in three-dimensional culture
SO NATURE
LA English
DT Article
ID retinal-pigment epithelium; embryonic stem-cells; eye development; apical constriction; mouse embryos; neural plate; shape change; vesicle; differentiation; rho
AB Balanced organogenesis requires the orchestration of multiple cellular interactions to create the collective cell behaviours that progressively shape developing tissues. It is currently unclear how individual, localized parts are able to coordinate with each other to develop a whole organ shape. Here we report the dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse embryonic stem cell aggregates. Embryonic-stem-cell-derived retinal epithelium spontaneously formed hemispherical epithelial vesicles that became patterned along their proximal-distal axis. Whereas the proximal portion differentiated into mechanically rigid pigment epithelium, the flexible distal portion progressively folded inward to form a shape reminiscent of the embryonic optic cup, exhibited interkinetic nuclear migration and generated stratified neural retinal tissue, as seen in vivo. We demonstrate that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulation of local epithelial properties.
C1 [Eiraku, Mototsugu; Takata, Nozomu; Kawada, Masako; Sakakura, Eriko; Sasai, Yoshiki] RIKEN Ctr Dev Biol, Organogenesis & Neurogenesis Grp, Kobe, Hyogo 6500047, Japan.
   [Eiraku, Mototsugu; Sakakura, Eriko; Sasai, Yoshiki] RIKEN Ctr Dev Biol, Dimens Tissue Anal Unit 4, Kobe, Hyogo 6500047, Japan.
   [Ishibashi, Hiroki; Okuda, Satoru; Adachi, Taiji] Kyoto Univ, Inst Frontier Med Sci, Dept Biomech, Kyoto 6068507, Japan.
   [Sekiguchi, Kiyotoshi] Osaka Univ, Inst Prot Res, Lab Extracellular Matrix Biochem, Suita, Osaka 5650871, Japan.
   [Adachi, Taiji] RIKEN, VCAD Syst Res Program, Computat Cell Biomech Team, Wako, Saitama 3510198, Japan.
C3 RIKEN; RIKEN; Kyoto University; University of Osaka; RIKEN
RP Eiraku, M (corresponding author), RIKEN Ctr Dev Biol, Organogenesis & Neurogenesis Grp, Kobe, Hyogo 6500047, Japan.
EM eiraku@cdb.riken.jp; yoshikisasai@cdb.riken.jp
FU MEXT; Knowledge Cluster Initiative at Kobe; S-Innovation Project; Leading Project for Realization of Regenerative Medicine; Grants-in-Aid for Scientific Research [20001007, 21370104, 22122006] Funding Source: KAKEN
NR 53
TC 1583
Z9 1903
U1 9
U2 334
PU 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 7
PY 2011
VL 472
IS 7341
BP 51
EP U73
DI 10.1038/nature09941
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400035
PM 21475194
DA 2026-03-09
ER

PT J
AU Beck, B
   Driessens, G
   Goossens, S
   Youssef, KK
   Kuchnio, A
   Caauwe, A
   Sotiropoulou, PA
   Loges, S
   Lapouge, G
   Candi, A
   Mascre, G
   Drogat, B
   Dekoninck, S
   Haigh, JJ
   Carmeliet, P
   Blanpain, C
AF Beck, Benjamin
   Driessens, Gregory
   Goossens, Steven
   Youssef, Khalil Kass
   Kuchnio, Anna
   Caauwe, Amelie
   Sotiropoulou, Panagiota A.
   Loges, Sonja
   Lapouge, Gaelle
   Candi, Aurelie
   Mascre, Guilhem
   Drogat, Benjamin
   Dekoninck, Sophie
   Haigh, Jody J.
   Carmeliet, Peter
   Blanpain, Cedric
TI A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours
SO NATURE
LA English
DT Article
ID vegf-a; cancer; growth; cells; neuropilin-1; catenin; mice
AB Angiogenesis is critical during tumour initiation and malignant progression(1). Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients(2). It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies(3). Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin(4,5). Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers.
C1 [Beck, Benjamin; Driessens, Gregory; Youssef, Khalil Kass; Caauwe, Amelie; Sotiropoulou, Panagiota A.; Lapouge, Gaelle; Candi, Aurelie; Mascre, Guilhem; Drogat, Benjamin; Dekoninck, Sophie; Blanpain, Cedric] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium.
   [Goossens, Steven; Haigh, Jody J.] Univ Ghent VIB, Dept Mol Biomed Res, Vasc Cell Biol Unit, B-9052 Ghent, Belgium.
   [Goossens, Steven; Kuchnio, Anna; Haigh, Jody J.] UGent Dept Mol Biomed Res, B-9052 Ghent, Belgium.
   [Kuchnio, Anna; Loges, Sonja; Carmeliet, Peter] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium.
   [Loges, Sonja; Carmeliet, Peter] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium.
C3 Universite Libre de Bruxelles; Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University; Flanders Institute for Biotechnology (VIB); KU Leuven; Flanders Institute for Biotechnology (VIB)
RP Blanpain, C (corresponding author), Univ Libre Bruxelles, IRIBHM, 808 Route Lennik, B-1070 Brussels, Belgium.
EM cedric.blanpain@ulb.ac.be
FU Brussels Region; Deutsche Krebshilfe; Hamburger Krebsgesellschaft; Roggenbuck Stiftung; Flemish Government; FNRS; Wallonia Region; Fondation Contre le Cancer; ULB foundation; fond Gaston Ithier; European Research Council (ERC); EMBO
NR 29
TC 379
Z9 444
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 399
EP +
DI 10.1038/nature10525
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100049
PM 22012397
DA 2026-03-09
ER

PT J
AU Batista, LFZ
   Pech, M
   Zhong, FL
   Nguyen, HN
   Xie, KT
   Zaug, AJ
   Crary, SM
   Choi, J
   Sebastiano, V
   Cherry, A
   Giri, N
   Wernig, M
   Alter, BP
   Cech, TR
   Savage, SA
   Pera, RAR
   Artandi, SE
AF Batista, Luis F. Z.
   Pech, MatthewF.
   Zhong, Franklin L.
   Nguyen, Ha Nam
   Xie, Kathleen T.
   Zaug, Arthur J.
   Crary, Sharon M.
   Choi, Jinkuk
   Sebastiano, Vittorio
   Cherry, Athena
   Giri, Neelam
   Wernig, Marius
   Alter, Blanche P.
   Cech, Thomas R.
   Savage, Sharon A.
   Pera, Renee A. Reijo
   Artandi, Steven E.
TI Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID reverse-transcriptase; mouse; rna; localization; anticipation; elongation; generation; mutations; length; leads
AB The differentiation of patient-derived induced pluripotent stem cells (iPSCs) to committed fates such as neurons, muscle and liver is a powerful approach for understanding key parameters of human development and disease(1-6). Whether undifferentiated iPSCs themselves can be used to probe disease mechanisms is uncertain. Dyskeratosis congenita is characterized by defective maintenance of blood, pulmonary tissue and epidermal tissues and is caused by mutations in genes controlling telomere homeostasis(7,8). Short telomeres, a hallmark of dyskeratosis congenita, impair tissue stem cell function in mouse models, indicating that a tissue stem cell defect may underlie the pathophysiology of dyskeratosis congenita(9,10). Here we show that even in the undifferentiated state, iPSCs from dyskeratosis congenita patients harbour the precise biochemical defects characteristic of each form of the disease and that the magnitude of the telomere maintenance defect in iPSCs correlates with clinical severity. In iPSCs from patients with heterozygous mutations in TERT, the telomerase reverse transcriptase, a 50% reduction in telomerase levels blunts the natural telomere elongation that accompanies reprogramming. In contrast, mutation of dyskerin (DKC1) in X-linked dyskeratosis congenita severely impairs telomerase activity by blocking telomerase assembly and disrupts telomere elongation during reprogramming. In iPSCs from a form of dyskeratosis congenita caused by mutations in TCAB1 (also known as WRAP53), telomerase catalytic activity is unperturbed, yet the ability of telomerase to lengthen telomeres is abrogated, because telomerase mislocalizes from Cajal bodies to nucleoli within the iPSCs. Extended culture of DKC1-mutant iPSCs leads to progressive telomere shortening and eventual loss of self-renewal, indicating that a similar process occurs in tissue stem cells in dyskeratosis congenita patients. These findings in iPSCs from dyskeratosis congenita patients reveal that undifferentiated iPSCs accurately recapitulate features of a human stem cell disease and may serve as a cell-culture-based system for the development of targeted therapeutics.
C1 [Batista, Luis F. Z.; Pech, MatthewF.; Zhong, Franklin L.; Choi, Jinkuk; Artandi, Steven E.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Pech, MatthewF.; Zhong, Franklin L.; Choi, Jinkuk; Pera, Renee A. Reijo; Artandi, Steven E.] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA.
   [Nguyen, Ha Nam; Sebastiano, Vittorio; Wernig, Marius; Pera, Renee A. Reijo] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Xie, Kathleen T.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Zaug, Arthur J.; Crary, Sharon M.; Cech, Thomas R.] Univ Colorado, Howard Hughes Med Inst, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Sebastiano, Vittorio; Cherry, Athena; Wernig, Marius] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20852 USA.
   [Artandi, Steven E.] Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; University of Colorado System; University of Colorado Boulder; Howard Hughes Medical Institute; Stanford University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Stanford University
RP Artandi, SE (corresponding author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM sartandi@stanford.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA125453, R01 CA111691, T32 CA009302] Funding Source: Medline; NHLBI NIH HHS [U01 HL100397, RC1 HL100361] Funding Source: Medline; NIA NIH HHS [R01 AG033747] Funding Source: Medline; Intramural NIH HHS Funding Source: Medline; National Cancer Institute [ZIACP010190, T32CA009302] Funding Source: NIH RePORTER
NR 37
TC 206
Z9 249
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 399
EP +
DI 10.1038/nature10084
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100050
PM 21602826
DA 2026-03-09
ER

PT J
AU Burgisser, A
   Bergantz, GW
AF Burgisser, Alain
   Bergantz, George W.
TI A rapid mechanism to remobilize and homogenize highly crystalline magma bodies
SO NATURE
LA English
DT Article
ID prandtl numbers; rejuvenation; evolution; body; emplacement; convection; generation; viscosity; colorado; plutons
AB The largest products of magmatic activity on Earth, the great bodies of granite and their corresponding large eruptions, have a dual nature: homogeneity at the large scale and spatial and temporal heterogeneity at the small scale(1-4). This duality calls for a mechanism that selectively removes the large-scale heterogeneities associated with the incremental assembly(4) of these magmatic systems and yet occurs rapidly despite crystal-rich, viscous conditions seemingly resistant to mixing(2,5). Here we show that a simple dynamic template can unify a wide range of apparently contradictory observations from both large plutonic bodies and volcanic systems by a mechanism of rapid remobilization (unzipping) of highly viscous crystal-rich mushes. We demonstrate that this remobilization can lead to rapid overturn and produce the observed juxtaposition of magmatic materials with very disparate ages and complex chemical zoning. What distinguishes our model is the recognition that the process has two stages. Initially, a stiff mushy magma is reheated from below, producing a reduction in crystallinity that leads to the growth of a subjacent buoyant mobile layer. When the thickening mobile layer becomes sufficiently buoyant, it penetrates the overlying viscous mushy magma. This second stage rapidly exports homogenized material from the lower mobile layer to the top of the system, and leads to partial overturn within the viscous mush itself as an additional mechanism of mixing. Model outputs illustrate that unzipping can rapidly produce large amounts of mobile magma available for eruption. The agreement between calculated and observed unzipping rates for historical eruptions at Pinatubo and at Montserrat demonstrates the general applicability of the model. This mechanism furthers our understanding of both the formation of periodically homogenized plutons (crust building) and of ignimbrites by large eruptions.
C1 [Burgisser, Alain] Univ Tours, Univ Orleans, CNRS INSU, Inst Sci Terre Orleans, F-45071 Orleans 2, France.
   [Bergantz, George W.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
C3 Universite de Tours; Universite de Orleans; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Washington; University of Washington Seattle
RP Burgisser, A (corresponding author), Univ Tours, Univ Orleans, CNRS INSU, Inst Sci Terre Orleans, 1A Rue Ferolerie, F-45071 Orleans 2, France.
EM burgisse@cnrs-orleans.fr
FU ERC [202844]; National Health and Medical Research Council (NHMRC) [1049884] Funding Source: National Health and Medical Research Council (NHMRC); Directorate For Geosciences; Division Of Earth Sciences [1049884] Funding Source: National Science Foundation; European Research Council (ERC) [202844] Funding Source: European Research Council (ERC)
NR 30
TC 218
Z9 251
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 212
EP U97
DI 10.1038/nature09799
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200036
PM 21368760
DA 2026-03-09
ER

PT J
AU Deltcheva, E
   Chylinski, K
   Sharma, CM
   Gonzales, K
   Chao, YJ
   Pirzada, ZA
   Eckert, MR
   Vogel, J
   Charpentier, E
AF Deltcheva, Elitza
   Chylinski, Krzysztof
   Sharma, Cynthia M.
   Gonzales, Karine
   Chao, Yanjie
   Pirzada, Zaid A.
   Eckert, Maria R.
   Vogel, Joerg
   Charpentier, Emmanuelle
TI CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III
SO NATURE
LA English
DT Article
ID provides acquired-resistance; immune-system; bacteria; repeats; gene; endoribonuclease; mechanisms; virulence; phages; dna
AB CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.
C1 [Deltcheva, Elitza; Chylinski, Krzysztof; Charpentier, Emmanuelle] Umea Univ, Dept Mol Biol, UCMR, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden.
   [Deltcheva, Elitza; Chylinski, Krzysztof; Gonzales, Karine; Pirzada, Zaid A.; Eckert, Maria R.; Charpentier, Emmanuelle] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
   [Sharma, Cynthia M.; Chao, Yanjie; Vogel, Joerg] Univ Wurzburg, ZINF Res Ctr Infect Dis, D-97080 Wurzburg, Germany.
   [Chao, Yanjie; Vogel, Joerg] Univ Wurzburg, RNA Biol Grp, Inst Mol Infect Biol, D-97080 Wurzburg, Germany.
C3 Umea University; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); University of Vienna; University of Wurzburg; University of Wurzburg
RP Charpentier, E (corresponding author), Umea Univ, Dept Mol Biol, UCMR, Lab Mol Infect Med Sweden MIMS, S-90187 Umea, Sweden.
EM emmanuelle.charpentier@mims.umu.se
FU European Community [BACRNAs-018618]; Austrian Science Fund (FWF) [P17238-B09, W1207-B09]; Austrian Agency for Research Promotion (FFG) [812138-SCK/KUG]; Theodor Korner Fonds; Umea University; Swedish Research Council; IMPRS-IDI; German Research Council (DFG) [SPP1258, Vo875/4]; German Ministry of Education and Research (BMBF) [01GS0806/JV-BMBF-01, 0315836]; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF)
NR 66
TC 1884
Z9 3186
U1 26
U2 1088
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 602
EP +
DI 10.1038/nature09886
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200035
PM 21455174
DA 2026-03-09
ER

PT J
AU Wakim, LM
   Bevan, MJ
AF Wakim, Linda M.
   Bevan, Michael J.
TI Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection
SO NATURE
LA English
DT Article
ID immune-responses; live cells; in-vivo; complexes; antigens
AB After an infection, cytotoxic T lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (MHC) class I molecules expressed by antigen-presenting cells (APCs)(1). Professional APCs specialized for T-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and MHC class I loading in a process referred to as cross-presentation(2). An alternative way, referred to as 'cross-dressing', by which an uninfected APC could present antigen was postulated to be by the transfer of preformed peptide-MHC complexes from the surface of an infected cell to the APC without the need of further processing(3). Here we show that this mechanism exists and boosts the antiviral response of mouse memory CD8(+) T cells. A number of publications have demonstrated sharing of peptide-loaded MHC molecules in vitro(4-7). Our in vitro experiments demonstrate that cross-dressing APCs do not acquire peptide-MHC complexes in the form of exosomes released by donor cells. Rather, the APCs and donor cells have to contact each other for the transfer to occur. After a viral infection, we could isolate cross-dressed APCs able to present viral antigen in vitro. Furthermore, using the diphtheria toxin system to selectively eliminate APCs that could only acquire viral peptide-MHC complexes by cross-dressing, we show that such presentation can promote the expansion of resting memory T cells. Notably, naive T cells were excluded from taking part in the response. Cross-dressing is a mechanism of antigen presentation used by dendritic cells that may have a significant role in activating previously primed CD8(+) T cells.
C1 [Wakim, Linda M.; Bevan, Michael J.] Univ Washington, Howard Hughes Med Inst, Dept Immunol, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Bevan, MJ (corresponding author), Univ Washington, Howard Hughes Med Inst, Dept Immunol, Box 357370, Seattle, WA 98195 USA.
EM mbevan@u.washington.edu
FU Howard Hughes Medical Institute; National Institutes of Health; National Health and Medical Research Council of Australia
NR 18
TC 250
Z9 307
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 629
EP 632
DI 10.1038/nature09863
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200041
PM 21455179
DA 2026-03-09
ER

PT J
AU Orvedahl, A
   Sumpter, R
   Xiao, GH
   Ng, A
   Zou, ZJ
   Tang, Y
   Narimatsu, M
   Gilpin, C
   Sun, QH
   Roth, M
   Forst, CV
   Wrana, JL
   Zhang, YE
   Luby-Phelps, K
   Xavier, RJ
   Xie, Y
   Levine, B
AF Orvedahl, Anthony
   Sumpter, Rhea, Jr.
   Xiao, Guanghua
   Ng, Aylwin
   Zou, Zhongju
   Tang, Yi
   Narimatsu, Masahiro
   Gilpin, Christopher
   Sun, Qihua
   Roth, Michael
   Forst, Christian V.
   Wrana, Jeffrey L.
   Zhang, Ying E.
   Luby-Phelps, Katherine
   Xavier, Ramnik J.
   Xie, Yang
   Levine, Beth
TI Image-based genome-wide siRNA screen identifies selective autophagy factors
SO NATURE
LA English
DT Article
ID ubiquitin ligase; degradation; p62/sqstm1; mitophagy; protein; system; parkin; vdac1
AB Selective autophagy involves the recognition and targeting of specific cargo, such as damaged organelles, misfolded proteins, or invading pathogens for lysosomal destruction(1-4). Yeast genetic screens have identified proteins required for different forms of selective autophagy, including cytoplasm-to-vacuole targeting, pexophagy and mitophagy, and mammalian genetic screens have identified proteins required for autophagy regulation(5). However, there have been no systematic approaches to identify molecular determinants of selective autophagy in mammalian cells. Here, to identify mammalian genes required for selective autophagy, we performed a high-content, image-based, genome-wide small interfering RNA screen to detect genes required for the colocalization of Sindbis virus capsid protein with autophagolysosomes. We identified 141 candidate genes required for viral autophagy, which were enriched for cellular pathways related to messenger RNA processing, interferon signalling, vesicle trafficking, cytoskeletal motor function and metabolism. Ninety-six of these genes were also required for Parkin-mediated mitophagy, indicating that common molecular determinants may be involved in autophagic targeting of viral nucleocapsids and autophagic targeting of damaged mitochondria. Murine embryonic fibroblasts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in the autophagosomal targeting of Sindbis and herpes simplex viruses and in the clearance of damaged mitochondria. Moreover, SMURF1-deficient mice accumulate damaged mitochondria in the heart, brain and liver. Thus, our study identifies candidate determinants of selective autophagy, and defines SMURF1 as a newly recognized mediator of both viral autophagy and mitophagy.
C1 [Orvedahl, Anthony; Sumpter, Rhea, Jr.; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Orvedahl, Anthony; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [Sumpter, Rhea, Jr.; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA.
   [Xiao, Guanghua; Forst, Christian V.; Xie, Yang] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Ng, Aylwin; Xavier, Ramnik J.] MIT, Cambridge, MA 02142 USA.
   [Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Tang, Yi; Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Narimatsu, Masahiro; Wrana, Jeffrey L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada.
   [Gilpin, Christopher; Luby-Phelps, Katherine] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Roth, Michael] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Roth, Michael; Xie, Yang; Levine, Beth] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
   [Wrana, Jeffrey L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Toronto
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 [AI109617, CA84254, UL1 RR024982, AI062773, DK83756, DK086502, DK043351]; NSF [DMS-0907562]; Center for Cancer Research, National Cancer Institute; National Cancer Institute [ZIABC011168] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351, P30DK040561] Funding Source: NIH RePORTER; Division Of Mathematical Sciences; Direct For Mathematical & Physical Scien [0906545, 0907562] Funding Source: National Science Foundation
NR 25
TC 416
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 DEC 1
PY 2011
VL 480
IS 7375
BP 113
EP 117
DI 10.1038/nature10546
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900045
PM 22020285
DA 2026-03-09
ER

PT J
AU Teufel, JD
   Li, D
   Allman, MS
   Cicak, K
   Sirois, AJ
   Whittaker, JD
   Simmonds, RW
AF Teufel, J. D.
   Li, Dale
   Allman, M. S.
   Cicak, K.
   Sirois, A. J.
   Whittaker, J. D.
   Simmonds, R. W.
TI Circuit cavity electromechanics in the strong-coupling regime
SO NATURE
LA English
DT Article
ID nanomechanical motion; mechanical resonator; induced transparency; ground-state; back-action; radiation
AB Demonstrating and exploiting the quantum nature of macroscopic mechanical objects would help us to investigate directly the limitations of quantum-based measurements and quantum information protocols, as well as to test long-standing questions about macroscopic quantum coherence(1-3). Central to this effort is the necessity of long-lived mechanical states. Previous efforts have witnessed quantum behaviour(4), but for a low-quality-factor mechanical system. The field of cavity optomechanics and electromechanics(5,6), in which a high-quality-factor mechanical oscillator is parametrically coupled to an electromagnetic cavity resonance, provides a practical architecture for cooling, manipulation and detection of motion at the quantum level(1). One requirement is strong coupling(7-9), in which the interaction between the two systems is faster than the dissipation of energy from either system. Here, by incorporating a free-standing, flexible aluminium membrane into a lumped-element superconducting resonant cavity, we have increased the single-photon coupling strength between these two systems by more than two orders of magnitude, compared to previously obtained coupling strengths. A parametric drive tone at the difference frequency between the mechanical oscillator and the cavity resonance dramatically increases the overall coupling strength, allowing us to completely enter the quantum-enabled, strong-coupling regime. This is evidenced by a maximum normal-mode splitting of nearly six bare cavity linewidths. Spectroscopic measurements of these 'dressed states' are in excellent quantitative agreement with recent theoretical predictions(10,11). The basic circuit architecture presented here provides a feasible path to ground-state cooling and subsequent coherent control and measurement of long-lived quantum states of mechanical motion.
C1 [Teufel, J. D.; Li, Dale; Allman, M. S.; Cicak, K.; Sirois, A. J.; Whittaker, J. D.; Simmonds, R. W.] NIST, Boulder, CO 80305 USA.
C3 National Institute of Standards & Technology (NIST) - USA
RP Teufel, JD (corresponding author), NIST, 325 Broadway, Boulder, CO 80305 USA.
EM john.teufel@nist.gov
NR 30
TC 733
Z9 822
U1 2
U2 184
PU 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 10
PY 2011
VL 471
IS 7337
BP 204
EP 208
DI 10.1038/nature09898
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200034
PM 21390127
DA 2026-03-09
ER

PT J
AU Manney, GL
   Santee, ML
   Rex, M
   Livesey, NJ
   Pitts, MC
   Veefkind, P
   Nash, ER
   Wohltmann, I
   Lehmann, R
   Froidevaux, L
   Poole, LR
   Schoeberl, MR
   Haffner, DP
   Davies, J
   Dorokhov, V
   Gernandt, H
   Johnson, B
   Kivi, R
   Kyrö, E
   Larsen, N
   Levelt, PF
   Makshtas, A
   McElroy, CT
   Nakajima, H
   Parrondo, MC
   Tarasick, DW
   von der Gathen, P
   Walker, KA
   Zinoviev, NS
AF Manney, Gloria L.
   Santee, Michelle L.
   Rex, Markus
   Livesey, Nathaniel J.
   Pitts, Michael C.
   Veefkind, Pepijn
   Nash, Eric R.
   Wohltmann, Ingo
   Lehmann, Ralph
   Froidevaux, Lucien
   Poole, Lamont R.
   Schoeberl, Mark R.
   Haffner, David P.
   Davies, Jonathan
   Dorokhov, Valery
   Gernandt, Hartwig
   Johnson, Bryan
   Kivi, Rigel
   Kyro, Esko
   Larsen, Niels
   Levelt, Pieternel F.
   Makshtas, Alexander
   McElroy, C. Thomas
   Nakajima, Hideaki
   Concepcion Parrondo, Maria
   Tarasick, David W.
   von der Gathen, Peter
   Walker, Kaley A.
   Zinoviev, Nikita S.
TI Unprecedented Arctic ozone loss in 2011
SO NATURE
LA English
DT Article
ID stratospheric polar vortex; microwave limb sounder; chemical depletion; cloud observations; transport; mls; climatology; antarctica; chemistry; dynamics
AB Chemical ozone destruction occurs over both polar regions in local winter-spring. In the Antarctic, essentially complete removal of lower-stratospheric ozone currently results in an ozone hole every year, whereas in the Arctic, ozone loss is highly variable and has until now been much more limited. Here we demonstrate that chemical ozone destruction over the Arctic in early 2011 was-for the first time in the observational record-comparable to that in the Antarctic ozone hole. Unusually long-lasting cold conditions in the Arctic lower stratosphere led to persistent enhancement in ozone-destroying forms of chlorine and to unprecedented ozone loss, which exceeded 80 per cent over 18-20 kilometres altitude. Our results show that Arctic ozone holes are possible even with temperatures much milder than those in the Antarctic. We cannot at present predict when such severe Arctic ozone depletion may be matched or exceeded.
C1 [Manney, Gloria L.; Santee, Michelle L.; Livesey, Nathaniel J.; Froidevaux, Lucien] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Manney, Gloria L.] New Mexico Inst Min & Technol, Socorro, NM 87801 USA.
   [Rex, Markus; Wohltmann, Ingo; Lehmann, Ralph; Gernandt, Hartwig; von der Gathen, Peter] Alfred Wegener Inst Polar & Marine Res, D-14473 Potsdam, Germany.
   [Pitts, Michael C.] NASA, Langley Res Ctr, Hampton, VA 23681 USA.
   [Veefkind, Pepijn; Levelt, Pieternel F.] Royal Netherlands Meteorol Inst, NL-3730 AE De Bilt, Netherlands.
   [Veefkind, Pepijn; Levelt, Pieternel F.] Delft Univ Technol, NL-2600 GA Delft, Netherlands.
   [Nash, Eric R.; Haffner, David P.] Sci Syst & Applicat Inc, Lanham, MD 20706 USA.
   [Poole, Lamont R.] Sci Syst & Applicat Inc, Hampton, VA 23666 USA.
   [Schoeberl, Mark R.] Sci & Technol Corp, Lanham, MD 20706 USA.
   [Davies, Jonathan; McElroy, C. Thomas; Tarasick, David W.] Environm Canada, Toronto, ON M3H 5T4, Canada.
   [Dorokhov, Valery] Cent Aerol Observ, Dolgoprudnyi 141700, Russia.
   [Johnson, Bryan] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Kivi, Rigel; Kyro, Esko] Finnish Meteorol Inst, Arctic Res Ctr, Sodankyla 99600, Finland.
   [Larsen, Niels] Danish Meteorol Inst, Danish Climate Ctr, DK-2100 Copenhagen, Denmark.
   [Levelt, Pieternel F.] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands.
   [Makshtas, Alexander; Zinoviev, Nikita S.] Arctic & Antarctic Res Inst, St Petersburg 199397, Russia.
   [Nakajima, Hideaki] Natl Inst Environm Studies, Tsukuba, Ibaraki 3058506, Japan.
   [Concepcion Parrondo, Maria] Natl Inst Aerosp Technol, Torrejon De Ardoz 28850, Spain.
   [Walker, Kaley A.] Univ Toronto, Toronto, ON M5S 1A7, Canada.
C3 California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); New Mexico Institute of Mining Technology; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; National Aeronautics & Space Administration (NASA); NASA Langley Research Center; Royal Netherlands Meteorological Institute; Delft University of Technology; Science Systems & Applications Inc; Science Systems & Applications Inc; Environment & Climate Change Canada; National Oceanic Atmospheric Admin (NOAA) - USA; Finnish Meteorological Institute; Danish Meteorological Institute DMI; Eindhoven University of Technology; Arctic & Antarctic Research Institute; National Institute for Environmental Studies - Japan; University of Toronto
RP Manney, GL (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM Gloria.L.Manney@jpl.nasa.gov; Michelle.L.Santee@jpl.nasa.gov
FU OMI; CALIPSO; Match science teams; Aura project; Environment Canada; Canadian Space Agency; Academy of Finland; EC DG Research; NASA; Grants-in-Aid for Scientific Research [20244077] Funding Source: KAKEN
NR 59
TC 515
Z9 579
U1 3
U2 291
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 469
EP U65
DI 10.1038/nature10556
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200034
PM 21964337
DA 2026-03-09
ER

PT J
AU Struck, TH
   Paul, C
   Hill, N
   Hartmann, S
   Hösel, C
   Kube, M
   Lieb, B
   Meyer, A
   Tiedemann, R
   Purschke, G
   Bleidorn, C
AF Struck, Torsten H.
   Paul, Christiane
   Hill, Natascha
   Hartmann, Stefanie
   Hoesel, Christoph
   Kube, Michael
   Lieb, Bernhard
   Meyer, Achim
   Tiedemann, Ralph
   Purschke, Guenter
   Bleidorn, Christoph
TI Phylogenomic analyses unravel annelid evolution
SO NATURE
LA English
DT Article
ID polychaetes annelida; character loss; lophotrochozoa; position; myzostomida; reconstruction; segmentation; clitellata; accuracy; models
AB Annelida, the ringed worms, is a highly diverse animal phylum that includes more than 15,000 described species and constitutes the dominant benthic macrofauna from the intertidal zone down to the deep sea. A robust annelid phylogeny would shape our understanding of animal body-plan evolution and shed light on the bilaterian ground pattern. Traditionally, Annelida has been split into two major groups: Clitellata (earthworms and leeches) and polychaetes (bristle worms), but recent evidence suggests that other taxa that were once considered to be separate phyla (Sipuncula, Echiura and Siboglinidae (also known as Pogonophora)) should be included in Annelida(1-4). However, the deep-level evolutionary relationships of Annelida are still poorly understood, and a robust reconstruction of annelid evolutionary history is needed. Here we show that phylogenomic analyses of 34 annelid taxa, using 47,953 amino acid positions, recovered a well-supported phylogeny with strong support for major splits. Our results recover chaetopterids, myzostomids and sipunculids in the basal part of the tree, although the position of Myzostomida remains uncertain owing to its long branch. The remaining taxa are split into two clades: Errantia (which includes the model annelid Platynereis), and Sedentaria (which includes Clitellata). Ancestral character trait reconstructions indicate that these clades show adaptation to either an errant or a sedentary lifestyle, with alteration of accompanying morphological traits such as peristaltic movement, parapodia and sensory perception. Finally, life history characters in Annelida seem to be phylogenetically informative.
C1 [Struck, Torsten H.; Hoesel, Christoph; Purschke, Guenter] Univ Osnabruck, Biol Chem FB05, AG Zool, D-49069 Osnabruck, Germany.
   [Paul, Christiane; Tiedemann, Ralph; Bleidorn, Christoph] Univ Potsdam, Inst Biochem & Biol, Unit Evolutionary Biol Systemat Zool, D-14476 Potsdam, Germany.
   [Hill, Natascha; Hartmann, Stefanie] Univ Potsdam, Inst Biochem & Biol, Unit Bioinformat, D-14476 Potsdam, Germany.
   [Kube, Michael] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Lieb, Bernhard; Meyer, Achim] Johannes Gutenberg Univ Mainz, Inst Zool, D-55099 Mainz, Germany.
   [Bleidorn, Christoph] Univ Leipzig, Inst Biol Mol Evolut & Systemat Anim 2, D-04103 Leipzig, Germany.
C3 University Osnabruck; University of Potsdam; University of Potsdam; Max Planck Society; Johannes Gutenberg University of Mainz; Leipzig University
RP Struck, TH (corresponding author), Univ Osnabruck, Biol Chem FB05, AG Zool, Barbarastr 11, D-49069 Osnabruck, Germany.
EM struck@biologie.uni-osnabrueck.de; bleidorn@uni-leipzig.de
FU marine biological stations in Bamfield; Helgoland; List and Roscoff for collection of annelids; Deutsche Forschungsgemeinschaft [DFG-STR 683/5-2, DFG-Pu-84/5-1, DFG-TI-349/4-1, DFG Li 998/3-1, DFG-HA 5744/1-1, DFG-BL-787/2-1]
NR 55
TC 368
Z9 413
U1 3
U2 292
PU 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 3
PY 2011
VL 471
IS 7336
BP 95
EP U113
DI 10.1038/nature09864
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100041
PM 21368831
DA 2026-03-09
ER

PT J
AU Foley, JA
   Ramankutty, N
   Brauman, KA
   Cassidy, ES
   Gerber, JS
   Johnston, M
   Mueller, ND
   O'Connell, C
   Ray, DK
   West, PC
   Balzer, C
   Bennett, EM
   Carpenter, SR
   Hill, J
   Monfreda, C
   Polasky, S
   Rockström, J
   Sheehan, J
   Siebert, S
   Tilman, D
   Zaks, DPM
AF Foley, Jonathan A.
   Ramankutty, Navin
   Brauman, Kate A.
   Cassidy, Emily S.
   Gerber, James S.
   Johnston, Matt
   Mueller, Nathaniel D.
   O'Connell, Christine
   Ray, Deepak K.
   West, Paul C.
   Balzer, Christian
   Bennett, Elena M.
   Carpenter, Stephen R.
   Hill, Jason
   Monfreda, Chad
   Polasky, Stephen
   Rockstrom, Johan
   Sheehan, John
   Siebert, Stefan
   Tilman, David
   Zaks, David P. M.
TI Solutions for a cultivated planet
SO NATURE
LA English
DT Article
ID greenhouse-gas emissions; crop yields; land-use; agricultural intensification; water-resources; climate; phosphorus; management; croplands; future
AB Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.
C1 [Foley, Jonathan A.; Brauman, Kate A.; Cassidy, Emily S.; Gerber, James S.; Johnston, Matt; Mueller, Nathaniel D.; O'Connell, Christine; Ray, Deepak K.; West, Paul C.; Hill, Jason; Polasky, Stephen; Sheehan, John; Tilman, David] Univ Minnesota, Inst Environm IonE, St Paul, MN 55108 USA.
   [Ramankutty, Navin] McGill Univ, Dept Geog, Montreal, PQ H3A 2K6, Canada.
   [Ramankutty, Navin] McGill Univ, Global Environm & Climate Change Ctr, Montreal, PQ H3A 2K6, Canada.
   [O'Connell, Christine] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Bennett, Elena M.] McGill Univ, Sch Environm, Ste Anne De Bellevue, PQ H9X 3V9, Canada.
   [Bennett, Elena M.] McGill Univ, Dept Nat Resource Sci, Ste Anne De Bellevue, PQ H9X 3V9, Canada.
   [Carpenter, Stephen R.] Univ Wisconsin, Ctr Limnol, Madison, WI 53706 USA.
   [Hill, Jason] Univ Minnesota, Dept Bioprod & Biosyst Engn, St Paul, MN 55108 USA.
   [Monfreda, Chad] Arizona State Univ, CSPO, Tempe, AZ 85287 USA.
   [Polasky, Stephen] Univ Minnesota, Dept Appl Econ, St Paul, MN 55108 USA.
   [Rockstrom, Johan] Stockholm Univ, Stockholm Resilience Ctr, SE-10691 Stockholm, Sweden.
   [Siebert, Stefan] Univ Bonn, Inst Crop Sci & Resource Conservat, D-53115 Bonn, Germany.
   [Tilman, David] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [Zaks, David P. M.] Univ Wisconsin, Ctr Sustainabil & Global Environm SAGE, Madison, WI 53726 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; McGill University; McGill University; University of California System; University of California Santa Barbara; McGill University; McGill University; University of Wisconsin System; University of Wisconsin Madison; University of Minnesota System; University of Minnesota Twin Cities; Arizona State University; Arizona State University-Tempe; University of Minnesota System; University of Minnesota Twin Cities; Stockholm University; University of Bonn; University of Minnesota System; University of Minnesota Twin Cities; University of Wisconsin System; University of Wisconsin Madison
RP Foley, JA (corresponding author), Univ Minnesota, Inst Environm IonE, 1954 Buford Ave, St Paul, MN 55108 USA.
EM jfoley@umn.edu
FU NASA; National Science Foundation; Stockholm Resilience Centre; Division Of Environmental Biology; Direct For Biological Sciences [0822700] Funding Source: National Science Foundation
NR 72
TC 5837
Z9 7017
U1 112
U2 5294
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 337
EP 342
DI 10.1038/nature10452
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100036
PM 21993620
DA 2026-03-09
ER

PT J
AU McConnell, NJ
   Ma, CP
   Gebhardt, K
   Wright, SA
   Murphy, JD
   Lauer, TR
   Graham, JR
   Richstone, DO
AF McConnell, Nicholas J.
   Ma, Chung-Pei
   Gebhardt, Karl
   Wright, Shelley A.
   Murphy, Jeremy D.
   Lauer, Tod R.
   Graham, James R.
   Richstone, Douglas O.
TI Two ten-billion-solar-mass black holes at the centres of giant elliptical galaxies
SO NATURE
LA English
DT Article
ID sigma; mass; evolution; quasars; mergers
AB Observational work conducted over the past few decades indicates that all massive galaxies have supermassive black holes at their centres. Although the luminosities and brightness fluctuations of quasars in the early Universe suggest that some were powered by black holes with masses greater than 10 billion solar masses(1,2), the remnants of these objects have not been found in the nearby Universe. The giant elliptical galaxy Messier 87 hosts the hitherto most massive known black hole, which has a mass of 6.3 billion solar masses(3,4). Here we report that NGC 3842, the brightest galaxy in a cluster at a distance from Earth of 98 megaparsecs, has a central black hole with a mass of 9.7 billion solar masses, and that a black hole of comparable or greater mass is present in NGC 4889, the brightest galaxy in the Coma cluster (at a distance of 103 megaparsecs). These two black holes are significantly more massive than predicted by linearly extrapolating the widely used correlations between black-hole mass and the stellar velocity dispersion or bulge luminosity of the host galaxy(5-9). Although these correlations remain useful for predicting black-hole masses in less massive elliptical galaxies, our measurements suggest that different evolutionary processes influence the growth of the largest galaxies and their black holes.
C1 [McConnell, Nicholas J.; Ma, Chung-Pei; Wright, Shelley A.; Graham, James R.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Gebhardt, Karl; Murphy, Jeremy D.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Lauer, Tod R.] Natl Opt Astron Observ, Tucson, AZ 85726 USA.
   [Graham, James R.] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Richstone, Douglas O.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
C3 University of California System; University of California Berkeley; University of Texas System; University of Texas Austin; National Optical Astronomy Observatory; University of Toronto; University of Michigan System; University of Michigan
RP McConnell, NJ (corresponding author), Univ Calif Berkeley, Dept Astron, 601 Campbell Hall, Berkeley, CA 94720 USA.
EM nmcc@berkeley.edu; cpma@berkeley.edu
FU National Science Foundation; NASA; Miller Institute for Basic Research in Science, University of California, Berkeley; G. and C. Mitchell; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1009663] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0908639] Funding Source: National Science Foundation
NR 25
TC 325
Z9 354
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 DEC 8
PY 2011
VL 480
IS 7376
BP 215
EP 218
DI 10.1038/nature10636
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200045
PM 22158244
DA 2026-03-09
ER

PT J
AU Jackson, MG
   Carlson, RW
AF Jackson, Matthew G.
   Carlson, Richard W.
TI An ancient recipe for flood-basalt genesis
SO NATURE
LA English
DT Article
ID deccan trap lavas; kerguelen plateau; geochemical evolution; continental-crust; mantle plumes; origin; nd; isotope; element; differentiation
AB Large outpourings of basaltic lava have punctuated geological time, but the mechanisms responsible for the generation of such extraordinary volumes of melt are not well known(1). Recent geochemical evidence suggests that an early-formed reservoir may have survived in the Earth's mantle for about 4.5 billion years (ref. 2), and melts of this reservoir contributed to the flood basalt emplaced on Baffin Island about 60 million years ago(3-5). However, the volume of this ancient mantle domain and whether it has contributed to other flood basalts is not known. Here we show that basalts from the largest volcanic event in geologic history-the Ontong Java plateau(1,6,7)-also exhibit the isotopic and trace element signatures proposed for the early-Earth reservoir2. Together with the Ontong Java plateau, we suggest that six of the largest volcanic events that erupted in the past 250 million years derive from the oldest terrestrial mantle reservoir. The association of these large volcanic events with an ancient primitive mantle source suggests that its unique geochemical characteristics-it is both hotter (it has greater abundances of the radioactive heat-producing elements) and more fertile than depleted mantle reservoirs-may strongly affect the generation of flood basalts.
C1 [Jackson, Matthew G.] Boston Univ, Dept Earth Sci, Boston, MA 02215 USA.
   [Carlson, Richard W.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 Boston University; Carnegie Institution for Science
RP Jackson, MG (corresponding author), Boston Univ, Dept Earth Sci, 675Commonwealth Ave, Boston, MA 02215 USA.
EM jacksonm@bu.edu
FU Boston University; Ocean Sciences Section of the National Science Foundation
NR 40
TC 78
Z9 85
U1 1
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 316
EP U77
DI 10.1038/nature10326
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500034
PM 21796117
DA 2026-03-09
ER

PT J
AU Park, E
   Rapoport, TA
AF Park, Eunyong
   Rapoport, Tom A.
TI Preserving the membrane barrier for small molecules during bacterial protein translocation
SO NATURE
LA English
DT Article
ID escherichia-coli; endoplasmic-reticulum; secy protein; conducting channel; translation arrest; signal sequence; ribosome; permeability; maintains; complex
AB Many proteins are translocated through the SecY channel in bacteria and archaea and through the related Sec61 channel in eukaryotes(1). The channel has an hourglass shape with a narrow constriction approximately halfway across the membrane, formed by a pore ring of amino acids(2). While the cytoplasmic cavity of the channel is empty, the extracellular cavity is filled with a short helix called the plug(2), which moves out of the way during protein translocation(3,4). The mechanism by which the channel transports large polypeptides and yet prevents the passage of small molecules, such as ions or metabolites, has been controversial(2,5-8). Here, we have addressed this issue in intact Escherichia coli cells by testing the permeation of small molecules through wild-type and mutant SecY channels, which are either in the resting state or contain a defined translocating polypeptide chain. We show that in the resting state, the channel is sealed by both the pore ring and the plug domain. During translocation, the pore ring forms a 'gasket-like' seal around the polypeptide chain, preventing the permeation of small molecules. The structural conservation of the channel in all organisms indicates that this may be a universal mechanism by which the membrane barrier is maintained during protein translocation.
C1 [Park, Eunyong; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Park, Eunyong; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Rapoport, TA (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA.
EM tom_rapoport@hms.harvard.edu
FU NIH [GM052586]; National Institute of General Medical Sciences [R01GM052586] Funding Source: NIH RePORTER
NR 30
TC 81
Z9 99
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 12
PY 2011
VL 473
IS 7346
BP 239
EP +
DI 10.1038/nature10014
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200044
PM 21562565
DA 2026-03-09
ER

PT J
AU Smear, M
   Shusterman, R
   O'Connor, R
   Bozza, T
   Rinberg, D
AF Smear, Matthew
   Shusterman, Roman
   O'Connor, Rodney
   Bozza, Thomas
   Rinberg, Dmitry
TI Perception of sniff phase in mouse olfaction
SO NATURE
LA English
DT Article
ID neurons; bulb; representations; computation; responses; dynamics; patterns; units
AB Olfactory systems encode odours by which neurons respond and by when they respond(1-3). In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons(4-6). Likewise, in a variety of neural systems, ranging from sensory periphery(7,8) to cognitive centres(9), neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system(10,11). However, there is no evidence that mammalian olfactory systems read such cues(12,13). To test whether mice perceive the timing of olfactory activation relative to the sniff cycle ('sniff phase'), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses(14,15). Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly(11,16).
C1 [Smear, Matthew; Shusterman, Roman; O'Connor, Rodney; Bozza, Thomas; Rinberg, Dmitry] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Smear, Matthew; Bozza, Thomas] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
C3 Howard Hughes Medical Institute; Northwestern University
RP Rinberg, D (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM bozza@northwestern.edu; rinbergd@janelia.hhmi.org
FU JFRC; NIDCD [R01DC009640, R21DC010911]; Whitehall Foundation; Brain Research Foundation
NR 33
TC 182
Z9 222
U1 3
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 397
EP U149
DI 10.1038/nature10521
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700045
PM 21993623
DA 2026-03-09
ER

PT J
AU Copley, A
   Avouac, JP
   Wernicke, BP
AF Copley, Alex
   Avouac, Jean-Philippe
   Wernicke, Brian P.
TI Evidence for mechanical coupling and strong Indian lower crust beneath southern Tibet
SO NATURE
LA English
DT Article
ID collision zone; plateau; himalaya; flow; tectonics; extension; dynamics; deformation; lithosphere; kinematics
AB How surface deformation within mountain ranges relates to tectonic processes at depth is not well understood. The upper crust of the Tibetan Plateau is generally thought to be poorly coupled to the underthrusting Indian crust because of an intervening low-viscosity channel(1). Here, however, we show that the contrast in tectonic regime between primarily strike-slip faulting in northern Tibet and dominantly normal faulting in southern Tibet requires mechanical coupling between the upper crust of southern Tibet and the underthrusting Indian crust. Such coupling is inconsistent with the presence of active 'channel flow' beneath southern Tibet, and suggests that the Indian crust retains its strength as it underthrusts the plateau. These results shed new light on the debates regarding the mechanical properties of the continental lithosphere(2-4), and the deformation of Tibet(1,5-10).
C1 [Copley, Alex; Avouac, Jean-Philippe; Wernicke, Brian P.] CALTECH, Div Geol & Planetary Sci, Tecton Observ, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Copley, A (corresponding author), Univ Cambridge, Dept Earth Sci, Bullard Labs, Cambridge CB3 0EZ, England.
EM acc41@cam.ac.uk
FU Gordon and Betty Moore Foundation through the Caltech Tectonics Observatory; Pembroke College in the University of Cambridge; NERC [come20001] Funding Source: UKRI; Natural Environment Research Council [come20001, earth010007] Funding Source: researchfish
NR 30
TC 171
Z9 183
U1 3
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 APR 7
PY 2011
VL 472
IS 7341
BP 79
EP 81
DI 10.1038/nature09926
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400040
PM 21475198
DA 2026-03-09
ER

PT J
AU Breitbach, CJ
   Burke, J
   Jonker, D
   Stephenson, J
   Haas, AR
   Chow, LQM
   Nieva, J
   Hwang, TH
   Moon, A
   Patt, R
   Pelusio, A
   Le Boeuf, F
   Burns, J
   Evgin, L
   De Silva, N
   Cvancic, S
   Robertson, T
   Je, JE
   Lee, YS
   Parato, K
   Diallo, JS
   Fenster, A
   Daneshmand, M
   Bell, JC
   Kirn, DH
AF Breitbach, Caroline J.
   Burke, James
   Jonker, Derek
   Stephenson, Joe
   Haas, Andrew R.
   Chow, Laura Q. M.
   Nieva, Jorge
   Hwang, Tae-Ho
   Moon, Anne
   Patt, Richard
   Pelusio, Adina
   Le Boeuf, Fabrice
   Burns, Joe
   Evgin, Laura
   De Silva, Naomi
   Cvancic, Sara
   Robertson, Terri
   Je, Ji-Eun
   Lee, Yeon-Sook
   Parato, Kelley
   Diallo, Jean-Simon
   Fenster, Aaron
   Daneshmand, Manijeh
   Bell, John C.
   Kirn, David H.
TI Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans
SO NATURE
LA English
DT Article
ID vaccinia virus; gm-csf; imatinib mesylate; thymidine kinase; measles-virus; growth-factor; therapy; tumors; criteria; progress
AB The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity(1). Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.
C1 [Breitbach, Caroline J.; Moon, Anne; Pelusio, Adina; Robertson, Terri; Kirn, David H.] Jennerex Inc, San Francisco, CA 94111 USA.
   [Burke, James; Nieva, Jorge] Billings Clin, Dept Hematol Oncol, Billings, MT 59101 USA.
   [Jonker, Derek; Chow, Laura Q. M.; Le Boeuf, Fabrice; Burns, Joe; Evgin, Laura; De Silva, Naomi; Cvancic, Sara; Parato, Kelley; Diallo, Jean-Simon; Daneshmand, Manijeh; Bell, John C.] Ottawa Hosp Res Inst, Ottawa, ON K1H 8L6, Canada.
   [Jonker, Derek; Chow, Laura Q. M.; Burns, Joe; Evgin, Laura; De Silva, Naomi; Cvancic, Sara; Daneshmand, Manijeh; Bell, John C.] Univ Ottawa, Ottawa, ON K1N 6N5, Canada.
   [Stephenson, Joe] Canc Ctr Carolinas, Greenville, SC 29605 USA.
   [Haas, Andrew R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
   [Hwang, Tae-Ho; Je, Ji-Eun; Lee, Yeon-Sook] Pusan Natl Univ, Pusan 609735, South Korea.
   [Patt, Richard] RadMD, Doylestown, PA 18901 USA.
   [Fenster, Aaron] Robarts Res Inst, London, ON N6A 5K8, Canada.
C3 University of Ottawa; Ottawa Hospital Research Institute; University of Ottawa; University of Pennsylvania; Pusan National University; Western University (University of Western Ontario); University Western Ontario Hospital
RP Kirn, DH (corresponding author), Jennerex Inc, 450 Sansome St,16th Floor, San Francisco, CA 94111 USA.
EM dkirn@jennerex.com
FU Terry Fox Foundation; Canadian Institute for Health Research (CIHR); Ministry for Health, Welfare and Family Affairs, Republic of Korea [A091047]; Vanier Scholarship; Natural Sciences and Engineering Research Council of Canada (NSERC); Ontario Graduate Scholarships in Science and Technology (OGSST); Canadian Institutes of Health Research/Small and Medium Enterprises (CIHR/SME); Ontario Institute for Cancer Research
NR 30
TC 450
Z9 545
U1 0
U2 141
PU 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 1
PY 2011
VL 477
IS 7362
BP 99
EP U102
DI 10.1038/nature10358
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300039
PM 21886163
DA 2026-03-09
ER

PT J
AU Cao, Y
   Jin, XS
   Huang, H
   Derebe, MG
   Levin, EJ
   Kabaleeswaran, V
   Pan, YP
   Punta, M
   Love, J
   Weng, J
   Quick, M
   Ye, S
   Kloss, B
   Bruni, R
   Martinez-Hackert, E
   Hendrickson, WA
   Rost, B
   Javitch, JA
   Rajashankar, KR
   Jiang, YX
   Zhou, M
AF Cao, Yu
   Jin, Xiangshu
   Huang, Hua
   Derebe, Mehabaw Getahun
   Levin, Elena J.
   Kabaleeswaran, Venkataraman
   Pan, Yaping
   Punta, Marco
   Love, James
   Weng, Jun
   Quick, Matthias
   Ye, Sheng
   Kloss, Brian
   Bruni, Renato
   Martinez-Hackert, Erik
   Hendrickson, Wayne A.
   Rost, Burkhard
   Javitch, Jonathan A.
   Rajashankar, Kanagalaghatta R.
   Jiang, Youxing
   Zhou, Ming
TI Crystal structure of a potassium ion transporter, TrkH
SO NATURE
LA English
DT Article
ID k+-uptake system; escherichia-coli; cation-transport; glycine residues; light-scattering; high-affinity; ktrab system; protein trka; channel; selectivity
AB The TrkH/TrkG/KtrB proteins mediate K+ uptake in bacteria and probably evolved from simple K+ channels by multiple gene duplications or fusions. Here we present the crystal structure of a TrkH from Vibrio parahaemolyticus. TrkH is a homodimer, and each protomer contains an ion permeation pathway. A selectivity filter, similar in architecture to those of K+ channels but significantly shorter, is lined by backbone and side-chain oxygen atoms. Functional studies showed that TrkH is selective for permeation of K+ and Rb+ over smaller ions such as Na+ or Li+. Immediately intracellular to the selectivity filter are an intramembrane loop and an arginine residue, both highly conserved, which constrict the permeation pathway. Substituting the arginine with an alanine significantly increases the rate of K+ flux. These results reveal the molecular basis of K+ selectivity and suggest a novel gating mechanism for this large and important family of membrane transport proteins.
C1 [Cao, Yu; Huang, Hua; Levin, Elena J.; Kabaleeswaran, Venkataraman; Pan, Yaping; Weng, Jun; Zhou, Ming] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Jin, Xiangshu] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Derebe, Mehabaw Getahun; Ye, Sheng; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Derebe, Mehabaw Getahun; Ye, Sheng; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Punta, Marco; Love, James; Kloss, Brian; Bruni, Renato; Rost, Burkhard] New York Struct Biol Ctr, NewYork Consortium Membrane Prot Struct, New York, NY 10027 USA.
   [Punta, Marco; Rost, Burkhard] Tech Univ Munich, Dept Comp Sci, D-85748 Munich, Germany.
   [Punta, Marco; Rost, Burkhard] Tech Univ Munich, Inst Adv Study, D-85748 Munich, Germany.
   [Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Ctr Mol Recognit, New York, NY 10032 USA.
   [Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Quick, Matthias] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
   [Javitch, Jonathan A.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, NE CAT, Adv Photon Source, Dept Chem & Chem Biol, Argonne, IL 60439 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; Technical University of Munich; Technical University of Munich; Columbia University; Columbia University; New York State Psychiatry Institute; Columbia University; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory
RP Zhou, M (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, 630 W 168th St, New York, NY 10032 USA.
EM mz2140@columbia.edu
FU U.S. National Institutes of Health [HL086392, DK088057, GM05026-sub0007]; American Heart Association [0630148N]; National Institute of General Medical Sciences [GM05026]; American Heart Association (AHA) [0630148N] Funding Source: American Heart Association (AHA)
NR 53
TC 118
Z9 140
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 MAR 17
PY 2011
VL 471
IS 7338
BP 336
EP +
DI 10.1038/nature09731
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000036
PM 21317882
DA 2026-03-09
ER

PT J
AU Trajkovski, M
   Hausser, J
   Soutschek, J
   Bhat, B
   Akin, A
   Zavolan, M
   Heim, MH
   Stoffel, M
AF Trajkovski, Mirko
   Hausser, Jean
   Soutschek, Juergen
   Bhat, Bal
   Akin, Akinc
   Zavolan, Mihaela
   Heim, Markus H.
   Stoffel, Markus
TI MicroRNAs 103 and 107 regulate insulin sensitivity
SO NATURE
LA English
DT Article
ID resistance; adipose; expression; caveolin; receptor; mechanisms; steatosis; hormone; obesity
AB Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes(1-3). MicroRNAs have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism(4,5). However, the direct regulation of insulin sensitivity by microRNAs in vivo has not been demonstrated. Here we show that the expression of microRNAs 103 and 107 (miR-103/107) is upregulated in obese mice. Silencing of miR-103/107 leads to improved glucose homeostasis and insulin sensitivity. In contrast, gain of miR-103/107 function in either liver or fat is sufficient to induce impaired glucose homeostasis. We identify caveolin-1, a critical regulator of the insulin receptor, as a direct target gene of miR-103/107. We demonstrate that caveolin-1 is upregulated upon miR-103/107 inactivation in adipocytes and that this is concomitant with stabilization of the insulin receptor, enhanced insulin signalling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake. These findings demonstrate the central importance of miR-103/107 to insulin sensitivity and identify a new target for the treatment of type 2 diabetes and obesity.
C1 [Trajkovski, Mirko; Hausser, Jean; Heim, Markus H.; Stoffel, Markus] ETH, Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland.
   [Trajkovski, Mirko; Stoffel, Markus] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Hausser, Jean; Zavolan, Mihaela] Univ Basel, Biozentrum Basel, CH-4056 Basel, Switzerland.
   [Soutschek, Juergen; Bhat, Bal] Regulus Therapeut Inc, San Diego, CA 92121 USA.
   [Akin, Akinc] Alnylam Pharmaceut, Cambridge, MA 02142 USA.
   [Heim, Markus H.] Univ Basel Hosp, CH-4031 Basel, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Basel; Ionis Pharmaceuticals, Inc.; Alnylam Pharmaceuticals; University of Basel
RP Stoffel, M (corresponding author), ETH, Competence Ctr Syst Physiol & Metab Dis, Schafmattstr 18,HPM F 39-1, CH-8093 Zurich, Switzerland.
EM stoffel@imsb.biol.ethz.ch
FU Juvenile Diabetes Research Foundation International; Swiss National Science Foundation (SNF); European Community; Leducq Foundation
NR 27
TC 866
Z9 976
U1 3
U2 116
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 649
EP U127
DI 10.1038/nature10112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300041
PM 21654750
DA 2026-03-09
ER

PT J
AU Lord, C
   Bhandari, D
   Menon, S
   Ghassemian, M
   Nycz, D
   Hay, J
   Ghosh, P
   Ferro-Novick, S
AF Lord, Christopher
   Bhandari, Deepali
   Menon, Shekar
   Ghassemian, Majid
   Nycz, Deborah
   Hay, Jesse
   Ghosh, Pradipta
   Ferro-Novick, Susan
TI Sequential interactions with Sec23 control the direction of vesicle traffic
SO NATURE
LA English
DT Article
ID casein kinase-i; endoplasmic-reticulum; copii vesicle; intermediate compartment; negative regulation; protein-transport; golgi transport; coat; complex; binding
AB How the directionality of vesicle traffic is achieved remains an important unanswered question in cell biology. The Sec23p/Sec24p coat complex sorts the fusion machinery (SNAREs) into vesicles as they bud from the endoplasmic reticulum (ER). Vesicle tethering to the Golgi begins when the tethering factor TRAPPI binds to Sec23p. Where the coat is released and how this event relates to membrane fusion is unknown. Here we use a yeast transport assay to demonstrate that an ER-derived vesicle retains its coat until it reaches the Golgi. A Golgi-associated kinase, Hrr25p (CK1 delta orthologue), then phosphorylates the Sec23p/Sec24p complex. Coat phosphorylation and dephosphorylation are needed for vesicle fusion and budding, respectively. Additionally, we show that Sec23p interacts in a sequential manner with different binding partners, including TRAPPI and Hrr25p, to ensure the directionality of ER-Golgi traffic and prevent the back-fusion of a COPII vesicle with the ER. These events are conserved in mammalian cells.
C1 [Lord, Christopher; Bhandari, Deepali; Menon, Shekar; Ferro-Novick, Susan] Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Ghassemian, Majid] Univ Calif San Diego, Dept Chem & Biochem, Biomol & Prote Mass Spectrometry Facil, La Jolla, CA 92093 USA.
   [Nycz, Deborah; Hay, Jesse] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Ghosh, Pradipta] 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; University of Montana System; University of Montana; University of California System; University of California San Diego
RP Ferro-Novick, S (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
EM sfnovick@ucsd.edu
FU Howard Hughes Medical Institute; Burroughs Wellcome Fund; SRP Super Fund Research Program; National Institutes of Health [GM-059378, RR-015583]
NR 29
TC 145
Z9 178
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 MAY 12
PY 2011
VL 473
IS 7346
BP 181
EP +
DI 10.1038/nature09969
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200031
PM 21532587
DA 2026-03-09
ER

PT J
AU Liu, M
   Yin, XB
   Ulin-Avila, E
   Geng, BS
   Zentgraf, T
   Ju, L
   Wang, F
   Zhang, X
AF Liu, Ming
   Yin, Xiaobo
   Ulin-Avila, Erick
   Geng, Baisong
   Zentgraf, Thomas
   Ju, Long
   Wang, Feng
   Zhang, Xiang
TI A graphene-based broadband optical modulator
SO NATURE
LA English
DT Article
ID quantum-well structures; large-area; films; electroabsorption; transistors
AB Integrated optical modulators with high modulation speed, small footprint and large optical bandwidth are poised to be the enabling devices for on-chip optical interconnects(1,2). Semiconductor modulators have therefore been heavily researched over the past few years. However, the device footprint of silicon-based modulators is of the order of millimetres, owing to its weak electro-optical properties(3). Germanium and compound semiconductors, on the other hand, face the major challenge of integration with existing silicon electronics and photonics platforms(4-6). Integrating silicon modulators with high-quality-factor optical resonators increases the modulation strength, but these devices suffer from intrinsic narrow bandwidth and require sophisticated optical design; they also have stringent fabrication requirements and limited temperature tolerances(7). Finding a complementary metal-oxide-semiconductor (CMOS)-compatible material with adequate modulation speed and strength has therefore become a task of not only scientific interest, but also industrial importance. Here we experimentally demonstrate a broadband, high-speed, waveguide-integrated electroabsorption modulator based on monolayer graphene. By electrically tuning the Fermi level of the graphene sheet, we demonstrate modulation of the guided light at frequencies over 1 GHz, together with a broad operation spectrum that ranges from 1.35 to 1.6 mm under ambient conditions. The high modulation efficiency of graphene results in an active device area of merely 25 mu m(2), which is among the smallest to date. This graphene-based optical modulation mechanism, with combined advantages of compact footprint, low operation voltage and ultrafast modulation speed across a broad range of wavelengths, can enable novel architectures for on-chip optical communications.
C1 [Liu, Ming; Yin, Xiaobo; Ulin-Avila, Erick; Zentgraf, Thomas; Zhang, Xiang] Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, Berkeley, CA 94720 USA.
   [Geng, Baisong; Ju, Long; Wang, Feng] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Wang, Feng; Zhang, Xiang] Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 National Science Foundation (NSF); University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Zhang, X (corresponding author), Univ Calif Berkeley, NSF Nanoscale Sci & Engn Ctr NSEC, 3112 Etcheverry Hall, Berkeley, CA 94720 USA.
EM fengwang76@berkeley.edu; xiang@berkeley.edu
FU National Science Foundation Nano-scale Science and Engineering Center (NSF-NSEC) for Scalable and Integrated Nano Manufacturing (SINAM) [CMMI-0751621]; US Department of Energy, Basic Energy Sciences Energy Frontier Research Center (DoE-LMI-EFRC) [DOE DE-AC02-05CH11231]; Div Of Civil, Mechanical, & Manufact Inn; Directorate For Engineering [0751621] Funding Source: National Science Foundation
NR 30
TC 2986
Z9 3375
U1 19
U2 1963
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 2
PY 2011
VL 474
IS 7349
BP 64
EP 67
DI 10.1038/nature10067
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700037
PM 21552277
DA 2026-03-09
ER

PT J
AU Seitan, VC
   Hao, BT
   Tachibana-Konwalski, K
   Lavagnolli, T
   Mira-Bontenbal, H
   Brown, KE
   Teng, G
   Carroll, T
   Terry, A
   Horan, K
   Marks, H
   Adams, DJ
   Schatz, DG
   Aragon, L
   Fisher, AG
   Krangel, MS
   Nasmyth, K
   Merkenschlager, M
AF Seitan, Vlad C.
   Hao, Bingtao
   Tachibana-Konwalski, Kikue
   Lavagnolli, Thais
   Mira-Bontenbal, Hegias
   Brown, Karen E.
   Teng, Grace
   Carroll, Tom
   Terry, Anna
   Horan, Katie
   Marks, Hendrik
   Adams, David J.
   Schatz, David G.
   Aragon, Luis
   Fisher, Amanda G.
   Krangel, Michael S.
   Nasmyth, Kim
   Merkenschlager, Matthias
TI A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
SO NATURE
LA English
DT Article
ID antigen-receptor; chromatin architecture; v(d)j recombination; positive selection; transgenic mice; dad1 genes; tcr-alpha; accessibility; region; locus
AB Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis(1). There is growing evidence that cohesin also forms long-range chromosomal cis-interactions(2-4) and may regulate gene expression(2-10) in association with CTCF8,9, mediator(4) or tissue-specific transcription factors(10). Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions(7), but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion-as exemplified in Drosophila(11-13)-has not been demonstrated in vertebrate systems. To address this, here we deleted the cohesin locus Rad21 in mouse thymocytes at a time in development when these cells stop cycling and rearrange their T-cell receptor (TCR) a locus (Tcra). Rad21-deficient thymocytes had a normal lifespan and retained the ability to differentiate, albeit with reduced efficiency. Loss of Rad21 led to defective chromatin architecture at the Tcra locus, where cohesion-binding sites flank the TEA promoter and the Ea enhancer, and demarcate Tcra from interspersed Tcrd elements and neighbouring housekeeping genes. Cohesin was required for long-range promoter-enhancer interactions, Tcra transcription, H3K4me3 histone modifications that recruit the recombination machinery(14,15) and Tcra rearrangement. Provision of pre-rearranged TCR transgenes largely rescued thymocyte differentiation, demonstrating that among thousands of potential target genes across the genome(4,8-10), defective Tcra rearrangement was limiting for the differentiation of cohesin-deficient thymocytes. These findings firmly establish a cell-division-independent role for cohesin in Tcra locus rearrangement and provide a comprehensive account of the mechanisms by which cohesin enables cellular differentiation in a well-characterized mammalian system.
C1 [Seitan, Vlad C.; Lavagnolli, Thais; Mira-Bontenbal, Hegias; Brown, Karen E.; Terry, Anna; Fisher, Amanda G.; Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, MRC, Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England.
   [Seitan, Vlad C.; Aragon, Luis] Univ London Imperial Coll Sci Technol & Med, MRC, Clin Sci Ctr, Cell Cycle Grp, London W12 0NN, England.
   [Seitan, Vlad C.; Lavagnolli, Thais; Mira-Bontenbal, Hegias; Brown, Karen E.; Carroll, Tom; Terry, Anna; Aragon, Luis; Fisher, Amanda G.; Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, MRC, Clin Sci Ctr, Epigenet Sect, London W12 0NN, England.
   [Hao, Bingtao; Krangel, Michael S.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
   [Tachibana-Konwalski, Kikue; Nasmyth, Kim] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [Teng, Grace; Schatz, David G.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Horan, Katie] Univ London Imperial Coll Sci Technol & Med, Cent Biol Serv, London W12 0NN, England.
   [Marks, Hendrik] Nijmegen Ctr Mol Life Sci, Dept Mol Biol, NL-6500 HB Nijmegen, Netherlands.
   [Adams, David J.] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Schatz, David G.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
C3 Imperial College London; Imperial College London; Imperial College London; Duke University; University of Oxford; Yale University; Imperial College London; Radboud University Nijmegen; Wellcome Trust Sanger Institute; Howard Hughes Medical Institute; Yale University
RP Krangel, MS (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC, Clin Sci Ctr, Lymphocyte Dev Grp, Du Cane Rd, London W12 0NN, England.
EM krang001@mc.duke.edu; kim.nasmyth@bioch.ox.ac.uk; matthias.merkenschlager@csc.mrc.ac.uk
FU Medical Research Council, UK; European Union; Boehringer Ingelheim Fonds; Wellcome Trust; National Institutes of Health; Medical Research Council [MC_U120081295, MC_U120027516] Funding Source: researchfish; MRC [MC_U120081295, MC_U120027516] Funding Source: UKRI
NR 39
TC 201
Z9 248
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 467
EP U126
DI 10.1038/nature10312
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400040
PM 21832993
DA 2026-03-09
ER

PT J
AU Gieger, C
   Radhakrishnan, A
   Cvejic, A
   Tang, WH
   Porcu, E
   Pistis, G
   Serbanovic-Canic, J
   Elling, U
   Goodall, AH
   Labrune, Y
   Lopez, LM
   Mägi, R
   Meacham, S
   Okada, Y
   Pirastu, N
   Sorice, R
   Teumer, A
   Voss, K
   Zhang, WH
   Ramirez-Solis, R
   Bis, JC
   Ellinghaus, D
   Gögele, M
   Hottenga, JJ
   Langenberg, C
   Kovacs, P
   O'Reilly, PF
   Shin, SY
   Esko, T
   Hartiala, J
   Kanoni, S
   Murgia, F
   Parsa, A
   Stephens, J
   van der Harst, P
   van der Schoot, CE
   Allayee, H
   Attwood, A
   Balkau, B
   Bastardot, F
   Basu, S
   Baumeister, SE
   Biino, G
   Bomba, L
   Bonnefond, A
   Cambien, F
   Chambers, JC
   Cucca, F
   D'Adamo, P
   Davies, G
   de Boer, RA
   de Geus, EJC
   Döring, A
   Elliott, P
   Erdmann, J
   Evans, DM
   Falchi, M
   Feng, W
   Folsom, AR
   Frazer, IH
   Gibson, QD
   Glazer, NL
   Hammond, C
   Hartikainen, AL
   Heckbert, SR
   Hengstenberg, C
   Hersch, M
   Illig, T
   Loos, RJF
   Jolley, J
   Khaw, KT
   Kühnel, B
   Kyrtsonis, MC
   Lagou, V
   Lloyd-Jones, H
   Lumley, T
   Mangino, M
   Maschio, A
   Leach, IM
   McKnight, B
   Memari, Y
   Mitchell, BD
   Montgomery, GW
   Nakamura, Y
   Nauck, M
   Navis, G
   Nöthlings, U
   Nolte, IM
   Porteous, DJ
   Pouta, A
   Pramstaller, PP
   Pullat, J
   Ring, SM
   Rotter, JI
   Ruggiero, D
   Ruokonen, A
   Sala, C
   Samani, NJ
   Sambrook, J
   Schlessinger, D
   Schreiber, S
   Schunkert, H
   Scott, J
   Smith, NL
   Snieder, H
   Starr, JM
   Stumvoll, M
   Takahashi, A
   Tang, WHW
   Taylor, K
   Tenesa, A
   Thein, SL
   Tönjes, A
   Uda, M
   Ulivi, S
   van Veldhuisen, DJ
   Visscher, PM
   Völker, U
   Wichmann, HE
   Wiggins, KL
   Willemsen, G
   Yang, TP
   Zhao, JH
   Zitting, P
   Bradley, JR
   Dedoussis, GV
   Gasparini, P
   Hazen, SL
   Metspalu, A
   Pirastu, M
   Shuldiner, AR
   van Pelt, LJ
   Zwaginga, JJ
   Boomsma, DI
   Deary, IJ
   Franke, A
   Froguel, P
   Ganesh, SK
   Jarvelin, MR
   Martin, NG
   Meisinger, C
   Psaty, BM
   Spector, TD
   Wareham, NJ
   Akkerman, JWN
   Ciullo, M
   Deloukas, P
   Greinacher, A
   Jupe, S
   Kamatani, N
   Khadake, J
   Kooner, JS
   Penninger, J
   Prokopenko, I
   Stemple, D
   Toniolo, D
   Wernisch, L
   Sanna, S
   Hicks, AA
   Rendon, A
   Ferreira, MA
   Ouwehand, WH
   Soranzo, N
AF Gieger, Christian
   Radhakrishnan, Aparna
   Cvejic, Ana
   Tang, Weihong
   Porcu, Eleonora
   Pistis, Giorgio
   Serbanovic-Canic, Jovana
   Elling, Ulrich
   Goodall, Alison H.
   Labrune, Yann
   Lopez, Lorna M.
   Maegi, Reedik
   Meacham, Stuart
   Okada, Yukinori
   Pirastu, Nicola
   Sorice, Rossella
   Teumer, Alexander
   Voss, Katrin
   Zhang, Weihua
   Ramirez-Solis, Ramiro
   Bis, Joshua C.
   Ellinghaus, David
   Goegele, Martin
   Hottenga, Jouke-Jan
   Langenberg, Claudia
   Kovacs, Peter
   O'Reilly, Paul F.
   Shin, So-Youn
   Esko, Toenu
   Hartiala, Jaana
   Kanoni, Stavroula
   Murgia, Federico
   Parsa, Afshin
   Stephens, Jonathan
   van der Harst, Pim
   van der Schoot, C. Ellen
   Allayee, Hooman
   Attwood, Antony
   Balkau, Beverley
   Bastardot, Francois
   Basu, Saonli
   Baumeister, Sebastian E.
   Biino, Ginevra
   Bomba, Lorenzo
   Bonnefond, Amelie
   Cambien, Francois
   Chambers, John C.
   Cucca, Francesco
   D'Adamo, Pio
   Davies, Gail
   de Boer, Rudolf A.
   de Geus, Eco J. C.
   Doering, Angela
   Elliott, Paul
   Erdmann, Jeanette
   Evans, David M.
   Falchi, Mario
   Feng, Wei
   Folsom, Aaron R.
   Frazer, Ian H.
   Gibson, Quince D.
   Glazer, Nicole L.
   Hammond, Chris
   Hartikainen, Anna-Liisa
   Heckbert, Susan R.
   Hengstenberg, Christian
   Hersch, Micha
   Illig, Thomas
   Loos, Ruth J. F.
   Jolley, Jennifer
   Khaw, Kay Tee
   Kuehnel, Brigitte
   Kyrtsonis, Marie-Christine
   Lagou, Vasiliki
   Lloyd-Jones, Heather
   Lumley, Thomas
   Mangino, Massimo
   Maschio, Andrea
   Leach, Irene Mateo
   McKnight, Barbara
   Memari, Yasin
   Mitchell, Braxton D.
   Montgomery, Grant W.
   Nakamura, Yusuke
   Nauck, Matthias
   Navis, Gerjan
   Noethlings, Ute
   Nolte, Ilja M.
   Porteous, David J.
   Pouta, Anneli
   Pramstaller, Peter P.
   Pullat, Janne
   Ring, Susan M.
   Rotter, Jerome I.
   Ruggiero, Daniela
   Ruokonen, Aimo
   Sala, Cinzia
   Samani, Nilesh J.
   Sambrook, Jennifer
   Schlessinger, David
   Schreiber, Stefan
   Schunkert, Heribert
   Scott, James
   Smith, Nicholas L.
   Snieder, Harold
   Starr, John M.
   Stumvoll, Michael
   Takahashi, Atsushi
   Tang, W. H. Wilson
   Taylor, Kent
   Tenesa, Albert
   Thein, Swee Lay
   Toenjes, Anke
   Uda, Manuela
   Ulivi, Sheila
   van Veldhuisen, Dirk J.
   Visscher, Peter M.
   Voelker, Uwe
   Wichmann, H-Erich
   Wiggins, Kerri L.
   Willemsen, Gonneke
   Yang, Tsun-Po
   Zhao, Jing Hua
   Zitting, Paavo
   Bradley, John R.
   Dedoussis, George V.
   Gasparini, Paolo
   Hazen, Stanley L.
   Metspalu, Andres
   Pirastu, Mario
   Shuldiner, Alan R.
   van Pelt, L. Joost
   Zwaginga, Jaap-Jan
   Boomsma, Dorret I.
   Deary, Ian J.
   Franke, Andre
   Froguel, Philippe
   Ganesh, Santhi K.
   Jarvelin, Marjo-Riitta
   Martin, Nicholas G.
   Meisinger, Christa
   Psaty, Bruce M.
   Spector, Timothy D.
   Wareham, Nicholas J.
   Akkerman, Jan-Willem N.
   Ciullo, Marina
   Deloukas, Panos
   Greinacher, Andreas
   Jupe, Steve
   Kamatani, Naoyuki
   Khadake, Jyoti
   Kooner, Jaspal S.
   Penninger, Josef
   Prokopenko, Inga
   Stemple, Derek
   Toniolo, Daniela
   Wernisch, Lorenz
   Sanna, Serena
   Hicks, Andrew A.
   Rendon, Augusto
   Ferreira, Manuel A.
   Ouwehand, Willem H.
   Soranzo, Nicole
TI New gene functions in megakaryopoiesis and platelet formation
SO NATURE
LA English
DT Article
ID genome-wide association; loci; blood
AB Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.
C1 [Gieger, Christian; Kuehnel, Brigitte] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
   [Radhakrishnan, Aparna; Cvejic, Ana; Serbanovic-Canic, Jovana; Meacham, Stuart; Voss, Katrin; Stephens, Jonathan; Attwood, Antony; Jolley, Jennifer; Lloyd-Jones, Heather; Sambrook, Jennifer; Rendon, Augusto; Ouwehand, Willem H.] Univ Cambridge & NHS Blood & Transplant, Dept Haematol, Cambridge CB2 0PT, England.
   [Radhakrishnan, Aparna; Cvejic, Ana; Serbanovic-Canic, Jovana; Meacham, Stuart; Ramirez-Solis, Ramiro; Shin, So-Youn; Kanoni, Stavroula; Attwood, Antony; Memari, Yasin; Yang, Tsun-Po; Deloukas, Panos; Stemple, Derek; Ouwehand, Willem H.; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Radhakrishnan, Aparna; Cvejic, Ana; Serbanovic-Canic, Jovana; Meacham, Stuart; Ramirez-Solis, Ramiro; Shin, So-Youn; Kanoni, Stavroula; Attwood, Antony; Memari, Yasin; Yang, Tsun-Po; Deloukas, Panos; Stemple, Derek; Ouwehand, Willem H.; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
   [Porcu, Eleonora; Cucca, Francesco; Uda, Manuela; Sanna, Serena] Cittadella Univ Monserrato, CNR, Ist Ric Genet & Biomed, I-09042 Cagliari, Italy.
   [Pistis, Giorgio; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, I-20132 Milan, Italy.
   [Elling, Ulrich; Penninger, Josef] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
   [Goodall, Alison H.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
   [Labrune, Yann; Bonnefond, Amelie; Froguel, Philippe] Inst Biol Lille, CNRS, UMR 8199, F-59019 Lille, France.
   [Lopez, Lorna M.; Porteous, David J.; Starr, John M.; Visscher, Peter M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Maegi, Reedik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Okada, Yukinori; Takahashi, Atsushi; Kamatani, Naoyuki] RIKEN Ctr Genom Med, Inst Phys & Chem Res, Lab Stat Anal, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Okada, Yukinori] Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Bunkyo Ku, Tokyo 1138654, Japan.
   [Pirastu, Nicola; D'Adamo, Pio; Ulivi, Sheila; Gasparini, Paolo] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy.
   [Sorice, Rossella; Ruggiero, Daniela; Ciullo, Marina] CNR, Inst Genet & Biophys A Buzzati Traverso, I-8031 Naples, Italy.
   [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany.
   [Zhang, Weihua; Chambers, John C.; Elliott, Paul] Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Bis, Joshua C.; Wiggins, Kerri L.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Ellinghaus, David; Schreiber, Stefan; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Goegele, Martin; Pramstaller, Peter P.; Hicks, Andrew A.] European Acad Bozen Bolzano, Ctr Biomed, I-39100 Bolzano, Italy.
   [Hottenga, Jouke-Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
   [Langenberg, Claudia; Loos, Ruth J. F.; Zhao, Jing Hua; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
   [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, D-04103 Leipzig, Germany.
   [O'Reilly, Paul F.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Shin, So-Youn; Hammond, Chris; Mangino, Massimo; Memari, Yasin; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Maegi, Reedik; Esko, Toenu; Pullat, Janne; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50410 Tartu, Estonia.
   [Esko, Toenu; Metspalu, Andres] Estonian Bioctr, EE-51010 Tartu, Estonia.
   [Esko, Toenu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50410 Tartu, Estonia.
   [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
   [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA.
   [Kanoni, Stavroula; Dedoussis, George V.] Harokopio Univ, Dept Nutr Dietet, Athens 17671, Greece.
   [Murgia, Federico; Biino, Ginevra; Pirastu, Mario] CNR, Inst Populat Genet, I-07100 Sassari, Italy.
   [Parsa, Afshin; Gibson, Quince D.; Maschio, Andrea; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
   [van der Harst, Pim; de Boer, Rudolf A.; Leach, Irene Mateo; van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands.
   [van der Schoot, C. Ellen] Sanquin Res, Dept Expt Immunohaematol, NL-1066 CX Amsterdam, Netherlands.
   [van der Schoot, C. Ellen] Univ Amsterdam, Acad Med Ctr, Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands.
   [Balkau, Beverley] INSERM, U1018, CESP Ctr Res Epidemiol & Populat Hlth, F-94807 Villejuif, France.
   [Balkau, Beverley] Univ Paris 11, UMRS 1018, F-94807 Villejuif, France.
   [Bastardot, Francois] CHU Vaudois, Serv Med Interne, CH-1011 Lausanne, Switzerland.
   [Basu, Saonli; Feng, Wei] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
   [Baumeister, Sebastian E.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
   [Biino, Ginevra; Pirastu, Mario] Shardna Life Sci, Loc Piscinamanna, I-09010 Pula, CA, Italy.
   [Biino, Ginevra; Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy.
   [Bomba, Lorenzo] Univ Cattolica Sacro Cuore Sede Piacenza, Ist Zootecnia, I-29122 Piacenza, Italy.
   [Cambien, Francois] Univ Paris 06, INSERM, UMRS 937, F-75013 Paris, France.
   [Cambien, Francois] Sch Med, F-75013 Paris, France.
   [Doering, Angela; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
   [Doering, Angela; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany.
   [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
   [Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
   [Evans, David M.; Ring, Susan M.] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England.
   [Falchi, Mario; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England.
   [Frazer, Ian H.] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
   [Glazer, Nicole L.] Boston Univ, Dept Med, Boston, MA 02118 USA.
   [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, SF-90220 Oulu, Finland.
   [Heckbert, Susan R.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
   [Hengstenberg, Christian] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
   [Hersch, Micha] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
   [Hersch, Micha] Swiss Inst Bioinformat, Lausanne, Switzerland.
   [Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
   [Khaw, Kay Tee] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
   [Khaw, Kay Tee] Addenbrookes Hosp, Clin Gerontol Unit, Cambridge CB2 2QQ, England.
   [Kyrtsonis, Marie-Christine] Univ Athens, Sch Med, Laikon Gen Hosp, Dept Propedeut Internal Med 1, Athens 11727, Greece.
   [Kyrtsonis, Marie-Christine] Univ Athens, Sch Med, Laikon Gen Hosp, Dept Hematol, Athens 11727, Greece.
   [Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [Lumley, Thomas; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Montgomery, Grant W.; Visscher, Peter M.; Martin, Nicholas G.; Ferreira, Manuel A.] Queensland Inst Med Res, Bancroft Ctr, Herston, Qld 4006, Australia.
   [Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1088639, Japan.
   [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
   [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9713 GZ Groningen, Netherlands.
   [Noethlings, Ute] Univ Kiel, Inst Expt Med, Epidemiol Sect, D-24105 Kiel, Germany.
   [Noethlings, Ute] Univ Clin Schleswig Holstein, D-24105 Kiel, Germany.
   [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, NL-9713 GZ Groningen, Netherlands.
   [Porteous, David J.] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Pouta, Anneli] Natl Inst Hlth & Welf, Oulu 90220, Finland.
   [Rotter, Jerome I.; Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Ruokonen, Aimo] Univ Oulu, Inst Diagnost, Oulu 90014, Finland.
   [Sambrook, Jennifer; Bradley, John R.; Ouwehand, Willem H.] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England.
   [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
   [Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, Fac Med, London W12 0HS, England.
   [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA 98108 USA.
   [Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh EH4 2DN, Midlothian, Scotland.
   [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
   [Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Dept Cell Biol & Cardiovasc Med, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA.
   [Tang, W. H. Wilson] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44195 USA.
   [Tenesa, Albert] MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Tenesa, Albert] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland.
   [Thein, Swee Lay] Kings Coll London, Dept Mol Haematol, London SE5 9NU, England.
   [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany.
   [Wichmann, H-Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
   [Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi 96101, Finland.
   [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21208 USA.
   [van Pelt, L. Joost] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, NL-9713 GZ Groningen, Netherlands.
   [Zwaginga, Jaap-Jan] Sanquin Res Leiden, Jon J van Rood Ctr Clin Transfus Res, NL-2333 Leiden, Netherlands.
   [Zwaginga, Jaap-Jan] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 Leiden, Netherlands.
   [Ganesh, Santhi K.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, SF-90220 Oulu, Finland.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Natl Inst Hlth & Welf, SF-90220 Oulu, Finland.
   [Psaty, Bruce M.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98101 USA.
   [Akkerman, Jan-Willem N.] Univ Med Ctr Utrecht, Dept Clin Chem & Haematol, NL-3584 CX Utrecht, Netherlands.
   [Greinacher, Andreas] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany.
   [Jupe, Steve; Khadake, Jyoti] EMBL European Bioinformat Inst, Prote Serv, Cambridge CB10 1SD, England.
   [Wernisch, Lorenz; Rendon, Augusto] Univ Forvie Site, Inst Publ Hlth, MRC, Biostat Unit, Cambridge CB2 0SR, England.
   [Erdmann, Jeanette; Schunkert, Heribert] Nord Ctr Cardiovasc Res, Lubeck, Germany.
   [Pirastu, Nicola; D'Adamo, Pio; Gasparini, Paolo] Univ Trieste, I-34127 Trieste, Italy.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Cambridge; Wellcome Trust Sanger Institute; Wellcome Trust Sanger Institute; University of Minnesota System; University of Minnesota Twin Cities; University of Cagliari; Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite de Lille; Institut Pasteur Lille; University of Edinburgh; University of Edinburgh; University of Oxford; Wellcome Centre for Human Genetics; RIKEN; University of Tokyo; IRCCS Burlo Garofolo; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e Biofisica Adriano Buzzati-Traverso (IGB-CNR); Universitat Greifswald; University of Washington; University of Washington Seattle; University of Kiel; European Academy of Bozen-Bolzano; Vrije Universiteit Amsterdam; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; Leipzig University; Imperial College London; University of London; King's College London; University of Tartu; Estonian Biocentre; University of Tartu; University of Southern California; University of Southern California; Harokopio University Athens; Consiglio Nazionale delle Ricerche (CNR); University System of Maryland; University of Maryland Baltimore; University of Groningen; University of Amsterdam; Academic Medical Center Amsterdam; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Minnesota System; University of Minnesota Twin Cities; Universitat Greifswald; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR); Catholic University of the Sacred Heart; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Imperial College London; University of Lubeck; University of Bristol; Imperial College London; Princess Alexandra Hospital; University of Queensland; Boston University; University of Oulu; University of Washington; University of Washington Seattle; Group Health Cooperative; University of Regensburg; University of Lausanne; Swiss Institute of Bioinformatics; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Cambridge; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; National & Kapodistrian University of Athens; Laiko General Hospital; National & Kapodistrian University of Athens; Laiko General Hospital; University of Oxford; University of Washington; University of Washington Seattle; QIMR Berghofer Medical Research Institute; University of Tokyo; Universitat Greifswald; University of Groningen; University of Kiel; University of Kiel; Schleswig Holstein University Hospital; University of Groningen; University of Edinburgh; Finland National Institute for Health & Welfare; Cedars Sinai Medical Center; University of Oulu; University of Cambridge; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Imperial College London; University of Edinburgh; Leipzig University; Cleveland Clinic Foundation; Cleveland Clinic Foundation; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of London; King's College London; University of Munich; University of Munich; Geriatric Research Education & Clinical Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); University of Groningen; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Michigan System; University of Michigan; University of Oulu; University of Oulu; Finland National Institute for Health & Welfare; University of Washington; University of Washington Seattle; Utrecht University; Utrecht University Medical Center; Universitat Greifswald; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Cambridge; MRC Biostatistics Unit; University of Trieste
RP Gieger, C (corresponding author), German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM christian.gieger@helmholtz-muenchen.de; who1000@cam.ac.uk; ns6@sanger.ac.uk
FU US National Institutes of Health [P41 HG003751]; EU [LSHG-CT-2005-518254 'ENFIN', 215820]; EBI Industry Programme; Wellcome Trust [WT 082597/Z/07/Z, WT 077037/Z/05/Z, WT 077047/Z/05/Z, 098051]; National Institute for Health Research, UK; British Heart Foundation [RG/09/012/28096]; ERC; EC under SLING [226073, FP7-HEALTH-2007-223411]; European Community; ENGAGE Consortium [HEALTH-F4-2007-201413]; Wellcome Trust [082597/Z/07/Z] Funding Source: Wellcome Trust; National Heart Lung and Blood Institute [R01HL059367, R01HL086694, R01HL105756] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000675] Funding Source: NIH RePORTER; NIH Office of the Director; National Heart Lung and Blood Institute [R01HL103866] Funding Source: NIH RePORTER; BBSRC [BB/F019394/1] Funding Source: UKRI; MRC [G0601966, G0700931, G0801056, G0000111, MC_U105260799, MC_U106188470, G0701863, G0700704] Funding Source: UKRI; Austrian Science Fund (FWF) [I 434] Funding Source: researchfish; Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish; British Heart Foundation [RG/09/012/28096] Funding Source: researchfish; Chief Scientist Office [CZB/4/505, ETM/55] Funding Source: researchfish; Medical Research Council [MC_U106179471, MC_U106188470, G0801056B, G0401527, G0700704, G0601966, G0701863, G0000111, G0700704B, G0801056, G1000143, G0701120, G0700931, MC_U105260799] Funding Source: researchfish
NR 25
TC 333
Z9 387
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 DEC 8
PY 2011
VL 480
IS 7376
BP 201
EP 208
DI 10.1038/nature10659
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200043
PM 22139419
DA 2026-03-09
ER

PT J
AU Tian, H
   Biehs, B
   Warming, S
   Leong, KG
   Rangell, L
   Klein, OD
   de Sauvage, FJ
AF Tian, Hua
   Biehs, Brian
   Warming, Soren
   Leong, Kevin G.
   Rangell, Linda
   Klein, Ophir D.
   de Sauvage, Frederic J.
TI A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable
SO NATURE
LA English
DT Article
ID transgenic mice; hair follicle; in-vivo; differentiation; expression; renewal; marks; lgr5; homeostasis; dynamics
AB The small intestine epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base(1). The other pool consists of Bmi1-expressing cells that largely reside above the crypt base(2). However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the small intestine epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.
C1 [Tian, Hua; Warming, Soren; de Sauvage, Frederic J.] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Biehs, Brian; Klein, Ophir D.] Univ Calif San Francisco, Inst Human Genet, Dept Orofacial Sci, San Francisco, CA 94143 USA.
   [Biehs, Brian; Klein, Ophir D.] Univ Calif San Francisco, Inst Human Genet, Dept Pediat, San Francisco, CA 94143 USA.
   [Biehs, Brian; Klein, Ophir D.] Univ Calif San Francisco, Program Craniofacial & Mesenchymal Biol, San Francisco, CA 94143 USA.
   [Leong, Kevin G.] Genentech Inc, Dept Res Oncol, San Francisco, CA 94080 USA.
   [Rangell, Linda] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; 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; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA
RP de Sauvage, FJ (corresponding author), Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM ophir.klein@ucsf.edu; desauvage.fred@gene.com
FU National Institutes of Health [1-DP2-OD007191];  [R01-DE021420]
NR 31
TC 967
Z9 1161
U1 1
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 255
EP U148
DI 10.1038/nature10408
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800053
PM 21927002
DA 2026-03-09
ER

PT J
AU Jomelli, V
   Khodri, M
   Favier, V
   Brunstein, D
   Ledru, MP
   Wagnon, P
   Blard, PH
   Sicart, JE
   Braucher, R
   Grancher, D
   Bourlès, DL
   Braconnot, P
   Vuille, M
AF Jomelli, Vincent
   Khodri, Myriam
   Favier, Vincent
   Brunstein, Daniel
   Ledru, Marie-Pierre
   Wagnon, Patrick
   Blard, Pierre-Henri
   Sicart, Jean-Emmanuel
   Braucher, Regis
   Grancher, Delphine
   Bourles, Didier Louis
   Braconnot, Pascale
   Vuille, Mathias
TI Irregular tropical glacier retreat over the Holocene epoch driven by progressive warming
SO NATURE
LA English
DT Article
ID central andes; overturning circulation; climate-change; glaciation; bolivia; fluctuations; 16-degrees-s; history
AB The causes and timing of tropical glacier fluctuations during the Holocene epoch (10,000 years ago to present) are poorly understood. Yet constraining their sensitivity to changes in climate(1) is important, as these glaciers are both sensitive indicators of climate change and serve as water reservoirs for highland regions(2). Studies have so far documented extra-tropical glacier fluctuations(3,4), but in the tropics, glacier-climate relationships are insufficiently understood. Here we present a Be-10 chronology for the past 11,000 years (11 kyr), using 57 moraines from the Bolivian Telata glacier (in the Cordillera Real mountain range). This chronology indicates that Telata glacier retreated irregularly. Arapid and strong melting from the maximum extent occurred from 10.8 +/- 0.9 to 8.5 +/- 0.4 kyr ago, followed by a slower retreat until the Little Ice Age, about 200 years ago. A dramatic increase in the rate of retreat occurred over the twentieth century. A glacier-climate model indicates that, relative to modern climate, annual mean temperature for the Telata glacier region was -3.3 +/- 0.8 degrees C cooler at 11 kyr ago and remained -2.1 +/- 0.8 degrees C cooler until the end of the Little Ice Age. We suggest that long-term warming of the eastern tropical Pacific and increased atmospheric temperature in response to enhanced austral summer insolation were the main drivers for the long-term Holocene retreat of glaciers in the southern tropics.
C1 [Jomelli, Vincent; Brunstein, Daniel; Grancher, Delphine] Univ Paris 01, CNRS, Lab Geog Phys, F-92195 Meudon, France.
   [Khodri, Myriam] IRD, IPSL, LOCEAN, F-75252 Paris 05, France.
   [Favier, Vincent] UJF, CNRS, LGGE, F-38402 St Martin Dheres, France.
   [Ledru, Marie-Pierre] UM2 CNRS IRD, ISEM, IRD UMR 226, F-34095 Montpellier, France.
   [Wagnon, Patrick; Sicart, Jean-Emmanuel] UJF Grenoble 1, CNRS, UMR 5183, IRD,G INP,LGGE,LTHE,UMR 5564, F-38402 Grenoble, France.
   [Blard, Pierre-Henri] Univ Lorraine, CNRS, UPR2300, CRPG, F-54501 Vandoeuvre Les Nancy, France.
   [Braucher, Regis; Bourles, Didier Louis] Aix Marseille Univ, CNRS, UMR 6635, CEREGE, F-13545 Aix En Provence, France.
   [Braconnot, Pascale] CEA Saclay, UVSQ, CNRS, CEA,Unite Mixte,Lab Sci Climat & Environm,IPSL, F-91191 Gif Sur Yvette, France.
   [Vuille, Mathias] SUNY Albany, Dept Atmospher & Environm Sci, Albany, NY 12222 USA.
C3 Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Institut Polytechnique de Paris; Ecole Polytechnique; Universite Paris Cite; Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); Universite de Lorraine; Universite PSL; College de France; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); CEA; Universite Paris Cite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); State University of New York (SUNY) System; University at Albany, SUNY
RP Jomelli, V (corresponding author), Univ Paris 01, CNRS, Lab Geog Phys, F-92195 Meudon, France.
EM jomelli@cnrs-bellevue.fr
FU French INSU; French ANR [06-Vuln-010, 10-Blan-608-01]; INSU/CNRS; French Ministry of Research and Higher Education; IRD and CEA; CNRS; EU [EVK2-CT-2002-00153]; Programme National d'Etude de la Dynamique du Climate (PNEDC)
NR 29
TC 78
Z9 90
U1 2
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 196
EP 199
DI 10.1038/nature10150
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800046
PM 21654802
DA 2026-03-09
ER

PT J
AU Zaratiegui, M
   Castel, SE
   Irvine, DV
   Kloc, A
   Ren, J
   Li, F
   de Castro, E
   Marín, L
   Chang, AY
   Goto, D
   Cande, WZ
   Antequera, F
   Arcangioli, B
   Martienssen, RA
AF Zaratiegui, Mikel
   Castel, Stephane E.
   Irvine, Danielle V.
   Kloc, Anna
   Ren, Jie
   Li, Fei
   de Castro, Elisa
   Marin, Laura
   Chang, An-Yun
   Goto, Derek
   Cande, W. Zacheus
   Antequera, Francisco
   Arcangioli, Benoit
   Martienssen, Robert A.
TI RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II
SO NATURE
LA English
DT Article
ID dna-replication; fission yeast; transcription termination; histone modification; genome integrity; s-phase; recombination; forks; mechanisms; rearrangements
AB Heterochromatin comprises tightly compacted repetitive regions of eukaryotic chromosomes. The inheritance of heterochromatin through mitosis requires RNA interference (RNAi), which guides histone modification(1) during the DNA replication phase of the cell cycle(2). Here we show that the alternating arrangement of origins of replication and non-coding RNA in pericentromeric heterochromatin results in competition between transcription and replication in Schizosaccharomyces pombe. Co-transcriptional RNAi releases RNA polymerase II (Pol II), allowing completion of DNA replication by the leading strand DNA polymerase, and associated histone modifying enzymes(3) that spread heterochromatin with the replication fork. In the absence of RNAi, stalled forks are repaired by homologous recombination without histone modification.
C1 [Castel, Stephane E.; Martienssen, Robert A.] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Li, Fei; Cande, W. Zacheus] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [de Castro, Elisa; Marin, Laura; Antequera, Francisco] Univ Salamanca, CSIC, Inst Biol Func & Genom, Salamanca 37007, Spain.
   [Chang, An-Yun] SUNY Stony Brook, Mol & Cell Biol Program, Stony Brook, NY 11794 USA.
   [Arcangioli, Benoit] Inst Pasteur, Paris, France.
C3 Cold Spring Harbor Laboratory; University of California System; University of California Berkeley; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-USAL - Instituto de Biologia Funcional y Genomica (IBFG); University of Salamanca; State University of New York (SUNY) System; Stony Brook University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
RP Martienssen, RA (corresponding author), Cold Spring Harbor Lab, Watson Sch Biol Sci, POB 100, Cold Spring Harbor, NY 11724 USA.
EM martiens@cshl.edu
FU NHMRC; Spanish Ministry of Science; Spanish Ministry of Science and Innovation [BFU2008-01919, CSD2007-00015]; NIH [R01 GM076396]; Grants-in-Aid for Scientific Research [22115501] Funding Source: KAKEN; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1025830] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0923128] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0963400] Funding Source: National Science Foundation
NR 34
TC 133
Z9 153
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 NOV 3
PY 2011
VL 479
IS 7371
BP 135
EP U175
DI 10.1038/nature10501
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600047
PM 22002604
DA 2026-03-09
ER

PT J
AU Schmidt, BE
   Blankenship, DD
   Patterson, GW
   Schenk, PM
AF Schmidt, B. E.
   Blankenship, D. D.
   Patterson, G. W.
   Schenk, P. M.
TI Active formation of 'chaos terrain' over shallow subsurface water on Europa
SO NATURE
LA English
DT Article
ID liquid water; ice-shelf; iceland; ocean; model
AB Europa, the innermost icy satellite of Jupiter, has a tortured young surface(1-4) and sustains a liquid water ocean(1-6) below an ice shell of highly debated thickness(1-5,7-10). Quasi-circular areas of ice disruption called chaos terrains are unique to Europa, and both their formation and the ice-shell thickness depend on Europa's thermal state(1-5,7-17). No model so far has been able to explain why features such as Conamara Chaos stand above surrounding terrain and contain matrix domes(10,18). Melt-through of a thin ( few-kilometre) shell(3,7,8) is thermodynamically improbable and cannot raise the ice(10,18). The buoyancy of material rising as either plumes of warm, pure ice called diapirs(1,9-15) or convective cells(16,17) in a thick (> 10 kilometres) shell is insufficient to produce the observed chaos heights, and no single plume can create matrix domes(10,18). Here we report an analysis of archival data from Europa, guided by processes observed within Earth's subglacial volcanoes and ice shelves. The data suggest that chaos terrains form above liquid water lenses perched within the ice shell as shallow as 3 kilometres. Our results suggest that ice-water interactions and freeze-out give rise to the diverse morphologies and topography of chaos terrains. The sunken topography of Thera Macula indicates that Europa is actively resurfacing over a lens comparable in volume to the Great Lakes in North America.
C1 [Schmidt, B. E.; Blankenship, D. D.] Univ Texas Austin, Inst Geophys, John A & Katherine G Jackson Sch Geosci, Austin, TX 78758 USA.
   [Patterson, G. W.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Schenk, P. M.] Lunar & Planetary Inst, Houston, TX 77058 USA.
C3 University of Texas System; University of Texas Austin; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory
RP Schmidt, BE (corresponding author), Univ Texas Austin, Inst Geophys, John A & Katherine G Jackson Sch Geosci, JJ Pickle Res Campus,Bldg 196 ROC,10100 Burnet Rd, Austin, TX 78758 USA.
EM britneys@ig.utexas.edu
FU Vetlesen Foundation; Institute for Geophysics of the Jackson School of Geosciences, University of Texas at Austin (UTIG); NASA; NSF
NR 30
TC 251
Z9 306
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 NOV 24
PY 2011
VL 479
IS 7374
BP 502
EP 505
DI 10.1038/nature10608
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600044
PM 22089135
DA 2026-03-09
ER

PT J
AU Karakas, E
   Simorowski, N
   Furukawa, H
AF Karakas, Erkan
   Simorowski, Noriko
   Furukawa, Hiro
TI Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors
SO NATURE
LA English
DT Article
ID amino-terminal domain; d-aspartate receptor; nr2b subunit; glutamate receptors; crystal-structure; ifenprodil; mechanisms; software; protein; models
AB Since it was discovered that the anti-hypertensive agent ifenprodil has neuroprotective activity through its effects on NMDA (N-methyl-D-aspartate) receptors(1), a determined effort has been made to understand the mechanism of action and to develop improved therapeutic compounds on the basis of this knowledge(2-4). Neurotransmission mediated by NMDA receptors is essential for basic brain development and function(5). These receptors form heteromeric ion channels and become activated after concurrent binding of glycine and glutamate to the GluN1 and GluN2 subunits, respectively. A functional hallmark of NMDA receptors is that their ion-channel activity is allosterically regulated by binding of small compounds to the amino-terminal domain (ATD) in a subtype-specific manner. Ifenprodil and related phenylethanolamine compounds, which specifically inhibit GluN1 and GluN2B NMDA receptors(6,7), have been intensely studied for their potential use in the treatment of various neurological disorders and diseases, including depression, Alzheimer's disease and Parkinson's disease(2,4). Despite considerable enthusiasm, mechanisms underlying the recognition of phenylethanolamines and ATD-mediated allosteric inhibition remain limited owing to a lack of structural information. Here we report that the GluN1 and GluN2B ATDs forma heterodimer and that phenylethanolamine binds at the interface between GluN1 and GluN2B, rather than within the GluN2B cleft. The crystal structure of the heterodimer formed between the GluN1b ATD from Xenopus laevis and the GluN2B ATD from Rattus norvegicus shows a highly distinct pattern of subunit arrangement that is different from the arrangements observed in homodimeric non-NMDA receptors and reveals the molecular determinants for phenylethanolamine binding. Restriction of domain movement in the bi-lobed structure of the GluN2B ATD, by engineering of an inter-subunit disulphide bond, markedly decreases sensitivity to ifenprodil, indicating that conformational freedom in the GluN2B ATD is essential for ifenprodil-mediated allosteric inhibition of NMDA receptors. These findings pave the way for improving the design of subtype-specific compounds with therapeutic value for neurological disorders and diseases.
C1 [Karakas, Erkan; Simorowski, Noriko; Furukawa, Hiro] WM Keck Struct Biol Lab, Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory
RP Furukawa, H (corresponding author), WM Keck Struct Biol Lab, Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM furukawa@cshl.edu
FU NIH [MH085926]; Alzheimer's Association; Fox family; NARSAD; National Institute of Mental Health [R01MH085926] Funding Source: NIH RePORTER
NR 29
TC 297
Z9 349
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 249
EP U170
DI 10.1038/nature10180
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500055
PM 21677647
DA 2026-03-09
ER

PT J
AU Grosjean, Y
   Rytz, R
   Farine, JP
   Abuin, L
   Cortot, J
   Jefferis, GSXE
   Benton, R
AF Grosjean, Yael
   Rytz, Raphael
   Farine, Jean-Pierre
   Abuin, Liliane
   Cortot, Jerome
   Jefferis, Gregory S. X. E.
   Benton, Richard
TI An olfactory receptor for food-derived odours promotes male courtship in Drosophila
SO NATURE
LA English
DT Article
ID ionotropic glutamate receptors; phenylacetic acid; sex-pheromone; behavior; melanogaster; neurons; representation; architecture; algorithm; responses
AB Many animals attract mating partners through the release of volatile sex pheromones, which can convey information on the species, gender and receptivity of the sender to induce innate courtship and mating behaviours by the receiver(1). Male Drosophila melanogaster fruitflies display stereotyped reproductive behaviours towards females, and these behaviours are controlled by the neural circuitry expressing male-specific isoforms of the transcription factor Fruitless (FRUM)(2-5). However, the volatile pheromone ligands, receptors and olfactory sensory neurons (OSNs) that promote male courtship have not been identified in this important model organism. Here we describe a novel courtship function of Ionotropic receptor 84a (IR84a), which is a member of the chemosensory ionotropic glutamate receptor family(6), in a previously uncharacterized population of FRUM-positive OSNs. IR84a-expressing neurons are activated not by fly-derived chemicals but by the aromatic odours phenylacetic acid and phenylacetaldehyde, which are widely found in fruit and other plant tissues(7) that serve as food sources and oviposition sites for drosophilid flies(8). Mutation of Ir84a abolishes both odour-evoked and spontaneous electrophysiological activity in these neurons and markedly reduces male courtship behaviour. Conversely, male courtship is increased-in an IR84a-dependent manner-in the presence of phenylacetic acid but not in the presence of another fruit odour that does not activate IR84a. Interneurons downstream of IR84a-expressing OSNs innervate a pheromone-processing centre in the brain. Whereas IR84a orthologues and phenylacetic-acid-responsive neurons are present in diverse drosophilid species, IR84a is absent from insects that rely on long-range sex pheromones. Our results suggest a model in which IR84a couples food presence to the activation of the fru(M) courtship circuitry in fruitflies. These findings reveal an unusual but effective evolutionary solution to coordinate feeding and oviposition site selection with reproductive behaviours through a specific sensory pathway.
C1 [Grosjean, Yael; Rytz, Raphael; Abuin, Liliane; Benton, Richard] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Grosjean, Yael; Farine, Jean-Pierre; Cortot, Jerome] Univ Bourgogne, INRA, UMR 1324, Ctr Sci Gout & Alimentat,CNRS,UMR 6265, F-21000 Dijon, France.
   [Jefferis, Gregory S. X. E.] MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 0QH, England.
C3 University of Lausanne; INRAE; Institut Agro; Institut Agro Dijon; Centre National de la Recherche Scientifique (CNRS); Universite Bourgogne Europe; CNRS - National Institute for Biology (INSB); MRC Laboratory Molecular Biology
RP Benton, R (corresponding author), Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
EM Richard.Benton@unil.ch
FU Centre National de la Recherche Scientifique (CNRS); Agence Nationale de la Recherche (ANR) [GGCB-2010]; Conseil Regional de Bourgogne (FABER); Roche Research Foundation; Medical Research Council; European Research Council; University of Lausanne; Swiss National Science Foundation; MRC [MC_U105188491] Funding Source: UKRI; Medical Research Council [MC_U105188491] Funding Source: researchfish
NR 44
TC 261
Z9 303
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 OCT 13
PY 2011
VL 478
IS 7368
BP 236
EP U123
DI 10.1038/nature10428
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800049
PM 21964331
DA 2026-03-09
ER

PT J
AU Caffau, E
   Bonifacio, P
   François, P
   Sbordone, L
   Monaco, L
   Spite, M
   Spite, F
   Ludwig, HG
   Cayrel, R
   Zaggia, S
   Hammer, F
   Randich, S
   Molaro, P
   Hill, V
AF Caffau, Elisabetta
   Bonifacio, Piercarlo
   Francois, Patrick
   Sbordone, Luca
   Monaco, Lorenzo
   Spite, Monique
   Spite, Francois
   Ludwig, Hans-G.
   Cayrel, Roger
   Zaggia, Simone
   Hammer, Francois
   Randich, Sofia
   Molaro, Paolo
   Hill, Vanessa
TI An extremely primitive star in the Galactic halo
SO NATURE
LA English
DT Article
ID 3d model atmosphere; metal-poor dwarfs; 1st stars; chemical-composition; early galaxy; abundances; lithium; telescope; carbon; yields
AB The early Universe had a chemical composition consisting of hydrogen, helium and traces of lithium(1); almost all other elements were subsequently created in stars and supernovae. The mass fraction of elements more massive than helium, Z, is known as 'metallicity'. A number of very metal-poor stars has been found(2,3), some of which have a low iron abundance but are rich in carbon, nitrogen and oxygen(4-6). For theoretical reasons(7,8) and because of an observed absence of stars with Z<1.5x10(-5), it has been suggested that low-mass stars cannot form from the primitive interstellar medium until it has been enriched above a critical value of Z, estimated to lie in the range 1.5x10(-8) to 1.5x10(-6) (ref. 8), although competing theories claiming the contrary do exist(9). (We use 'low-mass' here to mean a stellar mass of less than 0.8 solar masses, the stars that survive to the present day.) Here we report the chemical composition of a star in the Galactic halo with a very low Z (<= 6.9x10(-7), which is 4.5x10(-5) times that of the Sun(10)) and a chemical pattern typical of classical extremely metal-poor stars(2,3)-that is, without enrichment of carbon, nitrogen and oxygen. This shows that low-mass stars can be formed at very low metallicity, that is, below the critical value of Z. Lithium is not detected, suggesting a low-metallicity extension of the previously observed trend in lithium depletion(11). Such lithium depletion implies that the stellar material must have experienced temperatures above two million kelvin in its history, given that this is necessary to destroy lithium.
C1 [Caffau, Elisabetta; Sbordone, Luca; Ludwig, Hans-G.] Univ Heidelberg, Zentrum Astron, Landessternwarte, D-69117 Heidelberg, Germany.
   [Caffau, Elisabetta; Bonifacio, Piercarlo; Francois, Patrick; Sbordone, Luca; Spite, Monique; Spite, Francois; Ludwig, Hans-G.; Cayrel, Roger; Hammer, Francois] Univ Paris Diderot, CNRS, Observ Paris, GEPI, F-92190 Meudon, France.
   [Francois, Patrick] Univ Picardie Jules Verne, UPJV, F-80080 Amiens, France.
   [Sbordone, Luca] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Monaco, Lorenzo] European So Observ, Santiago 19, Chile.
   [Zaggia, Simone] Osserv Astron Padova, Ist Nazl Astrofis, I-35122 Padua, Italy.
   [Randich, Sofia] Osserv Astrofis Arcetri, Ist Nazl Astrofis, I-50125 Florence, Italy.
   [Molaro, Paolo] Osserv Astron Trieste, Ist Nazl Astrofis, I-34143 Trieste, Italy.
   [Hill, Vanessa] Univ Nice Sophia Antipolis, Observ Cote Azur, CNRS, Lab Cassiopee, F-06300 Nice, France.
C3 Ruprecht Karls University Heidelberg; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; Universite de Picardie Jules Verne (UPJV); Max Planck Society; European Southern Observatory; Istituto Nazionale Astrofisica (INAF); University of Padua; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS)
RP Caffau, E (corresponding author), Univ Heidelberg, Zentrum Astron, Landessternwarte, Konigstuhl 12, D-69117 Heidelberg, Germany.
EM Elisabetta.Caffau@obspm.fr
NR 29
TC 301
Z9 314
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 67
EP 69
DI 10.1038/nature10377
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300031
PM 21886158
DA 2026-03-09
ER

PT J
AU Maillet, F
   Poinsot, V
   André, O
   Puech-Pagès, V
   Haouy, A
   Gueunier, M
   Cromer, L
   Giraudet, D
   Formey, D
   Niebel, A
   Martinez, EA
   Driguez, H
   Bécard, G
   Dénarié, J
AF Maillet, Fabienne
   Poinsot, Verena
   Andre, Olivier
   Puech-Pages, Virginie
   Haouy, Alexandra
   Gueunier, Monique
   Cromer, Laurence
   Giraudet, Delphine
   Formey, Damien
   Niebel, Andreas
   Martinez, Eduardo Andres
   Driguez, Hugues
   Becard, Guillaume
   Denarie, Jean
TI Fungal lipochitooligosaccharide symbiotic signals in arbuscular mycorrhiza
SO NATURE
LA English
DT Article
ID medicago-truncatula; nodulation factors; diffusible factor; nod factors; rhizobium; gene; bacterial; family; expression; proteins
AB Arbuscular mycorrhiza (AM) is a root endosymbiosis between plants and glomeromycete fungi. It is the most widespread terrestrial plant symbiosis, improving plant uptake of water and mineral nutrients. Yet, despite its crucial role in land ecosystems, molecular mechanisms leading to its formation are just beginning to be unravelled. Recent evidence suggests that AM fungi produce diffusible symbiotic signals. Here we show that Glomus intraradices secretes symbiotic signals that are a mixture of sulphated and non-sulphated simple lipochitooligosaccharides (LCOs), which stimulate formation of AM in plant species of diverse families (Fabaceae, Asteraceae and Umbelliferae). In the legume Medicago truncatula these signals stimulate root growth and branching by the symbiotic DMI signalling pathway. These findings provide a better understanding of the evolution of signalling mechanisms involved in plant root endosymbioses and will greatly facilitate their molecular dissection. They also open the way to using these natural and very active molecules in agriculture.
C1 [Maillet, Fabienne; Andre, Olivier; Haouy, Alexandra; Gueunier, Monique; Cromer, Laurence; Giraudet, Delphine; Niebel, Andreas; Denarie, Jean] INRA, CNRS 2594, UMR 441, Lab Interact Plantes Microorganismes, F-31326 Castanet Tolosan, France.
   [Poinsot, Verena] Univ Toulouse 3, CNRS, UMR 5623, Lab IMRCP, F-31062 Toulouse, France.
   [Puech-Pages, Virginie; Gueunier, Monique; Formey, Damien; Becard, Guillaume] Univ Toulouse, UPS, UMR 5546, F-31326 Castanet Tolosan, France.
   [Puech-Pages, Virginie; Gueunier, Monique; Formey, Damien; Becard, Guillaume] CNRS, UMR 5546, F-31326 Castanet Tolosan, France.
   [Martinez, Eduardo Andres; Driguez, Hugues] Univ Grenoble 1, CNRS, Ctr Rech Macromol Vegetales, F-38041 Grenoble 9, France.
C3 INRAE; Universite de Toulouse; Universite Federale Toulouse Midi-Pyrenees (ComUE); Universite Toulouse III - Paul Sabatier; Institut National des Sciences Appliquees de Toulouse; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Dénarié, J (corresponding author), INRA, CNRS 2594, UMR 441, Lab Interact Plantes Microorganismes, BP 52627, F-31326 Castanet Tolosan, France.
FU EMD Crop BioScience; Charles-Leopold Mayer Prize; French Academy of Sciences; Institut National de la Recherche Agronomique
NR 55
TC 731
Z9 891
U1 13
U2 433
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 58
EP U1501
DI 10.1038/nature09622
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600030
PM 21209659
DA 2026-03-09
ER

PT J
AU Hannedouche, S
   Zhang, J
   Yi, TS
   Shen, WJ
   Nguyen, D
   Pereira, JP
   Guerini, D
   Baumgarten, BU
   Roggo, S
   Wen, B
   Knochenmuss, R
   Noël, S
   Gessier, F
   Kelly, LM
   Vanek, M
   Laurent, S
   Preuss, I
   Miault, C
   Christen, I
   Karuna, R
   Li, W
   Koo, DI
   Suply, T
   Schmedt, C
   Peters, EC
   Falchetto, R
   Katopodis, A
   Spanka, C
   Roy, MO
   Detheux, M
   Chen, YA
   Schultz, PG
   Cho, CY
   Seuwen, K
   Cyster, JG
   Sailer, AW
AF Hannedouche, Sebastien
   Zhang, Juan
   Yi, Tangsheng
   Shen, Weijun
   Nguyen, Deborah
   Pereira, Joao P.
   Guerini, Danilo
   Baumgarten, Birgit U.
   Roggo, Silvio
   Wen, Ben
   Knochenmuss, Richard
   Noel, Sophie
   Gessier, Francois
   Kelly, Lisa M.
   Vanek, Mirka
   Laurent, Stephane
   Preuss, Inga
   Miault, Charlotte
   Christen, Isabelle
   Karuna, Ratna
   Li, Wei
   Koo, Dong-In
   Suply, Thomas
   Schmedt, Christian
   Peters, Eric C.
   Falchetto, Rocco
   Katopodis, Andreas
   Spanka, Carsten
   Roy, Marie-Odile
   Detheux, Michel
   Chen, Yu Alice
   Schultz, Peter G.
   Cho, Charles Y.
   Seuwen, Klaus
   Cyster, Jason G.
   Sailer, Andreas W.
TI Oxysterols direct immune cell migration via EBI2
SO NATURE
LA English
DT Article
ID dendritic cells; cholesterol; expression; macrophages; enzymes
AB Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases(1-3). The natural ligand for EBI2 has been unknown. Here we describe the identification of 7 alpha,25-dihydroxycholesterol (also called 7 alpha,25-OHC or 5-cholesten-3 beta,7 alpha,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7 alpha,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7 alpha,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7 alpha,25-OHC is cholesterol 25-hydroxylase (CH25H)(4). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.
C1 [Zhang, Juan; Guerini, Danilo; Baumgarten, Birgit U.; Roggo, Silvio; Knochenmuss, Richard; Gessier, Francois; Vanek, Mirka; Laurent, Stephane; Preuss, Inga; Miault, Charlotte; Christen, Isabelle; Karuna, Ratna; Suply, Thomas; Falchetto, Rocco; Katopodis, Andreas; Spanka, Carsten; Seuwen, Klaus; Sailer, Andreas W.] Novartis Inst BioMed Res, CH-4056 Basel, Switzerland.
   [Hannedouche, Sebastien; Noel, Sophie; Roy, Marie-Odile; Detheux, Michel] Euroscreen SA, B-6041 Gosselies, Belgium.
   [Yi, Tangsheng; Pereira, Joao P.; Kelly, Lisa M.; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Yi, Tangsheng; Pereira, Joao P.; Kelly, Lisa M.; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Shen, Weijun; Nguyen, Deborah; Wen, Ben; Li, Wei; Schmedt, Christian; Peters, Eric C.; Chen, Yu Alice; Schultz, Peter G.; Cho, Charles Y.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
   [Shen, Weijun; Koo, Dong-In] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Novartis; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Novartis; Novartis USA; Scripps Research Institute
RP Sailer, AW (corresponding author), Novartis Inst BioMed Res, CH-4056 Basel, Switzerland.
EM andreas.sailer@novartis.com
FU National Institute of Allergy and Infectious Diseases [R01AI040098] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NIAID NIH HHS [R01 AI040098] Funding Source: Medline
NR 21
TC 390
Z9 448
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 524
EP 527
DI 10.1038/nature10280
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900046
PM 21796212
DA 2026-03-09
ER

PT J
AU Takeda, Y
   Costa, S
   Delamarre, E
   Roncal, C
   de Oliveira, RL
   Squadrito, ML
   Finisguerra, V
   Deschoemaeker, S
   Bruyère, F
   Wenes, M
   Hamm, A
   Serneels, J
   Magat, J
   Bhattacharyya, T
   Anisimov, A
   Jordan, BF
   Alitalo, K
   Maxwell, P
   Gallez, B
   Zhuang, ZW
   Saito, Y
   Simons, M
   De Palma, M
   Mazzone, M
AF Takeda, Yukiji
   Costa, Sandra
   Delamarre, Estelle
   Roncal, Carmen
   de Oliveira, Rodrigo Leite
   Squadrito, Mario Leonardo
   Finisguerra, Veronica
   Deschoemaeker, Sofie
   Bruyere, Francoise
   Wenes, Mathias
   Hamm, Alexander
   Serneels, Jens
   Magat, Julie
   Bhattacharyya, Tapan
   Anisimov, Andrey
   Jordan, Benedicte F.
   Alitalo, Kari
   Maxwell, Patrick
   Gallez, Bernard
   Zhuang, Zhen W.
   Saito, Yoshihiko
   Simons, Michael
   De Palma, Michele
   Mazzone, Massimiliano
TI Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis
SO NATURE
LA English
DT Article
ID nf-kappa-b; tumor angiogenesis; ikk-beta; inhibition; mouse; oxygenation; deficiency; injury; cells
AB PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage(1-5). However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion(6-8). We show that Phd2 (also known as Egln1) haplodeficient (Phd2(+/-)) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2(+/-) mice was due to an expansion of tissue-resident, M2-like macrophages(9,10) and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a pro-arteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-kappa B pathway in Phd2(+/-) macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders.
C1 [Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Finisguerra, Veronica; Deschoemaeker, Sofie; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Mazzone, Massimiliano] VIB, Vesalius Res Ctr, Lab Mol Oncol & Angiogenesis, B-3000 Louvain, Belgium.
   [Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Finisguerra, Veronica; Deschoemaeker, Sofie; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Mazzone, Massimiliano] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Mol Oncol & Angiogenesis, B-3000 Louvain, Belgium.
   [Takeda, Yukiji; Roncal, Carmen; de Oliveira, Rodrigo Leite; Bruyere, Francoise] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium.
   [Takeda, Yukiji; Roncal, Carmen; de Oliveira, Rodrigo Leite; Bruyere, Francoise] Katholieke Univ Leuven, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium.
   [Costa, Sandra] Univ Minho, Life & Hlth Sci Res Inst, P-4710057 Braga, Portugal.
   [Roncal, Carmen] CIMA Univ Navarra, Atherosclerosis Res Lab, Pamplona 31008, Spain.
   [Squadrito, Mario Leonardo; De Palma, Michele] San Raffaele Inst, Angiogenesis & Tumor Targeting Unit, I-20132 Milan, Italy.
   [Squadrito, Mario Leonardo; De Palma, Michele] San Raffaele Inst, HSR TIGET, I-20132 Milan, Italy.
   [Squadrito, Mario Leonardo] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
   [Magat, Julie; Jordan, Benedicte F.; Gallez, Bernard] Catholic Univ Louvain, Biomed Magnet Resonance Unit, B-1200 Brussels, Belgium.
   [Bhattacharyya, Tapan; Maxwell, Patrick] UCL, Rayne Inst, London WC1E 6JF, England.
   [Anisimov, Andrey; Alitalo, Kari] Biomedicum Helsinki, Res Programs Unit, Mol Canc Biol Lab, Helsinki 00014, Finland.
   [Anisimov, Andrey; Alitalo, Kari] Biomedicum Helsinki, Inst Mol Med, Helsinki 00014, Finland.
   [Zhuang, Zhen W.; Simons, Michael] Yale Univ, Sch Med, New Haven, CT 06510 USA.
   [Saito, Yoshihiko] Nara Med Univ, Dept Internal Med 1, Nara 6348522, Japan.
C3 Flanders Institute for Biotechnology (VIB); KU Leuven; Flanders Institute for Biotechnology (VIB); Flanders Institute for Biotechnology (VIB); KU Leuven; Universidade do Minho; University of Navarra; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Fondazione Telethon; San Raffaele Telethon Institute For Gene Therapy (Sr-Tiget); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Vita-Salute San Raffaele University; Universite Catholique Louvain; University of London; University College London; King's College London; University of Helsinki; University of Helsinki; Yale University; Nara Medical University
RP Mazzone, M (corresponding author), VIB, Vesalius Res Ctr, Lab Mol Oncol & Angiogenesis, B-3000 Louvain, Belgium.
EM massimiliano.mazzone@vib-kuleuven.be
FU FWO, Belgium [G.0726.10]; VIB; ARC; FCT; FWO; DFG; COST action [TD0901]; ERC
NR 34
TC 253
Z9 292
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 NOV 3
PY 2011
VL 479
IS 7371
BP 122
EP U153
DI 10.1038/nature10507
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600044
PM 21983962
DA 2026-03-09
ER

PT J
AU Knigge, C
   Coe, MJ
   Podsiadlowski, P
AF Knigge, Christian
   Coe, Malcolm J.
   Podsiadlowski, Philipp
TI Two populations of X-ray pulsars produced by two types of supernova
SO NATURE
LA English
DT Article
ID small-magellanic-cloud; electron-capture supernovae; star-formation history; core-collapse; binary; evolution; spin; periods
AB Two types of supernova are thought to produce the overwhelming majority of neutron stars in the Universe(1). The first type, iron-core-collapse supernovae, occurs when a high-mass star develops a degenerate iron core that exceeds the Chandrasekhar limit(2). The second type, electron-capture supernovae, is associated with the collapse of a lower-mass oxygen-neon-magnesium core as it loses pressure support owing to the sudden capture of electrons by neon and/or magnesium nuclei(3,4). It has hitherto been impossible to identify the two distinct families of neutron stars produced in these formation channels. Here we report that a large, well-known class of neutron-star-hosting X-ray pulsars is actually composed of two distinct subpopulations with different characteristic spin periods, orbital periods and orbital eccentricities. This class, the Be/X-ray binaries, contains neutron stars that accrete material from a more massive companion star(5). The two subpopulations are most probably associated with the two distinct types of neutron-star-forming supernova, with electron-capture supernovae preferentially producing systems with short spin periods, short orbital periods and low eccentricities. Intriguingly, the split between the two subpopulations is clearest in the distribution of the logarithm of spin period, a result that had not been predicted and which still remains to be explained.
C1 [Knigge, Christian; Coe, Malcolm J.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Podsiadlowski, Philipp] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
C3 University of Southampton; University of Oxford
RP Knigge, C (corresponding author), Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
EM c.knigge@soton.ac.uk
FU UK Science and Technology Facilities Council; STFC [ST/H002456/1, ST/G003084/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H002456/1, ST/G003084/1] Funding Source: researchfish
NR 25
TC 93
Z9 98
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 372
EP 375
DI 10.1038/nature10529
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700039
PM 22080948
DA 2026-03-09
ER

PT J
AU Ceol, CJ
   Houvras, Y
   Jane-Valbuena, J
   Bilodeau, S
   Orlando, DA
   Battisti, V
   Fritsch, L
   Lin, WM
   Hollmann, TJ
   Ferré, F
   Bourque, C
   Burke, CJ
   Turner, L
   Uong, A
   Johnson, LA
   Beroukhim, R
   Mermel, CH
   Loda, M
   Ait-Si-Ali, S
   Garraway, LA
   Young, RA
   Zon, LI
AF Ceol, Craig J.
   Houvras, Yariv
   Jane-Valbuena, Judit
   Bilodeau, Steve
   Orlando, David A.
   Battisti, Valentine
   Fritsch, Lauriane
   Lin, William M.
   Hollmann, Travis J.
   Ferre, Fabrizio
   Bourque, Caitlin
   Burke, Christopher J.
   Turner, Laura
   Uong, Audrey
   Johnson, Laura A.
   Beroukhim, Rameen
   Mermel, Craig H.
   Loda, Massimo
   Ait-Si-Ali, Slimane
   Garraway, Levi A.
   Young, Richard A.
   Zon, Leonard I.
TI The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset
SO NATURE
LA English
DT Article
ID malignant-melanoma; braf mutations; human cancer; genes; nevi; senescence; expression; repression; lysine-9; cells
AB The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway(1,2). BRAF(V600E) mutations are also present in benign melanocytic naevi(3), highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes(4,5). For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.
C1 [Ceol, Craig J.; Houvras, Yariv; Bourque, Caitlin; Burke, Christopher J.; Turner, Laura; Uong, Audrey; Zon, Leonard I.] Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Houvras, Yariv] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
   [Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
   [Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Harvard Univ, Ctr Canc Genome Discovery, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
   [Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
   [Bilodeau, Steve; Orlando, David A.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Battisti, Valentine; Fritsch, Lauriane; Ait-Si-Ali, Slimane] Univ Paris Diderot, Epigenet & Destin Cellulaire UMR7216, CNRS, F-75013 Paris, France.
   [Hollmann, Travis J.; Loda, Massimo] Harvard Univ, Ctr Mol Oncol Pathol, Brigham & Womens Hosp, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA.
   [Ferre, Fabrizio] Univ Roma La Sapienza, A Rossi Fanelli Biochem Sci Dept, I-00185 Rome, Italy.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Dana-Farber Cancer Institute; Sapienza University Rome
RP Zon, LI (corresponding author), Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU Damon Runyon Cancer Research Foundation [DRG-1855-05]; Charles A. King Trust Foundation; American Society of Clinical Oncology; Canadian Institutes of Health Research; National Institutes of Health [K99AR056899-02, K08DK075432-04, CA146455, HG002668, CA103846, DK055381]; National Cancer Institute [R01CA103846] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 23
TC 434
Z9 536
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 MAR 24
PY 2011
VL 471
IS 7339
BP 513
EP +
DI 10.1038/nature09806
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200062
PM 21430779
DA 2026-03-09
ER

PT J
AU D'Costa, VM
   King, CE
   Kalan, L
   Morar, M
   Sung, WWL
   Schwarz, C
   Froese, D
   Zazula, G
   Calmels, F
   Debruyne, R
   Golding, GB
   Poinar, HN
   Wright, GD
AF D'Costa, Vanessa M.
   King, Christine E.
   Kalan, Lindsay
   Morar, Mariya
   Sung, Wilson W. L.
   Schwarz, Carsten
   Froese, Duane
   Zazula, Grant
   Calmels, Fabrice
   Debruyne, Regis
   Golding, G. Brian
   Poinar, Hendrik N.
   Wright, Gerard D.
TI Antibiotic resistance is ancient
SO NATURE
LA English
DT Article
ID yukon-territory; permafrost; resistome; sediments; bacteria; mammals; ice
AB The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes(1,2). This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics(3). Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to beta-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.
C1 [D'Costa, Vanessa M.; Kalan, Lindsay; Morar, Mariya; Poinar, Hendrik N.; Wright, Gerard D.] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8N 3Z5, Canada.
   [D'Costa, Vanessa M.; Kalan, Lindsay; Morar, Mariya; Wright, Gerard D.] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada.
   [King, Christine E.; Schwarz, Carsten; Poinar, Hendrik N.] McMaster Univ, Dept Anthropol, McMaster Ancient DNA Ctr, Hamilton, ON L8S 4L9, Canada.
   [King, Christine E.; Sung, Wilson W. L.; Golding, G. Brian; Poinar, Hendrik N.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada.
   [Froese, Duane; Calmels, Fabrice] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Zazula, Grant] Yukon Govt, Dept Tourism & Culture, Yukon Palaeontol Program, Whitehorse, YT Y1A 2C6, Canada.
   [Debruyne, Regis] Museum Natl Hist Nat, UMR Ecoanthropol 7206, F-75231 Paris 05, France.
C3 McMaster University; McMaster University; McMaster University; McMaster University; University of Alberta; Museum National d'Histoire Naturelle (MNHN); Universite Paris Cite
RP Wright, GD (corresponding author), McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8N 3Z5, Canada.
EM poinarh@mcmaster.ca; wrightge@mcmaster.ca
FU Canada Research Chairs; Canadian Institutes of Health Research [MOP-79488]; Natural Sciences and Engineering Research Council of Canada
NR 21
TC 1936
Z9 2431
U1 25
U2 1383
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 457
EP 461
DI 10.1038/nature10388
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500039
PM 21881561
DA 2026-03-09
ER

PT J
AU Chen, XW
   Leischner, U
   Rochefort, NL
   Nelken, I
   Konnerth, A
AF Chen, Xiaowei
   Leischner, Ulrich
   Rochefort, Nathalie L.
   Nelken, Israel
   Konnerth, Arthur
TI Functional mapping of single spines in cortical neurons in vivo
SO NATURE
LA English
DT Article
ID mouse auditory-cortex; pyramidal neurons; dendritic spines; fluorescence microscopy; visual-cortex; organization; excitation; dynamics; signals; spikes
AB The individual functional properties and spatial arrangement of afferent synaptic inputs on dendrites have a critical role in the processing of information by neurons in the mammalian brain(1-4). Although recent work has identified visually-evoked local dendritic calcium signals in the rodent visual cortex(5), sensory-evoked signalling on the level of dendritic spines, corresponding to individual afferent excitatory synapses, remains unexplored(6). Here we used a new variant of high-resolution two-photon imaging(7) to detect sensory-evoked calcium transients in single dendritic spines of mouse cortical neurons in vivo. Calcium signals evoked by sound stimulation required the activation of NMDA (N-methyl-D-aspartate) receptors. Active spines are widely distributed on basal and apical dendrites and pure-tone stimulation at different frequencies revealed both narrowly and widely tuned spines. Notably, spines tuned for different frequencies were highly interspersed on the same dendrites: even neighbouring spines were mostly tuned to different frequencies. Thus, our results demonstrate that NMDA-receptor-dependent single-spine synaptic inputs to the same dendrite are highly heterogeneous. Furthermore, our study opens the way for in vivo mapping of functionally defined afferent sensory inputs with single-synapse resolution.
C1 [Chen, Xiaowei; Leischner, Ulrich; Rochefort, Nathalie L.; Konnerth, Arthur] Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany.
   [Chen, Xiaowei; Leischner, Ulrich; Rochefort, Nathalie L.; Konnerth, Arthur] Tech Univ Munich, Ctr Integrated Prot Sci, D-80802 Munich, Germany.
   [Nelken, Israel] Hebrew Univ Jerusalem, Dept Neurobiol, Silberman Inst Life Sci, IL-91904 Jerusalem, Israel.
   [Nelken, Israel] Hebrew Univ Jerusalem, Edmond & Lily Safra Ctr Brain Sci, IL-91904 Jerusalem, Israel.
C3 Technical University of Munich; University of Munich; Technical University of Munich; Hebrew University of Jerusalem; Hebrew University of Jerusalem
RP Konnerth, A (corresponding author), Tech Univ Munich, Inst Neurosci, Biedersteinerstr 29, D-80802 Munich, Germany.
EM arthur.konnerth@lrz.tum.de
FU Schiedel Foundation; German-Israeli Foundation (GIF) [1002/2008]; Deutsche Forschungsgemeinschaft [IRTG 1373]; Bundesministerium fur Bildung und Forschung (BMBF)
NR 43
TC 298
Z9 336
U1 0
U2 80
PU 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 28
PY 2011
VL 475
IS 7357
BP 501
EP U97
DI 10.1038/nature10193
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900041
PM 21706031
DA 2026-03-09
ER

PT J
AU Sahin, E
   Colla, S
   Liesa, M
   Moslehi, J
   Müller, FL
   Guo, MR
   Cooper, M
   Kotton, D
   Fabian, AJ
   Walkey, C
   Maser, RS
   Tonon, G
   Foerster, F
   Xiong, R
   Wang, YA
   Shukla, SA
   Jaskelioff, M
   Martin, ES
   Heffernan, TP
   Protopopov, A
   Ivanova, E
   Mahoney, JE
   Kost-Alimova, M
   Perry, SR
   Bronson, R
   Liao, RL
   Mulligan, R
   Shirihai, OS
   Chin, L
   DePinho, RA
AF Sahin, Erguen
   Colla, Simona
   Liesa, Marc
   Moslehi, Javid
   Mueller, Florian L.
   Guo, Mira
   Cooper, Marcus
   Kotton, Darrell
   Fabian, Attila J.
   Walkey, Carl
   Maser, Richard S.
   Tonon, Giovanni
   Foerster, Friedrich
   Xiong, Robert
   Wang, Y. Alan
   Shukla, Sachet A.
   Jaskelioff, Mariela
   Martin, Eric S.
   Heffernan, Timothy P.
   Protopopov, Alexei
   Ivanova, Elena
   Mahoney, John E.
   Kost-Alimova, Maria
   Perry, Samuel R.
   Bronson, Roderick
   Liao, Ronglih
   Mulligan, Richard
   Shirihai, Orian S.
   Chin, Lynda
   DePinho, Ronald A.
TI Telomere dysfunction induces metabolic and mitochondrial compromise
SO NATURE
LA English
DT Article
ID heart-failure; stem-cells; damage; leads; pgc-1-alpha; mice; coactivators; homeostasis; biogenesis; carcinoma
AB Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1 alpha and PGC-1 beta, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1a expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1 alpha and PGC-1 beta promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.
C1 [Sahin, Erguen; Colla, Simona; Mueller, Florian L.; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Xiong, Robert; Wang, Y. Alan; Shukla, Sachet A.; Jaskelioff, Mariela; Martin, Eric S.; Heffernan, Timothy P.; Protopopov, Alexei; Ivanova, Elena; Mahoney, John E.; Kost-Alimova, Maria; Perry, Samuel R.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Sahin, Erguen; Colla, Simona; Moslehi, Javid; Mueller, Florian L.; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Jaskelioff, Mariela; Martin, Eric S.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Liesa, Marc; Kotton, Darrell; Shirihai, Orian S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
   [Moslehi, Javid; Liao, Ronglih; DePinho, Ronald A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Guo, Mira] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Cooper, Marcus] Univ Massachusetts, Div Cardiovasc Med, Worcester, MA 01605 USA.
   [Fabian, Attila J.; Mulligan, Richard; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Walkey, Carl] Univ Melbourne, St Vincents Hosp, St Vincents Inst, Victoria 3065, Australia.
   [Walkey, Carl] Univ Melbourne, St Vincents Hosp, Dept Med, Victoria 3065, Australia.
   [Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Lab, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Boston University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; University of Massachusetts System; University of Massachusetts Worcester; Harvard University; Harvard Medical School; University of Melbourne; St Vincent's Health; St Vincent's Hospital Melbourne; NSW Health; St Vincents Hospital Sydney; St. Vincent's Institute of Medical Research; NSW Health; St Vincents Hospital Sydney; St Vincent's Health; St Vincent's Hospital Melbourne; University of Melbourne; Harvard University; Harvard Medical School
RP DePinho, RA (corresponding author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM ron_depinho@dfci.harvard.edu
FU Deutsche Forschungsgemeinschaft; NIH National Cancer Institute; Robert A. and Renee E. Belfer Foundation; Ellison Foundation; American Cancer Society; Fundacion Ramon Areces; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK046200] Funding Source: NIH RePORTER
NR 45
TC 1083
Z9 1204
U1 1
U2 221
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 359
EP 365
DI 10.1038/nature09787
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100034
PM 21307849
DA 2026-03-09
ER

PT J
AU Huang, PY
   He, ZY
   Ji, SY
   Sun, HW
   Xiang, D
   Liu, CC
   Hu, YP
   Wang, X
   Hui, LJ
AF Huang, Pengyu
   He, Zhiying
   Ji, Shuyi
   Sun, Huawang
   Xiang, Dao
   Liu, Changcheng
   Hu, Yiping
   Wang, Xin
   Hui, Lijian
TI Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
SO NATURE
LA English
DT Article
ID enriched transcription factors; embryonic stem-cells; tyrosinemia type-i; pancreas progenitors; hepatic-dysfunction; direct conversion; gene-expression; factor network; liver-function; murine model
AB The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease(1). Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells(2-8). Particularly, hepatocytes generated froma patient's own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes frominduced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages(9-12), including neurons(13), cardiomyocytes(14) and blood progenitors(15); however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocytelike (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1 alpha and Foxa3, and inactivation of p19(Arf). iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah(-/-)) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
C1 [Huang, Pengyu; He, Zhiying; Ji, Shuyi; Sun, Huawang; Liu, Changcheng; Hu, Yiping; Wang, Xin; Hui, Lijian] Chinese Acad Sci, Lab Mol Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
   [He, Zhiying; Xiang, Dao; Liu, Changcheng; Hu, Yiping] Second Mil Med Univ, Dept Cell Biol, Shanghai 200433, Peoples R China.
   [Wang, Xin] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Wang, Xin] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Naval Medical University; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities
RP Hui, LJ (corresponding author), Chinese Acad Sci, Lab Mol Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Yueyang Rd 320, Shanghai 200031, Peoples R China.
EM ljhui@sibs.ac.cn
FU National Science Foundation of China [91019014, 30801115]; Chinese Academy of Sciences [KSCX2-YW-R-241, XDA01010402]; Chinese National 863 Plan Project [2006AA02Z474]; National Key Basic Research and Development Program of China [2007CB947102, 2009CB941100]
NR 29
TC 697
Z9 893
U1 4
U2 248
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 386
EP U142
DI 10.1038/nature10116
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200044
PM 21562492
DA 2026-03-09
ER

PT J
AU Selyunin, AS
   Sutton, SE
   Weigele, BA
   Reddick, LE
   Orchard, RC
   Bresson, SM
   Tomchick, DR
   Alto, NM
AF Selyunin, Andrey S.
   Sutton, Sarah E.
   Weigele, Bethany A.
   Reddick, L. Evan
   Orchard, Robert C.
   Bresson, Stefan M.
   Tomchick, Diana R.
   Alto, Neal M.
TI The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold
SO NATURE
LA English
DT Article
ID structural basis; protein; activation; shigella; model; arf; secretion; coatomer; software; reveals
AB The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits(1,2). These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components(3-6). However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding(7,8), and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5 angstrom crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8 angstrom crystal structure of EspG in complex with the autoinhibitory I alpha 3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.
C1 [Selyunin, Andrey S.; Sutton, Sarah E.; Weigele, Bethany A.; Reddick, L. Evan; Orchard, Robert C.; Bresson, Stefan M.; Alto, Neal M.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [Tomchick, Diana R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP 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 US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; NIH [5T32AI007520-12]; Welch Foundation [I-1704]; NIH (NIAID) [1RO1AI083359-01]; National Institute of Allergy and Infectious Diseases [T32AI007520, R01AI083359] Funding Source: NIH RePORTER
NR 39
TC 87
Z9 108
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 JAN 6
PY 2011
VL 469
IS 7328
BP 107
EP U127
DI 10.1038/nature09593
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600041
PM 21170023
DA 2026-03-09
ER

PT J
AU Wu, H
   D'Alessio, AC
   Ito, S
   Xia, K
   Wang, ZB
   Cui, KR
   Zhao, KJ
   Sun, YE
   Zhang, Y
AF Wu, Hao
   D'Alessio, Ana C.
   Ito, Shinsuke
   Xia, Kai
   Wang, Zhibin
   Cui, Kairong
   Zhao, Keji
   Sun, Yi Eve
   Zhang, Yi
TI Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
SO NATURE
LA English
DT Article
ID dna methylation; histone h3; developmental regulators; chromatin-structure; polycomb; genome; genes; complex; binding; protein
AB Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity(1). The recent demonstration that members of the Ten-eleven translocation (Tet) family of proteins can convert 5-methylcytosine to 5-hydroxymethylcytosine raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state(2,3). We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell maintenance(2). Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing, here we show in mouse ES cells that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite an increase in levels of DNA methylation at many Tet1-binding sites, Tet1 depletion does not lead to downregulation of all the Tet1 targets. Interestingly, although Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also involved in repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators.
C1 [D'Alessio, Ana C.; Ito, Shinsuke; Xia, Kai; Zhang, Yi] Univ N Carolina, Dept Biochem & Biophys, Howard Hughes Med Inst, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, David Geffen Sch Med, IDDRC Semel Inst Neurosci & Human Behav, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
   [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, David Geffen Sch Med, IDDRC Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
   [Wang, Zhibin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Lab Human Environm Epigenomes, Baltimore, MD 21025 USA.
   [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
C3 Howard Hughes Medical Institute; University of North Carolina; University of North Carolina Chapel Hill; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Zhang, Y (corresponding author), Univ N Carolina, Dept Biochem & Biophys, Howard Hughes Med Inst, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM yi_zhang@med.unc.edu
FU NIH [GM68804, R56MH082068]; Division of Intramural Research of National Heart, Lung and Blood Institute, NIH; National Heart Lung and Blood Institute [ZIAHL005801, ZIAHL006031] Funding Source: NIH RePORTER
NR 30
TC 546
Z9 638
U1 0
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 389
EP U578
DI 10.1038/nature09934
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400052
PM 21451524
DA 2026-03-09
ER

PT J
AU Smillie, CS
   Smith, MB
   Friedman, J
   Cordero, OX
   David, LA
   Alm, EJ
AF Smillie, Chris S.
   Smith, Mark B.
   Friedman, Jonathan
   Cordero, Otto X.
   David, Lawrence A.
   Alm, Eric J.
TI Ecology drives a global network of gene exchange connecting the human microbiome
SO NATURE
LA English
DT Article
ID evolution; bacteria; pathogenesis; genm; search
AB Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution(1,2). In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence(3), antibiotic resistance(4) and xenobiotic metabolism(5) to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events(4,5). Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 x 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.
C1 [Cordero, Otto X.; Alm, Eric J.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA.
   [Smillie, Chris S.; Friedman, Jonathan] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA.
   [Smith, Mark B.] MIT, Microbiol Grad Program, Cambridge, MA 02139 USA.
   [David, Lawrence A.] Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA.
   [Alm, Eric J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Alm, Eric J.] Broad Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Alm, EJ (corresponding author), MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ejalm@mit.edu
FU National Science Foundation [0918333, 0936234]; Department of Energy's ENIGMA Scientific Focus Area; Division Of Environmental Biology; Direct For Biological Sciences [0936234, 0918333] Funding Source: National Science Foundation
NR 29
TC 691
Z9 842
U1 6
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 DEC 8
PY 2011
VL 480
IS 7376
BP 241
EP 244
DI 10.1038/nature10571
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200051
PM 22037308
DA 2026-03-09
ER

PT J
AU Cang, H
   Labno, A
   Lu, CG
   Yin, XB
   Liu, M
   Gladden, C
   Liu, YM
   Zhang, X
AF Cang, Hu
   Labno, Anna
   Lu, Changgui
   Yin, Xiaobo
   Liu, Ming
   Gladden, Christopher
   Liu, Yongmin
   Zhang, Xiang
TI Probing the electromagnetic field of a 15-nanometre hotspot by single molecule imaging
SO NATURE
LA English
DT Article
ID enhanced raman-scattering; surface-plasmons; silver electrode; diffraction-limit; energy-transfer; microscopy; spectroscopy; pyridine; localization; excitation
AB When light illuminates a rough metallic surface, hotspots can appear, where the light is concentrated on the nanometre scale, producing an intense electromagnetic field. This phenomenon, called the surface enhancement effect(1,2), has a broad range of potential applications, such as the detection of weak chemical signals. Hotspots are believed to be associated with localized electromagnetic modes(3,4), caused by the randomness of the surface texture. Probing the electromagnetic field of the hotspots would offer much insight towards uncovering the mechanism generating the enhancement; however, it requires a spatial resolution of 1-2 nm, which has been a long-standing challenge in optics. The resolution of an optical microscope is limited to about half the wavelength of the incident light, approximately 200-300 nm. Although current state-of-the-art techniques, including near-field scanning optical microscopy(5), electron energy-loss spectroscopy(6), cathode luminescence imaging(7) and two-photon photoemission imaging(8) have subwavelength resolution, they either introduce a non-negligible amount of perturbation, complicating interpretation of the data, or operate only in a vacuum. As a result, after more than 30 years since the discovery of the surface enhancement effect(9-11), how the local field is distributed remains unknown. Here we present a technique that uses Brownian motion of single molecules to probe the local field. It enables two-dimensional imaging of the fluorescence enhancement profile of single hotspots on the surfaces of aluminium thin films and silver nanoparticle clusters, with accuracy down to 1.2 nm. Strong fluorescence enhancements, up to 54 and 136 times respectively, are observed in those two systems. This strong enhancement indicates that the local field, which decays exponentially from the peak of a hotspot, dominates the fluorescence enhancement profile.
C1 [Cang, Hu; Yin, Xiaobo; Zhang, Xiang] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Cang, Hu; Labno, Anna; Lu, Changgui; Yin, Xiaobo; Liu, Ming; Gladden, Christopher; Liu, Yongmin; Zhang, Xiang] Univ Calif Berkeley, NSF Nano Scale Sci & Engn Ctr, Berkeley, CA 94720 USA.
   [Labno, Anna] Univ Calif Berkeley, Biophys Program, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; National Science Foundation (NSF); University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Zhang, X (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
EM xiang@berkeley.edu
FU US Department of Energy Office of Science, Basic Energy Sciences and Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]
NR 30
TC 225
Z9 249
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 JAN 20
PY 2011
VL 469
IS 7330
BP 385
EP +
DI 10.1038/nature09698
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600049
PM 21248848
DA 2026-03-09
ER

PT J
AU Schiermeier, Q
AF Schiermeier, Quirin
TI Defying disaster
SO NATURE
LA English
DT Article
NR 0
TC 1
Z9 1
U1 0
U2 7
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 505
EP 505
DI 10.1038/nj7344-505a
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600042
DA 2026-03-09
ER

PT J
AU Gill, BC
   Lyons, TW
   Young, SA
   Kump, LR
   Knoll, AH
   Saltzman, MR
AF Gill, Benjamin C.
   Lyons, Timothy W.
   Young, Seth A.
   Kump, Lee R.
   Knoll, Andrew H.
   Saltzman, Matthew R.
TI Geochemical evidence for widespread euxinia in the Later Cambrian ocean
SO NATURE
LA English
DT Article
ID carbon; anoxia; extinction; burial; event; spice; iron
AB Widespread anoxia in the ocean is frequently invoked as a primary driver of mass extinction as well as a long-term inhibitor of evolutionary radiation on early Earth. In recent biogeochemical studies it has been hypothesized that oxygen deficiency was widespread in subsurface water masses of later Cambrian oceans(1,2), possibly influencing evolutionary events during this time(1-3). Physical evidence of widespread anoxia in Cambrian oceans has remained elusive and thus its potential relationship to the palaeontological record remains largely unexplored. Here we present sulphur isotope records from six globally distributed stratigraphic sections of later Cambrian marine rocks (about 499 million years old). We find a positive sulphur isotope excursion in phase with the Steptoean Positive Carbon Isotope Excursion (SPICE), a large and rapid excursion in the marine carbon isotope record, which is thought to be indicative of a global carbon cycle perturbation(4,5). Numerical box modelling of the paired carbon sulphur isotope data indicates that these isotope shifts reflect transient increases in the burial of organic carbon and pyrite sulphur in sediments deposited under large-scale anoxic and sulphidic (euxinic) conditions. Independently, molybdenum abundances in a coeval black shale point convincingly to the transient spread of anoxia. These results identify the SPICE interval as the best characterized ocean anoxic event in the pre-Mesozoic ocean and an extreme example of oxygen deficiency in the later Cambrian ocean. Thus, a redox structure similar to those in Proterozoic oceans(6-8) may have persisted or returned in the oceans of the early Phanerozoic eon. Indeed, the environmental challenges presented by widespread anoxia may have been a prevalent if not dominant influence on animal evolution in Cambrian oceans.
C1 [Gill, Benjamin C.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Young, Seth A.] Indiana Univ, Dept Geol Sci, Bloomington, IN 47405 USA.
   [Kump, Lee R.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Knoll, Andrew H.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Saltzman, Matthew R.] Ohio State Univ, Sch Earth Sci, Columbus, OH 43210 USA.
C3 University of California System; University of California Riverside; Indiana University System; Indiana University Bloomington; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Harvard University; University System of Ohio; Ohio State University
RP Gill, BC (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM bgill@fas.harvard.edu
FU NSF-EAR; NASA Astrobiology
CR Adams DD, 2010, NAT GEOSCI, V3, P201, DOI 10.1038/NGEO743
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NR 30
TC 386
Z9 466
U1 3
U2 201
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 80
EP 83
DI 10.1038/nature09700
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600035
PM 21209662
DA 2026-03-09
ER

PT J
AU Kirkby, J
   Curtius, J
   Almeida, J
   Dunne, E
   Duplissy, J
   Ehrhart, S
   Franchin, A
   Gagné, S
   Ickes, L
   Kürten, A
   Kupc, A
   Metzger, A
   Riccobono, F
   Rondo, L
   Schobesberger, S
   Tsagkogeorgas, G
   Wimmer, D
   Amorim, A
   Bianchi, F
   Breitenlechner, M
   David, A
   Dommen, J
   Downard, A
   Ehn, M
   Flagan, RC
   Haider, S
   Hansel, A
   Hauser, D
   Jud, W
   Junninen, H
   Kreissl, F
   Kvashin, A
   Laaksonen, A
   Lehtipalo, K
   Lima, J
   Lovejoy, ER
   Makhmutov, V
   Mathot, S
   Mikkilä, J
   Minginette, P
   Mogo, S
   Nieminen, T
   Onnela, A
   Pereira, P
   Petäjä, T
   Schnitzhofer, R
   Seinfeld, JH
   Sipilä, M
   Stozhkov, Y
   Stratmann, F
   Tomé, A
   Vanhanen, J
   Viisanen, Y
   Vrtala, A
   Wagner, PE
   Walther, H
   Weingartner, E
   Wex, H
   Winkler, PM
   Carslaw, KS
   Worsnop, DR
   Baltensperger, U
   Kulmala, M
AF Kirkby, Jasper
   Curtius, Joachim
   Almeida, Joao
   Dunne, Eimear
   Duplissy, Jonathan
   Ehrhart, Sebastian
   Franchin, Alessandro
   Gagne, Stephanie
   Ickes, Luisa
   Kuerten, Andreas
   Kupc, Agnieszka
   Metzger, Axel
   Riccobono, Francesco
   Rondo, Linda
   Schobesberger, Siegfried
   Tsagkogeorgas, Georgios
   Wimmer, Daniela
   Amorim, Antonio
   Bianchi, Federico
   Breitenlechner, Martin
   David, Andre
   Dommen, Josef
   Downard, Andrew
   Ehn, Mikael
   Flagan, Richard C.
   Haider, Stefan
   Hansel, Armin
   Hauser, Daniel
   Jud, Werner
   Junninen, Heikki
   Kreissl, Fabian
   Kvashin, Alexander
   Laaksonen, Ari
   Lehtipalo, Katrianne
   Lima, Jorge
   Lovejoy, Edward R.
   Makhmutov, Vladimir
   Mathot, Serge
   Mikkila, Jyri
   Minginette, Pierre
   Mogo, Sandra
   Nieminen, Tuomo
   Onnela, Antti
   Pereira, Paulo
   Petaja, Tuukka
   Schnitzhofer, Ralf
   Seinfeld, John H.
   Sipila, Mikko
   Stozhkov, Yuri
   Stratmann, Frank
   Tome, Antonio
   Vanhanen, Joonas
   Viisanen, Yrjo
   Vrtala, Aron
   Wagner, Paul E.
   Walther, Hansueli
   Weingartner, Ernest
   Wex, Heike
   Winkler, Paul M.
   Carslaw, Kenneth S.
   Worsnop, Douglas R.
   Baltensperger, Urs
   Kulmala, Markku
TI Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation
SO NATURE
LA English
DT Article
ID ion-induced nucleation; particle formation; mass-spectrometer; upper troposphere; nanoparticles; h2so4; water; h2o
AB Atmospheric aerosols exert an important influence on climate(1) through their effects on stratiform cloud albedo and lifetime(2) and the invigoration of convective storms(3). Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours(4), although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small(5,6). Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia(7). Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H2SO4-H2O can occur in the midtroposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.
C1 [Curtius, Joachim; Almeida, Joao; Ehrhart, Sebastian; Ickes, Luisa; Kuerten, Andreas; Rondo, Linda; Wimmer, Daniela; Kreissl, Fabian] Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.
   [Almeida, Joao; Amorim, Antonio; Lima, Jorge; Mogo, Sandra; Pereira, Paulo; Tome, Antonio] Univ Lisbon, SIM, P-1749016 Lisbon, Portugal.
   [Almeida, Joao; Amorim, Antonio; Lima, Jorge; Mogo, Sandra; Pereira, Paulo; Tome, Antonio] Univ Beira Interior, P-1749016 Lisbon, Portugal.
   [Dunne, Eimear; Carslaw, Kenneth S.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Duplissy, Jonathan; Franchin, Alessandro; Gagne, Stephanie; Schobesberger, Siegfried; Ehn, Mikael; Junninen, Heikki; Lehtipalo, Katrianne; Mikkila, Jyri; Nieminen, Tuomo; Petaja, Tuukka; Sipila, Mikko; Vanhanen, Joonas; Worsnop, Douglas R.; Kulmala, Markku] Univ Helsinki, Dept Phys, FI-00014 Helsinki, Finland.
   [Duplissy, Jonathan; Gagne, Stephanie; Sipila, Mikko] Univ Helsinki, Helsinki Inst Phys, FI-00014 Helsinki, Finland.
   [Kirkby, Jasper; Duplissy, Jonathan; David, Andre; Haider, Stefan; Mathot, Serge; Minginette, Pierre; Onnela, Antti] CERN, CH-1211 Geneva, Switzerland.
   [Kupc, Agnieszka; Vrtala, Aron; Wagner, Paul E.; Winkler, Paul M.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Metzger, Axel; Breitenlechner, Martin; Hansel, Armin; Hauser, Daniel; Jud, Werner; Schnitzhofer, Ralf] Univ Innsbruck, Inst Ion & Appl Phys, A-6020 Innsbruck, Austria.
   [Metzger, Axel; Breitenlechner, Martin; Hansel, Armin; Hauser, Daniel; Jud, Werner; Schnitzhofer, Ralf] Ionicon Analyt GmbH, A-6020 Innsbruck, Austria.
   [Riccobono, Francesco; Bianchi, Federico; Dommen, Josef; Walther, Hansueli; Weingartner, Ernest; Baltensperger, Urs] Paul Scherrer Inst, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
   [Tsagkogeorgas, Georgios; Stratmann, Frank; Wex, Heike] Leibniz Inst Tropospher Res, D-04318 Leipzig, Germany.
   [Bianchi, Federico] Univ Milan, Dept Inorgan Metallorgan & Analyt Chem, I-20133 Milan, Italy.
   [Downard, Andrew; Flagan, Richard C.; Seinfeld, John H.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Kvashin, Alexander; Makhmutov, Vladimir; Stozhkov, Yuri] PN Lebedev Phys Inst, Solar & Cosm Ray Res Lab, Moscow 119991, Russia.
   [Laaksonen, Ari] Univ Eastern Finland, FI-70211 Kuopio, Finland.
   [Lovejoy, Edward R.] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Viisanen, Yrjo] Finnish Meteorol Inst, FI-00101 Helsinki, Finland.
   [Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
C3 Goethe University Frankfurt; Universidade de Lisboa; Universidade da Beira Interior; University of Leeds; University of Helsinki; Helsinki Institute of Physics; University of Helsinki; European Organization for Nuclear Research (CERN); University of Vienna; University of Innsbruck; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); University of Milan; California Institute of Technology; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute; University of Eastern Finland; National Oceanic Atmospheric Admin (NOAA) - USA; Finnish Meteorological Institute; Aerodyne Research
RP Kirkby, J (corresponding author), CERN, CH-1211 Geneva, Switzerland.
EM jasper.kirkby@cern.ch
FU EC [215072]; ERC [227463]; German Federal Ministry of Education and Research [01LK0902A]; Swiss National Science Foundation [206621_125025, 206620_130527]; Academy of Finland Center of Excellence [1118615]; Austrian Science Fund (FWF) [P19546, L593]; Russian Academy of Sciences; Russian Foundation for Basic Research [N08-02-91006-CERN]; CERN; Austrian Science Fund (FWF) [P19546, L593] Funding Source: Austrian Science Fund (FWF); Austrian Science Fund (FWF) [L 593, P 19546] Funding Source: researchfish; Swiss National Science Foundation (SNF) [206621_125025, 206620_130527] Funding Source: Swiss National Science Foundation (SNF)
NR 44
TC 1040
Z9 1165
U1 10
U2 796
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 429
EP U77
DI 10.1038/nature10343
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400031
PM 21866156
DA 2026-03-09
ER

PT J
AU Ito, H
   Gaubert, H
   Bucher, E
   Mirouze, M
   Vaillant, I
   Paszkowski, J
AF Ito, Hidetaka
   Gaubert, Herve
   Bucher, Etienne
   Mirouze, Marie
   Vaillant, Isabelle
   Paszkowski, Jerzy
TI An siRNA pathway prevents transgenerational retrotransposition in plants subjected to stress
SO NATURE
LA English
DT Article
ID dna-methylation; transposable elements; epigenetic regulation; repetitive elements; genome size; arabidopsis; demethylation; expression; dynamics
AB Eukaryotic genomes consist to a significant extent of retrotransposons that are suppressed by host epigenetic mechanisms, preventing their uncontrolled propagation(1,2). However, it is not clear how this is achieved. Here we show that in Arabidopsis seedlings subjected to heat stress, a copia-type retrotransposon named ONSEN (Japanese 'hot spring') not only became transcriptionally active but also synthesized extrachromosomal DNA copies. Heat-induced ONSEN accumulation was stimulated in mutants impaired in the biogenesis of small interfering RNAs (siRNAs); however, there was no evidence of transposition occurring in vegetative tissues. After stress, both ONSEN transcripts and extrachromosomal DNA gradually decayed and were no longer detected after 20-30 days. Surprisingly, a high frequency of new ONSEN insertions was observed in the progeny of stressed plants deficient in siRNAs. Insertion patterns revealed that this transgenerational retrotransposition occurred during flower development and before gametogenesis. Therefore in plants with compromised siRNA biogenesis, memory of stress was maintained throughout development, priming ONSEN to transpose during differentiation of generative organs. Retrotransposition was not observed in the progeny of wild-type plants subjected to stress or in non-stressed mutant controls, pointing to a crucial role of the siRNA pathway in restricting retrotransposition triggered by environmental stress. Finally, we found that natural and experimentally induced variants in ONSEN insertions confer heat responsiveness to nearby genes, and therefore mobility bursts may generate novel, stress-responsive regulatory gene networks.
C1 [Ito, Hidetaka; Gaubert, Herve; Bucher, Etienne; Mirouze, Marie; Vaillant, Isabelle; Paszkowski, Jerzy] Univ Geneva, Dept Plant Biol, CH-1211 Geneva 4, Switzerland.
C3 University of Geneva
RP Paszkowski, J (corresponding author), Univ Geneva, Dept Plant Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
EM jerzy.paszkowski@unige.ch
FU Swiss National Science Foundation [31003A-125005]; European Commission [FP7 226477]; RECBREED consortium [FP7 227190]; Epigenome Network of Excellence [FP6 503433]; Swiss National Science Foundation (SNF) [31003A_125005] Funding Source: Swiss National Science Foundation (SNF)
NR 30
TC 501
Z9 561
U1 4
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 115
EP U151
DI 10.1038/nature09861
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400048
PM 21399627
DA 2026-03-09
ER

PT J
AU Berger, MF
   Lawrence, MS
   Demichelis, F
   Drier, Y
   Cibulskis, K
   Sivachenko, AY
   Sboner, A
   Esgueva, R
   Pflueger, D
   Sougnez, C
   Onofrio, R
   Carter, SL
   Park, K
   Habegger, L
   Ambrogio, L
   Fennell, T
   Parkin, M
   Saksena, G
   Voet, D
   Ramos, AH
   Pugh, TJ
   Wilkinson, J
   Fisher, S
   Winckler, W
   Mahan, S
   Ardlie, K
   Baldwin, J
   Simons, JW
   Kitabayashi, N
   MacDonald, TY
   Kantoff, PW
   Chin, L
   Gabriel, SB
   Gerstein, MB
   Golub, TR
   Meyerson, M
   Tewari, A
   Lander, ES
   Getz, G
   Rubin, MA
   Garraway, LA
AF Berger, Michael F.
   Lawrence, Michael S.
   Demichelis, Francesca
   Drier, Yotam
   Cibulskis, Kristian
   Sivachenko, Andrey Y.
   Sboner, Andrea
   Esgueva, Raquel
   Pflueger, Dorothee
   Sougnez, Carrie
   Onofrio, Robert
   Carter, Scott L.
   Park, Kyung
   Habegger, Lukas
   Ambrogio, Lauren
   Fennell, Timothy
   Parkin, Melissa
   Saksena, Gordon
   Voet, Douglas
   Ramos, Alex H.
   Pugh, Trevor J.
   Wilkinson, Jane
   Fisher, Sheila
   Winckler, Wendy
   Mahan, Scott
   Ardlie, Kristin
   Baldwin, Jennifer
   Simons, Jonathan W.
   Kitabayashi, Naoki
   MacDonald, Theresa Y.
   Kantoff, Philip W.
   Chin, Lynda
   Gabriel, Stacey B.
   Gerstein, Mark B.
   Golub, Todd R.
   Meyerson, Matthew
   Tewari, Ashutosh
   Lander, Eric S.
   Getz, Gad
   Rubin, Mark A.
   Garraway, Levi A.
TI The genomic complexity of primary human prostate cancer
SO NATURE
LA English
DT Article
ID gene fusions; androgen receptor; tumor-suppressor; human breast; pten; mutation; pathway; rearrangements; immunotherapy; tmprss2-erg
AB Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, 'copy-neutral') rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2-ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
C1 [Demichelis, Francesca; Esgueva, Raquel; Pflueger, Dorothee; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
   [Berger, Michael F.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Carter, Scott L.; Ambrogio, Lauren; Fennell, Timothy; Parkin, Melissa; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Pugh, Trevor J.; Wilkinson, Jane; Fisher, Sheila; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Chin, Lynda; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
   [Berger, Michael F.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Carter, Scott L.; Ambrogio, Lauren; Fennell, Timothy; Parkin, Melissa; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Pugh, Trevor J.; Wilkinson, Jane; Fisher, Sheila; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Chin, Lynda; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] MIT, Cambridge, MA 02142 USA.
   [Demichelis, Francesca] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA.
   [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Sboner, Andrea; Gerstein, Mark B.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Sboner, Andrea; Habegger, Lukas; Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Ramos, Alex H.; Pugh, Trevor J.; Kantoff, Philip W.; Chin, Lynda; Meyerson, Matthew; Lander, Eric S.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Pugh, Trevor J.; Kantoff, Philip W.; Chin, Lynda; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Simons, Jonathan W.] Prostate Canc Fdn, Santa Monica, CA 90401 USA.
   [Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Golub, Todd R.; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Tewari, Ashutosh] Weill Cornell Med Coll, Inst Prostate Canc, Dept Urol, New York, NY 10065 USA.
   [Tewari, Ashutosh] Weill Cornell Med Coll, Lefrak Ctr Robot Surg, New York, NY 10065 USA.
   [Tewari, Ashutosh] New York Presbyterian Hosp, New York, NY 10065 USA.
   [Lander, Eric S.] 9 Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
C3 Cornell University; Weill Cornell Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Cornell University; Weill Cornell Medicine; Weizmann Institute of Science; Yale University; Yale University; 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; Yale University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital; Massachusetts Institute of Technology (MIT); Whitehead Institute
RP Rubin, MA (corresponding author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
EM rubinma@med.cornell.edu; levi_garraway@dfci.harvard.edu
FU Prostate Cancer Foundation/Movember; Howard Hughes Medical Institute; National Human Genome Research Institute; Kohlberg Foundation; National Cancer Institute (NCI); NCI Early Detection Research Network; National Institutes of Health; Department of Defense; Dana-Farber/Harvard Cancer Center [2 P50 CA090381-11]; Starr Cancer Consortium
NR 50
TC 997
Z9 1181
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 FEB 10
PY 2011
VL 470
IS 7333
BP 214
EP 220
DI 10.1038/nature09744
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200035
PM 21307934
DA 2026-03-09
ER

PT J
AU Shinzato, C
   Shoguchi, E
   Kawashima, T
   Hamada, M
   Hisata, K
   Tanaka, M
   Fujie, M
   Fujiwara, M
   Koyanagi, R
   Ikuta, T
   Fujiyama, A
   Miller, DJ
   Satoh, N
AF Shinzato, Chuya
   Shoguchi, Eiichi
   Kawashima, Takeshi
   Hamada, Mayuko
   Hisata, Kanako
   Tanaka, Makiko
   Fujie, Manabu
   Fujiwara, Mayuki
   Koyanagi, Ryo
   Ikuta, Tetsuro
   Fujiyama, Asao
   Miller, David J.
   Satoh, Nori
TI Using the Acropora digitifera genome to understand coral responses to environmental change
SO NATURE
LA English
DT Article
ID immune gene repertoire; climate-change; reveals; complexity; biosynthesis; alignments; mechanisms; evolution; sequence; database
AB Despite the enormous ecological and economic importance of coral reefs, the keystone organisms in their establishment, the scleractinian corals, increasingly face a range of anthropogenic challenges including ocean acidification and seawater temperature rise(1-4). To understand better the molecular mechanisms underlying coral biology, here we decoded the approximately 420-megabase genome of Acropora digitifera using next-generation sequencing technology. This genome contains approximately 23,700 gene models. Molecular phylogenetics indicate that the coral and the sea anemone Nematostella vectensis diverged approximately 500 million years ago, considerably earlier than the time over which modern corals are represented in the fossil record (similar to 240 million years ago)(5). Despite the long evolutionary history of the endosymbiosis, no evidence was found for horizontal transfer of genes from symbiont to host. However, unlike several other corals, Acropora seems to lack an enzyme essential for cysteine biosynthesis, implying dependency of this coral on its symbionts for this amino acid. Corals inhabit environments where they are frequently exposed to high levels of solar radiation, and analysis of the Acropora genome data indicates that the coral host can independently carry out de novo synthesis of mycosporine-like amino acids, which are potent ultraviolet-protective compounds. In addition, the coral innate immunity repertoire is notably more complex than that of the sea anemone, indicating that some of these genes may have roles in symbiosis or coloniality. A number of genes with putative roles in calcification were identified, and several of these are restricted to corals. The coral genome provides a platform for understanding the molecular basis of symbiosis and responses to environmental changes.
C1 [Shinzato, Chuya; Shoguchi, Eiichi; Kawashima, Takeshi; Hamada, Mayuko; Hisata, Kanako; Tanaka, Makiko; Fujiwara, Mayuki; Koyanagi, Ryo; Ikuta, Tetsuro; Satoh, Nori] Okinawa Inst Sci & Technol Promot Corp, Marine Genom Unit, Okinawa 9040412, Japan.
   [Fujiyama, Asao] Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
   [Fujie, Manabu] Okinawa Inst Sci & Technol Promot Corp, DNA Sequencing Ctr Sect, Okinawa 9040412, Japan.
   [Miller, David J.] James Cook Univ, ARC Ctr Excellence Coral Reef Studies, Townsville, Qld 4811, Australia.
   [Miller, David J.] James Cook Univ, Sch Pharm & Mol Sci, Townsville, Qld 4811, Australia.
C3 Okinawa Institute of Science & Technology Graduate University; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Okinawa Institute of Science & Technology Graduate University; James Cook University; ARC Centre of Excellence for Coral Reef Studies; James Cook University
RP Satoh, N (corresponding author), Okinawa Inst Sci & Technol Promot Corp, Marine Genom Unit, Okinawa 9040412, Japan.
EM norisky@oist.jp
FU IT Section of OIST; Human Genome Center, University of Tokyo; MEXT; JSPS, Japan; Grants-in-Aid for Scientific Research [20121002] Funding Source: KAKEN
NR 44
TC 647
Z9 748
U1 4
U2 423
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 320
EP U82
DI 10.1038/nature10249
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500035
PM 21785439
DA 2026-03-09
ER

PT J
AU Cederwall, B
   Moradi, FG
   Bäck, T
   Johnson, A
   Blomqvist, J
   Clément, E
   de France, G
   Wadsworth, R
   Andgren, K
   Lagergren, K
   Dijon, A
   Jaworski, G
   Liotta, R
   Qi, C
   Nyakó, BM
   Nyberg, J
   Palacz, M
   Al-Azri, H
   Algora, A
   de Angelis, G
   Ataç, A
   Bhattacharyya, S
   Brock, T
   Brown, JR
   Davies, P
   Di Nitto, A
   Dombrádi, Z
   Gadea, A
   Gál, J
   Hadinia, B
   Johnston-Theasby, F
   Joshi, P
   Juhász, K
   Julin, R
   Jungclaus, A
   Kalinka, G
   Kara, SO
   Khaplanov, A
   Kownacki, J
   La Rana, G
   Lenzi, SM
   Molnár, J
   Moro, R
   Napoli, DR
   Singh, BSN
   Persson, A
   Recchia, F
   Sandzelius, M
   Scheurer, JN
   Sletten, G
   Sohler, D
   Söderström, PA
   Taylor, MJ
   Timár, J
   Valiente-Dobón, JJ
   Vardaci, E
   Williams, S
AF Cederwall, B.
   Moradi, F. Ghazi
   Back, T.
   Johnson, A.
   Blomqvist, J.
   Clement, E.
   de France, G.
   Wadsworth, R.
   Andgren, K.
   Lagergren, K.
   Dijon, A.
   Jaworski, G.
   Liotta, R.
   Qi, C.
   Nyako, B. M.
   Nyberg, J.
   Palacz, M.
   Al-Azri, H.
   Algora, A.
   de Angelis, G.
   Atac, A.
   Bhattacharyya, S.
   Brock, T.
   Brown, J. R.
   Davies, P.
   Di Nitto, A.
   Dombradi, Zs.
   Gadea, A.
   Gal, J.
   Hadinia, B.
   Johnston-Theasby, F.
   Joshi, P.
   Juhasz, K.
   Julin, R.
   Jungclaus, A.
   Kalinka, G.
   Kara, S. O.
   Khaplanov, A.
   Kownacki, J.
   La Rana, G.
   Lenzi, S. M.
   Molnar, J.
   Moro, R.
   Napoli, D. R.
   Singh, B. S. Nara
   Persson, A.
   Recchia, F.
   Sandzelius, M.
   Scheurer, J. -N.
   Sletten, G.
   Sohler, D.
   Soderstrom, P. -A.
   Taylor, M. J.
   Timar, J.
   Valiente-Dobon, J. J.
   Vardaci, E.
   Williams, S.
TI Evidence for a spin-aligned neutron-proton paired phase from the level structure of 92Pd
SO NATURE
LA English
DT Article
ID shell-model description; generalized seniority; spectrometer; states
AB Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work(1) that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing(2-6), in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus Pd-92. Gamma rays emitted following the Ni-58(Ar-36,2n)Pd-92 fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution c-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction(2-6). We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling(7,8)) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.
C1 [Cederwall, B.; Moradi, F. Ghazi; Back, T.; Johnson, A.; Blomqvist, J.; Andgren, K.; Lagergren, K.; Liotta, R.; Qi, C.; Hadinia, B.; Khaplanov, A.; Persson, A.; Sandzelius, M.] Royal Inst Technol, Dept Phys, SE-10691 Stockholm, Sweden.
   [Clement, E.; de France, G.; Dijon, A.; Bhattacharyya, S.] CNRS, IN2P3, CEA, DSM,GANIL, F-14076 Caen 5, France.
   [Wadsworth, R.; Al-Azri, H.; Brock, T.; Brown, J. R.; Davies, P.; Johnston-Theasby, F.; Joshi, P.; Singh, B. S. Nara; Taylor, M. J.] Univ York, Dept Phys, York YO10 5DD, N Yorkshire, England.
   [Lagergren, K.] Holifield Radioact Ion Beam Facil, Joint Inst Heavy Ion Res, Oak Ridge, TN 37831 USA.
   [Jaworski, G.; Palacz, M.; Kownacki, J.] Univ Warsaw, Heavy Ion Lab, PL-02093 Warsaw, Poland.
   [Jaworski, G.] Warsaw Univ Technol, Fac Phys, PL-00662 Warsaw, Poland.
   [Nyako, B. M.; Dombradi, Zs.; Gal, J.; Kalinka, G.; Molnar, J.; Sohler, D.; Timar, J.] Hungarian Acad Sci, Inst Nucl Res, H-4001 Debrecen, Hungary.
   [Nyberg, J.; Soderstrom, P. -A.] Uppsala Univ, Dept Phys & Astron, SE-75121 Uppsala, Sweden.
   [Algora, A.; Gadea, A.] Univ Valencia, CSIC, IFIC, E-46071 Valencia, Spain.
   [de Angelis, G.; Napoli, D. R.; Valiente-Dobon, J. J.] Inst Nazl Fis Nucl, Lab Nazl Legnaro, I-35020 Legnaro, Italy.
   [Atac, A.; Kara, S. O.] Ankara Univ, Dept Phys, TR-06100 Tandogan, Turkey.
   [Di Nitto, A.; La Rana, G.; Moro, R.; Vardaci, E.] Univ Naples Federico II, Dipartimento Sci Fis, I-80126 Naples, Italy.
   [Di Nitto, A.; La Rana, G.; Moro, R.; Vardaci, E.] Inst Nazl Fis Nucl, I-80126 Naples, Italy.
   [Juhasz, K.] Univ Debrecen, Dept Informat Technol, H-4010 Debrecen, Hungary.
   [Julin, R.] Univ Jyvaskyla, Dept Phys, FIN-40014 Jyvaskyla, Finland.
   [Jungclaus, A.] CSIC, Inst Estruct Mat, E-28006 Madrid, Spain.
   [Lenzi, S. M.; Recchia, F.] Univ Padua, Dipartimento Fis, I-35122 Padua, Italy.
   [Lenzi, S. M.; Recchia, F.] Inst Nazl Fis Nucl, Sez Padova, I-35122 Padua, Italy.
   [Scheurer, J. -N.] Univ Bordeaux 1, CNRS, IN2P3, Ctr Etud Nucl Bordeaux Gradignan, F-33175 Gradignan, France.
   [Sletten, G.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Williams, S.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
C3 Royal Institute of Technology; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); CEA; University of York - UK; University of Warsaw; Warsaw University of Technology; Hungarian Academy of Sciences; HUN-REN; HUN-REN Institute for Nuclear Research; Uppsala University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Fisica Corpuscular (IFIC); University of Valencia; Istituto Nazionale di Fisica Nucleare (INFN); Ankara University; University of Naples Federico II; Istituto Nazionale di Fisica Nucleare (INFN); University of Debrecen; University of Jyvaskyla; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Estructura de la Materia (IEM); University of Padua; Istituto Nazionale di Fisica Nucleare (INFN); Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Copenhagen; Niels Bohr Institute; University of British Columbia
RP Cederwall, B (corresponding author), Royal Inst Technol, Dept Phys, SE-10691 Stockholm, Sweden.
EM cederwall@nuclear.kth.se
FU Swedish Research Council [2007-4067, 2008-5793]; Goran Gustafsson Foundation; European Union [506065]; Hungarian Scientific Research Fund, OTKA [K72566, K68801]; UK Science and Technology Facilities Council (STFC); Polish Ministry of Science and Higher Education [N N202 073935]; Spanish Ministerio de Ciencia e Innovacion [FPA2007-66069]; Spanish Consolider-Ingenio 2010 Programme CPAN [CSD2007-00042]; Ankara University [DPT 2005120140]; STFC [ST/J000124/1, ST/F012071/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J000124/1, ST/F012071/1] Funding Source: researchfish
NR 24
TC 154
Z9 165
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 6
PY 2011
VL 469
IS 7328
BP 68
EP 71
DI 10.1038/nature09644
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600032
PM 21179086
DA 2026-03-09
ER

PT J
AU Takemoto, T
   Uchikawa, M
   Yoshida, M
   Bell, DM
   Lovell-Badge, R
   Papaioannou, VE
   Kondoh, H
AF Takemoto, Tatsuya
   Uchikawa, Masanori
   Yoshida, Megumi
   Bell, Donald M.
   Lovell-Badge, Robin
   Papaioannou, Virginia E.
   Kondoh, Hisato
TI Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells
SO NATURE
LA English
DT Article
ID mouse embryo; paraxial mesoderm; presomitic mesoderm; nervous-system; expression; gene; wnt; tbx6; gastrulation; elements
AB The classical view of neural plate development held that it arises from the ectoderm, after its separation from the mesodermal and endodermal lineages. However, recent cell-lineage-tracing experiments indicate that the caudal neural plate and paraxial mesoderm are generated from common bipotential axial stem cells originating from the caudal lateral epiblast(1,2). Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm(3) must provide a clue to the regulatory mechanism underlying this neural versus mesodermal fate choice. Here we demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate(4-6). In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wild-type embryos resulted in ectopic neural tube development. Thus, Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells.
C1 [Takemoto, Tatsuya; Uchikawa, Masanori; Yoshida, Megumi; Kondoh, Hisato] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Bell, Donald M.; Lovell-Badge, Robin] Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England.
   [Papaioannou, Virginia E.] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
C3 University of Osaka; MRC National Institute for Medical Research; Columbia University
RP Kondoh, H (corresponding author), Osaka Univ, Grad Sch Frontier Biosci, 1-3 Yamadaoka, Suita, Osaka 5650871, Japan.
EM kondohh@fbs.osaka-u.ac.jp
FU MEXT Japan; NIH; MRC; MRC [MC_U117562207] Funding Source: UKRI; Grants-in-Aid for Scientific Research [22247035] Funding Source: KAKEN; Medical Research Council [MC_U117562207] Funding Source: researchfish
NR 43
TC 214
Z9 258
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 FEB 17
PY 2011
VL 470
IS 7334
BP 394
EP 398
DI 10.1038/nature09729
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100042
PM 21331042
DA 2026-03-09
ER

PT J
AU Kwok, S
   Zhang, Y
AF Kwok, Sun
   Zhang, Yong
TI Mixed aromatic-aliphatic organic nanoparticles as carriers of unidentified infrared emission features
SO NATURE
LA English
DT Article
ID interstellar dust; protoplanetary nebulae; reflection nebulae; bands; hydrocarbons; spectrum; carbon; model; condensation; excitation
AB Unidentified infrared emission bands at wavelengths of 3-20 micrometres are widely observed in a range of environments in our Galaxy and in others(1). Some features have been identified as the stretching and bending modes of aromatic compounds(2,3), and are commonly attributed to polycyclic aromatic hydrocarbon molecules(4,5). The central argument supporting this attribution is that single-photon excitation of the molecule can account for the unidentified infrared emission features observed in 'cirrus' clouds in the diffuse interstellar medium(6). Of the more than 160 molecules identified in the circumstellar and interstellar environments, however, not one is a polycyclic aromatic hydrocarbon molecule. The detections of discrete and broad aliphatic spectral features suggest that the carrier of the unidentified infrared emission features cannot be a pure aromatic compound. Here we report an analysis of archival spectroscopic observations and demonstrate that the data are most consistent with the carriers being amorphous organic solids with a mixed aromatic-aliphatic structure. This structure is similar to that of the organic materials found in meteorites, as would be expected if the Solar System had inherited these organic materials from interstellar sources.
C1 [Kwok, Sun; Zhang, Yong] Univ Hong Kong, Fac Sci, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
C3 University of Hong Kong
RP Kwok, S (corresponding author), Univ Hong Kong, Fac Sci, Dept Phys, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China.
EM sunkwok@hku.hk
FU Research Grants Council of the Hong Kong Special Administrative Region, China [HKU 7027/11P]
NR 30
TC 224
Z9 239
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 3
PY 2011
VL 479
IS 7371
BP 80
EP 83
DI 10.1038/nature10542
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600035
PM 22031328
DA 2026-03-09
ER

PT J
AU Leeb, M
   Wutz, A
AF Leeb, Martin
   Wutz, Anton
TI Derivation of haploid embryonic stem cells from mouse embryos
SO NATURE
LA English
DT Article
ID genetic screens; lines; activation; expression; generation; identity
AB Most animals are diploid, but haploid-only and male-haploid (such as honeybee and ant) species have been described(1). The diploid genomes of complex organisms limit genetic approaches in biomedical model species such as mice. To overcome this problem, experimental induction of haploidy has been used in fish(2,3). Haploid development in zebrafish has been applied for genetic screening(2). Recently, haploid pluripotent cell lines from medaka fish (Oryzias latipes) have also been established(3). In contrast, haploidy seems less compatible with development in mammals(4,5). Although haploid cells have been observed in egg cylinder stage parthenogenetic mouse embryos(6), most cells in surviving embryos become diploid. Here we describe haploid mouse embryonic stem cells and show their application in forward genetic screening.
C1 [Leeb, Martin; Wutz, Anton] Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Cambridge CB2 1QR, England.
C3 University of Cambridge
RP Wutz, A (corresponding author), Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Tennis Court Rd, Cambridge CB2 1QR, England.
EM aw512@cam.ac.uk
FU Wellcome Trust [087530/Z/08/A]; EMBO Long Term Fellowship; Medical Research Council [G0800784, G0800784B] Funding Source: researchfish; Wellcome Trust [087530/Z/08/A] Funding Source: Wellcome Trust; MRC [G0800784] Funding Source: UKRI
NR 30
TC 208
Z9 266
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 3
PY 2011
VL 479
IS 7371
BP 131
EP U164
DI 10.1038/nature10448
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600046
PM 21900896
DA 2026-03-09
ER

PT J
AU Mortlock, DJ
   Warren, SJ
   Venemans, BP
   Patel, M
   Hewett, PC
   McMahon, RG
   Simpson, C
   Theuns, T
   Gonzáles-Solares, EA
   Adamson, A
   Dye, S
   Hambly, NC
   Hirst, P
   Irwin, MJ
   Kuiper, E
   Lawrence, A
   Röttgering, HJA
AF Mortlock, Daniel J.
   Warren, Stephen J.
   Venemans, Bram P.
   Patel, Mitesh
   Hewett, Paul C.
   McMahon, Richard G.
   Simpson, Chris
   Theuns, Tom
   Gonzales-Solares, Eduardo A.
   Adamson, Andy
   Dye, Simon
   Hambly, Nigel C.
   Hirst, Paul
   Irwin, Mike J.
   Kuiper, Ernst
   Lawrence, Andy
   Rottgering, Huub J. A.
TI A luminous quasar at a redshift of z=7.085
SO NATURE
LA English
DT Article
ID digital sky survey; neutral hydrogen; black-holes; z-greater-than-6; reionization; z-similar-to-6; ionization; discovery; emission; universe
AB The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed(1) by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified(2-4) in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULASJ112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULASJ1120+0641 has a luminosity of 6.3 x 10(13)L(circle dot) and hosts a black hole with a mass of 2 x 10(9)M(circle dot) (where L(circle dot) and M(circle dot) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULASJ1120+0641 is 1.9 megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Ly alpha d damping wing(5), suggesting that the neutral fraction of the intergalactic medium in front of ULASJ1120+0641 exceeded 0.1.
C1 [Mortlock, Daniel J.; Warren, Stephen J.; Patel, Mitesh] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, London SW7 2AZ, England.
   [Venemans, Bram P.] European So Observ, D-85748 Garching, Germany.
   [Hewett, Paul C.; McMahon, Richard G.; Gonzales-Solares, Eduardo A.; Irwin, Mike J.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Simpson, Chris] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Theuns, Tom] Univ Durham, Inst Computat Cosmol, Dept Phys, Durham DH1 3LE, England.
   [Theuns, Tom] Univ Antwerp, B-2020 Antwerp, Belgium.
   [Adamson, Andy] Joint Astron Ctr, Hilo, HI 96720 USA.
   [Dye, Simon] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Hambly, Nigel C.; Lawrence, Andy] Univ Edinburgh, SUPA, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Hirst, Paul] Gemini Observ, Hilo, HI 96720 USA.
   [Kuiper, Ernst; Rottgering, Huub J. A.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
C3 Imperial College London; European Southern Observatory; University of Cambridge; Liverpool John Moores University; Durham University; University of Antwerp; University of Nottingham; University of Edinburgh; Leiden University - Excl LUMC; Leiden University
RP Mortlock, DJ (corresponding author), Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, Prince Consort Rd, London SW7 2AZ, England.
EM mortlock@ic.ac.uk
FU University of London; STFC; Science and Technology Facilities Council [PP/C002229/1, ST/G009465/1, ST/H000496/1, ST/H008519/1, ST/H00243X/1, PP/E001149/1, ST/H00047X/1, ST/F002289/1, ST/H004165/1, ST/I00162X/1, ST/G001901/1, ST/H004912/1, ST/H004157/1, ST/G001979/1, ST/H002391/1, ST/I001166/1, ST/H001913/1, ST/H004211/1] Funding Source: researchfish; STFC [ST/H00047X/1, ST/G009465/1, ST/H001913/1, ST/H002391/1, ST/H004165/1, ST/H004912/1, ST/H004211/1, ST/G001901/1, PP/E001149/1, ST/I001166/1, ST/I00162X/1, PP/C002229/1, ST/H000496/1, ST/G001979/1, ST/H004157/1, ST/F002289/1, ST/H008519/1] Funding Source: UKRI
NR 30
TC 1310
Z9 1421
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 JUN 30
PY 2011
VL 474
IS 7353
BP 616
EP 619
DI 10.1038/nature10159
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300033
PM 21720366
DA 2026-03-09
ER

PT J
AU Teufel, JD
   Donner, T
   Li, DL
   Harlow, JW
   Allman, MS
   Cicak, K
   Sirois, AJ
   Whittaker, JD
   Lehnert, KW
   Simmonds, RW
AF Teufel, J. D.
   Donner, T.
   Li, Dale
   Harlow, J. W.
   Allman, M. S.
   Cicak, K.
   Sirois, A. J.
   Whittaker, J. D.
   Lehnert, K. W.
   Simmonds, R. W.
TI Sideband cooling of micromechanical motion to the quantum ground state
SO NATURE
LA English
DT Article
ID mechanical resonator; back-action; cavity; amplification; oscillator; transducer; noise; limit
AB The advent of laser cooling techniques revolutionized the study of many atomic-scale systems, fuelling progress towards quantum computing with trapped ions(1) and generating new states of matter with Bose-Einstein condensates(2). Analogous cooling techniques(3,4) can provide a general and flexible method of preparing macroscopic objects in their motional ground state. Cavity optomechanical or electromechanical systems achieve sideband cooling through the strong interaction between light and motion(5-15). However, entering the quantum regime-in which a system has less than a single quantum of motion-has been difficult because sideband cooling has not sufficiently overwhelmed the coupling of low-frequency mechanical systems to their hot environments. Here we demonstrate sideband cooling of an approximately 10-MHz micromechanical oscillator to the quantum ground state. This achievement required a large electromechanical interaction, which was obtained by embedding a micromechanical membrane into a superconducting microwave resonant circuit. To verify the cooling of the membrane motion to a phonon occupation of 0.34 +/- 0.05 phonons, we perform a near Heisenberg-limited position measurement(3) within (5.1 +/- 0.4)h/2 pi, where h is Planck's constant. Furthermore, our device exhibits strong coupling, allowing coherent exchange of microwave photons and mechanical phonons(16). Simultaneously achieving strong coupling, ground state preparation and efficient measurement sets the stage for rapid advances in the control and detection of non-classical states of motion(17,18), possibly even testing quantum theory itself in the unexplored region of larger size and mass(19). Because mechanical oscillators can couple to light of any frequency, they could also serve as a unique intermediary for transferring quantum information between microwave and optical domains(20).
C1 [Teufel, J. D.; Li, Dale; Allman, M. S.; Cicak, K.; Sirois, A. J.; Whittaker, J. D.; Simmonds, R. W.] NIST, Boulder, CO 80305 USA.
   [Donner, T.; Harlow, J. W.; Lehnert, K. W.] Univ Colorado, JILA, Boulder, CO 80309 USA.
   [Donner, T.; Harlow, J. W.; Lehnert, K. W.] NIST, Boulder, CO 80309 USA.
   [Donner, T.; Harlow, J. W.; Allman, M. S.; Sirois, A. J.; Whittaker, J. D.; Lehnert, K. W.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder
RP Teufel, JD (corresponding author), NIST, Boulder, CO 80305 USA.
EM john.teufel@nist.gov
FU NIST; DARPA; Deutsche Forschungsgemeinschft (DFG); Division Of Physics; Direct For Mathematical & Physical Scien [1125844] Funding Source: National Science Foundation
NR 30
TC 1801
Z9 2017
U1 2
U2 383
PU 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 21
PY 2011
VL 475
IS 7356
BP 359
EP 363
DI 10.1038/nature10261
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200038
PM 21734657
DA 2026-03-09
ER

PT J
AU Arner, P
   Bernard, S
   Salehpour, M
   Possnert, G
   Liebl, J
   Steier, P
   Buchholz, BA
   Eriksson, M
   Arner, E
   Hauner, H
   Skurk, T
   Rydén, M
   Frayn, KN
   Spalding, KL
AF Arner, Peter
   Bernard, Samuel
   Salehpour, Mehran
   Possnert, Goran
   Liebl, Jakob
   Steier, Peter
   Buchholz, Bruce A.
   Eriksson, Mats
   Arner, Erik
   Hauner, Hans
   Skurk, Thomas
   Ryden, Mikael
   Frayn, Keith N.
   Spalding, Kirsty L.
TI Dynamics of human adipose lipid turnover in health and metabolic disease
SO NATURE
LA English
DT Article
ID familial combined hyperlipidemia; cell turnover; fatty-acids; in-vivo; tissue; assimilation; radiocarbon; oxidation; lipolysis
AB Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes(1). Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring C-14 derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.
C1 [Arner, Peter; Eriksson, Mats; Arner, Erik; Ryden, Mikael] Karolinska Univ Hosp, Dept Med, SE-14186 Stockholm, Sweden.
   [Bernard, Samuel] Univ Lyon, CNRS UMR 5208, Inst Camille Jordan, F-69622 Villeurbanne, France.
   [Salehpour, Mehran; Possnert, Goran] Uppsala Univ, Dept Phys & Astron, SE-75120 Uppsala, Sweden.
   [Liebl, Jakob; Steier, Peter] Univ Vienna, Fac Phys Isotope Res, A-1090 Vienna, Austria.
   [Buchholz, Bruce A.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA.
   [Hauner, Hans; Skurk, Thomas] Tech Univ Munich, Else Kroner Fresenius Ctr Nutr Med, D-85350 Weihenstephan, Germany.
   [Frayn, Keith N.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [Spalding, Kirsty L.] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
C3 Karolinska Institutet; Karolinska University Hospital; Institut National des Sciences Appliquees de Lyon - INSA Lyon; Ecole Centrale de Lyon; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Mathematical Sciences (INSMI); Universite Jean Monnet; Uppsala University; University of Vienna; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Technical University of Munich; University of Oxford; Karolinska Institutet
RP Arner, P (corresponding author), Karolinska Univ Hosp, Dept Med, SE-14186 Stockholm, Sweden.
EM peter.arner@ki.se; kirsty.spalding@ki.se
FU Swedish Research Council; Swedish Foundation for Strategic Research; Swedish Heart and Lung Foundation; Novo Nordic Foundation; Swedish Diabetes Foundation; Karolinska Institutet; Swedish Cancer Society; Uppsala BIO, Sweden; NIH/NCRR [RR13461]; ERC [261258-HUFATREG]; European Commission [LSHM-CT-2005-018734, HEALTH-F2-2008-201100]; US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]
NR 24
TC 306
Z9 349
U1 1
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 110
EP 113
DI 10.1038/nature10426
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400044
PM 21947005
DA 2026-03-09
ER

PT J
AU Chen, DY
   Stern, SA
   Garcia-Osta, A
   Saunier-Rebori, B
   Pollonini, G
   Bambah-Mukku, D
   Blitzer, RD
   Alberini, CM
AF Chen, Dillon Y.
   Stern, Sarah A.
   Garcia-Osta, Ana
   Saunier-Rebori, Bernadette
   Pollonini, Gabriella
   Bambah-Mukku, Dhananjay
   Blitzer, Robert D.
   Alberini, Cristina M.
TI A critical role for IGF-II in memory consolidation and enhancement
SO NATURE
LA English
DT Article
ID growth-factor-ii; long-term potentiation; protein-synthesis; binding-protein; persistent disruption; rat hippocampus; reconsolidation; receptor; gene; mechanisms
AB We report that, in the rat, administering insulin-like growth factor II (IGF-II, also known as IGF2) significantly enhances memory retention and prevents forgetting. Inhibitory avoidance learning leads to an increase in hippocampal expression of IGF-II, which requires the transcription factor CCAAT enhancer binding protein beta and is essential for memory consolidation. Furthermore, injections of recombinant IGF-II into the hippocampus after either training or memory retrieval significantly enhance memory retention and prevent forgetting. To be effective, IGF-II needs to be administered within a sensitive period of memory consolidation. IGF-II-dependent memory enhancement requires IGF-II receptors, new protein synthesis, the function of activity-regulated cytoskeletal-associated protein and glycogen-synthase kinase 3 (GSK3). Moreover, it correlates with a significant activation of synaptic GSK3 beta and increased expression of GluR1 (also known as GRIA1) alpha-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid receptor subunits. In hippocampal slices, IGF-II promotes IGF-II receptor-dependent, persistent long-term potentiation after weak synaptic stimulation. Thus, IGF-II may represent a novel target for cognitive enhancement therapies.
C1 [Chen, Dillon Y.; Stern, Sarah A.; Garcia-Osta, Ana; Pollonini, Gabriella; Bambah-Mukku, Dhananjay; Alberini, Cristina M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
   [Saunier-Rebori, Bernadette; Blitzer, Robert D.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [Blitzer, Robert D.; Alberini, Cristina M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Alberini, CM (corresponding author), Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
EM Cristina.Alberini@mssm.edu
FU NARSAD [R01-MH065635, R01-MH074736]; Hirschl Foundation; Philoctetes Foundation [F31-MH816213, T32-MH087004, R21-DA29298, R01-GM054508]; National Institute of Mental Health [T32MH087004, R01MH065635] Funding Source: NIH RePORTER
NR 50
TC 347
Z9 402
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 JAN 27
PY 2011
VL 469
IS 7331
BP 491
EP U63
DI 10.1038/nature09667
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500024
PM 21270887
DA 2026-03-09
ER

PT J
AU Hayes, M
   Scarlata, C
   Siana, B
AF Hayes, Matthew
   Scarlata, Claudia
   Siana, Brian
TI Central powering of the largest Lyman-α nebula is revealed by polarized radiation
SO NATURE
LA English
DT Article
ID resonance-line radiation; cold accretion; galaxy; blobs
AB High-redshift Lyman-alpha (Ly alpha) blobs(1,2) are extended, luminous but rare structures that seem to be associated with the highest peaks in the matter density of the Universe(3-6). Their energy output and morphology are similar to those of powerful radio galaxies(7), but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole(8-10). Another possibility is gas that is shock-excited by supernovae(11,12). But not all blobs are associated with galaxies(13,14), and these ones may instead be heated by gas falling into a dark-matter halo(15-19). The polarization of the Lya emission can in principle distinguish between these options(20-22), but a previous attempt to detect this signature returned a null detection(23). Here we report observations of polarized Ly alpha from the blob LAB1 (ref. 2). Although the central region shows no measurable polarization, the polarized fraction (P) increases to similar to 20 per cent at a radius of 45 kiloparsecs, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Ly alpha photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen.
C1 [Hayes, Matthew] Univ Toulouse, UPS OMP IRAP, Toulouse, France.
   [Hayes, Matthew] CNRS, IRAP, F-31400 Toulouse, France.
   [Hayes, Matthew] Univ Geneva, Observ Geneva, CH-1290 Versoix, Switzerland.
   [Scarlata, Claudia] Univ Minnesota, Sch Phys & Astron, Minnesota Inst Astrophys, Minneapolis, MN 55455 USA.
   [Scarlata, Claudia] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Siana, Brian] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of Geneva; University of Minnesota System; University of Minnesota Twin Cities; California Institute of Technology; California Institute of Technology
RP Hayes, M (corresponding author), Univ Toulouse, UPS OMP IRAP, Toulouse, France.
EM matthew.hayes@ast.obs-mip.fr
FU European Southern Observatory telescopes at the Paranal Observatory [084.A-0954]; Swiss National Science Foundation; Agence Nationale de la Recherche [ANR-09-BLAN-0234-01]
NR 29
TC 89
Z9 94
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 304
EP 307
DI 10.1038/nature10320
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500032
PM 21850104
DA 2026-03-09
ER

PT J
AU Fujisaki, J
   Wu, J
   Carlson, AL
   Silberstein, L
   Putheti, P
   Larocca, R
   Gao, WD
   Saito, TI
   Lo Celso, C
   Tsuyuzaki, H
   Sato, T
   Côté, D
   Sykes, M
   Strom, TB
   Scadden, DT
   Lin, CP
AF Fujisaki, Joji
   Wu, Juwell
   Carlson, Alicia L.
   Silberstein, Lev
   Putheti, Prabhakar
   Larocca, Rafael
   Gao, Wenda
   Saito, Toshiki I.
   Lo Celso, Cristina
   Tsuyuzaki, Hitoshi
   Sato, Tatsuyuki
   Cote, Daniel
   Sykes, Megan
   Strom, Terry B.
   Scadden, David T.
   Lin, Charles P.
TI In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche
SO NATURE
LA English
DT Article
ID bone-marrow niche; engraftment
AB Stem cells reside in a specialized regulatory microenvironment or niche(1,2), where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity(1-3). The niche may also protect stem cells from environmental insults(3) including cytotoxic chemotherapy and perhaps pathogenic immunity(4). The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression(4). We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche(1,2,5-7) in the bone marrow, a site where immune reactivity exists(8,9). We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T-reg) cells. High-resolutionin vivo imaging over time demonstrated marked co-localization of HSPCs with T-reg cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T-reg cells seem to participate in creating a localized zone where HSPCs reside and where T-reg cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.
C1 [Fujisaki, Joji; Wu, Juwell; Carlson, Alicia L.; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Adv Microscopy Program, Boston, MA 02114 USA.
   [Fujisaki, Joji; Wu, Juwell; Carlson, Alicia L.; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Fujisaki, Joji; Wu, Juwell; Silberstein, Lev; Lo Celso, Cristina; Scadden, David T.; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Wu, Juwell] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   [Silberstein, Lev; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Putheti, Prabhakar; Larocca, Rafael; Gao, Wenda; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Inst Transplantat, Boston, MA 02215 USA.
   [Putheti, Prabhakar; Larocca, Rafael; Gao, Wenda; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Saito, Toshiki I.; Sykes, Megan] Massachusetts Gen Hosp E, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA.
   [Tsuyuzaki, Hitoshi; Sato, Tatsuyuki] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan.
   [Cote, Daniel] Dept Phys Genie Phys & Opt, Quebec City, PQ G1J 2G3, Canada.
   [Cote, Daniel] Univ Laval Robert Giffard, Ctr Rech, Quebec City, PQ G1J 2G3, Canada.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Tokyo; Laval University
RP Fujisaki, J (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Adv Microscopy Program, CPZN 8238,185 Cambridge St, Boston, MA 02114 USA.
EM jfujisaki@partners.org; lin@helix.mgh.harvard.edu
FU Bullock fellowship; Harvard Stem Cell Institute; DoD [W81XWH-10-1-0217]; NIH [HL097748, HL97794, CA111519, AI041521]; EMBO; HFSP; philanthropic sources; Grants-in-Aid for Scientific Research [22591027] Funding Source: KAKEN; Medical Research Council [G0600698B] Funding Source: researchfish
NR 19
TC 472
Z9 534
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 216
EP U256
DI 10.1038/nature10160
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800051
PM 21654805
DA 2026-03-09
ER

PT J
AU Zhu, Q
   Pao, GM
   Huynh, AM
   Suh, H
   Tonnu, N
   Nederlof, PM
   Gage, FH
   Verma, IM
AF Zhu, Quan
   Pao, Gerald M.
   Huynh, Alexis M.
   Suh, Hoonkyo
   Tonnu, Nina
   Nederlof, Petra M.
   Gage, Fred H.
   Verma, Inder M.
TI BRCA1 tumour suppression occurs via heterochromatin-mediated silencing
SO NATURE
LA English
DT Article
ID neural stem-cells; ligase activity; protein; breast; ubiquitination; maintenance; mutations; cancers; repair; binds
AB Mutations in the tumour suppressor gene BRCA1 lead to breast and/or ovarian cancer. Here we show that loss of Brca1 in mice results in transcriptional de-repression of the tandemly repeated satellite DNA. Brca1 deficiency is accompanied by a reduction of condensed DNA regions in the genome and loss of ubiquitylation of histone H2A at satellite repeats. BRCA1 binds to satellite DNA regions and ubiquitylates H2A in vivo. Ectopic expression of H2A fused to ubiquitin reverses the effects of BRCA1 loss, indicating that BRCA1 maintains heterochromatin structure via ubiquitylation of histone H2A. Satellite DNA de-repression was also observed in mouse and human BRCA1-deficient breast cancers. Ectopic expression of satellite DNA can phenocopy BRCA1 loss in centrosome amplification, cell-cycle checkpoint defects, DNA damage and genomic instability. We propose that the role of BRCA1 in maintaining global heterochromatin integrity accounts for many of its tumour suppressor functions.
C1 [Zhu, Quan; Pao, Gerald M.; Huynh, Alexis M.; Suh, Hoonkyo; Tonnu, Nina; Gage, Fred H.; Verma, Inder M.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Nederlof, Petra M.] Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands.
C3 Salk Institute; Netherlands Cancer Institute
RP Pao, GM (corresponding author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM pao@salk.edu; verma@salk.edu
FU California Breast Cancer Research Program; Ruth L. Kirschtein National Research Service Award; California Institute of Regenerative Medicine; ASPET-Merck fellowship; NIH [NS52842, NS50217]; Ipsen/Biomeasure; Sanofi Aventis; H.N. and Frances C. Berger Foundation; Lookout Fund
NR 29
TC 388
Z9 463
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 SEP 8
PY 2011
VL 477
IS 7363
BP 179
EP U76
DI 10.1038/nature10371
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900028
PM 21901007
DA 2026-03-09
ER

PT J
AU Colantuoni, C
   Lipska, BK
   Ye, TZ
   Hyde, TM
   Tao, R
   Leek, JT
   Colantuoni, EA
   Elkahloun, AG
   Herman, MM
   Weinberger, DR
   Kleinman, JE
AF Colantuoni, Carlo
   Lipska, Barbara K.
   Ye, Tianzhang
   Hyde, Thomas M.
   Tao, Ran
   Leek, Jeffrey T.
   Colantuoni, Elizabeth A.
   Elkahloun, Abdel G.
   Herman, Mary M.
   Weinberger, Daniel R.
   Kleinman, Joel E.
TI Temporal dynamics and genetic control of transcription in the human prefrontal cortex
SO NATURE
LA English
DT Article
ID human brain; expression; disease; mouse; microrna; rna
AB Previous investigations have combined transcriptional and genetic analyses in human cell lines(1-3), but few have applied these techniques to human neural tissue(4-8). To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud).
C1 [Colantuoni, Carlo; Lipska, Barbara K.; Ye, Tianzhang; Hyde, Thomas M.; Tao, Ran; Herman, Mary M.; Weinberger, Daniel R.; Kleinman, Joel E.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Bethesda, MD 20892 USA.
   [Colantuoni, Carlo; Leek, Jeffrey T.; Colantuoni, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
   [Colantuoni, Carlo] Illuminato Biotechnol Inc, Baltimore, MD 21211 USA.
   [Colantuoni, Carlo; Hyde, Thomas M.; Weinberger, Daniel R.] Johns Hopkins Univ, Med Ctr, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
   [Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins University; University System of Maryland; University of Maryland Baltimore; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Kleinman, JE (corresponding author), NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Bethesda, MD 20892 USA.
EM kleinmaj@mail.nih.gov
FU Intramural NIH HHS [ZIC HG200365] Funding Source: Medline; National Human Genome Research Institute [ZICHG200365] Funding Source: NIH RePORTER; National Institute of Mental Health [ZICMH002903] Funding Source: NIH RePORTER
NR 27
TC 559
Z9 634
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 OCT 27
PY 2011
VL 478
IS 7370
BP 519
EP U117
DI 10.1038/nature10524
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200044
PM 22031444
DA 2026-03-09
ER

PT J
AU Huang, HJ
   Fei, YW
   Cai, LC
   Jing, FQ
   Hu, XJ
   Xie, HS
   Zhang, LM
   Gong, ZZ
AF Huang, Haijun
   Fei, Yingwei
   Cai, Lingcang
   Jing, Fuqian
   Hu, Xiaojun
   Xie, Hongsen
   Zhang, Lianmeng
   Gong, Zizheng
TI Evidence for an oxygen-depleted liquid outer core of the Earth
SO NATURE
LA English
DT Article
ID shock compression; hugoniot data; iron; state; constraints; equations
AB On the basis of geophysical observations, cosmochemical constraints, and high-pressure experimental data, the Earth's liquid outer core consists of mainly liquid iron alloyed with about ten per cent (by weight) of light elements(1,2). Although the concentrations of the light elements are small, they nevertheless affect the Earth's core: its rate of cooling, the growth of the inner core, the dynamics of core convection, and the evolution of the geodynamo(3,4). Several light elements-including sulphur, oxygen, silicon, carbon and hydrogen-have been suggested(2), but the precise identity of the light elements in the Earth's core is still unclear. Oxygen has been proposed as a major light element in the core on the basis of cosmochemical arguments and chemical reactions during accretion(5,6). Its presence in the core has direct implications for Earth accretion conditions of oxidation state, pressure and temperature. Here we report new shockwave data in the Fe-S-O system that are directly applicable to the outer core. The data include both density and sound velocity measurements, which we compare with the observed density and velocity profiles of the liquid outer core. The results show that we can rule out oxygen as a major light element in the liquid outer core because adding oxygen into liquid iron would not reproduce simultaneously the observed density and sound velocity profiles of the outer core. An oxygen-depleted core would imply a more reduced environment during early Earth accretion.
C1 [Fei, Yingwei] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Huang, Haijun; Jing, Fuqian; Hu, Xiaojun] Wuhan Univ Technol, Sch Sci, Wuhan 430070, Hubei, Peoples R China.
   [Fei, Yingwei] Peking Univ, Sch Earth & Space Sci, Beijing 100871, Peoples R China.
   [Cai, Lingcang; Jing, Fuqian] China Acad Engn Phys, Inst Fluid Phys, Natl Key Lab Shock Wave & Detonat Phys, Mianyang 621900, Sichuan, Peoples R China.
   [Xie, Hongsen] Chinese Acad Sci, Inst Geochem, Guiyang 550002, Guizhou, Peoples R China.
   [Zhang, Lianmeng] Wuhan Univ Technol, State Key Lab Adv Technol Mat Synth & Proc, Wuhan 430070, Hubei, Peoples R China.
   [Gong, Zizheng] Beijing Inst Spacecraft Environm Engn, Natl Key Lab Sci & Technol Reliabil & Environm En, Beijing 100094, Peoples R China.
C3 Carnegie Institution for Science; Wuhan University of Technology; Peking University; Chinese Academy of Engineering Physics; Chinese Academy of Sciences; Institute of Geochemistry, CAS; Wuhan University of Technology
RP Fei, YW (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
EM fei@gl.ciw.edu
FU National Natural Science Foundation of China [41074056, 40604007]; Fundamental Research Funds for the Central Universities; National Basic Research of China [2010CB731600]; National Science Foundation [EAR-0809539]; Carnegie Institution of Washington; Directorate For Geosciences; Division Of Earth Sciences [0809539] Funding Source: National Science Foundation
NR 30
TC 98
Z9 120
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 NOV 24
PY 2011
VL 479
IS 7374
BP 513
EP U236
DI 10.1038/nature10621
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600047
PM 22113693
DA 2026-03-09
ER

PT J
AU Watanabe, T
   Suzuki, A
   Minobe, S
   Kawashima, T
   Kameo, K
   Minoshima, K
   Aguilar, YM
   Wani, R
   Kawahata, H
   Sowa, K
   Nagai, T
   Kase, T
AF Watanabe, Tsuyoshi
   Suzuki, Atsushi
   Minobe, Shoshiro
   Kawashima, Tatsunori
   Kameo, Koji
   Minoshima, Kayo
   Aguilar, Yolanda M.
   Wani, Ryoji
   Kawahata, Hodaka
   Sowa, Kohki
   Nagai, Takaya
   Kase, Tomoki
TI Permanent El Nino during the Pliocene warm period not supported by coral evidence
SO NATURE
LA English
DT Article
ID sea-surface temperature; southern-oscillation; tropical pacific; climate; variability; precipitation; patterns; epoch
AB The El Nino/Southern Oscillation (ENSO) system during the Pliocene warm period (PWP; 3-5 million years ago) may have existed in a permanent El Nino state with a sharply reduced zonal sea surface temperature (SST) gradient in the equatorial Pacific Ocean(1). This suggests that during the PWP, when global mean temperatures and atmospheric carbon dioxide concentrations were similar to those projected for near-term climate change(2), ENSO variability-and related global climate teleconnections-could have been radically different from that today. Yet, owing to a lack of observational evidence on seasonal and interannual SST variability from crucial low-latitude sites, this fundamental climate characteristic of the PWP remains controversial(1,3-10). Here we show that permanent El Nino conditions did not exist during the PWP. Our spectral analysis of the delta(18)O SST and salinity proxy, extracted from two 35-year, monthly resolved PWP Porites corals in the Philippines, reveals variability that is similar to present ENSO variation. Although our fossil corals cannot be directly compared with modern ENSO records, two lines of evidence suggest that Philippine corals are appropriate ENSO proxies. First, delta(18)O anomalies from a nearby live Porites coral are correlated with modern records of ENSO variability. Second, negative-delta(18)O events in the fossil corals closely resemble the decreases in delta(18)O seen in the live coral during El Nino events. Prior research advocating a permanent El Nino state may have been limited by the coarse resolution of many SST proxies, whereas our coral-based analysis identifies climate variability at the temporal scale required to resolve ENSO structure firmly.
C1 [Watanabe, Tsuyoshi; Minobe, Shoshiro; Kawashima, Tatsunori; Sowa, Kohki; Nagai, Takaya] Hokkaido Univ, Dept Nat Hist Sci, Fac Sci, Sapporo, Hokkaido 0600810, Japan.
   [Suzuki, Atsushi; Minoshima, Kayo] Natl Inst Adv Ind Sci & Technol, Geol Survey Japan, Tsukuba, Ibaraki 3058567, Japan.
   [Kameo, Koji] Chiba Univ, Dept Earth Sci, Fac Sci, Chiba 2638522, Japan.
   [Aguilar, Yolanda M.] Mines & Geosci Bur, Petrolab, Quezon City 1101, Philippines.
   [Wani, Ryoji] Yokohama Natl Univ, Interdisciplinary Res Ctr, Yokohama, Kanagawa 2408501, Japan.
   [Kawahata, Hodaka] Univ Tokyo, Atmosphere & Ocean Res Inst, Kashiwa, Chiba 2775564, Japan.
   [Kase, Tomoki] Natl Museum Nat & Sci, Dept Geol & Paleontol, Tokyo 1690073, Japan.
C3 Hokkaido University; National Institute of Advanced Industrial Science & Technology (AIST); Chiba University; Yokohama National University; University of Tokyo; National Museum of Nature and Science
RP Watanabe, T (corresponding author), Hokkaido Univ, Dept Nat Hist Sci, Fac Sci, Sapporo, Hokkaido 0600810, Japan.
EM nabe@mail.sci.hokudai.ac.jp
FU Grants-in-Aid for Scientific Research [21740369, 21684031] Funding Source: KAKEN
NR 23
TC 107
Z9 124
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 209
EP 211
DI 10.1038/nature09777
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200035
PM 21390128
DA 2026-03-09
ER

PT J
AU Pomowski, A
   Zumft, WG
   Kroneck, PMH
   Einsle, O
AF Pomowski, Anja
   Zumft, Walter G.
   Kroneck, Peter M. H.
   Einsle, Oliver
TI N2O binding at a [4Cu:2S] copper-sulphur cluster in nitrous oxide reductase
SO NATURE
LA English
DT Article
ID cu-z cluster; achromobacter-cycloclastes; pseudomonas-stutzeri; angstrom resolution; multicopper enzyme; cupric site; denitrification; purification; activation; dinitrogen
AB Nitrous oxide (N2O) is generated by natural and anthropogenic processes and has a critical role in environmental chemistry. It has an ozone-depleting potential similar to that of hydrochlorofluorocarbons as well as a global warming potential exceeding that of CO2 300-fold(1,2). In bacterial denitrification, N2O is reduced to N-2 by the copper-dependent nitrous oxide reductase (N2OR)(3). This enzyme carries the mixed-valent Cu-A centre and the unique, tetranuclear Cu-Z site. Previous structural data were obtained with enzyme isolated in the presence of air that is catalytically inactive without prior reduction. Its Cu-Z site was described as a [4Cu:S] centre, and the substrate-binding mode and reduction mechanism remained elusive. Here we report the structure of purple N2OR from Pseudomonas stutzeri, handled under the exclusion of dioxygen, and locate the substrate in N2O-pressurized crystals. The active Cu-Z cluster contains two sulphur atoms, yielding a [4Cu:2S] stoichiometry; and N2O bound side-on at Cu-Z, in close proximity to Cu-A. With the substrate located between the two clusters, electrons are transferred directly from Cu-A to N2O, which is activated by side-on binding in a specific binding pocket on the face of the [4Cu:2S] centre. These results reconcile a multitude of available biochemical data on N2OR that could not be explained by earlier structures, and outline a mechanistic pathway in which both metal centres and the intervening protein act in concert to achieve catalysis. This structure represents the first direct observation, to our knowledge, of N2O bound to its reductase, and sheds light on the functionality of metalloenzymes that activate inert small-molecule substrates. The principle of using distinct clusters for substrate activation and for reduction may be relevant for similar systems, in particular nitrogen-fixing nitrogenase(4).
C1 [Pomowski, Anja; Einsle, Oliver] Univ Freiburg, Inst Organ Chem & Biochem, Lehrstuhl Biochem, D-79104 Freiburg, Germany.
   [Zumft, Walter G.] Karlsruher Inst Technol, Abt Mol Mikrobiol, Inst Angew Biowissensch, D-76187 Karlsruhe, Germany.
   [Kroneck, Peter M. H.] Univ Konstanz, Fachbereich Biol, D-78457 Constance, Germany.
   [Einsle, Oliver] Univ Freiburg, Ctr Biol Signalling Studies Bioss, D-79104 Freiburg, Germany.
C3 University of Freiburg; Helmholtz Association; Karlsruhe Institute of Technology; University of Konstanz; University of Freiburg
RP Einsle, O (corresponding author), Univ Freiburg, Inst Organ Chem & Biochem, Lehrstuhl Biochem, Albertstr 21, D-79104 Freiburg, Germany.
EM einsle@biochemie.uni-freiburg.de
FU Deutsche Forschungsgemeinschaft [IRTG 1422]; Center for Biological Signalling Studies [EXC 294]
NR 33
TC 183
Z9 223
U1 2
U2 203
PU 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 8
PY 2011
VL 477
IS 7363
BP 234
EP U143
DI 10.1038/nature10332
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900041
PM 21841804
DA 2026-03-09
ER

PT J
AU Kotler, S
   Akerman, N
   Glickman, Y
   Keselman, A
   Ozeri, R
AF Kotler, Shlomi
   Akerman, Nitzan
   Glickman, Yinnon
   Keselman, Anna
   Ozeri, Roee
TI Single-ion quantum lock-in amplifier
SO NATURE
LA English
DT Article
ID metrology; diamond; memory; spin
AB Quantum metrology(1) uses tools from quantum information science to improve measurement signal-to-noise ratios. The challenge is to increase sensitivity while reducing susceptibility to noise, tasks that are often in conflict. Lock-in measurement is a detection scheme designed to overcome this difficulty by spectrally separating signal from noise. Here we report on the implementation of a quantum analogue to the classical lock-in amplifier. All the lock-in operations-modulation, detection and mixing-are performed through the application of non-commuting quantum operators to the electronic spin state of a single, trapped Sr(+) ion. We significantly increase its sensitivity to external fields while extending phase coherence by three orders of magnitude, to more than one second. Using this technique, we measure frequency shifts with a sensitivity of 0.42 Hz Hz(-1/2) (corresponding to a magnetic field measurement sensitivity of 15 pT Hz(-1/2)), obtaining an uncertainty of less than 10 mHz (350 fT) after 3,720 seconds of averaging. These sensitivities are limited by quantum projection noise and improve on other single-spin probe technologies(2,3) by two orders of magnitude. Our reported sensitivity is sufficient for the measurement of parity non-conservation(4), as well as the detection of the magnetic field of a single electronic spin one micrometre from an ion detector with nanometre resolution. As a first application, we perform light shift spectroscopy of a narrow optical quadrupole transition. Finally, we emphasize that the quantum lock-in technique is generic and can potentially enhance the sensitivity of any quantum sensor.
C1 [Kotler, Shlomi; Akerman, Nitzan; Glickman, Yinnon; Keselman, Anna; Ozeri, Roee] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science
RP Kotler, S (corresponding author), Weizmann Inst Sci, Dept Phys Complex Syst, POB 26, IL-76100 Rehovot, Israel.
EM shlomi.kotler@weizmann.ac.il
FU ISF; Crown Photonics Center; Minerva Foundation
NR 27
TC 187
Z9 218
U1 5
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 5
PY 2011
VL 473
IS 7345
BP 61
EP 65
DI 10.1038/nature10010
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300030
PM 21544142
DA 2026-03-09
ER

PT J
AU Rosenblum, MD
   Gratz, IK
   Paw, JS
   Lee, K
   Marshak-Rothstein, A
   Abbas, AK
AF Rosenblum, Michael D.
   Gratz, Iris K.
   Paw, Jonathan S.
   Lee, Karen
   Marshak-Rothstein, Ann
   Abbas, Abul K.
TI Response to self antigen imprints regulatory memory in tissues
SO NATURE
LA English
DT Article
ID t-cells; in-vivo; expression; autoantigen; homeostasis; autoimmune; depletion; diseases; mice
AB Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are currently unknown. Clinical evidence suggests that chronic or repeated exposure to self antigen within tissues leads to an attenuation of pathological autoimmune responses, possibly as a means to mitigate inflammatory damage and preserve function. Many human organ-specific autoimmune diseases are characterized by the initial presentation of the disease being the most severe, with subsequent flares being of lesser severity and duration(1). In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression(2). In the practice of antigen-specific immunotherapy, allergens or self antigens are repeatedly injected in the skin, with a diminution of the inflammatory response occurring after each successive exposure(3). Although these findings indicate that tissues acquire the ability to attenuate autoimmune reactions upon repeated responses to antigens, the mechanism by which this occurs is unknown. Here we show that upon expression of self antigen in a peripheral tissue, thymus-derived regulatory T cells (T-reg cells) become activated, proliferate and differentiate into more potent suppressors, which mediate resolution of organ-specific autoimmunity in mice. After resolution of the inflammatory response, activated T-reg cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, T-reg cells function to confer 'regulatory memory' to the target tissue. These findings provide a framework for understanding how T-reg cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.
C1 [Gratz, Iris K.; Paw, Jonathan S.; Abbas, Abul K.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Rosenblum, Michael D.; Paw, Jonathan S.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA.
   [Lee, Karen] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10032 USA.
   [Marshak-Rothstein, Ann] Univ Massachusetts, Div Rheumatol, Dept Med, Worcester, MA 01655 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Columbia University; University of Massachusetts System; University of Massachusetts Worcester
RP Abbas, AK (corresponding author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
EM Abul.Abbas@ucsf.edu
FU Dermatology Foundation; UCSF Department of Dermatology; NIH [P01 AI35297, R01 AI73656, U19 AI56388, AR055634]; Scleroderma Research Foundation; Austrian Science Fund (FWF) [J2997-B13]
NR 17
TC 232
Z9 269
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 538
EP U164
DI 10.1038/nature10664
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000064
PM 22121024
DA 2026-03-09
ER

PT J
AU Gan, XC
   Stegle, O
   Behr, J
   Steffen, JG
   Drewe, P
   Hildebrand, KL
   Lyngsoe, R
   Schultheiss, SJ
   Osborne, EJ
   Sreedharan, VT
   Kahles, A
   Bohnert, R
   Jean, G
   Derwent, P
   Kersey, P
   Belfield, EJ
   Harberd, NP
   Kemen, E
   Toomajian, C
   Kover, PX
   Clark, RM
   Rätsch, G
   Mott, R
AF Gan, Xiangchao
   Stegle, Oliver
   Behr, Jonas
   Steffen, Joshua G.
   Drewe, Philipp
   Hildebrand, Katie L.
   Lyngsoe, Rune
   Schultheiss, Sebastian J.
   Osborne, Edward J.
   Sreedharan, Vipin T.
   Kahles, Andre
   Bohnert, Regina
   Jean, Geraldine
   Derwent, Paul
   Kersey, Paul
   Belfield, Eric J.
   Harberd, Nicholas P.
   Kemen, Eric
   Toomajian, Christopher
   Kover, Paula X.
   Clark, Richard M.
   Raetsch, Gunnar
   Mott, Richard
TI Multiple reference genomes and transcriptomes for Arabidopsis thaliana
SO NATURE
LA English
DT Article
ID genetic architecture; sequence; map; vernalization; association; diversity; reveals; complex
AB Genetic differences between Arabidopsis thaliana accessions underlie the plant's extensive phenotypic variation, and until now these have been interpreted largely in the context of the annotated reference accession Col-0. Here we report the sequencing, assembly and annotation of the genomes of 18 natural A. thaliana accessions, and their transcriptomes. When assessed on the basis of the reference annotation, one-third of protein-coding genes are predicted to be disrupted in at least one accession. However, re-annotation of each genome revealed that alternative gene models often restore coding potential. Gene expression in seedlings differed for nearly half of expressed genes and was frequently associated with cis variants within 5 kilobases, as were intron retention alternative splicing events. Sequence and expression variation is most pronounced in genes that respond to the biotic environment. Our data further promote evolutionary and functional studies in A. thaliana, especially the MAGIC genetic reference population descended from these accessions.
C1 [Gan, Xiangchao; Mott, Richard] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Stegle, Oliver] Max Planck Inst Intelligent Syst, D-72076 Tubingen, Germany.
   [Stegle, Oliver] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Behr, Jonas; Drewe, Philipp; Schultheiss, Sebastian J.; Sreedharan, Vipin T.; Kahles, Andre; Bohnert, Regina; Jean, Geraldine; Raetsch, Gunnar] Max Planck Gesell, Friedrich Miescher Lab, D-72076 Tubingen, Germany.
   [Steffen, Joshua G.; Osborne, Edward J.; Clark, Richard M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Hildebrand, Katie L.; Toomajian, Christopher] Kansas State Univ, Dept Plant Pathol, Manhattan, KS 66506 USA.
   [Lyngsoe, Rune] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Derwent, Paul; Kersey, Paul] European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Belfield, Eric J.; Harberd, Nicholas P.] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
   [Kemen, Eric] Sainsbury Lab, Norwich NR4 7UH, Norfolk, England.
   [Kover, Paula X.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
C3 University of Oxford; Wellcome Centre for Human Genetics; Max Planck Society; Max Planck Society; Eberhard Karls University of Tubingen; Max Planck Society; Utah System of Higher Education; University of Utah; Kansas State University; University of Oxford; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Oxford; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; University of Bath
RP Mott, R (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
EM toomajia@ksu.edu; p.x.kover@bath.ac.uk; clark@biology.utah.edu; Gunnar.Raetsch@tuebingen.mpg.de; richard.mott@well.ox.ac.uk
FU Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F022697/1, BB/D016029/2, BB/F020759/1, BB/F019793/1]; Max Planck Society; German Research Foundation [RA1894/1-1, RA1894/2-1]; Volkswagen Stiftung; National Science Foundation (NSF) [0929262, 0820985]; King Abdullah University of Science and Technology (KAUST) [KUK-I1-002-03]; Wellcome Trust [090532/Z/09/Z]; BBSRC [BB/D016029/2, BB/F020759/1, BB/F019793/1, BB/D016029/1, BB/F022697/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D016029/2, BB/F022697/1, BB/F020759/1, BB/F019793/1, BB/D016029/1] Funding Source: researchfish; Direct For Biological Sciences; Div Of Biological Infrastructure [0820985] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0929262] Funding Source: National Science Foundation
CR Anders S, 2010, GENOME BIOL, V11, P0, DOI 10.1186/gb-2010-11-10-r106
   Arabidopsis Genome Initiative, 2000, NATURE (LONDON), V408, P796, DOI 10.1038/35048692
   Atwell S, 2010, NATURE, V465, P627, DOI 10.1038/nature08800
   Bentley DR, 2008, NATURE, V456, P53, DOI 10.1038/nature07517
   Cao J, 2011, NAT GENET, V43, P956, DOI 10.1038/ng.911
   Clark RM, 2007, SCIENCE, V317, P338, DOI 10.1126/science.1138632
   Durrant C, 2011, GENOME RES, V21, P1239, DOI 10.1101/gr.118786.110
   Gagne JM, 2002, P NATL ACAD SCI USA, V99, P11519, DOI 10.1073/pnas.162339999
   Gore MA, 2009, SCIENCE, V326, P1115, DOI 10.1126/science.1177837
   Howe GA, 2008, ANNU REV PLANT BIOL, V59, P41, DOI 10.1146/annurev.arplant.59.032607.092825
   Hu TT, 2011, NAT GENET, V43, P476, DOI 10.1038/ng.807
   Jean Geraldine, 2010, CURRENT PROTOCOLS IN BIOINFORMATICS, V0, P0
   Johanson U, 2000, SCIENCE, V290, P344, DOI 10.1126/science.290.5490.344
   Kaufmann K, 2005, GENE, V347, P183, DOI 10.1016/j.gene.2004.12.014
   Keane TM, 2011, NATURE, V477, P289, DOI 10.1038/nature10413
   Keurentjes JJB, 2007, P NATL ACAD SCI USA, V104, P1708, DOI 10.1073/pnas.0610429104
   Kover PX, 2009, PLOS GENET, V5, P0, DOI 10.1371/journal.pgen.1000551
   Lai AG, 2011, GENOME BIOL EVOL, V3, P627, DOI 10.1093/gbe/evr038
   Lempe J, 2005, PLOS GENET, V1, P109, DOI 10.1371/journal.pgen.0010006
   Li RQ, 2010, GENOME RES, V20, P265, DOI 10.1101/gr.097261.109
   Lunter G, 2011, GENOME RES, V21, P936, DOI 10.1101/gr.111120.110
   McMullen MD, 2009, SCIENCE, V325, P737, DOI 10.1126/science.1174320
   Nordborg M, 2005, PLOS BIOL, V3, P1289, DOI 10.1371/journal.pbio.0030196
   Ossowski S, 2008, GENOME RES, V18, P2024, DOI 10.1101/gr.080200.108
   Plantegenet S, 2009, MOL SYST BIOL, V5, P0, DOI 10.1038/msb.2008.79
   Ratcliffe OJ, 2003, PLANT CELL, V15, P1159, DOI 10.1105/tpc.009506
   Schmid M, 2005, NAT GENET, V37, P501, DOI 10.1038/ng1543
   Schneeberger K, 2011, P NATL ACAD SCI USA, V108, P10249, DOI 10.1073/pnas.1107739108
   Schweikert G, 2009, GENOME RES, V19, P2133, DOI 10.1101/gr.090597.108
   Sheldon CC, 1999, PLANT CELL, V11, P445, DOI 10.1105/tpc.11.3.445
   Silverstein KAT, 2005, PLANT PHYSIOL, V138, P600, DOI 10.1104/pp.105.060079
   Song YS, 2005, J COMPUT BIOL, V12, P147, DOI 10.1089/cmb.2005.12.147
   Trapnell C, 2010, NAT BIOTECHNOL, V28, P511, DOI 10.1038/nbt.1621
   Weigel D, 2009, GENOME BIOL, V10, P0, DOI 10.1186/gb-2009-10-5-107
   West MAL, 2007, GENETICS, V175, P1441, DOI 10.1534/genetics.106.064972
   Zeller G, 2008, GENOME RES, V18, P918, DOI 10.1101/gr.070169.107
   Zhang X, 2011, GENOME RES, V21, P725, DOI 10.1101/gr.115337.110
NR 37
TC 504
Z9 591
U1 1
U2 155
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 419
EP 423
DI 10.1038/nature10414
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500031
PM 21874022
DA 2026-03-09
ER

PT J
AU Duderstadt, KE
   Chuang, K
   Berger, JM
AF Duderstadt, Karl E.
   Chuang, Kevin
   Berger, James M.
TI DNA stretching by bacterial initiators promotes replication origin opening
SO NATURE
LA English
DT Article
ID escherichia-coli; structural basis; crystal-structure; protein; recognition; mechanism; complexes; helicase; atpases; binding
AB Many replication initiators form higher-order oligomers that process host replication origins to promote replisome formation. In addition to dedicated duplex-DNA-binding domains, cellular initiators possess AAA+ (ATPases associated with various cellular activities) elements that drive functions ranging from protein assembly to origin recognition. In bacteria, the AAA+ domain of the initiator DnaA has been proposed to assist in single-stranded DNA formation during origin melting. Here we show crystallographically and in solution that the ATP-dependent assembly of Aquifex aeolicus DnaA into a spiral oligomer creates a continuous surface that allows successive AAA+ domains to bind and extend single-stranded DNA segments. The mechanism of binding is unexpectedly similar to that of RecA, a homologous recombination factor, but it differs in that DnaA promotes a nucleic acid conformation that prevents pairing of a complementary strand. These findings, combined with strand-displacement assays, indicate that DnaA opens replication origins by a direct ATP-dependent stretching mechanism. Comparative studies reveal notable commonalities between the approach used by DnaA to engage DNA substrates and other, nucleic-acid-dependent, AAA+ systems.
C1 [Duderstadt, Karl E.; Berger, James M.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Chuang, Kevin; Berger, James M.] Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Berger, JM (corresponding author), Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
EM jmberger@berkeley.edu
FU NIGMS [GM071747]; National Institute of Health [T32 GM008295]; National Institute of General Medical Sciences [T32GM008295] Funding Source: NIH RePORTER
NR 60
TC 156
Z9 181
U1 0
U2 41
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 209
EP U91
DI 10.1038/nature10455
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800042
PM 21964332
DA 2026-03-09
ER

PT J
AU Cocinero, EJ
   Çarçabal, P
   Vaden, TD
   Simons, JP
   Davis, BG
AF Cocinero, Emilio J.
   Carcabal, Pierre
   Vaden, Timothy D.
   Simons, John P.
   Davis, Benjamin G.
TI Sensing the anomeric effect in a solvent-free environment
SO NATURE
LA English
DT Article
ID conformational-analysis; gas-phase; glucose; systems; model; bond
AB The anomeric effect is a chemical phenomenon(1-9) that refers to an observed stabilization(10) of six-membered carbohydrate rings when they contain an electronegative substituent at the C1 position of the ring. This stereoelectronic effect influences the three-dimensional shapes of many biological molecules. It can be manifested not only in this classical manner involving interaction of the endocyclic oxygen atom (O5) found in such sugars with the C1 substituent (endo-anomeric effect) but also through a corresponding interaction of the electronegative exocyclic substituent with O5 (exoanomeric effect). However, the underlying physical origin(s) of this phenomenon is still not clear(1,3,4,11-14). Here we show, using a combination of laser spectroscopy and computational analysis, that a truncated peptide motif can engage the two anomers of an isolated sugar in the gas phase, an environment lacking extraneous factors which could confound the analysis. (Anomers are isomers that differ in the orientation of the substituent at C1.) Complexes formed between the peptide and the alpha- or beta-anomers of D-galactose are nearly identical structurally; however, the strength of the polarization of their interactions with the peptide differs greatly. Natural bond order calculations support this observation, and together they reveal the dominance of the exo- over the endo-anomeric effect. As interactions between oxygen atoms at positions C1 and C2 (O1 and O2, respectively) on the pyranose ring can alter the exo/endo ratio of a carbohydrate, our results suggest that it will be important to reevaluate the influence, and biological effects, of substituents at position C2 in sugars.
C1 [Davis, Benjamin G.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
   [Cocinero, Emilio J.; Carcabal, Pierre; Vaden, Timothy D.; Simons, John P.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
C3 University of Oxford; University of Oxford
RP Davis, BG (corresponding author), Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England.
EM John.Simons@chem.ox.ac.uk; Ben.Davis@chem.ox.ac.uk
FU EPSRC [GR/T26542]; Leverhulme Trust; Spanish Ministry (MCINN) for a Juan de la Cierva; Royal Society for a USA/Canada; Linacre College; Royal Society; Biotechnology and Biological Sciences Research Council [BB/C510824/1, BB/E004350/1, EGA17763] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/G026688/1, EP/G03088X/1, GR/T26542/01, EP/I500200/1, EP/E000614/1, EP/D023343/1, EP/D023335/1] Funding Source: researchfish; BBSRC [BB/E004350/1] Funding Source: UKRI; EPSRC [EP/G026688/1, EP/G03088X/1, EP/E000614/1, EP/I500200/1] Funding Source: UKRI
NR 22
TC 136
Z9 148
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 JAN 6
PY 2011
VL 469
IS 7328
BP 76
EP U1400
DI 10.1038/nature09693
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600034
PM 21209661
DA 2026-03-09
ER

PT J
AU Gibson, L
   Lee, TM
   Koh, LP
   Brook, BW
   Gardner, TA
   Barlow, J
   Peres, CA
   Bradshaw, CJA
   Laurance, WF
   Lovejoy, TE
   Sodhi, NS
AF Gibson, Luke
   Lee, Tien Ming
   Koh, Lian Pin
   Brook, Barry W.
   Gardner, Toby A.
   Barlow, Jos
   Peres, Carlos A.
   Bradshaw, Corey J. A.
   Laurance, William F.
   Lovejoy, Thomas E.
   Sodhi, Navjot S.
TI Primary forests are irreplaceable for sustaining tropical biodiversity
SO NATURE
LA English
DT Article
ID countryside biogeography; global biodiversity; conservation; opportunity; disturbance; scenarios
AB Human-driven land-use changes increasingly threaten biodiversity, particularly in tropical forests where both species diversity and human pressures on natural environments are high(1). The rapid conversion of tropical forests for agriculture, timber production and other uses has generated vast, human-dominated landscapes with potentially dire consequences for tropical biodiversity(2-5). Today, few truly undisturbed tropical forests exist, whereas those degraded by repeated logging and fires, as well as secondary and plantation forests, are rapidly expanding(6,7). Here we provide a global assessment of the impact of disturbance and land conversion on biodiversity in tropical forests using a meta-analysis of 138 studies. We analysed 2,220 pairwise comparisons of biodiversity values in primary forests (with little or no human disturbance) and disturbed forests. We found that biodiversity values were substantially lower in degraded forests, but that this varied considerably by geographic region, taxonomic group, ecological metric and disturbance type. Even after partly accounting for confounding colonization and succession effects due to the composition of surrounding habitats, isolation and time since disturbance, we find that most forms of forest degradation have an overwhelmingly detrimental effect on tropical biodiversity. Our results clearly indicate that when it comes to maintaining tropical biodiversity, there is no substitute for primary forests.
C1 [Gibson, Luke; Koh, Lian Pin; Sodhi, Navjot S.] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
   [Lee, Tien Ming] Univ Calif San Diego, Ecol Behav & Evolut Sect, Div Biol Sci, La Jolla, CA 92093 USA.
   [Lee, Tien Ming] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
   [Koh, Lian Pin] ETH, Dept Environm Sci, CH-8092 Zurich, Switzerland.
   [Brook, Barry W.; Bradshaw, Corey J. A.] Univ Adelaide, Inst Environm, Adelaide, SA 5005, Australia.
   [Brook, Barry W.; Bradshaw, Corey J. A.] Univ Adelaide, Sch Earth & Environm Sci, Adelaide, SA 5005, Australia.
   [Gardner, Toby A.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Barlow, Jos] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Peres, Carlos A.] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Bradshaw, Corey J. A.] S Australian Res & Dev Inst, Henley Beach, SA 5022, Australia.
   [Laurance, William F.] James Cook Univ, Ctr Trop Environm & Sustainabil Sci TESS, Cairns, Qld 4870, Australia.
   [Laurance, William F.] James Cook Univ, Sch Marine & Trop Biol, Cairns, Qld 4870, Australia.
   [Lovejoy, Thomas E.] Natl Inst Amazonian Res INPA, Biol Dynam Forest Fragments Project, BR-69011970 Manaus, AM, Brazil.
   [Lovejoy, Thomas E.] H John Heinz III Ctr Sci Econ & Environm, Washington, DC 20004 USA.
C3 National University of Singapore; University of California System; University of California San Diego; Yale University; Swiss Federal Institutes of Technology Domain; ETH Zurich; Adelaide University; University of Adelaide; Adelaide University; University of Adelaide; University of Cambridge; Lancaster University; University of East Anglia; James Cook University; James Cook University; Institute Nacional de Pesquisas da Amazonia
RP Gibson, L (corresponding author), Natl Univ Singapore, Dept Biol Sci, 14 Sci Dr 4, Singapore 117543, Singapore.
EM lggibson@nus.edu.sg; tmlee@ucsd.edu
FU National University of Singapore [R-154-000-479-112]; Singapore International; Swiss National Science Foundation; ETH North-South Centre; Natural Environmental Research Council [NE/F01614X/1]; Instituto Nacional de Ciencia e Tecnologia - Biodiversidade e Uso da Terra na Amazonia [CNPq 574008/2008-0]; NERC [NE/F01614X/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/E500811/1] Funding Source: researchfish; Natural Environment Research Council [NE/F01614X/1] Funding Source: researchfish
CR Asner GP, 2009, CONSERV BIOL, V23, P1386, DOI 10.1111/j.1523-1739.2009.01333.x
   Barlow J, 2007, P NATL ACAD SCI USA, V104, P18555, DOI 10.1073/pnas.0703333104
   Borenstein M, 2009, INTRODUCTION TO META-ANALYSIS, V0, P0, DOI DOI 10.1002/9781119558378
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   Daily GC, 2003, CONSERV BIOL, V17, P1814, DOI 10.1111/j.1523-1739.2003.00298.x
   Dent DH, 2009, BIOL CONSERV, V142, P2833, DOI 10.1016/j.biocon.2009.05.035
   Dirzo R, 2003, ANNU REV ENV RESOUR, V28, P137, DOI 10.1146/annurev.energy.28.050302.105532
   Edwards DP, 2011, P ROY SOC B-BIOL SCI, V278, P82, DOI 10.1098/rspb.2010.1062
   EFRON B, 1991, SCIENCE, V253, P390, DOI 10.1126/science.253.5018.390
   Foley JA, 2005, SCIENCE, V309, P570, DOI 10.1126/science.1111772
   Gardner TA, 2007, BIOTROPICA, V39, P25, DOI 10.1111/j.1744-7429.2006.00228.x
   Gardner TA, 2010, BIOL CONSERV, V143, P2293, DOI 10.1016/j.biocon.2010.05.017
   Gardner TA, 2009, ECOL LETT, V12, P561, DOI 10.1111/j.1461-0248.2009.01294.x
   Harvey CA, 2010, CONSERV LETT, V3, P53, DOI 10.1111/j.1755-263X.2009.00086.x
   Horner-Devine MC, 2003, CONSERV BIOL, V17, P168, DOI 10.1046/j.1523-1739.2003.01310.x
   Hughes JB, 2002, ECOL LETT, V5, P121, DOI 10.1046/j.1461-0248.2002.00294.x
   Koh LP, 2008, CONSERV LETT, V1, P60, DOI 10.1111/j.1755-263X.2008.00011.x
   Koh LP, 2010, P NATL ACAD SCI USA, V107, P11140, DOI 10.1073/pnas.1000530107
   Laurance WF, 2007, TRENDS ECOL EVOL, V22, P65, DOI 10.1016/j.tree.2006.09.014
   Laurance WF, 2009, TRENDS ECOL EVOL, V24, P659, DOI 10.1016/j.tree.2009.06.009
   Pereira HM, 2010, SCIENCE, V330, P1496, DOI 10.1126/science.1196624
   Peres CA, 2006, TRENDS ECOL EVOL, V21, P227, DOI 10.1016/j.tree.2006.03.007
   Prugh LR, 2008, P NATL ACAD SCI USA, V105, P20770, DOI 10.1073/pnas.0806080105
   R Development Core Team, 2011, R PROJ STAT COMP VER, V0, P0
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   Sodhi NS, 2004, TRENDS ECOL EVOL, V19, P654, DOI 10.1016/j.tree.2004.09.006
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   Wright SJ, 2005, TRENDS ECOL EVOL, V20, P553, DOI 10.1016/j.tree.2005.07.009
NR 34
TC 1609
Z9 1884
U1 18
U2 1096
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 378
EP +
DI 10.1038/nature10425
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100044
PM 21918513
DA 2026-03-09
ER

PT J
AU Sanai, N
   Nguyen, T
   Ihrie, RA
   Mirzadeh, Z
   Tsai, HH
   Wong, M
   Gupta, N
   Berger, MS
   Huang, E
   Garcia-Verdugo, JM
   Rowitch, DH
   Alvarez-Buylla, A
AF Sanai, Nader
   Thuhien Nguyen
   Ihrie, Rebecca A.
   Mirzadeh, Zaman
   Tsai, Hui-Hsin
   Wong, Michael
   Gupta, Nalin
   Berger, Mitchel S.
   Huang, Eric
   Garcia-Verdugo, Jose-Manuel
   Rowitch, David H.
   Alvarez-Buylla, Arturo
TI Corridors of migrating neurons in the human brain and their decline during infancy
SO NATURE
LA English
DT Article
ID neural stem-cells; ventromedial prefrontal cortex; subventricular zone; olfactory-bulb; adult neurogenesis; lateral ventricle; plasticity; forebrain; neuroblasts; ependyma
AB The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb(1-6). Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes(7). Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans(7). In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS8,9. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports(8), this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb-we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.
C1 [Sanai, Nader; Thuhien Nguyen; Ihrie, Rebecca A.; Mirzadeh, Zaman; Tsai, Hui-Hsin; Wong, Michael; Rowitch, David H.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Eli & Edythe Broad Inst Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Sanai, Nader; Thuhien Nguyen; Ihrie, Rebecca A.; Mirzadeh, Zaman; Tsai, Hui-Hsin; Wong, Michael; Rowitch, David H.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Sanai, Nader; Gupta, Nalin; Berger, Mitchel S.; Rowitch, David H.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Sanai, Nader; Mirzadeh, Zaman] Barrow Neurol Inst, Barrow Brain Tumor Res Ctr, Phoenix, AZ 85013 USA.
   [Huang, Eric] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Garcia-Verdugo, Jose-Manuel] CIBERNED, Unidad Mixta CIPF UVEG, Lab Morfol Celular, Valencia 46012, Spain.
   [Rowitch, David H.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Barrow Neurological Institute; University of California System; University of California San Francisco; Prince Felipe Research Center; CIBERNED; University of California System; University of California San Francisco
RP Alvarez-Buylla, A (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Inst Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
EM rowitchd@peds.ucsf.edu; abuylla@stemcell.ucsf.edu
FU NIH [NS 058180]; Damon Runyon Cancer Research Foundation [DRG1935-07]; American Association for Cancer Research/National Brain Tumor Society; American Association for Cancer Research; Pediatric Brain Tumor Foundation of the United States; John G. Bowes Research Fund; National Institute of Neurological Disorders and Stroke [R01NS028478] Funding Source: NIH RePORTER
NR 31
TC 673
Z9 805
U1 1
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 382
EP +
DI 10.1038/nature10487
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100045
PM 21964341
DA 2026-03-09
ER

PT J
AU Bonnin, A
   Goeden, N
   Chen, K
   Wilson, ML
   King, J
   Shih, JC
   Blakely, RD
   Deneris, ES
   Levitt, P
AF Bonnin, Alexandre
   Goeden, Nick
   Chen, Kevin
   Wilson, Melissa L.
   King, Jennifer
   Shih, Jean C.
   Blakely, Randy D.
   Deneris, Evan S.
   Levitt, Pat
TI A transient placental source of serotonin for the fetal forebrain
SO NATURE
LA English
DT Article
ID normal anxiety-like; tryptophan 2,3-dioxygenase; aggressive-behavior; monoamine-oxidase; brain-serotonin; expression; mice; transporter; neurons; pregnancy
AB Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy(1,2) but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT3. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.
C1 [Bonnin, Alexandre; Goeden, Nick; Levitt, Pat] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
   [Bonnin, Alexandre; Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA.
   [Chen, Kevin; Shih, Jean C.] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA.
   [Wilson, Melissa L.; King, Jennifer] Univ So Calif, Keck Sch Med, Dept OB GYN, Los Angeles, CA 90089 USA.
   [Wilson, Melissa L.; King, Jennifer] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
   [Blakely, Randy D.] Vanderbilt Univ, Dept Pharmacol, Med Ctr, Nashville, TN 37221 USA.
   [Blakely, Randy D.] Vanderbilt Univ, Ctr Mol Neurosci, Med Ctr, Nashville, TN 37221 USA.
   [Deneris, Evan S.] Case Western Reserve Univ, Dept Neurosci, Sch Med, Cleveland, OH 44106 USA.
C3 University of Southern California; University of Southern California; University of Southern California; University of Southern California; University of Southern California; Vanderbilt University; Vanderbilt University; University System of Ohio; Case Western Reserve University
RP Bonnin, A (corresponding author), Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
EM bonnin@usc.edu; plevitt@usc.edu
FU NICHD [5R21HD065287]; NARSAD; NIMH [R01MH39085, 1P50MH078280A1]
NR 35
TC 476
Z9 556
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 APR 21
PY 2011
VL 472
IS 7343
BP 347
EP U246
DI 10.1038/nature09972
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600039
PM 21512572
DA 2026-03-09
ER

PT J
AU Esvelt, KM
   Carlson, JC
   Liu, DR
AF Esvelt, Kevin M.
   Carlson, Jacob C.
   Liu, David R.
TI A system for the continuous directed evolution of biomolecules
SO NATURE
LA English
DT Article
ID t7 rna-polymerase; start site selection; phage; transcription; recognition; initiation; vectors; mutants; yeast; assay
AB Laboratory evolution has generated many biomolecules with desired properties, but a single round of mutation, gene expression, screening or selection, and replication typically requires days or longer with frequent human intervention(1). Because evolutionary success is dependent on the total number of rounds performed(2), a means of performing laboratory evolution continuously and rapidly could dramatically enhance its effectiveness(3). Although researchers have accelerated individual steps in the evolutionary cycle(4-9), the only previous example of continuous directed evolution was the landmark study of Wright and Joyce(10), who continuously evolved RNA ligase ribozymes with an in vitro replication cycle that unfortunately cannot be easily adapted to other biomolecules. Here we describe a system that enables the continuous directed evolution of gene-encoded molecules that can be linked to protein production in Escherichia coli. During phage-assisted continuous evolution (PACE), evolving genes are transferred from host cell to host cell through a modified bacteriophage life cycle in a manner that is dependent on the activity of interest. Dozens of rounds of evolution can occur in a single day of PACE without human intervention. Using PACE, we evolved T7 RNA polymerase (RNAP) variants that recognize a distinct promoter, initiate transcripts with ATP instead of GTP, and initiate transcripts with CTP. In one example, PACE executed 200 rounds of protein evolution over the course of 8 days. Starting from undetectable activity levels in two of these cases, enzymes with each of the three target activities emerged in less than 1 week of PACE. In all three cases, PACE-evolved polymerase activities exceeded or were comparable to that of the wild-type T7 RNAP on its wild-type promoter, representing improvements of up to several hundred-fold. By greatly accelerating laboratory evolution, PACE may provide solutions to otherwise intractable directed evolution problems and address novel questions about molecular evolution.
C1 [Carlson, Jacob C.; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Esvelt, Kevin M.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Harvard University; Howard Hughes Medical Institute
RP Liu, DR (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM drliu@fas.harvard.edu
FU National Institutes of Health/National Institute of General Medical Sciences [R01 GM065400]; HHMI; Hertz Foundation; National Science Foundation; Harvard Chemical Biology Graduate Program
NR 32
TC 526
Z9 847
U1 13
U2 530
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 499
EP U550
DI 10.1038/nature09929
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600040
PM 21478873
DA 2026-03-09
ER

PT J
AU Kaneko, H
   Dridi, S
   Tarallo, V
   Gelfand, BD
   Fowler, BJ
   Cho, WG
   Kleinman, ME
   Ponicsan, SL
   Hauswirth, WW
   Chiodo, VA
   Karikó, K
   Yoo, JW
   Lee, DK
   Hadziahmetovic, M
   Song, Y
   Misra, S
   Chaudhuri, G
   Buaas, FW
   Braun, RE
   Hinton, DR
   Zhang, Q
   Grossniklaus, HE
   Provis, JM
   Madigan, MC
   Milam, AH
   Justice, NL
   Albuquerque, RJC
   Blandford, AD
   Bogdanovich, S
   Hirano, Y
   Witta, J
   Fuchs, E
   Littman, DR
   Ambati, BK
   Rudin, CM
   Chong, MMW
   Provost, P
   Kugel, JF
   Goodrich, JA
   Dunaief, JL
   Baffi, JZ
   Ambati, J
AF Kaneko, Hiroki
   Dridi, Sami
   Tarallo, Valeria
   Gelfand, Bradley D.
   Fowler, Benjamin J.
   Cho, Won Gil
   Kleinman, Mark E.
   Ponicsan, Steven L.
   Hauswirth, William W.
   Chiodo, Vince A.
   Kariko, Katalin
   Yoo, Jae Wook
   Lee, Dong-ki
   Hadziahmetovic, Majda
   Song, Ying
   Misra, Smita
   Chaudhuri, Gautam
   Buaas, Frank W.
   Braun, Robert E.
   Hinton, David R.
   Zhang, Qing
   Grossniklaus, Hans E.
   Provis, Jan M.
   Madigan, Michele C.
   Milam, Ann H.
   Justice, Nikki L.
   Albuquerque, Romulo J. C.
   Blandford, Alexander D.
   Bogdanovich, Sasha
   Hirano, Yoshio
   Witta, Jassir
   Fuchs, Elaine
   Littman, Dan R.
   Ambati, Balamurali K.
   Rudin, Charles M.
   Chong, Mark M. W.
   Provost, Patrick
   Kugel, Jennifer F.
   Goodrich, James A.
   Dunaief, Joshua L.
   Baffi, Judit Z.
   Ambati, Jayakrishna
TI DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
SO NATURE
LA English
DT Article
ID embryonic stem-cells; microrna biogenesis; mouse oocytes; ldl receptor; recombination; argonaute2; expression; cancer; sirnas; differentiation
AB Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.
C1 [Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D.; Fowler, Benjamin J.; Cho, Won Gil; Kleinman, Mark E.; Justice, Nikki L.; Albuquerque, Romulo J. C.; Blandford, Alexander D.; Bogdanovich, Sasha; Hirano, Yoshio; Baffi, Judit Z.; Ambati, Jayakrishna] Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
   [Cho, Won Gil] Yonsei Univ, Wonju Coll Med, Dept Anat, Wonju 220701, South Korea.
   [Ponicsan, Steven L.; Kugel, Jennifer F.; Goodrich, James A.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Hauswirth, William W.; Chiodo, Vince A.] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
   [Kariko, Katalin] Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA.
   [Yoo, Jae Wook; Lee, Dong-ki] Sungkyunkwan Univ, Sch Chem Mat Sci BK21, Suwon 440746, South Korea.
   [Yoo, Jae Wook; Lee, Dong-ki] Sungkyunkwan Univ, Dept Chem, Suwon 440746, South Korea.
   [Hadziahmetovic, Majda; Song, Ying; Milam, Ann H.; Dunaief, Joshua L.] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
   [Misra, Smita; Chaudhuri, Gautam] Meharry Med Coll, Dept Microbiol & Immunol, Nashville, TN 37208 USA.
   [Buaas, Frank W.; Braun, Robert E.] Jackson Lab, Bar Harbor, ME 04609 USA.
   [Hinton, David R.] Univ So Calif, Doheny Eye Inst, Arnold & Mabel Beckman Macular Res Ctr, Los Angeles, CA 90033 USA.
   [Zhang, Qing; Grossniklaus, Hans E.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA.
   [Zhang, Qing; Grossniklaus, Hans E.] Emory Univ, Atlanta, GA 30322 USA.
   [Provis, Jan M.] Australian Natl Univ, ANU Med Sch, ARC Ctr Excellence Vis Sci, Canberra, ACT 0200, Australia.
   [Provis, Jan M.] Australian Natl Univ, Res Sch Biol, Canberra, ACT 0200, Australia.
   [Madigan, Michele C.] Univ New S Wales, Sch Optometry & Vis Sci, Kensington, NSW 2033, Australia.
   [Madigan, Michele C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2001, Australia.
   [Witta, Jassir] Univ Kentucky, Dept Internal Med, Lexington, KY 40506 USA.
   [Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
   [Littman, Dan R.; Chong, Mark M. W.] NYU, Sch Med, Howard Hughes Med Inst, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA.
   [Ambati, Balamurali K.] Univ Utah, Sch Med, Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA.
   [Ambati, Balamurali K.] Vet Affairs Salt Lake City Healthcare Syst, Dept Ophthalmol, Salt Lake City, UT 84148 USA.
   [Rudin, Charles M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD 21231 USA.
   [Chong, Mark M. W.] Walter & Eliza Hall Inst Med Res, Autoimmun & Transplantat Div, Parkville, Vic 3052, Australia.
   [Provost, Patrick] Univ Laval, CHUL Res Ctr CHUQ, Quebec City, PQ G1K 7P4, Canada.
   [Provost, Patrick] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada.
   [Ambati, Jayakrishna] Univ Kentucky, Dept Physiol, Lexington, KY 40506 USA.
   [Yoo, Jae Wook; Lee, Dong-ki] Sungkyunkwan Univ, Global Res Lab RNAi Med, Suwon 440746, South Korea.
C3 University of Kentucky; Yonsei University; University of Colorado System; University of Colorado Boulder; State University System of Florida; University of Florida; University of Pennsylvania; Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); University of Pennsylvania; Pennsylvania Medicine; Meharry Medical College; Jackson Laboratory; University of Southern California; Doheny Eye Institute; Emory University; Emory University; Australian National University; Australian National University; University of New South Wales Sydney; University of Sydney; University of Kentucky; Rockefeller University; Howard Hughes Medical Institute; New York University; Howard Hughes Medical Institute; Utah System of Higher Education; University of Utah; US Department of Veterans Affairs; Johns Hopkins University; Johns Hopkins Medicine; Walter & Eliza Hall Institute; Laval University; Laval University Hospital; Laval University; University of Kentucky; Sungkyunkwan University (SKKU)
RP Ambati, J (corresponding author), Univ Kentucky, Dept Ophthalmol & Visual Sci, Lexington, KY 40506 USA.
EM jamba2@email.uky.edu
FU National Eye Institute (NEI)/National Institutes of Health (NIH) [R01EY015422, R01EY018350, R01EY018836, R01EY020672, R21EY019778, RC1EY020442, R01EY017182, R01EY017950, R01HD027215, R21AI076757, P30EY06360, U10EY013729, R01EY011123, P30EY008571, R01GM068414, R01EY015240, P30EY003040, R01EY001545, T32HL091812]; Doris Duke Distinguished Clinical Scientist Award; Burroughs Wellcome Fund Clinical Scientist Award in Translational Research; Dr E. Vernon Smith and Eloise C. Smith Macular Degeneration Endowed Chair; Research to Prevent Blindness Senior Scientist Investigator Awards; University of Kentucky Physician Scientist Award; International Retinal Research Foundation; American Health Assistance Foundation; VA Merit Award; Department of Defense; MEST, Korea; Arnold and Mabel Beckman Foundation; Macular Vision Research Foundation and Foundation Fighting Blindness; ARC Centres of Excellence [CE0561903]; Sydney Foundation for Medical Research; National Health and Medical Research Council, Australia [637228]; National Eye Institute [R01EY017950, P30EY014800, R01EY015240, P30EY006360] Funding Source: NIH RePORTER
NR 52
TC 498
Z9 618
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 MAR 17
PY 2011
VL 471
IS 7338
BP 325
EP +
DI 10.1038/nature09830
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000034
PM 21297615
DA 2026-03-09
ER

PT J
AU Hung, CL
   Zhang, XB
   Gemelke, N
   Chin, C
AF Hung, Chen-Lung
   Zhang, Xibo
   Gemelke, Nathan
   Chin, Cheng
TI Observation of scale invariance and universality in two-dimensional Bose gases
SO NATURE
LA English
DT Article
ID symmetry; systems; atoms
AB The collective behaviour of a many-body system near a continuous phase transition is insensitive to the details of its microscopic physics; for example, thermodynamic observables follow generalized scaling laws near the phase transition(1). The Berezinskii-Kosterlitz-Thouless (BKT) phase transition(2,3) in two-dimensional Bose gases presents a particularly interesting case because the marginal dimensionality and intrinsic scaling symmetry(4) result in a broad fluctuation regime and an extended range of universal scaling behaviour. Studies of the BKT transition in cold atoms have stimulated great interest in recent years(5-10), but a clear demonstration of critical behaviour near the phase transition has remained elusive. Here we report in situ density and density-fluctuation measurements of two-dimensional Bose gases of caesium at different temperatures and interaction strengths, observing scale-invariant, universal behaviours. The extracted thermodynamic functions confirm the existence of a wide universal region near the BKT phase transition, and provide a sensitive test of the universality predicted by classical-field theory(11,12) and quantum Monte Carlo calculations(13). Our experimental results provide evidence for growing density-density correlations in the fluctuation region, and call for further explorations of universal phenomena in classical and quantum critical physics.
C1 [Hung, Chen-Lung; Zhang, Xibo; Gemelke, Nathan; Chin, Cheng] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   [Hung, Chen-Lung; Zhang, Xibo; Gemelke, Nathan; Chin, Cheng] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Hung, CL (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM clhung@uchicago.edu
FU NSF [PHY-0747907, NSF-MRSEC DMR-0213745]; Packard Foundation; Army Research Office; DARPA; Grainger Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0747907] Funding Source: National Science Foundation
NR 31
TC 233
Z9 257
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 FEB 10
PY 2011
VL 470
IS 7333
BP 236
EP +
DI 10.1038/nature09722
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200039
PM 21270797
DA 2026-03-09
ER

PT J
AU Sosulski, DL
   Bloom, ML
   Cutforth, T
   Axel, R
   Datta, SR
AF Sosulski, Dara L.
   Bloom, Maria Lissitsyna
   Cutforth, Tyler
   Axel, Richard
   Datta, Sandeep Robert
TI Distinct representations of olfactory information in different cortical centres
SO NATURE
LA English
DT Article
ID tufted cells; bulb; projections; cortex; odor; organization; patterns; system; genes; axons
AB Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in the nose is converted into a segregated map in the olfactory bulb(1-3). Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.
C1 [Sosulski, Dara L.; Bloom, Maria Lissitsyna; Cutforth, Tyler; Axel, Richard; Datta, Sandeep Robert] Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
   [Sosulski, Dara L.; Bloom, Maria Lissitsyna; Cutforth, Tyler; Axel, Richard; Datta, Sandeep Robert] Columbia Univ, Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University
RP Axel, R (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
EM ra27@columbia.edu
FU Burroughs Wellcome Fund; National Institutes of Health [DP2-OD-007109]; Howard Hughes Medical Institute; Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative; Helen Hay Whitney Foundation
NR 31
TC 353
Z9 457
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 APR 14
PY 2011
VL 472
IS 7342
BP 213
EP 216
DI 10.1038/nature09868
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100041
PM 21451525
DA 2026-03-09
ER

PT J
AU Berger, T
   Testa, P
   Hillier, A
   Boerner, P
   Low, BC
   Shibata, K
   Schrijver, C
   Tarbell, T
   Title, A
AF Berger, Thomas
   Testa, Paola
   Hillier, Andrew
   Boerner, Paul
   Low, Boon Chye
   Shibata, Kazunari
   Schrijver, Carolus
   Tarbell, Ted
   Title, Alan
TI Magneto-thermal convection in solar prominences
SO NATURE
LA English
DT Article
ID quiescent prominence; helical flux; mass ejections; hinode; emergence; confinement; telescope; corona; flows; soho
AB Coronal cavities are large low-density regions formed by hemispheric-scale magnetic flux ropes suspended in the Sun's outer atmosphere(1). They evolve over time, eventually erupting as the dark cores of coronal mass ejections(2,3). Although coronal mass ejections are common and can significantly affect planetary magnetospheres, the mechanisms by which cavities evolve to an eruptive state remain poorly understood. Recent optical observations(4) of high-latitude 'polar crown' prominences within coronal cavities reveal dark, low-density(5) 'bubbles' that undergo Rayleigh-Taylor instabilities(6,7) to form dark plumes rising into overlying coronal cavities. These observations offered a possible mechanism for coronal cavity evolution, although the nature of the bubbles, particularly their buoyancy, was hitherto unclear. Here we report simultaneous optical and extreme-ultraviolet observations of polar crown prominences that show that these bubbles contain plasma at temperatures in the range (2.5-12) x 10(5) kelvin, which is 25-120 times hotter than the overlying prominence. This identifies a source of the buoyancy, and suggests that the coronal cavity-prominence system supports a novel form of magneto-thermal convection in the solar atmosphere, challenging current hydromagnetic concepts of prominences and their relation to coronal cavities.
C1 [Berger, Thomas; Boerner, Paul; Schrijver, Carolus; Tarbell, Ted; Title, Alan] Lockheed Martin Adv Technol Ctr, Solar & Astrophys Lab, Palo Alto, CA 94304 USA.
   [Testa, Paola] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Hillier, Andrew; Shibata, Kazunari] Kyoto Univ, Grad Sch Sci, Kwasan Observ, Kyoto 6078471, Japan.
   [Hillier, Andrew; Shibata, Kazunari] Kyoto Univ, Grad Sch Sci, Hida Observ, Kyoto 6078471, Japan.
   [Low, Boon Chye] Natl Ctr Atmospher Res, High Altitude Observ, Boulder, CO 80307 USA.
C3 Lockheed Martin; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Kyoto University; Kyoto University; National Center Atmospheric Research (NCAR) - USA
RP Berger, T (corresponding author), Lockheed Martin Adv Technol Ctr, Solar & Astrophys Lab, O ADBS B 252,3251 Hanover St, Palo Alto, CA 94304 USA.
EM berger@lmsal.com
FU JAXA and NAOJ (Japan); STFC (UK); NASA; ESA; NSC (Norway); Universality and Emergence
NR 27
TC 132
Z9 138
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 197
EP 200
DI 10.1038/nature09925
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100037
PM 21490669
DA 2026-03-09
ER

PT J
AU Kegel, A
   Betts-Lindroos, H
   Kanno, T
   Jeppsson, K
   Ström, L
   Katou, Y
   Itoh, T
   Shirahige, K
   Sjögren, C
AF Kegel, Andreas
   Betts-Lindroos, Hanna
   Kanno, Takaharu
   Jeppsson, Kristian
   Strom, Lena
   Katou, Yuki
   Itoh, Takehiko
   Shirahige, Katsuhiko
   Sjogren, Camilla
TI Chromosome length influences replication-induced topological stress
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; dna-replication; topoisomerase-i; recq helicase; budding yeast; repair; proteins; complex; forks; damage
AB During chromosome duplication the parental DNA molecule becomes overwound, or positively supercoiled, in the region ahead of the advancing replication fork. To allow fork progression, this superhelical tension has to be removed by topoisomerases, which operate by introducing transient DNA breaks(1). Positive supercoiling can also be diminished if the advancing fork rotates along the DNA helix, but then sister chromatid intertwinings form in its wake(1,2). Despite these insights it remains largely unknown how replication-induced superhelical stress is dealt with on linear, eukaryotic chromosomes. Here we show that this stress increases with the length of Saccharomyces cerevisiae chromosomes. This highlights the possibility that superhelical tension is handled on a chromosome scale and not only within topologically closed chromosomal domains as the current view predicts. We found that inhibition of type I topoisomerases leads to a late replication delay of longer, but not shorter, chromosomes. This phenotype is also displayed by cells expressing mutated versions of the cohesin-and condensin-related Smc5/6 complex. The frequency of chromosomal association sites of the Smc5/6 complex increases in response to chromosome lengthening, chromosome circularization, or inactivation of topoisomerase 2, all having the potential to increase the number of sister chromatid intertwinings(3). Furthermore, nonfunctional Smc6 reduces the accumulation of intertwined sister plasmids after one round of replication in the absence of topoisomerase 2 function. Our results demonstrate that the length of a chromosome influences the need of superhelical tension release in Saccharomyces cerevisiae, and allow us to propose a model where the Smc5/6 complex facilitates fork rotation by sequestering nascent chromatid intertwinings that form behind the replication machinery.
C1 [Kegel, Andreas; Betts-Lindroos, Hanna; Kanno, Takaharu; Jeppsson, Kristian; Strom, Lena; Sjogren, Camilla] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Katou, Yuki; Itoh, Takehiko] Tokyo Inst Technol, Grad Sch Biosci, Lab Silico Funct Genom, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
   [Shirahige, Katsuhiko] Univ Tokyo, Inst Mol & Cellular Biosci, Res Ctr Epigenet Dis, Bunkyo Ku, Tokyo 1130032, Japan.
C3 Karolinska Institutet; Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo
RP Sjögren, C (corresponding author), Karolinska Inst, Dept Cell & Mol Biol, Eulersvag 3, S-17177 Stockholm, Sweden.
EM camilla.sjogren@ki.se
FU JST; SSF; Vinnova; Grants-in-Aid for Scientific Research [22125001, 22221009] Funding Source: KAKEN
NR 36
TC 95
Z9 107
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2011
VL 471
IS 7338
BP 392
EP +
DI 10.1038/nature09791
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000048
PM 21368764
DA 2026-03-09
ER

PT J
AU Capak, PL
   Riechers, D
   Scoville, NZ
   Carilli, C
   Cox, P
   Neri, R
   Robertson, B
   Salvato, M
   Schinnerer, E
   Yan, L
   Wilson, GW
   Yun, M
   Civano, F
   Elvis, M
   Karim, A
   Mobasher, B
   Staguhn, JG
AF Capak, Peter L.
   Riechers, Dominik
   Scoville, Nick Z.
   Carilli, Chris
   Cox, Pierre
   Neri, Roberto
   Robertson, Brant
   Salvato, Mara
   Schinnerer, Eva
   Yan, Lin
   Wilson, Grant W.
   Yun, Min
   Civano, Francesca
   Elvis, Martin
   Karim, Alexander
   Mobasher, Bahram
   Staguhn, Johannes G.
TI A massive protocluster of galaxies at a redshift of z ≈ 5.3
SO NATURE
LA English
DT Article
ID lyman-break galaxy; molecular gas; submillimeter galaxy; cosmos survey; evolution; quasars; z-similar-to-6; population; cluster; field
AB Massive clusters of galaxies have been found that date from as early as 3.9 billion years(1) (3.9 Gyr; z = 1.62) after the Big Bang, containing stars that formed at even earlier epochs(2,3). Cosmological simulations using the current cold dark matter model predict that these systems should descend from 'protoclusters'-early overdensities of massive galaxies that merge hierarchically to form a cluster(4,5). These protocluster regions themselves are built up hierarchically and so are expected to contain extremely massive galaxies that can be observed as luminous quasars and starbursts(4-6). Observational evidence for this picture, however, is sparse because high-redshift protoclusters are rare and difficult to observe(6,7). Here we report a protocluster region that dates from 1 Gyr (z = 55.3) after the Big Bang. This cluster of massive galaxies extends over more than 13 megaparsecs and contains a luminous quasar as well as a system rich in molecular gas(8). These massive galaxies place a lower limit of more than 4 x 10(11) solar masses of dark and luminous matter in this region, consistent with that expected from cosmological simulations for the earliest galaxy clusters(4,5,7).
C1 [Capak, Peter L.; Yan, Lin] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Riechers, Dominik; Scoville, Nick Z.; Robertson, Brant] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Carilli, Chris] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Cox, Pierre; Neri, Roberto] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Salvato, Mara] Max Planck Inst Plasma Phys, D-85748 Garching, Germany.
   [Schinnerer, Eva; Karim, Alexander] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Wilson, Grant W.; Yun, Min] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
   [Civano, Francesca; Elvis, Martin] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Mobasher, Bahram] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA.
   [Staguhn, Johannes G.] Johns Hopkins Univ, Lab Observat Cosmol, NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
C3 California Institute of Technology; California Institute of Technology; National Radio Astronomy Observatory (NRAO); Max Planck Society; Max Planck Society; University of Massachusetts System; University of Massachusetts Amherst; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of California System; University of California Riverside; Johns Hopkins University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Capak, PL (corresponding author), CALTECH, Spitzer Sci Ctr, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM capak@astro.caltech.edu
FU NASA; NSF; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1020981, 0907952] Funding Source: National Science Foundation
NR 28
TC 260
Z9 277
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 233
EP 235
DI 10.1038/nature09681
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200038
PM 21228776
DA 2026-03-09
ER

PT J
AU Timoney, N
   Baumgart, I
   Johanning, M
   Varón, AF
   Plenio, MB
   Retzker, A
   Wunderlich, C
AF Timoney, N.
   Baumgart, I.
   Johanning, M.
   Varon, A. F.
   Plenio, M. B.
   Retzker, A.
   Wunderlich, Ch.
TI Quantum gates and memory using microwave-dressed states
SO NATURE
LA English
DT Article
ID decoherence; simulation
AB Trapped atomic ions have been used successfully to demonstrate(1) basic elements of universal quantum information processing. Nevertheless, scaling up such methods to achieve large-scale, universal quantum information processing (or more specialized quantum simulations(2-5)) remains challenging. The use of easily controllable and stable microwave sources, rather than complex laser systems(6,7), could remove obstacles to scalability. However, the microwave approach has drawbacks: it involves the use of magnetic-field sensitive states, which shorten coherence times considerably, and requires large, stable magnetic field gradients. Here we show how to overcome both problems by using stationary atomic quantum states as qubits that are induced by microwave fields (that is, by dressing magnetic-field-sensitive states with microwave fields). This permits fast quantum logic, even in the presence of a small (effective) Lamb-Dicke parameter (and, therefore, moderate magnetic field gradients). We experimentally demonstrate the basic building blocks of this scheme, showing that the dressed states are long lived and that coherence times are increased by more than two orders of magnitude relative to those of bare magnetic-field-sensitive states. This improves the prospects of microwave-driven ion trap quantum information processing, and offers a route to extending coherence times in all systems that suffer from magnetic noise, such as neutral atoms, nitrogen-vacancy centres, quantum dots or circuit quantum electrodynamic systems.
C1 [Timoney, N.; Baumgart, I.; Johanning, M.; Varon, A. F.; Wunderlich, Ch.] Univ Siegen, Dept Phys, Fac Sci & Technol, D-57068 Siegen, Germany.
   [Plenio, M. B.; Retzker, A.] Univ Ulm, Inst Theoret Phys, D-89069 Ulm, Germany.
C3 Universitat Siegen; Ulm University
RP Wunderlich, C (corresponding author), Univ Siegen, Dept Phys, Fac Sci & Technol, D-57068 Siegen, Germany.
EM alex.retzker@uni-ulm.de; wunderlich@physik.uni-siegen.de
FU Bundesministerium fur Bildung und Forschung [FK 01BQ1012, P3352014]; Deutsche Forschungsgemeinschaft; European Commission under the STREP PICC; German-Israeli Foundation; secunet AG; Alexander von Humboldt Foundation
NR 30
TC 216
Z9 231
U1 1
U2 71
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 185
EP U83
DI 10.1038/nature10319
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900031
PM 21833085
DA 2026-03-09
ER

PT J
AU Strünker, T
   Goodwin, N
   Brenker, C
   Kashikar, ND
   Weyand, I
   Seifert, R
   Kaupp, UB
AF Struenker, Timo
   Goodwin, Normann
   Brenker, Christoph
   Kashikar, Nachiket D.
   Weyand, Ingo
   Seifert, Reinhard
   Kaupp, U. Benjamin
TI The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
SO NATURE
LA English
DT Article
ID human spermatozoa; calcium influx; chemotaxis; activation; receptors; mechanism; cells
AB In the oviduct, cumulus cells that surround the oocyte release progesterone. In human sperm, progesterone stimulates a Ca2+ increase by a non-genomic mechanism(1-3). The Ca2+ signal has been proposed to control chemotaxis, hyperactivation and acrosomal exocytosis of sperm(4-8). However, the underlying signalling mechanism has remained mysterious. Here we show that progesterone activates the sperm-specific, pH-sensitive CatSper Ca2+ channel(9-11). We found that both progesterone and alkaline pH stimulate a rapid Ca2+ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers. The Ca2+ signals evoked by alkaline pH and progesterone are inhibited by the Ca-v channel blockers NNC 55-0396 and mibefradil. Patch-clamp recordings from sperm reveal an alkaline-activated current carried by mono-and divalent ions that exhibits all the hallmarks of sperm-specific CatSper Ca2+ channels(10,11). Progesterone substantially enhances the CatSper current. The alkaline- and progesterone-activated CatSper current is inhibited by both drugs. Our results resolve a long-standing controversy over the non-genomic progesterone signalling. In human sperm, either the CatSper channel itself or an associated protein serves as the non-genomic progesterone receptor. The identification of CatSper channel blockers will greatly facilitate the study of Ca2+ signalling in sperm and help to define further the physiological role of progesterone and CatSper.
C1 [Struenker, Timo; Goodwin, Normann; Brenker, Christoph; Kashikar, Nachiket D.; Seifert, Reinhard; Kaupp, U. Benjamin] Ctr Adv European Studies & Res, Abt Mol Neurosensor, D-53175 Bonn, Germany.
   [Weyand, Ingo] Forschungszentrum Julich, Inst Complex Syst Cellular Biophys ICS 4, D-52425 Julich, Germany.
C3 Center of Advanced European Studies & Research (CAESAR); Helmholtz Association; Julich Research Centre
RP Kaupp, UB (corresponding author), Ctr Adv European Studies & Res, Abt Mol Neurosensor, Ludwig Erhard Allee 2, D-53175 Bonn, Germany.
EM timo.struenker@caesar.de; u.b.kaupp@caesar.de
FU German Research Foundation [SFB 645]; International Helmholtz Research School on Biophysics and Soft Matter
NR 30
TC 468
Z9 528
U1 3
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 17
PY 2011
VL 471
IS 7338
BP 382
EP +
DI 10.1038/nature09769
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000046
PM 21412338
DA 2026-03-09
ER

PT J
AU Kartal, B
   Maalcke, WJ
   de Almeida, NM
   Cirpus, I
   Gloerich, J
   Geerts, W
   den Camp, HJMO
   Harhangi, HR
   Janssen-Megens, EM
   Francoijs, KJ
   Stunnenberg, HG
   Keltjens, JT
   Jetten, MSM
   Strous, M
AF Kartal, Boran
   Maalcke, Wouter J.
   de Almeida, Naomi M.
   Cirpus, Irina
   Gloerich, Jolein
   Geerts, Wim
   den Camp, Huub J. M. Op
   Harhangi, Harry R.
   Janssen-Megens, Eva M.
   Francoijs, Kees-Jan
   Stunnenberg, Hendrik G.
   Keltjens, Jan T.
   Jetten, Mike S. M.
   Strous, Marc
TI Molecular mechanism of anaerobic ammonium oxidation
SO NATURE
LA English
DT Article
ID assisted-laser-desorption/ionization; hydrazine-oxidizing enzyme; nitric-oxide; nitrosomonas-europaea; anammox bacterium; polyacrylamide-gels; mass-spectrometry; multiheme protein; microorganisms; monooxygenase
AB Two distinct microbial processes, denitrification and anaerobic ammonium oxidation (anammox), are responsible for the release of fixed nitrogen as dinitrogen gas (N(2)) to the atmosphere(1-4). Denitrification has been studied for over 100 years and its intermediates and enzymes are well known(5). Even though anammox is a key biogeochemical process of equal importance, its molecular mechanism is unknown, but it was proposed to proceed through hydrazine (N(2)H(4))(6,7). Here we show that N(2)H(4) is produced from the anammox substrates ammonium and nitrite and that nitric oxide (NO) is the direct precursor of N(2)H(4). We resolved the genes and proteins central to anammox metabolism and purified the key enzymes that catalyse N(2)H(4) synthesis and its oxidation to N(2). These results present a new biochemical reaction forging an N-N bond and fill a lacuna in our understanding of the biochemical synthesis of the N(2) in the atmosphere. Furthermore, they reinforce the role of nitric oxide in the evolution of the nitrogen cycle.
C1 [Kartal, Boran; Maalcke, Wouter J.; de Almeida, Naomi M.; Cirpus, Irina; Geerts, Wim; den Camp, Huub J. M. Op; Harhangi, Harry R.; Keltjens, Jan T.; Jetten, Mike S. M.; Strous, Marc] Radboud Univ Nijmegen, Dept Microbiol, Inst Water & Wetland Res, NL-6525 AJ Nijmegen, Netherlands.
   [Gloerich, Jolein] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Nijmegen Prote Facil,Dept Lab Med, NL-6500 HB Nijmegen, Netherlands.
   [Janssen-Megens, Eva M.; Francoijs, Kees-Jan; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Dept Mol Biol, Nijmegen Ctr Mol Life Sci, NL-6525 GA Nijmegen, Netherlands.
   [Jetten, Mike S. M.] Delft Univ Technol, Dept Biotechnol, NL-2628 BC Delft, Netherlands.
   [Strous, Marc] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
C3 Radboud University Nijmegen; Radboud University Nijmegen; Radboud University Nijmegen; Delft University of Technology; Max Planck Society
RP Kartal, B (corresponding author), Radboud Univ Nijmegen, Dept Microbiol, Inst Water & Wetland Res, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.
EM kartal@science.ru.nl
FU Dutch Foundation for Applied Research [05987]; Darwin Center for Biogeosciences [142161201]; Netherlands Organization for Scientific Research [81802015]; European Research Council [242635]; ERC [232987]; European Research Council (ERC) [242635] Funding Source: European Research Council (ERC)
NR 41
TC 757
Z9 929
U1 45
U2 1584
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 127
EP U159
DI 10.1038/nature10453
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600045
PM 21964329
DA 2026-03-09
ER

PT J
AU Baughman, JM
   Perocchi, F
   Girgis, HS
   Plovanich, M
   Belcher-Timme, CA
   Sancak, Y
   Bao, XR
   Strittmatter, L
   Goldberger, O
   Bogorad, RL
   Koteliansky, V
   Mootha, VK
AF Baughman, Joshua M.
   Perocchi, Fabiana
   Girgis, Hany S.
   Plovanich, Molly
   Belcher-Timme, Casey A.
   Sancak, Yasemin
   Bao, X. Robert
   Strittmatter, Laura
   Goldberger, Olga
   Bogorad, Roman L.
   Koteliansky, Victor
   Mootha, Vamsi K.
TI Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
SO NATURE
LA English
DT Article
ID rat kidney mitochondria; oxidative-phosphorylation; rnai therapeutics; protein topology; transport; delivery; respiration; inhibition; library; complex
AB Mitochondria from diverse organisms are capable of transporting large amounts of Ca(2+) via a ruthenium-red-sensitive, membrane-potential-dependent mechanism called the uniporter(1-4). Although the uniporter's biophysical properties have been studied extensively, its molecular composition remains elusive. We recently used comparative proteomics to identify MICU1 (also known as CBARA1), an EF-hand-containing protein that serves as a putative regulator of the uniporter(5). Here, we use whole-genome phylogenetic profiling, genome-wide RNA co-expression analysis and organelle-wide protein coexpression analysis to predict proteins functionally related to MICU1. All three methods converge on a novel predicted transmembrane protein, CCDC109A, that we now call 'mitochondrial calcium uniporter' (MCU). MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU in cultured cells or in vivo in mouse liver severely abrogates mitochondrial Ca(2+) uptake, whereas mitochondrial respiration and membrane potential remain fully intact. MCU has two predicted transmembrane helices, which are separated by a highly conserved linker facing the intermembrane space. Acidic residues in this linker are required for its full activity. However, an S259A point mutation retains function but confers resistance to Ru360, the most potent inhibitor of the uniporter. Our genomic, physiological, biochemical and pharmacological data firmly establish MCU as an essential component of the mitochondrial Ca(2+) uniporter.
C1 [Baughman, Joshua M.; Perocchi, Fabiana; Girgis, Hany S.; Plovanich, Molly; Belcher-Timme, Casey A.; Sancak, Yasemin; Bao, X. Robert; Strittmatter, Laura; Goldberger, Olga; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
   [Baughman, Joshua M.; Perocchi, Fabiana; Girgis, Hany S.; Plovanich, Molly; Belcher-Timme, Casey A.; Sancak, Yasemin; Bao, X. Robert; Strittmatter, Laura; Goldberger, Olga; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
   [Baughman, Joshua M.; Perocchi, Fabiana; Girgis, Hany S.; Plovanich, Molly; Belcher-Timme, Casey A.; Sancak, Yasemin; Bao, X. Robert; Strittmatter, Laura; Goldberger, Olga; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Baughman, Joshua M.; Perocchi, Fabiana; Girgis, Hany S.; Plovanich, Molly; Belcher-Timme, Casey A.; Sancak, Yasemin; Bao, X. Robert; Strittmatter, Laura; Goldberger, Olga; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA.
   [Bogorad, Roman L.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Koteliansky, Victor] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Alnylam Pharmaceuticals
RP Mootha, VK (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
EM vamsi@hms.harvard.edu
FU National Science Foundation; National Institutes of Health [GM0077465, DK080261]
NR 28
TC 1560
Z9 1778
U1 6
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 AUG 18
PY 2011
VL 476
IS 7360
BP 341
EP U111
DI 10.1038/nature10234
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500040
PM 21685886
DA 2026-03-09
ER

PT J
AU Gong, CG
   Maquat, LE
AF Gong, Chenguang
   Maquat, Lynne E.
TI lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements
SO NATURE
LA English
DT Article
ID thermodynamic parameters; noncoding rnas; expression; prediction; database; repeats; binding; protein; impact
AB Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3'-untranslated regions (39 UTRs) bind to STAU1, a protein that binds to double-stranded RNA(1,2). Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex(2). However, we were unable to identify comparable structures in the 3' UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3' UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements(3-5). Not all mRNAs that contain an Alu element in the 3' UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs).
C1 [Gong, Chenguang; Maquat, Lynne E.] Univ Rochester, Ctr RNA Biol, Rochester, NY 14642 USA.
   [Gong, Chenguang; Maquat, Lynne E.] Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA.
C3 University of Rochester; University of Rochester
RP Maquat, LE (corresponding author), Univ Rochester, Ctr RNA Biol, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM lynne_maquat@urmc.rochester.edu
FU National Institutes of Health [GM074593]; Elon Huntington Hooker Graduate Student Fellowship; National Institute of General Medical Sciences [R37GM074593] Funding Source: NIH RePORTER
NR 23
TC 1040
Z9 1261
U1 0
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 FEB 10
PY 2011
VL 470
IS 7333
BP 284
EP +
DI 10.1038/nature09701
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200049
PM 21307942
DA 2026-03-09
ER

PT J
AU McLellan, JS
   Pancera, M
   Carrico, C
   Gorman, J
   Julien, JP
   Khayat, R
   Louder, R
   Pejchal, R
   Sastry, M
   Dai, KF
   O'Dell, S
   Patel, N
   Shahzad-ul-Hussan, S
   Yang, YP
   Zhang, BS
   Zhou, TQ
   Zhu, J
   Boyington, JC
   Chuang, GY
   Diwanji, D
   Georgiev, I
   Do Kwon, Y
   Lee, D
   Louder, MK
   Moquin, S
   Schmidt, SD
   Yang, ZY
   Bonsignori, M
   Crump, JA
   Kapiga, SH
   Sam, NE
   Haynes, BF
   Burton, DR
   Koff, WC
   Walker, LM
   Phogat, S
   Wyatt, R
   Orwenyo, J
   Wang, LX
   Arthos, J
   Bewley, CA
   Mascola, JR
   Nabel, GJ
   Schief, WR
   Ward, AB
   Wilson, IA
   Kwong, PD
AF McLellan, Jason S.
   Pancera, Marie
   Carrico, Chris
   Gorman, Jason
   Julien, Jean-Philippe
   Khayat, Reza
   Louder, Robert
   Pejchal, Robert
   Sastry, Mallika
   Dai, Kaifan
   O'Dell, Sijy
   Patel, Nikita
   Shahzad-ul-Hussan, Syed
   Yang, Yongping
   Zhang, Baoshan
   Zhou, Tongqing
   Zhu, Jiang
   Boyington, Jeffrey C.
   Chuang, Gwo-Yu
   Diwanji, Devan
   Georgiev, Ivelin
   Do Kwon, Young
   Lee, Doyung
   Louder, Mark K.
   Moquin, Stephanie
   Schmidt, Stephen D.
   Yang, Zhi-Yong
   Bonsignori, Mattia
   Crump, John A.
   Kapiga, Saidi H.
   Sam, Noel E.
   Haynes, Barton F.
   Burton, Dennis R.
   Koff, Wayne C.
   Walker, Laura M.
   Phogat, Sanjay
   Wyatt, Richard
   Orwenyo, Jared
   Wang, Lai-Xi
   Arthos, James
   Bewley, Carole A.
   Mascola, John R.
   Nabel, Gary J.
   Schief, William R.
   Ward, Andrew B.
   Wilson, Ian A.
   Kwong, Peter D.
TI Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
SO NATURE
LA English
DT Article
ID envelope glycoproteins; potent neutralization; dextran sulfate; immunodeficiency; epitope; software; binding; region; crystallization; architecture
AB Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded beta-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.
C1 [McLellan, Jason S.; Pancera, Marie; Gorman, Jason; Louder, Robert; Sastry, Mallika; Dai, Kaifan; O'Dell, Sijy; Shahzad-ul-Hussan, Syed; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Zhu, Jiang; Boyington, Jeffrey C.; Chuang, Gwo-Yu; Georgiev, Ivelin; Do Kwon, Young; Lee, Doyung; Louder, Mark K.; Moquin, Stephanie; Schmidt, Stephen D.; Yang, Zhi-Yong; Mascola, John R.; Nabel, Gary J.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Carrico, Chris; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Julien, Jean-Philippe; Khayat, Reza; Pejchal, Robert; Diwanji, Devan; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Julien, Jean-Philippe; Khayat, Reza; Pejchal, Robert; Diwanji, Devan; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Patel, Nikita; Arthos, James] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Shahzad-ul-Hussan, Syed; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
   [Crump, John A.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.
   [Crump, John A.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [Crump, John A.; Sam, Noel E.] Tumaini Univ, Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
   [Crump, John A.; Sam, Noel E.] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania.
   [Kapiga, Saidi H.; Sam, Noel E.] Kilimanjaro Reprod Hlth Programme, Moshi, Tanzania.
   [Wyatt, Richard] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, TSRI, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA.
   [Koff, Wayne C.; Phogat, Sanjay] IAVI, New York, NY 10004 USA.
   [Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
   [Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Washington; University of Washington Seattle; Scripps Research Institute; Scripps Research Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Duke University; Duke University; Duke University; Kilimanjaro Christian Medical Centre; Scripps Research Institute; International AIDS Vaccine Initiative; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; International AIDS Vaccine Initiative; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore
RP Kwong, PD (corresponding author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
FU National Institutes of Health (NIH); International AIDS Vaccine Initiative; Ragon Institute; Canadian Institute of Health Research; NIH through the National Center for Research Resources [RR017573]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Institute of Allergy and Infectious Diseases [ZIAAI000883, ZIAAI005022] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases; NIH Office of the Director [ZIADK032103] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Allergy and Infectious Diseases [ZIAAI005095] Funding Source: NIH RePORTER
NR 69
TC 711
Z9 907
U1 1
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 336
EP U86
DI 10.1038/nature10696
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000044
PM 22113616
DA 2026-03-09
ER

PT J
AU Choudhury, N
   Walizer, L
   Lisenkov, S
   Bellaiche, L
AF Choudhury, Narayani
   Walizer, Laura
   Lisenkov, Sergey
   Bellaiche, L.
TI Geometric frustration in compositionally modulated ferroelectrics
SO NATURE
LA English
DT Article
ID cholesteric blue phase; superconductivity; superlattices; multiferroics; curvature; diagrams; glasses; physics; oxides; state
AB Geometric frustration is a broad phenomenon that results from an intrinsic incompatibility between some fundamental interactions and the underlying lattice geometry(1-7). Geometric frustration gives rise to new fundamental phenomena and is known to yield intriguing effects such as the formation of exotic states like spin ice, spin liquids and spin glasses(1-17). It has also led to interesting findings of fractional charge quantization and magnetic monopoles(5,6). Mechanisms related to geometric frustration have been proposed to understand the origins of relaxor and multiferroic behaviour, colossal magneto-capacitive coupling, and unusual and novel mechanisms of high-transition-temperature superconductivity(3-5,12,16). Although geometric frustration has been particularly well studied in magnetic systems in the past 20 years or so, its manifestation in the important class formed by ferroelectric materials (which are compounds with electric rather than magnetic dipoles) is basically unknown. Here we show, using a technique based on first principles, that compositionally graded ferroelectrics possess the characteristic 'fingerprints' associated with geometric frustration. These systems have a highly degenerate energy surface and display critical phenomena. They further reveal exotic orderings with novel stripe phases involving complex spatial organization. These stripes display spiral states, topological defects and curvature. Compositionally graded ferroelectrics can thus be considered the 'missing link' that brings ferroelectrics into the broad category of materials able to exhibit geometric frustration. Our ab initio calculations allow deep microscopic insight into this novel geometrically frustrated system.
C1 [Choudhury, Narayani; Bellaiche, L.] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA.
   [Walizer, Laura] Engineer Res & Dev Ctr, Vicksburg, MS 39180 USA.
   [Lisenkov, Sergey] Univ S Florida, Dept Phys, Tampa, FL 33620 USA.
C3 University of Arkansas System; University of Arkansas Fayetteville; United States Department of Defense; United States Army; U.S. Army Corps of Engineers; U.S. Army Engineer Research & Development Center (ERDC); State University System of Florida; University of South Florida
RP Choudhury, N (corresponding author), Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA.
EM narayani@uark.edu
FU US National Science Foundation; Office of Naval Research; Department of Energy; Direct For Computer & Info Scie & Enginr; Division Of Computer and Network Systems [0959124] Funding Source: National Science Foundation; Office Of The Director; EPSCoR [0918970] Funding Source: National Science Foundation
NR 30
TC 77
Z9 86
U1 1
U2 192
PU 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 24
PY 2011
VL 470
IS 7335
BP 513
EP 517
DI 10.1038/nature09752
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900037
PM 21307851
DA 2026-03-09
ER

PT J
AU Naoz, S
   Farr, WM
   Lithwick, Y
   Rasio, FA
   Teyssandier, J
AF Naoz, Smadar
   Farr, Will M.
   Lithwick, Yoram
   Rasio, Frederic A.
   Teyssandier, Jean
TI Hot Jupiters from secular planet-planet interactions
SO NATURE
LA English
DT Article
ID tidal friction; star systems; evolution; eccentricity; binary; perturbations; scattering; migration; orbits; cygni
AB About 25 per cent of 'hot Jupiters' (extrasolar Jovian-mass planets with close-in orbits) are actually orbiting counter to the spin direction of the star(1). Perturbations from a distant binary star companion(2,3) can produce high inclinations, but cannot explain orbits that are retrograde with respect to the total angular momentum of the system. Such orbits in a stellar context can be produced through secular (that is, long term) perturbations in hierarchical triple-star systems. Here we report a similar analysis of planetary bodies, including both octupole-order effects and tidal friction, and find that we can produce hot Jupiters in orbits that are retrograde with respect to the total angular momentum. With distant stellar mass perturbers, such an outcome is not possible(2,3). With planetary perturbers, the inner orbit's angular momentum component parallel to the total angular momentum need not be constant(4). In fact, as we show here, it can even change sign, leading to a retrograde orbit. A brief excursion to very high eccentricity during the chaotic evolution of the inner orbit allows planet-star tidal interactions to rapidly circularize that orbit, decoupling the planets and forming a retrograde hot Jupiter.
C1 [Naoz, Smadar; Farr, Will M.; Lithwick, Yoram; Rasio, Frederic A.; Teyssandier, Jean] Northwestern Univ, CIERA, Evanston, IL 60208 USA.
C3 Northwestern University
RP Naoz, S (corresponding author), Northwestern Univ, CIERA, Evanston, IL 60208 USA.
EM snaoz@northwestern.edu
FU Gruber Foundation; Weizmann Institute of Science; NSF MRI
NR 29
TC 435
Z9 491
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 MAY 12
PY 2011
VL 473
IS 7346
BP 187
EP 189
DI 10.1038/nature10076
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200032
PM 21562558
DA 2026-03-09
ER

PT J
AU Schroeder, BO
   Wu, ZH
   Nuding, S
   Groscurth, S
   Marcinowski, M
   Beisner, J
   Buchner, J
   Schaller, M
   Stange, EF
   Wehkamp, J
AF Schroeder, Bjoern O.
   Wu, Zhihong
   Nuding, Sabine
   Groscurth, Sandra
   Marcinowski, Moritz
   Beisner, Julia
   Buchner, Johannes
   Schaller, Martin
   Stange, Eduard F.
   Wehkamp, Jan
TI Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1
SO NATURE
LA English
DT Article
ID single-nucleotide polymorphisms; immune-responses; peptides; thioredoxin; association; beta-defensin-1; disease; assays; colon
AB Human epithelia are permanently challenged by bacteria and fungi, including commensal and pathogenic microbiota(1,2). In the gut, the fraction of strict anaerobes increases from proximal to distal, reaching 99% of bacterial species in the colon(3). At colonic mucosa, oxygen partial pressure is below 25% of airborne oxygen content, moreover microbial metabolism causes reduction to a low redox potential of -200 mV to -300 mV in the colon(4). Defensins, characterized by three intramolecular disulphide-bridges, are key effector molecules of innate immunity that protect the host from infectious microbes and shape the composition of microbiota at mucosal surfaces(5-8). Human beta-defensin 1 (hBD-1) is one of the most prominent peptides of its class but despite ubiquitous expression by all human epithelia, comparison with other defensins suggested only minor antibiotic killing activity(9,10). Whereas much is known about the activity of antimicrobial peptides in aerobic environments, data about reducing environments are limited. Herein we show that after reduction of disulphide-bridges hBD-1 becomes a potent antimicrobial peptide against the opportunistic pathogenic fungus Candida albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species. Reduced hBD-1 differs structurally from oxidized hBD-1 and free cysteines in the carboxy terminus seem important for the bactericidal effect. In vitro, the thioredoxin (TRX) system(11) is able to reduce hBD-1 and TRX co-localizes with reduced hBD-1 in human epithelia. Hence our study indicates that reduced hBD-1 shields the healthy epithelium against colonisation by commensal bacteria and opportunistic fungi. Accordingly, an intimate interplay between redox-regulation and innate immune defence seems crucial for an effective barrier protecting human epithelia.
C1 [Schroeder, Bjoern O.; Nuding, Sabine; Beisner, Julia; Wehkamp, Jan] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
   [Schroeder, Bjoern O.; Nuding, Sabine; Beisner, Julia; Wehkamp, Jan] Univ Tubingen, D-72076 Tubingen, Germany.
   [Wu, Zhihong] Univ Hosp Schleswig Holstein, Dept Dermatol, D-24105 Kiel, Germany.
   [Groscurth, Sandra] Max Planck Inst Dev Biol, Dept Prot Evolut 1, D-72076 Tubingen, Germany.
   [Marcinowski, Moritz; Buchner, Johannes] Tech Univ Munich, Dept Chem, Ctr Integrated Prot Sci Munich, D-85747 Garching, Germany.
   [Schaller, Martin] Univ Tubingen Hosp, Dept Dermatol, D-72076 Tubingen, Germany.
   [Stange, Eduard F.; Wehkamp, Jan] Robert Bosch Krankenhaus, Dept Internal Med 1, D-70376 Stuttgart, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; University of Kiel; Schleswig Holstein University Hospital; Max Planck Society; Technical University of Munich; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Bosch; Robert Bosch Krankenhaus
RP Wehkamp, J (corresponding author), Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
EM jan.wehkamp@ikp-stuttgart.de
FU Deutsche Forschungsgemeinschaft [WE 436/1-1, SCH 897/1-3, SFB685]; Robert-Bosch Foundation (Stuttgart, Germany)
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   Tollin M, 2003, PEPTIDES, V24, P523, DOI 10.1016/S0196-9781(03)00114-1
   Wilson M, 2005, MICROBIAL INHABITANT, V0, P251
   Wu Z, 2011, PROTOCOL EXCHANGE, V0, P0, DOI DOI 10.1038/protex.2010.205
   Zasloff M, 2002, NATURE, V415, P389, DOI 10.1038/415389a
NR 32
TC 383
Z9 447
U1 1
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 JAN 20
PY 2011
VL 469
IS 7330
BP 419
EP +
DI 10.1038/nature09674
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600057
PM 21248850
DA 2026-03-09
ER

PT J
AU Fischer, G
   Kurth, WS
   Gurnett, DA
   Zarka, P
   Dyudina, UA
   Ingersoll, AP
   Ewald, SP
   Porco, CC
   Wesley, A
   Go, C
   Delcroix, M
AF Fischer, G.
   Kurth, W. S.
   Gurnett, D. A.
   Zarka, P.
   Dyudina, U. A.
   Ingersoll, A. P.
   Ewald, S. P.
   Porco, C. C.
   Wesley, A.
   Go, C.
   Delcroix, M.
TI A giant thunderstorm on Saturn
SO NATURE
LA English
DT Article
ID cassini imaging science; atmosphere; ionosphere; voyager-1; features; motions; radio; storm; water; model
AB Lightning discharges in Saturn's atmosphere emit radio waves(1) with intensities about 10,000 times stronger than those of their terrestrial counterparts(2). These radio waves are the characteristic features of lightning from thunderstorms on Saturn, which last for days to months(2). Convective storms about 2,000 kilometres in size have been observed in recent years at planetocentric latitude 35 degrees south(3-5) (corresponding to a planetographic latitude of 41 degrees south). Here we report observations of a giant thunderstorm at planetocentric latitude 35 degrees north that reached a latitudinal extension of 10,000 kilometres-comparable in size to a 'Great White Spot'(6,7)-about three weeks after it started in early December 2010. The visible plume consists of high-altitude clouds that overshoot the outermost ammonia cloud layer owing to strong vertical convection, as is typical for thunderstorms. The flash rates of this storm are about an order of magnitude higher than previous ones, and peak rates larger than ten per second were recorded. This main storm developed an elongated eastward tail with additional but weaker storm cells that wrapped around the whole planet by February 2011. Unlike storms on Earth, the total power of this storm is comparable to Saturn's total emitted power. The appearance of such storms in the northern hemisphere could be related to the change of seasons(7), given that Saturn experienced vernal equinox in August 2009.
C1 [Fischer, G.] Austrian Acad Sci, Space Res Inst, A-8042 Graz, Austria.
   [Kurth, W. S.; Gurnett, D. A.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
   [Zarka, P.] Observ Paris, F-92195 Meudon, France.
   [Dyudina, U. A.; Ingersoll, A. P.; Ewald, S. P.] CALTECH, Pasadena, CA 91125 USA.
   [Porco, C. C.] Space Sci Inst, Cassini Imaging Cent Lab Operat, Boulder, CO 80301 USA.
   [Go, C.] Univ San Carlos, Dept Phys, Cebu 6000, Philippines.
   [Delcroix, M.] Soc Astron France, Commiss Observat Planetaires, F-31170 Tournefeuilee, France.
C3 Austrian Academy of Sciences; University of Iowa; Universite PSL; Observatoire de Paris; California Institute of Technology; University of San Carlos
RP Fischer, G (corresponding author), Austrian Acad Sci, Space Res Inst, Schmiedlstr 6, A-8042 Graz, Austria.
EM georg.fischer@oeaw.ac.at
FU Austrian Science Fund (FWF); NASA/JPL
CR Atreya SK, 2010, IAU SYMP P SERIES, V0, PP130, DOI 10.1017/S1743921310007349
   Baines KH, 2009, PLANET SPACE SCI, V57, P1650, DOI 10.1016/j.pss.2009.06.025
   Christian HJ, 2003, J GEOPHYS RES-ATMOS, V108, P0, DOI 10.1029/2002JD002347
   CONNERNEY JEP, 1984, NATURE, V312, P136, DOI 10.1038/312136a0
   Dyudina UA, 2010, GEOPHYS RES LETT, V37, P0, DOI 10.1029/2010GL043188
   Dyudina UA, 2007, ICARUS, V190, P545, DOI 10.1016/j.icarus.2007.03.035
   Fischer G, 2007, J GEOPHYS RES-SPACE, V112, P0, DOI 10.1029/2007JA012592
   Fischer G, 2007, ICARUS, V190, P528, DOI 10.1016/j.icarus.2007.04.002
   Fischer G, 2011, J GEOPHYS RES-SPACE, V116, P0, DOI 10.1029/2010JA016187
   Fischer G, 2008, SPACE SCI REV, V137, P271, DOI 10.1007/s11214-008-9370-z
   Gurnett DA, 2004, SPACE SCI REV, V114, P395, DOI 10.1007/s11214-004-1434-0
   HANEL RA, 1983, ICARUS, V53, P262, DOI 10.1016/0019-1035(83)90147-1
   Hueso R, 2004, ICARUS, V172, P255, DOI 10.1016/j.icarus.2004.06.010
   HUNT GE, 1982, NATURE, V297, P132, DOI 10.1038/297132a0
   Ingersoll AP, 1984, SATURN, V0, P195
   KAISER ML, 1984, J GEOPHYS RES-SPACE, V89, P2371, DOI 10.1029/JA089iA04p02371
   KAISER ML, 1983, NATURE, V303, P50, DOI 10.1038/303050a0
   Li LM, 2010, J GEOPHYS RES-PLANET, V115, P0, DOI 10.1029/2010JE003631
   Moore L, 2006, GEOPHYS RES LETT, V33, P0, DOI 10.1029/2006GL027375
   Pérez-Hoyos S, 2006, ICARUS, V180, P368, DOI 10.1016/j.icarus.2005.10.009
   Porco CC, 2004, SPACE SCI REV, V115, P363, DOI 10.1007/s11214-004-1456-7
   Porco CC, 2005, SCIENCE, V307, P1243, DOI 10.1126/science.1107691
   SANCHEZ-LAVEGA A, 1982, ICARUS, V49, P1, DOI 10.1016/0019-1035(82)90052-5
   SANCHEZLAVEGA A, 1991, NATURE, V353, P397, DOI 10.1038/353397a0
   SROMOVSKY LA, 1983, J GEOPHYS RES-SPACE, V88, P8650, DOI 10.1029/JA088iA11p08650
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   Zarka P, 1983, J GEOPHYS RES-SPACE, V88, P9007
NR 27
TC 94
Z9 102
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 7
PY 2011
VL 475
IS 7354
BP 75
EP 77
DI 10.1038/nature10205
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300047
PM 21734705
DA 2026-03-09
ER

PT J
AU Fowler, CD
   Lu, Q
   Johnson, PM
   Marks, MJ
   Kenny, PJ
AF Fowler, Christie D.
   Lu, Qun
   Johnson, Paul M.
   Marks, Michael J.
   Kenny, Paul J.
TI Habenular α5 nicotinic receptor subunit signalling controls nicotine intake
SO NATURE
LA English
DT Article
ID intracranial self-stimulation; brain reward systems; lung-cancer; interpeduncular nucleus; acetylcholine-receptors; susceptibility locus; risk; association; rats; activation
AB Genetic variation in CHRN alpha 5, the gene encoding the alpha 5 nicotinic acetylcholine receptor subunit, increases vulnerability to tobacco addiction and lung cancer, but the underlying mechanisms are unknown. Here we report markedly increased nicotine intake in mice with a null mutation in Chrn alpha 5. This effect was 'rescued' in knockout mice by re-expressing alpha 5 subunits in the medial habenula (MHb), and recapitulated in rats through alpha 5 subunit knockdown in MHb. Remarkably, alpha 5 subunit knockdown in MHb did not alter the rewarding effects of nicotine but abolished the inhibitory effects of higher nicotine doses on brain reward systems. The MHb extends projections almost exclusively to the interpeduncular nucleus (IPN). We found diminished IPN activation in response to nicotine in alpha 5 knockout mice. Further, disruption of IPN signalling increased nicotine intake in rats. Our findings indicate that nicotine activates the habenulo-interpeduncular pathway through alpha 5-containing nAChRs, triggering an inhibitory motivational signal that acts to limit nicotine intake.
C1 [Fowler, Christie D.; Lu, Qun; Johnson, Paul M.; Kenny, Paul J.] Scripps Res Inst Scripps Florida, Dept Mol Therapeut, Lab Behav & Mol Neurosci, Jupiter, FL 33458 USA.
   [Marks, Michael J.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
C3 State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; University of Colorado System; University of Colorado Boulder
RP Kenny, PJ (corresponding author), Scripps Res Inst Scripps Florida, Dept Mol Therapeut, Lab Behav & Mol Neurosci, Jupiter, FL 33458 USA.
EM pjkenny@scripps.edu
FU National Institute on Drug Abuse [DA020686, DA026693, P30DA015663]; Florida Department of Health [07KN-06]
NR 56
TC 516
Z9 587
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 597
EP 601
DI 10.1038/nature09797
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200034
PM 21278726
DA 2026-03-09
ER

PT J
AU Xu, X
   Pan, SK
   Cheng, SF
   Zhang, B
   Mu, DS
   Ni, PX
   Zhang, GY
   Yang, S
   Li, RQ
   Wang, J
   Orjeda, G
   Guzman, F
   Torres, M
   Lozano, R
   Ponce, O
   Martinez, D
   De la Cruz, G
   Chakrabarti, SK
   Patil, VU
   Skryabin, KG
   Kuznetsov, BB
   Ravin, NV
   Kolganova, TV
   Beletsky, AV
   Mardanov, AV
   Di Genova, A
   Bolser, DM
   Martin, DMA
   Li, GC
   Yang, Y
   Kuang, HH
   Hu, Q
   Xiong, XY
   Bishop, GJ
   Sagredo, B
   Mejía, N
   Zagorski, W
   Gromadka, R
   Gawor, J
   Szczesny, P
   Huang, SW
   Zhang, ZH
   Liang, CB
   He, J
   Li, Y
   He, Y
   Xu, JF
   Zhang, YJ
   Xie, BY
   Du, YC
   Qu, DY
   Bonierbale, M
   Ghislain, M
   Herrera, MD
   Giuliano, G
   Pietrella, M
   Perrotta, G
   Facella, P
   O'Brien, K
   Feingold, SE
   Barreiro, LE
   Massa, GA
   Diambra, L
   Whitty, BR
   Vaillancourt, B
   Lin, HN
   Massa, A
   Geoffroy, M
   Lundback, S
   DellaPenna, D
   Buell, CR
   Sharma, SK
   Marshall, DF
   Waugh, R
   Bryan, GJ
   Destefanis, M
   Nagy, I
   Milbourne, D
   Thomson, SJ
   Fiers, M
   Jacobs, JME
   Nielsen, KL
   Sonderkær, M
   Iovene, M
   Torres, GA
   Jiang, JM
   Veilleux, RE
   Bachem, CWB
   de Boer, J
   Borm, T
   Kloosterman, B
   van Eck, H
   Datema, E
   Hekkert, BTL
   Goverse, A
   van Ham, RCHJ
   Visser, RGF
AF Xu, Xun
   Pan, Shengkai
   Cheng, Shifeng
   Zhang, Bo
   Mu, Desheng
   Ni, Peixiang
   Zhang, Gengyun
   Yang, Shuang
   Li, Ruiqiang
   Wang, Jun
   Orjeda, Gisella
   Guzman, Frank
   Torres, Michael
   Lozano, Roberto
   Ponce, Olga
   Martinez, Diana
   De la Cruz, German
   Chakrabarti, S. K.
   Patil, Virupaksh U.
   Skryabin, Konstantin G.
   Kuznetsov, Boris B.
   Ravin, Nikolai V.
   Kolganova, Tatjana V.
   Beletsky, Alexey V.
   Mardanov, Andrei V.
   Di Genova, Alex
   Bolser, Daniel M.
   Martin, David M. A.
   Li, Guangcun
   Yang, Yu
   Kuang, Hanhui
   Hu, Qun
   Xiong, Xingyao
   Bishop, Gerard J.
   Sagredo, Boris
   Mejia, Nilo
   Zagorski, Wlodzimierz
   Gromadka, Robert
   Gawor, Jan
   Szczesny, Pawel
   Huang, Sanwen
   Zhang, Zhonghua
   Liang, Chunbo
   He, Jun
   Li, Ying
   He, Ying
   Xu, Jianfei
   Zhang, Youjun
   Xie, Binyan
   Du, Yongchen
   Qu, Dongyu
   Bonierbale, Merideth
   Ghislain, Marc
   del Rosario Herrera, Maria
   Giuliano, Giovanni
   Pietrella, Marco
   Perrotta, Gaetano
   Facella, Paolo
   O'Brien, Kimberly
   Feingold, Sergio E.
   Barreiro, Leandro E.
   Massa, Gabriela A.
   Diambra, Luis
   Whitty, Brett R.
   Vaillancourt, Brieanne
   Lin, Haining
   Massa, AliciaN.
   Geoffroy, Michael
   Lundback, Steven
   DellaPenna, Dean
   Buell, C. Robin
   Sharma, Sanjeev Kumar
   Marshall, David F.
   Waugh, Robbie
   Bryan, Glenn J.
   Destefanis, Marialaura
   Nagy, Istvan
   Milbourne, Dan
   Thomson, Susan J.
   Fiers, Mark
   Jacobs, Jeanne M. E.
   Nielsen, Kare L.
   Sonderkaer, Mads
   Iovene, Marina
   Torres, Giovana A.
   Jiang, Jiming
   Veilleux, Richard E.
   Bachem, Christian W. B.
   de Boer, Jan
   Borm, Theo
   Kloosterman, Bjorn
   van Eck, Herman
   Datema, Erwin
   Hekkert, Bas Te Lintel
   Goverse, Aska
   van Ham, Roeland C. H. J.
   Visser, Richard G. F.
TI Genome sequence and analysis of the tuber crop potato
SO NATURE
LA English
DT Article
ID eukaryotic genm; resistance genes; in-vitro; rna-seq; solanum; tool; identification; elements; reveals; maize
AB Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.
C1 [Huang, Sanwen; Zhang, Zhonghua; Liang, Chunbo; He, Jun; Li, Ying; He, Ying; Xu, Jianfei; Zhang, Youjun; Xie, Binyan; Du, Yongchen; Qu, Dongyu] Chinese Acad Agr Sci, Key Lab Hort Crops Genet Improvement, Sino Dutch Joint Lab Hort Genom, Inst Vegetables & Flowers,Minist Agr, Beijing 100081, Peoples R China.
   [Xu, Xun; Pan, Shengkai; Cheng, Shifeng; Zhang, Bo; Mu, Desheng; Ni, Peixiang; Zhang, Gengyun; Yang, Shuang; Li, Ruiqiang; Wang, Jun] Chinese Minist Agr, Key Lab Genom, BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Orjeda, Gisella; Guzman, Frank; Torres, Michael; Lozano, Roberto; Ponce, Olga; Martinez, Diana; De la Cruz, German] Cayetano Heredia Univ, Genom Res Unit, Lima 13, Peru.
   [Orjeda, Gisella; Guzman, Frank; Torres, Michael; Lozano, Roberto; Ponce, Olga; Martinez, Diana; De la Cruz, German] San Cristobal Huamanga Univ, Biotechnol & Plant Genet Lab, Ayacucho, Peru.
   [Chakrabarti, S. K.; Patil, Virupaksh U.] Cent Potato Res Inst, Shimla 171001, Himachal Prades, India.
   [Skryabin, Konstantin G.; Kuznetsov, Boris B.; Ravin, Nikolai V.; Kolganova, Tatjana V.; Beletsky, Alexey V.; Mardanov, Andrei V.] Ctr Bioengn RAS, Moscow 117312, Russia.
   [Di Genova, Alex] Univ Chile, UMI CNRS 2807, Ctr Genome Regulat, CGR CMM, Santiago, Chile.
   [Di Genova, Alex] Univ Chile, UMI CNRS 2807, Ctr Math Modeling, Santiago, Chile.
   [Bolser, Daniel M.; Martin, David M. A.] Univ Dundee, Coll Life Sci, Dundee DD1 5EH, Scotland.
   [Li, Guangcun; Yang, Yu] Shandong Acad Agr Sci, High Technol Res Ctr, Jinan 250100, Peoples R China.
   [Kuang, Hanhui; Hu, Qun] Huazhong Agr Univ, Minist Educ, Coll Hort & Forestry, Dept Vegetable Crops,Key Lab Hort Biol, Wuhan 430070, Peoples R China.
   [Xiong, Xingyao] Hunan Agr Univ, Coll Hort & Landscape, Changsha 410128, Hunan, Peoples R China.
   [Bishop, Gerard J.] Univ London Imperial Coll Sci Technol & Med, Div Biol, London SW7 1AZ, England.
   [Sagredo, Boris; Mejia, Nilo] Inst Invest Agropecuarias, Sector Los Choapinos, Rengo 2940000, Region Libertad, Chile.
   [Zagorski, Wlodzimierz; Gromadka, Robert; Gawor, Jan; Szczesny, Pawel] PAS, DNA Sequencing & Oligonucleotides Synth Lab, Inst Biochem & Biophys, PL-02106 Warsaw, Poland.
   [Bonierbale, Merideth; Ghislain, Marc; del Rosario Herrera, Maria] Int Potato Ctr, Lima 12, Peru.
   [Giuliano, Giovanni; Pietrella, Marco; Perrotta, Gaetano; Facella, Paolo] Italian Natl Agcy New Technol, Energy & Sustainable Dev ENEA, Casaccia Res Ctr, I-00123 Rome, Italy.
   [Giuliano, Giovanni; Pietrella, Marco; Perrotta, Gaetano; Facella, Paolo] Trisaia Res Ctr, I-75026 Rotondella, Matera, Italy.
   [O'Brien, Kimberly] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Feingold, Sergio E.; Barreiro, Leandro E.; Massa, Gabriela A.] INTA, Estn Expt Agropecuaria Balcarce, Lab Agrobiotecnol, RA-7620 Balcarce, Argentina.
   [Diambra, Luis] Univ Nacl LaPlata, CREG, Lab Biol Sistemas, RA-1888 La Plata, Argentina.
   [Vaillancourt, Brieanne; Lin, Haining; Massa, AliciaN.; Geoffroy, Michael; Lundback, Steven; DellaPenna, Dean; Buell, C. Robin] Michigan State Univ, E Lansing, MI 48824 USA.
   [Sharma, Sanjeev Kumar; Marshall, David F.; Waugh, Robbie; Bryan, Glenn J.] Scottish Crop Res Inst, Genet Programme, Dundee DD2 5DA, Scotland.
   [Destefanis, Marialaura; Nagy, Istvan; Milbourne, Dan] Teagasc Crops Res Ctr, Oak Pk, Carlow, Ireland.
   [Thomson, Susan J.; Fiers, Mark; Jacobs, Jeanne M. E.] New Zealand Inst Plant & Food Res Ltd, Christchurch 8140, New Zealand.
   [Nielsen, Kare L.; Sonderkaer, Mads] Aalborg Univ, AAU, Dept Biotechnol Chem & Environm Engn, DK-9000 Aalborg, Denmark.
   [Iovene, Marina; Torres, Giovana A.; Jiang, Jiming] Univ Wisconsin, Dept Hort, Madison, WI 53706 USA.
   [Veilleux, Richard E.] Virginia Polytech Inst & State Univ, Dept Hort, Blacksburg, VA 24061 USA.
   [Bachem, Christian W. B.; de Boer, Jan; Borm, Theo; Kloosterman, Bjorn; Visser, Richard G. F.] Univ Wageningen & Res Ctr, Dept Plant Sci, Lab Plant Breeding, NL-6708 PB Wageningen, Netherlands.
   [Goverse, Aska; van Ham, Roeland C. H. J.; Visser, Richard G. F.] Ctr BioSyst Genom, NL-6708 PB Wageningen, Netherlands.
   [Goverse, Aska] Univ Wageningen & Res Ctr, Dept Plant Sci, Nematol Lab, NL-6708 PB Wageningen, Netherlands.
C3 Chinese Academy of Agricultural Sciences; Institute of Vegetables & Flowers, CAAS; Beijing Genomics Institute (BGI); Universidad Peruana Cayetano Heredia; Universidad Nacional De San Cristobal De Huamanga; Indian Council of Agricultural Research (ICAR); ICAR - Central Potato Research Institute; Russian Academy of Sciences; Research Center of Biotechnology RAS; Universidad de Chile; Universidad de Chile; University of Dundee; Shandong Academy of Agricultural Sciences; Huazhong Agricultural University; Hunan Agricultural University; Imperial College London; Instituto de Investigacion Agropecuaria (INIA); Polish Academy of Sciences; Institute of Biochemistry & Biophysics - Polish Academy of Sciences; CGIAR; International Potato Center (CIP); Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development; J. Craig Venter Institute; Instituto Nacional de Tecnologia Agropecuaria (INTA); National University of La Plata; Michigan State University; James Hutton Institute; Teagasc; New Zealand Institute for Plant & Food Research Ltd; Aalborg University; University of Wisconsin System; University of Wisconsin Madison; Virginia Polytechnic Institute & State University; Wageningen University & Research; Centre for BioSystems Genomics; Wageningen University & Research
RP Huang, SW (corresponding author), Chinese Acad Agr Sci, Key Lab Hort Crops Genet Improvement, Sino Dutch Joint Lab Hort Genom, Inst Vegetables & Flowers,Minist Agr, Beijing 100081, Peoples R China.
EM huangsanwen@caas.net.cn; buell@msu.edu; Richard.Visser@wur.nl
FU EU [APOPHYS EU-QLRT-2001-01849]; US Department of Agriculture National Institute of Food and Agriculture [2008-55300-04757, 2009-85606-05673]; "863'' National High Tech Research Development Program in China [2006AA100107]; "973'' National Key Basic Research Program in China [2006CB101904, 2007CB815703, 2007CB815705, 2009CB119000]; Board of Wageningen University and Research Centre; CAPES Brazilian Ministry of Education; Chinese Academy of Agricultural Sciences; Chinese Ministry of Agriculture; Chinese Ministry of Finance [1251610601001]; Chinese Ministry of Science and Technology [2007DFB30080]; China Postdoctoral Science Foundation [20070420446]; CONICET (Argentina); DAFF Research Stimulus Fund [07-567]; CONICYT-Chile [PBCT-PSD-03]; Danish Council for Strategic Research Programme Commission on Health, Food and Welfare [2101-07-0116]; Danish Council for Strategic Research Programme Commission on Strategic Growth Technologies [2106-07-0021]; FINCyT [099-FINCyT-EQUIP-2009, 076-FINCyT-PIN-2008]; Prestamo BID [1663/OC-PE]; Fund for Economic Structural Support (FES); HarvestPlus Challenge Program; Indian Council of Agricultural Research; INIA-Ministry of Agriculture of Chile; Instituto Nacional de Innovacion Agraria-Ministry of Agriculture of Peru; Instituto Nacional de Tecnologia Agropecuaria (INTA); Italian Ministry of Research (Special Fund for Basic Research); International Potato Center; LBMG of Center for Genome Regulation and Center for Mathematical Modeling; Universidad de Chile [UMI 2807 CNRS]; Ministry of Education and Science of Russia [02.552.11.7073]; National Nature Science Foundation of China [30671319, 30725008, 30890032, 30971995]; Natural Science Foundation of Shandong Province in China [Y2006D21]; Netherlands Technology Foundation (STW); Netherlands Genomics Initiative (NGI); Netherlands Ministries of Economic Affairs (EZ) and Agriculture (LNV); New Zealand Institute for Crop & Food Research Ltd Strategic Science Initiative; Perez Guerrero Fund; Peruvian Ministry of Agriculture-Technical Secretariat of coordination; CGIAR; Peruvian National Council of Science and Technology (CONCYTEC); Polish Ministry of Science and Higher Education [47/PGS/2006/01]; Programa Cooperativo para el Desarrollo Tecnologico Agroalimentario y Agroindustrial del Cono Sur (PROCISUR); Project Programa Bicentenario de Ciencia y Tecnologia - Conicyt; PBCT - Conicyt [PSD-03]; Russian Foundation for Basic Research [09-04-12275]; Secretaria de Ciencia y Tecnologia (SECyT) actual Ministerio de Ciencia y Tecnologia (MINCyT), Argentina; Shenzhen Municipal Government of China [CXB200903110066A, ZYC200903240077A, ZYC200903240076A]; Solexa project [272-07-0196]; Inter-American Council for Integral Development (FEMCIDI); Teagasc; Teagasc Walsh Fellowship Scheme; New Zealand Institute for Plant & Food Research Ltd; Scottish Government Rural and Environment Research and Analysis Directorate (RERAD); Department for Environment, Food and Rural Affairs (DEFRA; Agriculture and Horticulture Development Board - Potato Council; UK Biotechnology and Biological Sciences Research Council [BB/F012640]; US National Science Foundation [DBI-0604907/DBI-0834044]; Virginia Agricultural Experiment Station USDA [135853]; Wellcome Trust [WT 083481]; BBSRC [BB/F012640/1, BB/F013280/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F012640/1, BB/F013280/1] Funding Source: researchfish
NR 57
TC 1600
Z9 1885
U1 12
U2 679
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 189
EP U94
DI 10.1038/nature10158
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500042
PM 21743474
DA 2026-03-09
ER

PT J
AU Wang, F
   Mei, ZQ
   Qi, YT
   Yan, CY
   Hu, Q
   Wang, JW
   Shi, YG
AF Wang, Feng
   Mei, Ziqing
   Qi, Yutao
   Yan, Chuangye
   Hu, Qi
   Wang, Jiawei
   Shi, Yigong
TI Structure and mechanism of the hexameric MecA-ClpC molecular machine
SO NATURE
LA English
DT Article
ID ray-diffraction data; crystal-structure; hsp100 chaperone; protein; adapter; domain; recognition; competence; complex; disaggregation
AB Regulated proteolysis by ATP-dependent proteases is universal in all living cells. Bacterial ClpC, a member of the Clp/Hsp100 family of AAA1 proteins (ATPases associated with diverse cellular activities) with two nucleotide-binding domains (D1 and D2), requires the adaptor protein MecA for activation and substrate targeting. The activated, hexameric MecA-ClpC molecular machine harnesses the energy of ATP binding and hydrolysis to unfold specific substrate proteins and translocate the unfolded polypeptide to the ClpP protease for degradation. Here we report three relatedcrystal structures: a heterodimer between MecA and the amino domain of ClpC, a heterododecamer between MecA and D2-deleted ClpC, and a hexameric complex between MecA and full-length ClpC. In conjunction with biochemical analyses, these structures reveal the organizational principles behind the hexameric MecA-ClpC complex, explain the molecular mechanisms for MecA-mediated ClpC activation and provide mechanistic insights into the function of the MecA-ClpC molecular machine. These findings have implications for related Clp/Hsp100 molecular machines.
C1 [Wang, Feng; Mei, Ziqing; Qi, Yutao; Yan, Chuangye; Hu, Qi; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Beijing 100084, Peoples R China.
   [Wang, Feng; Mei, Ziqing; Qi, Yutao; Yan, Chuangye; Hu, Qi; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University
RP Wang, JW (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Beijing 100084, Peoples R China.
EM jwwang@tsinghua.edu.cn; shi-lab@tsinghua.edu.cn
FU National Natural Science Foundation of China [30888001]; China Postdoctoral Science Foundation [023201058]
NR 49
TC 123
Z9 142
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2011
VL 471
IS 7338
BP 331
EP +
DI 10.1038/nature09780
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000035
PM 21368759
DA 2026-03-09
ER

PT J
AU Hori, M
   Sótér, A
   Barna, D
   Dax, A
   Hayano, R
   Friedreich, S
   Juhász, B
   Pask, T
   Widmann, E
   Horváth, D
   Venturelli, L
   Zurlo, N
AF Hori, Masaki
   Soter, Anna
   Barna, Daniel
   Dax, Andreas
   Hayano, Ryugo
   Friedreich, Susanne
   Juhasz, Bertalan
   Pask, Thomas
   Widmann, Eberhard
   Horvath, Dezso
   Venturelli, Luca
   Zurlo, Nicola
TI Two-photon laser spectroscopy of antiprotonic helium and the antiproton-to-electron mass ratio
SO NATURE
LA English
DT Article
ID cpt
AB Physical laws are believed to be invariant under the combined transformations of charge, parity and time reversal (CPT symmetry(1)). This implies that an antimatter particle has exactly the same mass and absolute value of charge as its particle counterpart. Metastable antiprotonic helium ((p) over bar He+) is a three-body atom(2) consisting of a normal helium nucleus, an electron in its ground state and an antiproton ((p) over bar) occupying a Rydberg state with high principal and angular momentum quantum numbers, respectively n and l, such that n approximate to l + 1 approximate to 38. These atoms are amenable to precision laser spectroscopy, the results of which can in principle be used to determine the antiproton-to-electron mass ratio and to constrain the equality between the antiproton and proton charges and masses. Here we report two-photon spectroscopy of antiprotonic helium, in which (p) over bar He-3(+) and (p) over bar He-4(+) isotopes are irradiated by two-counter-propagating laser beams. This excites nonlinear, two-photon transitions of the antiproton of the type (n, l) -> (n - 2, l - 2) at deep-ultraviolet wavelengths (lambda = 139.8, 193.0 and 197.0 nm), which partly cancel the Doppler broadening of the laser resonance caused by the thermal motion of the atoms. The resulting narrow spectral lines allowed us to measure three transition frequencies with fractional precisions of 2.3-5 parts in 10(9). By comparing the results with three-body quantum electrodynamics calculations, we derived an antiproton-to-electron mass ratio of 1,836.1526736(23), where the parenthetical error represents one standard deviation. This agrees with the proton-to-electron value known to a similar precision.
C1 [Hori, Masaki; Soter, Anna] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Hori, Masaki; Barna, Daniel; Dax, Andreas; Hayano, Ryugo] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130033, Japan.
   [Barna, Daniel; Horvath, Dezso] KFKI Res Inst Particle & Nucl Phys, H-1525 Budapest, Hungary.
   [Friedreich, Susanne; Juhasz, Bertalan; Pask, Thomas; Widmann, Eberhard] Stefan Meyer Inst Subatomare Phys, A-1090 Vienna, Austria.
   [Horvath, Dezso] Inst Nucl Res, H-4001 Debrecen, Hungary.
   [Venturelli, Luca; Zurlo, Nicola] Univ Brescia, Dipartimento Chim & Fis Ingn & Mat, I-25133 Brescia, Italy.
   [Venturelli, Luca; Zurlo, Nicola] Grp Col Brescia, Ist Nazl Fis Nucl, I-25133 Brescia, Italy.
C3 Max Planck Society; University of Tokyo; HUN-REN; HUN-REN Wigner Research Centre for Physics; Institute for Particle & Nuclear Physics - HAS; HUN-REN; HUN-REN Institute for Nuclear Research; University of Brescia; Istituto Nazionale di Fisica Nucleare (INFN)
RP Hori, M (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM masaki.hori@mpq.mpg.de
FU European Science Foundation (EURYI); Monbukagakusho [20002003]; Deutsche Forschungsgemeinschaft; Hungarian Research Foundation [K72172]; Austrian Federal Ministry of Science and Research; Grants-in-Aid for Scientific Research [20002003] Funding Source: KAKEN
NR 30
TC 155
Z9 165
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 JUL 28
PY 2011
VL 475
IS 7357
BP 484
EP 488
DI 10.1038/nature10260
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900037
PM 21796208
DA 2026-03-09
ER

PT J
AU Gardner, AS
   Moholdt, G
   Wouters, B
   Wolken, GJ
   Burgess, DO
   Sharp, MJ
   Cogley, JG
   Braun, C
   Labine, C
AF Gardner, Alex S.
   Moholdt, Geir
   Wouters, Bert
   Wolken, Gabriel J.
   Burgess, David O.
   Sharp, Martin J.
   Cogley, J. Graham
   Braun, Carsten
   Labine, Claude
TI Sharply increased mass loss from glaciers and ice caps in the Canadian Arctic Archipelago
SO NATURE
LA English
DT Article
ID elevation changes; balance; island; sheet
AB Mountain glaciers and ice caps are contributing significantly to present rates of sea level rise and will continue to do so over the next century and beyond(1-5). The Canadian Arctic Archipelago, located off the northwestern shore of Greenland, contains one-third of the global volume of land ice outside the ice sheets(6), but its contribution to sea-level change remains largely unknown. Here we show that the Canadian Arctic Archipelago has recently lost 61 +/- 7 gigatonnes per year (Gt yr(-1)) of ice, contributing 0.17 +/- 0.02 mm yr(-1) to sea-level rise. Our estimates are of regional mass changes for the ice caps and glaciers of the Canadian Arctic Archipelago referring to the years 2004 to 2009 and are based on three independent approaches: surface mass-budget modelling plus an estimate of ice discharge (SMB+D), repeat satellite laser altimetry (ICESat) and repeat satellite gravimetry (GRACE). All three approaches show consistent and large mass-loss estimates. Between the periods 2004-2006 and 2007-2009, the rate of mass loss sharply increased from 31 +/- 8 Gt yr(-1) to 92 +/- 12 Gt yr(-1) in direct response to warmer summer temperatures, to which rates of ice loss are highly sensitive (64 +/- 14 Gt yr(-1) per 1 K increase). The duration of the study is too short to establish a long-term trend, but for 2007-2009, the increase in the rate of mass loss makes the Canadian Arctic Archipelago the single largest contributor to eustatic sea-level rise outside Greenland and Antarctica.
C1 [Gardner, Alex S.; Sharp, Martin J.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Gardner, Alex S.] Univ Michigan, Dept Atmospher Ocean & Space Sci, Ann Arbor, MI 48109 USA.
   [Moholdt, Geir] Univ Oslo, Dept Geosci, N-0316 Oslo, Norway.
   [Moholdt, Geir] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
   [Wouters, Bert] Royal Netherlands Meteorol Inst, NL-3730 AE De Bilt, Netherlands.
   [Wolken, Gabriel J.] Alaska Dept Nat Resources, Div Geol & Geophys Surveys, Fairbanks, AK 99709 USA.
   [Burgess, David O.] Geol Survey Canada, Ottawa, ON K1A 0E8, Canada.
   [Cogley, J. Graham] Trent Univ, Dept Geog, Peterborough, ON K9J 7B8, Canada.
   [Braun, Carsten] Westfield State Univ, Dept Geog & Reg Planning, Westfield, MA 01086 USA.
   [Labine, Claude] Campbell Sci Canada Corp, Edmonton, AB T5M 1W7, Canada.
C3 University of Alberta; University of Michigan System; University of Michigan; University of Oslo; University of California System; University of California San Diego; Scripps Institution of Oceanography; Royal Netherlands Meteorological Institute; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; Trent University; Massachusetts System of Public Higher Education; Westfield State University
RP Gardner, AS (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
EM alexsg@umich.edu
FU NSERC Canada; Alberta Ingenuity Fund; European Union [226375]; NSERC; CFCAS through the Polar Climate Stability Network
NR 29
TC 251
Z9 293
U1 3
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 357
EP 360
DI 10.1038/nature10089
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400044
PM 21508960
DA 2026-03-09
ER

PT J
AU Min, SK
   Zhang, XB
   Zwiers, FW
   Hegerl, GC
AF Min, Seung-Ki
   Zhang, Xuebin
   Zwiers, Francis W.
   Hegerl, Gabriele C.
TI Human contribution to more-intense precipitation extremes
SO NATURE
LA English
DT Article
ID climate; temperature; model
AB Extremes of weather and climate can have devastating effects on human society and the environment(1,2). Understanding past changes in the characteristics of such events, including recent increases in the intensity of heavy precipitation events over a large part of the Northern Hemisphere land area(3-5), is critical for reliable projections of future changes. Given that atmospheric water-holding capacity is expected to increase roughly exponentially with temperature-and that atmospheric water content is increasing in accord with this theoretical expectation(6-11)-it has been suggested that human-influenced global warming may be partly responsible for increases in heavy precipitation(3,5,7). Because of the limited availability of daily observations, however, most previous studies have examined only the potential detectability of changes in extreme precipitation through model-model comparisons(12-15). Here we show that human-induced increases in greenhouse gases have contributed to the observed intensification of heavy precipitation events found over approximately two-thirds of data-covered parts of Northern Hemisphere land areas. These results are based on a comparison of observed and multi-model simulated changes in extreme precipitation over the latter half of the twentieth century analysed with an optimal fingerprinting technique. Changes in extreme precipitation projected by models, and thus the impacts of future changes in extreme precipitation, may be underestimated because models seem to underestimate the observed increase in heavy precipitation with warming(16).
C1 [Min, Seung-Ki; Zhang, Xuebin; Zwiers, Francis W.] Environm Canada, Div Climate Res, Toronto, ON M3H 5T4, Canada.
   [Hegerl, Gabriele C.] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JW, Midlothian, Scotland.
C3 Environment & Climate Change Canada; University of Edinburgh
RP Min, SK (corresponding author), Environm Canada, Div Climate Res, Toronto, ON M3H 5T4, Canada.
EM seung-ki.min@ec.gc.ca; fwzwiers@uvic.ca
FU International Detection and Attribution Group (IDAG) by the US Department of Energy's Office of Science, Office of Biological and Environmental Research; National Oceanic and Atmospheric Administration's Climate Program Office; Canadian International Polar Year (IPY) programme; NSF [ATM-0296007]; Natural Environment Research Council [ncas10009] Funding Source: researchfish
NR 30
TC 1673
Z9 1946
U1 13
U2 829
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 378
EP 381
DI 10.1038/nature09763
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100038
PM 21331039
DA 2026-03-09
ER

PT J
AU Warne, T
   Moukhametzianov, R
   Baker, JG
   Nehmé, R
   Edwards, PC
   Leslie, AGW
   Schertler, GFX
   Tate, CG
AF Warne, Tony
   Moukhametzianov, Rouslan
   Baker, Jillian G.
   Nehme, Rony
   Edwards, Patricia C.
   Leslie, Andrew G. W.
   Schertler, Gebhard F. X.
   Tate, Christopher G.
TI The structural basis for agonist and partial agonist action on a β1-adrenergic receptor
SO NATURE
LA English
DT Article
ID protein-coupled receptor; beta-adrenergic-receptors; high-affinity binding; beta(2)-adrenergic receptor; crystal-structure; ligand-binding; amino-acid; activation; crystallography; crystallization
AB beta-adrenergic receptors (beta ARs) are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline(1,2). Synthetic ligands have been developed that either activate or inhibit beta ARs for the treatment of asthma, hypertension or cardiac dysfunction. These ligands are classified as either full agonists, partial agonists or antagonists, depending on whether the cellular response is similar to that of the native ligand, reduced or inhibited, respectively. However, the structural basis for these different ligand efficacies is unknown. Here we present four crystal structures of the thermo-stabilized turkey (Meleagris gallopavo) beta(1)-adrenergic receptor (beta(1)AR-m23) bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induces a 1 angstrom contraction of the catecholamine-binding pocket relative to the antagonist bound receptor. Full agonists can form hydrogen bonds with two conserved serine residues in transmembrane helix 5 (Ser(5.42) and Ser(5.46)), but partial agonists only interact with Ser(5.42) (superscripts refer to Ballesteros-Weinstein numbering(3)). The structures provide an understanding of the pharmacological differences between different ligand classes, illuminating how GPCRs function and providing a solid foundation for the structure-based design of novel ligands with predictable efficacies.
C1 [Warne, Tony; Moukhametzianov, Rouslan; Nehme, Rony; Edwards, Patricia C.; Leslie, Andrew G. W.; Schertler, Gebhard F. X.; Tate, Christopher G.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Baker, Jillian G.] Univ Nottingham, Sch Med, Inst Cell Signalling, Queens Med Ctr, Nottingham NG7 2UH, England.
C3 MRC Laboratory Molecular Biology; University of Nottingham
RP Tate, CG (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM gebhard.schertler@psi.ch; cgt@mrc-lmb.cam.ac.uk
FU MRC; BBSRC [BB/G003653/1]; Human Frontier Science Project (HFSP) [RG/0052]; European Commission [LSH-2003-1.1.0-1]; ESRF; Wellcome Trust; BBSRC [BB/G003653/1] Funding Source: UKRI; MRC [MC_U105197215, MC_U105184325] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/G003653/1] Funding Source: researchfish; Medical Research Council [MC_U105184325, MC_U105197215] Funding Source: researchfish
NR 42
TC 543
Z9 618
U1 0
U2 138
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 241
EP 244
DI 10.1038/nature09746
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400044
PM 21228877
DA 2026-03-09
ER

PT J
AU Mühlebach, MD
   Mateo, M
   Sinn, PL
   Prüfer, S
   Uhlig, KM
   Leonard, VHJ
   Navaratnarajah, CK
   Frenzke, M
   Wong, XX
   Sawatsky, B
   Ramachandran, S
   McCray, PB
   Cichutek, K
   von Messling, V
   Lopez, M
   Cattaneo, R
AF Muhlebach, Michael D.
   Mateo, Mathieu
   Sinn, Patrick L.
   Pruefer, Steffen
   Uhlig, Katharina M.
   Leonard, Vincent H. J.
   Navaratnarajah, Chanakha K.
   Frenzke, Marie
   Wong, Xiao X.
   Sawatsky, Bevan
   Ramachandran, Shyam
   McCray, Paul B., Jr.
   Cichutek, Klaus
   von Messling, Veronika
   Lopez, Marc
   Cattaneo, Roberto
TI Adherens junction protein nectin-4 is the epithelial receptor for measles virus
SO NATURE
LA English
DT Article
ID activation molecule slam; cellular receptor; v-domain; infection; cells; member; blind
AB Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths(1,2). Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor(3-6). These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously(7). How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer(9-11), which has implications for ongoing measles-virus-based clinical trials of oncolysis(12).
C1 [Mateo, Mathieu; Leonard, Vincent H. J.; Navaratnarajah, Chanakha K.; Frenzke, Marie; Cattaneo, Roberto] Mayo Clin, Dept Mol Med, Rochester, MN 55902 USA.
   [Muhlebach, Michael D.; Pruefer, Steffen; Uhlig, Katharina M.; Cichutek, Klaus] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany.
   [Sinn, Patrick L.; Ramachandran, Shyam; McCray, Paul B., Jr.] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA.
   [Wong, Xiao X.; Sawatsky, Bevan; von Messling, Veronika] Univ Quebec, INRS, Laval, PQ H7V 1B7, Canada.
   [Wong, Xiao X.; Sawatsky, Bevan; von Messling, Veronika] Univ Quebec, Inst Armand Frappier, Laval, PQ H7V 1B7, Canada.
   [von Messling, Veronika] Duke Univ, Singapore 169857, Singapore.
   [von Messling, Veronika] Natl Univ Singapore, Singapore 169857, Singapore.
   [Lopez, Marc] CRCM, INSERM, UMR891, F-13009 Marseille, France.
   [Lopez, Marc] Univ Aix Marseille, F-13009 Marseille, France.
C3 Mayo Clinic; Paul Ehrlich Institute; University of Iowa; University of Quebec; Institut national de la recherche scientifique (INRS); University of Quebec; National University of Singapore; National University of Singapore; UNICANCER; Institut Paoli-Calmette (IPC); Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Aix-Marseille Universite
RP Cattaneo, R (corresponding author), Mayo Clin, Dept Mol Med, Rochester, MN 55902 USA.
EM Cattaneo.Roberto@mayo.edu
FU BMG [2510-FSB-705]; NIH [R01 AI063476, R01 CA090636]; Roy J. Carver Charitable Trust; Cell Culture Core and Cell Morphology Cores; Center for Gene Therapy for Cystic Fibrosis [NIH P30 DK-54759]; Cystic Fibrosis Foundation; CIHR [MOP-66989, CFI 9488]; INSERM; Institut Paoli-Calmettes; Ligue Nationale Contre le Cancer; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK054759] Funding Source: NIH RePORTER
NR 30
TC 462
Z9 541
U1 0
U2 76
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 530
EP U153
DI 10.1038/nature10639
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000062
PM 22048310
DA 2026-03-09
ER

PT J
AU Jin, K
   Butch, NP
   Kirshenbaum, K
   Paglione, J
   Greene, RL
AF Jin, K.
   Butch, N. P.
   Kirshenbaum, K.
   Paglione, J.
   Greene, R. L.
TI Link between spin fluctuations and electron pairing in copper oxide superconductors
SO NATURE
LA English
DT Article
ID temperature; transition
AB Although it is generally accepted that superconductivity is unconventional in the high-transition-temperature copper oxides, the relative importance of phenomena such as spin and charge (stripe) order, superconductivity fluctuations, proximity to a Mott insulator, a pseudogap phase and quantum criticality are still a matter of debate(1). In electron-doped copper oxides, the absence of an anomalous pseudogap phase in the underdoped region of the phase diagram(2) and weaker electron correlations(3,4) suggest that Mott physics and other unidentified competing orders are less relevant and that antiferromagnetic spin fluctuations are the dominant feature. Here we report a study of magnetotransport in thin films of the electron-doped copper oxide La2-xCexCuO4. We show that a scattering rate that is linearly dependent on temperature-a key feature of the anomalous normal state properties of the copper oxides-is correlated with the electron pairing. We also show that an envelope of such scattering surrounds the superconducting phase, surviving to zero temperature when superconductivity is suppressed by magnetic fields. Comparison with similar behaviour found in organic superconductors(5) strongly suggests that the linear dependence on temperature of the resistivity in the electron-doped copper oxides is caused by spin-fluctuation scattering.
C1 [Jin, K.; Butch, N. P.; Kirshenbaum, K.; Paglione, J.; Greene, R. L.] Univ Maryland, Ctr Nanophys Adv Mat, College Pk, MD 20742 USA.
   [Jin, K.; Butch, N. P.; Kirshenbaum, K.; Paglione, J.; Greene, R. L.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
C3 University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park
RP Greene, RL (corresponding author), Univ Maryland, Ctr Nanophys Adv Mat, College Pk, MD 20742 USA.
EM rgreene@squid.umd.edu
FU NSF [DMR-0952716, DMR-0653535]; Maryland Center for Nanophysics and Advanced Materials
NR 29
TC 193
Z9 217
U1 7
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 AUG 4
PY 2011
VL 476
IS 7358
BP 73
EP 75
DI 10.1038/nature10308
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300031
PM 21814279
DA 2026-03-09
ER

PT J
AU Koehl, WF
   Buckley, BB
   Heremans, FJ
   Calusine, G
   Awschalom, DD
AF Koehl, William F.
   Buckley, Bob B.
   Heremans, F. Joseph
   Calusine, Greg
   Awschalom, David D.
TI Room temperature coherent control of defect spin qubits in silicon carbide
SO NATURE
LA English
DT Article
ID diamond; identification; state
AB Electronic spins in semiconductors have been used extensively to explore the limits of external control over quantum mechanical phenomena(1). A long-standing goal of this research has been to identify or develop robust quantum systems that can be easily manipulated, for future use in advanced information and communication technologies(2). Recently, a point defect in diamond known as the nitrogen-vacancy centre has attracted a great deal of interest because it possesses an atomic-scale electronic spin state that can be used as an individually addressable, solid-state quantum bit (qubit), even at room temperature(3). These exceptional quantum properties have motivated efforts to identify similar defects in other semiconductors, as they may offer an expanded range of functionality not available to the diamond nitrogen-vacancy centre(4). Notably, several defects in silicon carbide (SiC) have been suggested as good candidates for exploration, owing to a combination of computational predictions and magnetic resonance data(4-10). Here we demonstrate that several defect spin states in the 4H polytype of SiC (4H-SiC) can be optically addressed and coherently controlled in the time domain at temperatures ranging from 20 to 300 kelvin. Using optical and microwave techniques similar to those used with diamond nitrogen-vacancy qubits, we study the spin-1 ground state of each of four inequivalent forms of the neutral carbon-silicon divacancy, as well as a pair of defect spin states of unidentified origin. These defects are optically active near telecommunication wavelengths(11), and are found in a host material for which there already exist industrial-scale crystal growth(12) and advanced microfabrication techniques(13). In addition, they possess desirable spin coherence properties that are comparable to those of the diamond nitrogen-vacancy centre. This makes them promising candidates for various photonic, spintronic and quantum information applications that merge quantum degrees of freedom with classical electronic and optical technologies(2,14-17).
C1 [Koehl, William F.; Buckley, Bob B.; Heremans, F. Joseph; Calusine, Greg; Awschalom, David D.] Univ Calif Santa Barbara, Ctr Spintron & Quantum Computat, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Awschalom, DD (corresponding author), Univ Calif Santa Barbara, Ctr Spintron & Quantum Computat, Santa Barbara, CA 93106 USA.
EM awsch@physics.ucsb.edu
FU Air Force Office of Scientific Research (AFOSR); Defense Advanced Research Projects Agency (DARPA)
NR 30
TC 721
Z9 863
U1 10
U2 349
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 84
EP U108
DI 10.1038/nature10562
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600036
PM 22051676
DA 2026-03-09
ER

PT J
AU Benazzi, S
   Douka, K
   Fornai, C
   Bauer, CC
   Kullmer, O
   Svoboda, J
   Pap, I
   Mallegni, F
   Bayle, P
   Coquerelle, M
   Condemi, S
   Ronchitelli, A
   Harvati, K
   Weber, GW
AF Benazzi, Stefano
   Douka, Katerina
   Fornai, Cinzia
   Bauer, Catherine C.
   Kullmer, Ottmar
   Svoboda, Jiri
   Pap, Ildiko
   Mallegni, Francesco
   Bayle, Priscilla
   Coquerelle, Michael
   Condemi, Silvana
   Ronchitelli, Annamaria
   Harvati, Katerina
   Weber, Gerhard W.
TI Early dispersal of modern humans in Europe and implications for Neanderthal behaviour
SO NATURE
LA English
DT Article
ID enamel thickness; remains; grotte; middle; renne; age
AB The appearance of anatomically modern humans in Europe and the nature of the transition from the Middle to Upper Palaeolithic are matters of intense debate. Most researchers accept that before the arrival of anatomically modern humans, Neanderthals had adopted several 'transitional' technocomplexes. Two of these, the Uluzzian of southern Europe and the Chatelperronian of western Europe, are key to current interpretations regarding the timing of arrival of anatomically modern humans in the region and their potential interaction with Neanderthal populations. They are also central to current debates regarding the cognitive abilities of Neanderthals and the reasons behind their extinction(1-6). However, the actual fossil evidence associated with these assemblages is scant and fragmentary(7-10), and recent work has questioned the attribution of the Chatelperronian to Neanderthals on the basis of taphonomic mixing and lithic analysis(11,12). Here we reanalyse the deciduous molars from the Grotta del Cavallo ( southern Italy), associated with the Uluzzian and originally classified as Neanderthal(13,14). Using two independent morphometric methods based on microtomographic data, we show that the Cavallo specimens can be attributed to anatomically modern humans. The secure context of the teeth provides crucial evidence that the makers of the Uluzzian technocomplex were therefore not Neanderthals. In addition, new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to similar to 45,000-43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals.
C1 [Benazzi, Stefano; Fornai, Cinzia; Weber, Gerhard W.] Univ Vienna, Dept Anthropol, A-1090 Vienna, Austria.
   [Douka, Katerina] Univ Oxford, Res Lab Archaeol Hist Art, Oxford Radiocarbon Accelerator Unit, Oxford OX1 3QY, England.
   [Bauer, Catherine C.; Harvati, Katerina] Univ Tubingen, Dept Early Prehist & Quaternary Ecol, D-72070 Tubingen, Germany.
   [Kullmer, Ottmar] Senckenberg Res Inst Frankfurt, Dept Paleoanthropol & Messel Res, D-60325 Frankfurt, Germany.
   [Svoboda, Jiri] Acad Sci Czech Republ, Inst Archaeol, Brno 61200, Czech Republic.
   [Svoboda, Jiri] Masaryk Univ, Fac Sci, Dept Anthropol, Brno 60300, Czech Republic.
   [Pap, Ildiko] Hungarian Nat Hist Museum, Dept Anthropol, H-1083 Budapest, Hungary.
   [Mallegni, Francesco] Univ Pisa, Dept Biol, I-56126 Pisa, Italy.
   [Bayle, Priscilla] Univ Bordeaux 1, UMR PACEA 5199, F-33405 Talence, France.
   [Coquerelle, Michael] CSIC, Museo Nacl Ciencias Nat, Dept Paleobiol, Paleoanthropol Grp, E-28006 Madrid, Spain.
   [Condemi, Silvana] Fac Med Marseille, CNRS, Sect Nord, UMR 6578,EFS,Lab Anthropol Bioculturelle, F-13344 Marseille 15, France.
   [Ronchitelli, Annamaria] Univ Siena, Dept Environm Sci G Sarfatti, UR Prehist Ecol, I-53100 Siena, Italy.
   [Harvati, Katerina] Univ Tubingen, Senckenberg Ctr Human Evolut & Paleoecol, D-72070 Tubingen, Germany.
C3 University of Vienna; University of Oxford; Eberhard Karls University of Tubingen; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Czech Academy of Sciences; Institute of Archaeology of the Czech Academy of Sciences - Brno; Masaryk University; University of Pisa; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Bordeaux; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Museo Nacional de Ciencias Naturales (MNCN); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); University of Siena; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Eberhard Karls University of Tubingen
RP Benazzi, S (corresponding author), Univ Vienna, Dept Anthropol, Althanstr 14, A-1090 Vienna, Austria.
EM stefano.benazzi@univie.ac.at
FU Natural Environment Research Council (NERC) NRCF; Leverhulme Trust; NSF [01-120]; A.E.R.S. Dental Medicine Organisations GmbH [FA547013]; Fondation Fyssen; DFG [INST 37/706-1 FUGG]; NERC [NE/D014077/1]; Natural Environment Research Council [NE/D014077/1] Funding Source: researchfish; NERC [NE/D014077/1] Funding Source: UKRI
NR 30
TC 372
Z9 411
U1 0
U2 235
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 525
EP U249
DI 10.1038/nature10617
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600050
PM 22048311
DA 2026-03-09
ER

PT J
AU Miron, IM
   Garello, K
   Gaudin, G
   Zermatten, PJ
   Costache, MV
   Auffret, S
   Bandiera, S
   Rodmacq, B
   Schuhl, A
   Gambardella, P
AF Mihai Miron, Ioan
   Garello, Kevin
   Gaudin, Gilles
   Zermatten, Pierre-Jean
   Costache, Marius V.
   Auffret, Stephane
   Bandiera, Sebastien
   Rodmacq, Bernard
   Schuhl, Alain
   Gambardella, Pietro
TI Perpendicular switching of a single ferromagnetic layer induced by in-plane current injection
SO NATURE
LA English
DT Article
ID magnetic-fields; spin; manipulation; rashba
AB Modern computing technology is based on writing, storing and retrieving information encoded as magnetic bits. Although the giant magnetoresistance effect has improved the electrical read out of memory elements, magnetic writing remains the object of major research efforts(1). Despite several reports of methods to reverse the polarity of nanosized magnets by means of local electric fields(2,3) and currents(4-6), the simple reversal of a high-coercivity, single-layer ferromagnet remains a challenge. Materials with large coercivity and perpendicular magnetic anisotropy represent the mainstay of data storage media, owing to their ability to retain a stable magnetization state over long periods of time and their amenability to miniaturization(7). However, the same anisotropy properties that make a material attractive for storage also make it hard to write to(8). Here we demonstrate switching of a perpendicularly magnetized cobalt dot driven by in-plane current injection at room temperature. Our device is composed of a thin cobalt layer with strong perpendicular anisotropy and Rashba interaction induced by asymmetric platinum and AlO(x) interface layers(9,10). The effective switching field is orthogonal to the direction of the magnetization and to the Rashba field. The symmetry of the switching field is consistent with the spin accumulation induced by the Rashba interaction and the spin-dependent mobility observed in non-magnetic semiconductors(11,12), as well as with the torque induced by the spin Hall effect in the platinum layer(13,14). Our measurements indicate that the switching efficiency increases with the magnetic anisotropy of the cobalt layer and the oxidation of the aluminium layer, which is uppermost, suggesting that the Rashba interaction has a key role in the reversal mechanism. To prove the potential of in-plane current switching for spintronic applications, we construct a reprogrammable magnetic switch that can be integrated into non-volatile memory and logic architectures. This device is simple, scalable and compatible with present-day magnetic recording technology.
C1 [Mihai Miron, Ioan; Garello, Kevin; Costache, Marius V.; Gambardella, Pietro] Catalan Inst Nanotechnol ICN CIN2, E-08193 Barcelona, Spain.
   [Gaudin, Gilles; Zermatten, Pierre-Jean; Auffret, Stephane; Bandiera, Sebastien; Rodmacq, Bernard; Schuhl, Alain] INAC, CEA CNRS UJF GINP, UMR 8191, SPINTEC, F-38054 Grenoble, France.
   [Gambardella, Pietro] ICREA, E-08010 Barcelona, Spain.
   [Gambardella, Pietro] Univ Autonoma Barcelona, Dept Fis, E-08193 Barcelona, Spain.
C3 Barcelona Institute of Science & Technology; Catalan Institute of Nanoscience & Nanotechnology (ICN2); Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); ICREA; Autonomous University of Barcelona
RP Miron, IM (corresponding author), Catalan Inst Nanotechnol ICN CIN2, E-08193 Barcelona, Spain.
EM mihai.miron.icn@uab.es; pietro.gambardella.icn@uab.es
FU European Research Council [StG 203239 NOMAD]; Ministerio de Ciencia y Innovacion [ERA-Net EUI2008-03884, MAT2010-15659]; Agencia de Gestio d'Ajuts Universitaris i de Recerca [2009 SGR 695]; ICREA Funding Source: Custom
NR 30
TC 2588
Z9 2963
U1 31
U2 1090
PU 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 11
PY 2011
VL 476
IS 7359
BP 189
EP U88
DI 10.1038/nature10309
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900032
PM 21804568
DA 2026-03-09
ER

PT J
AU Vader, G
   Blitzblau, HG
   Tame, MA
   Falk, JE
   Curtin, L
   Hochwagen, A
AF Vader, Gerben
   Blitzblau, Hannah G.
   Tame, Mihoko A.
   Falk, Jill E.
   Curtin, Lisa
   Hochwagen, Andreas
TI Protection of repetitive DNA borders from self-induced meiotic instability
SO NATURE
LA English
DT Article
ID double-strand-break; saccharomyces-cerevisiae; recombination initiation; histone deacetylase; budding yeast; protein; gene; replication; metabolism; mechanisms
AB DNA double strand breaks (DSBs) in repetitive sequences are a potent source of genomic instability, owing to the possibility of non-allelic homologous recombination (NAHR). Repetitive sequences are especially at risk during meiosis, when numerous programmed DSBs are introduced into the genome to initiate meiotic recombination(1). In the repetitive ribosomal DNA (rDNA) array of the budding yeast Saccharomyces cerevisiae, meiotic DSB formation is prevented in part through Sir2-dependent heterochromatin formation(2,3). Here we show that the edges of the rDNA array are exceptionally susceptible to meiotic DSBs, revealing an inherent heterogeneity in the rDNA array. We find that this localized DSB susceptibility necessitates a border-specific protection system consisting of the meiotic ATPase Pch2 and the origin recognition complex subunit Orc1. Upon disruption of these factors, DSB formation and recombination increased specifically in the outermost rDNA repeats, leading to NAHR and rDNA instability. Notably, the Sir2-dependent heterochromatin of the rDNA itself was responsible for the induction of DSBs at the rDNA borders in pch2 Delta cells. Thus, although the activity of Sir2 globally prevents meiotic DSBs in the rDNA, it creates a highly permissive environment for DSB formation at the junctions between heterochromatin and euchromatin. Heterochromatinized repetitive DNA arrays are abundant in most eukaryotic genomes. Our data define the borders of such chromatin domains as distinct high-risk regions for meiotic NAHR, the protection of which may be a universal requirement to prevent meiotic genome rearrangements that are associated with genomic diseases and birth defects.
C1 [Vader, Gerben; Blitzblau, Hannah G.; Tame, Mihoko A.; Falk, Jill E.; Curtin, Lisa; Hochwagen, Andreas] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
   [Curtin, Lisa] Somerville High Sch, Somerville, MA 02143 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute
RP Hochwagen, A (corresponding author), NYU, Dept Biol, 100 Washington Sq E, New York, NY 10003 USA.
EM andi@nyu.edu
FU NIH [GM088248]; Netherlands Organisation for Scientific Research [NWO Rubicon-825.08.009, NWO VENI-016.111.004]; HHMI [52005879]
NR 30
TC 85
Z9 100
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 SEP 1
PY 2011
VL 477
IS 7362
BP 115
EP U141
DI 10.1038/nature10331
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300043
PM 21822291
DA 2026-03-09
ER

PT J
AU Hinch, AG
   Tandon, A
   Patterson, N
   Song, YL
   Rohland, N
   Palmer, CD
   Chen, GK
   Wang, K
   Buxbaum, SG
   Akylbekova, EL
   Aldrich, MC
   Ambrosone, CB
   Amos, C
   Bandera, EV
   Berndt, SI
   Bernstein, L
   Blot, WJ
   Bock, CH
   Boerwinkle, E
   Cai, QY
   Caporaso, N
   Casey, G
   Cupples, LA
   Deming, SL
   Diver, WR
   Divers, J
   Fornage, M
   Gillanders, EM
   Glessner, J
   Harris, CC
   Hu, JJ
   Ingles, SA
   Isaacs, W
   John, EM
   Kao, WHL
   Keating, B
   Kittles, RA
   Kolonel, LN
   Larkin, E
   Le Marchand, L
   McNeill, LH
   Millikan, RC
   Murphy, A
   Musani, S
   Neslund-Dudas, C
   Nyante, S
   Papanicolaou, GJ
   Press, MF
   Psaty, BM
   Reiner, AP
   Rich, SS
   Rodriguez-Gil, JL
   Rotter, JI
   Rybicki, BA
   Schwartz, AG
   Signorello, LB
   Spitz, M
   Strom, SS
   Thun, MJ
   Tucker, MA
   Wang, ZM
   Wiencke, JK
   Witte, JS
   Wrensch, M
   Wu, XF
   Yamamura, Y
   Zanetti, KA
   Zheng, W
   Ziegler, RG
   Zhu, XF
   Redline, S
   Hirschhorn, JN
   Henderson, BE
   Taylor, HA
   Price, AL
   Hakonarson, H
   Chanock, SJ
   Haiman, CA
   Wilson, JG
   Reich, D
   Myers, SR
AF Hinch, Anjali G.
   Tandon, Arti
   Patterson, Nick
   Song, Yunli
   Rohland, Nadin
   Palmer, Cameron D.
   Chen, Gary K.
   Wang, Kai
   Buxbaum, Sarah G.
   Akylbekova, Ermeg L.
   Aldrich, Melinda C.
   Ambrosone, Christine B.
   Amos, Christopher
   Bandera, Elisa V.
   Berndt, Sonja I.
   Bernstein, Leslie
   Blot, William J.
   Bock, Cathryn H.
   Boerwinkle, Eric
   Cai, Qiuyin
   Caporaso, Neil
   Casey, Graham
   Cupples, L. Adrienne
   Deming, Sandra L.
   Diver, W. Ryan
   Divers, Jasmin
   Fornage, Myriam
   Gillanders, Elizabeth M.
   Glessner, Joseph
   Harris, Curtis C.
   Hu, Jennifer J.
   Ingles, Sue A.
   Isaacs, William
   John, Esther M.
   Kao, W. H. Linda
   Keating, Brendan
   Kittles, Rick A.
   Kolonel, Laurence N.
   Larkin, Emma
   Le Marchand, Loic
   McNeill, Lorna H.
   Millikan, Robert C.
   Murphy, Adam
   Musani, Solomon
   Neslund-Dudas, Christine
   Nyante, Sarah
   Papanicolaou, George J.
   Press, Michael F.
   Psaty, Bruce M.
   Reiner, Alex P.
   Rich, Stephen S.
   Rodriguez-Gil, Jorge L.
   Rotter, Jerome I.
   Rybicki, Benjamin A.
   Schwartz, Ann G.
   Signorello, Lisa B.
   Spitz, Margaret
   Strom, Sara S.
   Thun, Michael J.
   Tucker, Margaret A.
   Wang, Zhaoming
   Wiencke, John K.
   Witte, John S.
   Wrensch, Margaret
   Wu, Xifeng
   Yamamura, Yuko
   Zanetti, Krista A.
   Zheng, Wei
   Ziegler, Regina G.
   Zhu, Xiaofeng
   Redline, Susan
   Hirschhorn, Joel N.
   Henderson, Brian E.
   Taylor, Herman A., Jr.
   Price, Alkes L.
   Hakonarson, Hakon
   Chanock, Stephen J.
   Haiman, Christopher A.
   Wilson, James G.
   Reich, David
   Myers, Simon R.
TI The landscape of recombination in African Americans
SO NATURE
LA English
DT Article
ID meiotic recombination; prdm9; map; sequence; gene; instability; hotspots
AB Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9(P value <10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.
C1 [Tandon, Arti; Patterson, Nick; Rohland, Nadin; Reich, David] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Hinch, Anjali G.; Myers, Simon R.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Tandon, Arti; Rohland, Nadin; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Song, Yunli; Myers, Simon R.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA.
   [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA.
   [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Program Genom, Boston, MA 02115 USA.
   [Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Press, Michael F.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Press, Michael F.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90033 USA.
   [Wang, Kai] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
   [Wang, Kai; Glessner, Joseph; Keating, Brendan; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Buxbaum, Sarah G.; Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS 39213 USA.
   [Akylbekova, Ermeg L.; Musani, Solomon; Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
   [Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37203 USA.
   [Aldrich, Melinda C.; Blot, William J.; Cai, Qiuyin; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
   [Aldrich, Melinda C.; Blot, William J.; Cai, Qiuyin; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
   [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
   [Amos, Christopher; Spitz, Margaret; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
   [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
   [Berndt, Sonja I.; Caporaso, Neil; Tucker, Margaret A.; Ziegler, Regina G.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Bernstein, Leslie] City Hope Natl Med Ctr, Div Canc Etiol, Dept Populat Sci, Beckman Res Inst, Duarte, CA 91010 USA.
   [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD 20850 USA.
   [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Karmanos Canc Inst, Detroit, MI 48201 USA.
   [Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Dept Oncol, Detroit, MI 48201 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Ctr Human Genet, Houston, TX 77030 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Div Epidemiol, Houston, TX 77030 USA.
   [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
   [Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
   [Divers, Jasmin] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
   [Fornage, Myriam; Gillanders, Elizabeth M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Inst Mol Med, Houston, TX 77030 USA.
   [Fornage, Myriam; Gillanders, Elizabeth M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX 77030 USA.
   [Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Harris, Curtis C.; Zanetti, Krista A.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
   [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
   [Isaacs, William] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA.
   [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
   [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [John, Esther M.] Stanford Canc Ctr, Stanford, CA 94305 USA.
   [Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   [Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL 60607 USA.
   [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
   [Larkin, Emma] Vanderbilt Univ, Med Ctr, Div Allergy Pulm & Crit Care, Dept Med,Med Ctr E, Nashville, TN 37232 USA.
   [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
   [McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Ctr Community Implementat & Disseminat Res, Duncan Family Inst, Houston, TX 77030 USA.
   [Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
   [Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
   [Neslund-Dudas, Christine; Rybicki, Benjamin A.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
   [Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Seattle, WA 98101 USA.
   [Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
   [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Wang, Zhaoming] Natl Canc Inst Frederick, Core Genotype Facil, SAIC Frederick Inc, Frederick, MD 20877 USA.
   [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94158 USA.
   [Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA 94158 USA.
   [Zhu, Xiaofeng] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Redline, Susan] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA.
   [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Taylor, Herman A., Jr.] Jackson State Univ, Jackson, MS 39217 USA.
   [Taylor, Herman A., Jr.] Tougaloo Coll, Tougaloo, MS 39174 USA.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Oxford; Wellcome Centre for Human Genetics; Harvard University; Harvard Medical School; University of Oxford; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Southern California; University of Southern California; University of Southern California; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Mississippi Medical Center; Jackson State University; University of Mississippi Medical Center; University of Mississippi; Vanderbilt University; Vanderbilt University; Vanderbilt University; Roswell Park Comprehensive Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rutgers Cancer Institute of New Jersey; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; City of Hope; Beckman Research Institute of City of Hope; Barbara Ann Karmanos Cancer Institute; Wayne State University; Wayne State University; University of Texas System; University of Texas Health Science Center Houston; University of Texas System; University of Texas Health Science Center Houston; Boston University; Framingham Heart Study; American Cancer Society; Wake Forest University; Wake Forest Baptist Medical Center; University of Texas System; University of Texas Health Science Center Houston; University of Texas School Public Health; University of Texas System; University of Texas Health Science Center Houston; University of Texas School Public Health; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH Division of Cancer Control & Population Sciences; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Miami; University of Miami; Johns Hopkins University; Johns Hopkins Medicine; Cancer Prevention Institute of California; Stanford University; Stanford Cancer Institute; Stanford University; Stanford Medicine; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Cancer Research Center of Hawaii; University of Hawaii System; Vanderbilt University; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Northwestern University; Henry Ford Health System; Henry Ford Hospital; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Group Health Cooperative; University of Washington; University of Washington Seattle; University of Virginia; Cedars Sinai Medical Center; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of California System; University of California San Francisco; University of California System; University of California San Francisco; University System of Ohio; Case Western Reserve University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Jackson State University; Tougaloo College; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; University of Pennsylvania; University of Mississippi; University of Mississippi Medical Center
RP Reich, D (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM reich@genetics.med.harvard.edu; myers@stats.ox.ac.uk
FU Wellcome Trust; NIH [HL084107, GM091332]; National Heart, Lung and Blood Institute [HHSN268200960009C]; Children's Hospital of Philadelphia; Landenberger Foundation; Cotswold Foundation; DoD; Norris Foundation; MEC [CA63464, CA54281]; CARE [HD33175]; WCHS [CA100598]; DAMD [170100334, 17966071, W81XWH0710645, W81XWH0710203, W81XWH0610066]; Breast Cancer Research Foundation; SFBC [CA77305]; CBCS [CA58223, ES10126]; PLCO; NHBS [CA100374]; WFBC [R01-CA73629]; CPS-II (the American Cancer Society); LAAPC [99-00524V-10258, PC35139, DP000807]; MEC; MDA [CA68578, CA140388, ES007784]; GECAP [ES011126]; CaP Genes [CA88164]; IPCG [W81XWH0710122]; DCPC [GM08016]; SCCS [CA092447, CA68485]; University Cancer Foundation; Duncan Family institute; Center for Community; Implementation and Dissemination Research Core; Maryland Studies;  [CA1326792];  [CA148085];  [HG004726];  [CA060691];  [CA87895];  [PC35145];  [CA22453];  [ES06717];  [CA55769];  [CA127219];  [CA1116460S1];  [CA1116460];  [CA121197];  [CA141716];  [CA121197S2];  [CPRIT RP100443];  [CA148127];  [DAMD W81XWH0710645]; U.S. Department of Defense (DOD) [W81XWH0710122, W81XWH0610066, W81XWH0710203, W81XWH0710645] Funding Source: U.S. Department of Defense (DOD); National Cancer Institute [P30CA068485, P30CA022453, P50CA058223] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [P30ES010126] Funding Source: NIH RePORTER
NR 29
TC 236
Z9 285
U1 0
U2 41
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 170
EP U67
DI 10.1038/nature10336
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900028
PM 21775986
DA 2026-03-09
ER

PT J
AU Kozlov, AS
   Baumgart, J
   Risler, T
   Versteegh, CPC
   Hudspeth, AJ
AF Kozlov, Andrei S.
   Baumgart, Johannes
   Risler, Thomas
   Versteegh, Corstiaen P. C.
   Hudspeth, A. J.
TI Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale
SO NATURE
LA English
DT Article
ID hair cell stereocilia; transduction channels; mechanical amplification; coherent motion; bundle; membrane
AB The detection of sound begins when energy derived from an acoustic stimulus deflects the hair bundles on top of hair cells(1). As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental physical challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification(2,3). Here we demonstrate that a complementary part of the solution involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors that stabilize the structure further reduce the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of viscous and elastic forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.
C1 [Kozlov, Andrei S.; Versteegh, Corstiaen P. C.; Hudspeth, A. J.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Kozlov, Andrei S.; Versteegh, Corstiaen P. C.; Hudspeth, A. J.] Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10065 USA.
   [Baumgart, Johannes] Tech Univ Dresden, Dept Math, Inst Comp Sci, D-01062 Dresden, Germany.
   [Risler, Thomas] Inst Curie, Ctr Rech, F-75005 Paris, France.
   [Risler, Thomas] Univ Paris 06, UMR 168, F-75005 Paris, France.
   [Risler, Thomas] CNRS, UMR 168, F-75005 Paris, France.
   [Versteegh, Corstiaen P. C.] Wageningen Univ, Expt Zool Grp, NL-6709 PG Wageningen, Netherlands.
C3 Howard Hughes Medical Institute; Rockefeller University; Rockefeller University; Technische Universitat Dresden; UNICANCER; Universite PSL; Institut Curie; Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; CNRS - Institute of Chemistry (INC); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; UNICANCER; Institut Curie; Sorbonne Universite; Wageningen University & Research
RP Hudspeth, AJ (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10065 USA.
EM hudspaj@rockefeller.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIDCD NIH HHS [F32 DC000241, R01 DC000241, DC000241] Funding Source: Medline
NR 19
TC 64
Z9 71
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 16
PY 2011
VL 474
IS 7351
BP 376
EP 379
DI 10.1038/nature10073
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100045
PM 21602823
DA 2026-03-09
ER

PT J
AU Johnson, DDP
   Fowler, JH
AF Johnson, Dominic D. P.
   Fowler, James H.
TI The evolution of overconfidence
SO NATURE
LA English
DT Article
ID fighting behavior; bias; war
AB Confidence is an essential ingredient of success in a wide range of domains ranging from job performance and mental health to sports, business and combat(1-4). Some authors have suggested that not just confidence but overconfidence-believing you are better than you are in reality-is advantageous because it serves to increase ambition, morale, resolve, persistence or the credibility of bluffing, generating a self-fulfilling prophecy in which exaggerated confidence actually increases the probability of success(3-8). However, overconfidence also leads to faulty assessments, unrealistic expectations and hazardous decisions, so it remains a puzzle how such a false belief could evolve or remain stable in a population of competing strategies that include accurate, unbiased beliefs. Here we present an evolutionary model showing that, counterintuitively, overconfidence maximizes individual fitness and populations tend to become overconfident, as long as benefits from contested resources are sufficiently large compared with the cost of competition. In contrast, unbiased strategies are only stable under limited conditions. The fact that overconfident populations are evolutionarily stable in a wide range of environments may help to explain why overconfidence remains prevalent today, even if it contributes to hubris, market bubbles, financial collapses, policy failures, disasters and costly wars(9-13).
C1 [Johnson, Dominic D. P.] Univ Edinburgh, Edinburgh EH8 9LD, Midlothian, Scotland.
   [Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA.
   [Fowler, James H.] Univ Calif San Diego, Div Med Genet, La Jolla, CA 92093 USA.
C3 University of Edinburgh; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Johnson, DDP (corresponding author), Univ Edinburgh, Edinburgh EH8 9LD, Midlothian, Scotland.
EM dominic.johnson@ed.ac.uk
NR 30
TC 383
Z9 496
U1 6
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 SEP 15
PY 2011
VL 477
IS 7364
BP 317
EP 320
DI 10.1038/nature10384
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400028
PM 21921915
DA 2026-03-09
ER

PT J
AU Burnett, C
   Valentini, S
   Cabreiro, F
   Goss, M
   Somogyvári, M
   Piper, MD
   Hoddinott, M
   Sutphin, GL
   Leko, V
   McElwee, JJ
   Vazquez-Manrique, RP
   Orfila, AM
   Ackerman, D
   Au, C
   Vinti, G
   Riesen, M
   Howard, K
   Neri, C
   Bedalov, A
   Kaeberlein, M
   Soti, C
   Partridge, L
   Gems, D
AF Burnett, Camilla
   Valentini, Sara
   Cabreiro, Filipe
   Goss, Martin
   Somogyvari, Milan
   Piper, Matthew D.
   Hoddinott, Matthew
   Sutphin, George L.
   Leko, Vid
   McElwee, Joshua J.
   Vazquez-Manrique, Rafael P.
   Orfila, Anne-Marie
   Ackerman, Daniel
   Au, Catherine
   Vinti, Giovanna
   Riesen, Michele
   Howard, Ken
   Neri, Christian
   Bedalov, Antonio
   Kaeberlein, Matt
   Soti, Csaba
   Partridge, Linda
   Gems, David
TI Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
SO NATURE
LA English
DT Article
ID small-molecule activators; saccharomyces-cerevisiae; resveratrol; longevity; sirtuins; restriction; genetics; extension
AB Overexpression of sirtuins(NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster(1-3). Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background(4). Here were-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C. elegans and Drosophila. In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression(1) abrogated the longevity increase, but did not abrogate sir-2.1 overexpression. Instead, longevity co-segregated with a second-site mutation affecting sensory neurons. Outcrossing of a line with low-copy-number sir-2.1 overexpression(2) also abrogated longevity. A Drosophila strain with ubiquitous overexpression of dSir2 using the UAS-GAL4 system was long-lived relative to wild-type controls, as previously reported(3), but was not long-lived relative to the appropriate transgenic controls, and nor was a new line with stronger overexpression of dSir2. These findings underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan. The life-extending effect of dietary restriction on ageing in Drosophila has also been reported to be dSir2 dependent(3). We found that dietary restriction increased fly lifespan independently of dSir2. Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila.
C1 [Burnett, Camilla; Valentini, Sara; Cabreiro, Filipe; Goss, Martin; Piper, Matthew D.; Hoddinott, Matthew; McElwee, Joshua J.; Ackerman, Daniel; Au, Catherine; Vinti, Giovanna; Riesen, Michele; Partridge, Linda; Gems, David] UCL, Inst Hlth Ageing, London WC1E 6BT, England.
   [Burnett, Camilla; Valentini, Sara; Cabreiro, Filipe; Goss, Martin; Piper, Matthew D.; Hoddinott, Matthew; McElwee, Joshua J.; Ackerman, Daniel; Au, Catherine; Vinti, Giovanna; Riesen, Michele; Partridge, Linda; Gems, David] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Somogyvari, Milan; Soti, Csaba] Semmelweis Univ, Dept Med Chem, H-1094 Budapest, Hungary.
   [Sutphin, George L.; Kaeberlein, Matt] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Sutphin, George L.; Kaeberlein, Matt] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA.
   [Leko, Vid; Bedalov, Antonio] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Vazquez-Manrique, Rafael P.; Orfila, Anne-Marie; Neri, Christian] INSERM, Lab Neuronal Cell Biol & Pathol, U894, F-75014 Paris, France.
   [Vazquez-Manrique, Rafael P.; Orfila, Anne-Marie; Neri, Christian] Univ Paris 05, F-75014 Paris, France.
   [Howard, Ken] UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England.
   [Partridge, Linda] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany.
C3 University of London; University College London; University of London; University College London; Semmelweis University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; University of London; University College London; MRC Laboratory Molecular Biology; Max Planck Society
RP Gems, D (corresponding author), UCL, Inst Hlth Ageing, Gower St, London WC1E 6BT, England.
EM david.gems@ucl.ac.uk
FU National Institutes of Health National Center for Research Resources; European Union [FP6-036894, FP6-518230]; Hungarian Science Foundation and Norway Grants [NNF-78794]; INSERM; ANR, Paris; National Institutes of Health [CA129132, R01AG031108, T32AG000057]; Wellcome Trust; Medical Research Council [G0700729B] Funding Source: researchfish
NR 36
TC 496
Z9 595
U1 1
U2 186
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 482
EP U136
DI 10.1038/nature10296
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500044
PM 21938067
DA 2026-03-09
ER

PT J
AU Auerbach, BD
   Osterweil, EK
   Bear, MF
AF Auerbach, Benjamin D.
   Osterweil, Emily K.
   Bear, Mark F.
TI Mutations causing syndromic autism define an axis of synaptic pathophysiology
SO NATURE
LA English
DT Article
ID long-term depression; fragile-x-syndrome; hippocampal area ca1; tuberous-sclerosis; protein-synthesis; mental-retardation; mouse model; mammalian target; rat hippocampus; mtor
AB Tuberous sclerosis complex and fragile X syndrome are genetic diseases characterized by intellectual disability and autism. Because both syndromes are caused by mutations in genes that regulate protein synthesis in neurons, it has been hypothesized that excessive protein synthesis is one core pathophysiological mechanism of intellectual disability and autism. Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2(+/-) and Fmr1(-/y) mice, here we show that synaptic dysfunction caused by these mutations actually falls at opposite ends of a physiological spectrum. Synaptic, biochemical and cognitive defects in these mutants are corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions, and deficits in the mutants disappear when the mice are bred to carry both mutations. Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments.
C1 [Auerbach, Benjamin D.; Osterweil, Emily K.; Bear, Mark F.] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Bear, MF (corresponding author), MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
EM mbear@mit.edu
FU National Institute of Mental Health [T32 MH-082718, T32-MH-074249]; National Institute of Child Health and Human Development [2R01HD046943]; Department of Defense [W81XWH-11-1-0252]; Simons Foundation
NR 43
TC 492
Z9 598
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 DEC 1
PY 2011
VL 480
IS 7375
BP 63
EP U222
DI 10.1038/nature10658
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900033
PM 22113615
DA 2026-03-09
ER

PT J
AU Wong, TS
   Kang, SH
   Tang, SKY
   Smythe, EJ
   Hatton, BD
   Grinthal, A
   Aizenberg, J
AF Wong, Tak-Sing
   Kang, Sung Hoon
   Tang, Sindy K. Y.
   Smythe, Elizabeth J.
   Hatton, Benjamin D.
   Grinthal, Alison
   Aizenberg, Joanna
TI Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicity
SO NATURE
LA English
DT Article
ID solid-surfaces; water; resistance; drops
AB Creating a robust synthetic surface that repels various liquids would have broad technological implications for areas ranging from biomedical devices and fuel transport to architecture but has proved extremely challenging(1). Inspirations from natural non-wetting structures(2-6), particularly the leaves of the lotus, have led to the development of liquid-repellent microtextured surfaces that rely on the formation of a stable air-liquid interface(7-9). Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis(9), failure under pressure(10-12) and upon physical damage(1,7,11), inability to self-heal and high production cost(1,11). To address these challenges, here we report a strategy to create self-healing, slippery liquid-infused porous surface(s) (SLIPS) with exceptional liquid- and ice-repellency, pressure stability and enhanced optical transparency. Our approach-inspired by Nepenthes pitcher plants(13)-is conceptually different from the lotus effect, because we use nano/microstructured substrates to lock in place the infused lubricating fluid. We define the requirements for which the lubricant forms a stable, defect-free and inert 'slippery' interface. This surface outperforms its natural counterparts(2-6) and state-of-the-art synthetic liquid-repellent surfaces(8,9,14-16) in its capability to repel various simple and complex liquids (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis (<2.5 degrees), quickly restore liquid-repellency after physical damage (within 0.1-1 s), resist ice adhesion, and function at high pressures (up to about 680 atm). We show that these properties are insensitive to the precise geometry of the underlying substrate, making our approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). We envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and antifouling materials operating in extreme environments.
C1 [Wong, Tak-Sing; Kang, Sung Hoon; Tang, Sindy K. Y.; Hatton, Benjamin D.; Grinthal, Alison; Aizenberg, Joanna] Harvard Univ, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Wong, Tak-Sing; Kang, Sung Hoon; Tang, Sindy K. Y.; Hatton, Benjamin D.; Grinthal, Alison; Aizenberg, Joanna] Harvard Univ, Kavli Inst Bionano Sci & Technol, Cambridge, MA 02138 USA.
   [Smythe, Elizabeth J.] Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University; Schlumberger
RP Aizenberg, J (corresponding author), Harvard Univ, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM jaiz@seas.harvard.edu
FU Croucher Foundation; AFOSR MURI [FA9550-09-1-0669-DOD35CAP]; ARO MURI [W911NF-09-1-0476]; NSF [ECS-0335765]
NR 30
TC 3645
Z9 4193
U1 129
U2 4632
PU 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 22
PY 2011
VL 477
IS 7365
BP 443
EP 447
DI 10.1038/nature10447
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500036
PM 21938066
DA 2026-03-09
ER

PT J
AU Zhou, RB
   Yazdi, AS
   Menu, P
   Tschopp, J
AF Zhou, Rongbin
   Yazdi, Amir S.
   Menu, Philippe
   Tschopp, Juerg
TI A role for mitochondria in NLRP3 inflammasome activation
SO NATURE
LA English
DT Article
ID thioredoxin-interacting protein; oxygen species production; nalp3 inflammasome; disease; cells; pathogenesis; dysfunction; apoptosis; autophagy; channel
AB An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation(1,2). Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
C1 [Zhou, Rongbin; Yazdi, Amir S.; Menu, Philippe; Tschopp, Juerg] Univ Lausanne, Ctr Immun & Infect, Dept Biochem, CH-1066 Epalinges, Switzerland.
C3 University of Lausanne
RP Tschopp, J (corresponding author), Univ Lausanne, Ctr Immun & Infect, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland.
EM jurg.tschopp@unil.ch
FU Swiss National Science Foundation; Institute for Arthritis Research; DFG
NR 28
TC 4671
Z9 5161
U1 18
U2 857
PU NATURE PUBLISHING 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 13
PY 2011
VL 469
IS 7329
BP 221
EP 225
DI 10.1038/nature09663
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400040
PM 21124315
DA 2026-03-09
ER

PT J
AU Varela, I
   Tarpey, P
   Raine, K
   Huang, D
   Ong, CK
   Stephens, P
   Davies, H
   Jones, D
   Lin, ML
   Teague, J
   Bignell, G
   Butler, A
   Cho, J
   Dalgliesh, GL
   Galappaththige, D
   Greenman, C
   Hardy, C
   Jia, MM
   Latimer, C
   Lau, KW
   Marshall, J
   McLaren, S
   Menzies, A
   Mudie, L
   Stebbings, L
   Largaespada, DA
   Wessels, LFA
   Richard, S
   Kahnoski, RJ
   Anema, J
   Tuveson, DA
   Perez-Mancera, PA
   Mustonen, V
   Fischer, A
   Adams, DJ
   Rust, A
   Chan-on, W
   Subimerb, C
   Dykema, K
   Furge, K
   Campbell, PJ
   Teh, BT
   Stratton, MR
   Futreal, PA
AF Varela, Ignacio
   Tarpey, Patrick
   Raine, Keiran
   Huang, Dachuan
   Ong, Choon Kiat
   Stephens, Philip
   Davies, Helen
   Jones, David
   Lin, Meng-Lay
   Teague, Jon
   Bignell, Graham
   Butler, Adam
   Cho, Juok
   Dalgliesh, Gillian L.
   Galappaththige, Danushka
   Greenman, Chris
   Hardy, Claire
   Jia, Mingming
   Latimer, Calli
   Lau, King Wai
   Marshall, John
   McLaren, Stuart
   Menzies, Andrew
   Mudie, Laura
   Stebbings, Lucy
   Largaespada, David A.
   Wessels, L. F. A.
   Richard, Stephane
   Kahnoski, Richard J.
   Anema, John
   Tuveson, David A.
   Perez-Mancera, Pedro A.
   Mustonen, Ville
   Fischer, Andrej
   Adams, David J.
   Rust, Alistair
   Chan-on, Waraporn
   Subimerb, Chutima
   Dykema, Karl
   Furge, Kyle
   Campbell, Peter J.
   Teh, Bin Tean
   Stratton, Michael R.
   Futreal, P. Andrew
TI Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
SO NATURE
LA English
DT Article
ID tumor-suppressor gene; cell carcinoma; cancer; mutagenesis; baf180; arid1a; mouse; inactivation; senescence; induction
AB The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of similar to 3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A)(1), JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control(3). However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.
C1 [Huang, Dachuan; Ong, Choon Kiat; Chan-on, Waraporn; Subimerb, Chutima; Teh, Bin Tean] Natl Canc Ctr Singapore, NCCS VARI Translat Res Lab, Singapore 169610, Singapore.
   [Varela, Ignacio; Tarpey, Patrick; Raine, Keiran; Stephens, Philip; Davies, Helen; Jones, David; Lin, Meng-Lay; Teague, Jon; Bignell, Graham; Butler, Adam; Cho, Juok; Dalgliesh, Gillian L.; Galappaththige, Danushka; Greenman, Chris; Hardy, Claire; Jia, Mingming; Latimer, Calli; Lau, King Wai; Marshall, John; McLaren, Stuart; Menzies, Andrew; Mudie, Laura; Stebbings, Lucy; Campbell, Peter J.; Stratton, Michael R.; Futreal, P. Andrew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA.
   [Wessels, L. F. A.] Netherlands Canc Inst, Dept Mol Biol, NL-1066 CX Amsterdam, Netherlands.
   [Richard, Stephane] Fac Med Paris Sud, INSERM, U753, Genet Oncol EPHE, F-94805 Villejuif, France.
   [Richard, Stephane] Inst Cancerol Gustave Roussy, F-94805 Villejuif, France.
   [Richard, Stephane] Hop Bicetre, AP HP, Serv Urol, Ctr Expert Natl Canc Rares INCa PREDIR, F-94276 Le Kremlin Bicetre, France.
   [Kahnoski, Richard J.; Anema, John] Spectrum Hlth Hosp, Dept Urol, Grand Rapids, MI 49503 USA.
   [Tuveson, David A.; Perez-Mancera, Pedro A.] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Mustonen, Ville; Fischer, Andrej; Adams, David J.; Rust, Alistair] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Fischer, Andrej] Univ Cologne, Inst Theoret Phys, D-50937 Cologne, Germany.
   [Dykema, Karl; Furge, Kyle] Van Andel Res Inst, Lab Computat Biol, Grand Rapids, MI 49503 USA.
   [Teh, Bin Tean] DUKE NUS Grad Med Sch, Lab Canc Therapeut, Singapore, Singapore.
   [Teh, Bin Tean] Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
C3 National Cancer Centre Singapore (NCCS); Wellcome Trust Sanger Institute; University of Minnesota System; University of Minnesota Twin Cities; Netherlands Cancer Institute; Universite PSL; Ecole Pratique des Hautes Etudes (EPHE); Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Gustave Roussy; Institut National du Cancer (INCA) France; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bicetre - APHP; Hopital Universitaire Antoine-Beclere - APHP; Universite Paris Saclay; University of Cambridge; CRUK Cambridge Institute; Cancer Research UK; Wellcome Trust Sanger Institute; University of Cologne; Van Andel Institute; Van Andel Research Institute; National University of Singapore; Van Andel Institute; Van Andel Research Institute; University of London; Institute of Cancer Research - UK
RP Teh, BT (corresponding author), Natl Canc Ctr Singapore, NCCS VARI Translat Res Lab, 11 Hosp Dr, Singapore 169610, Singapore.
EM Bin.Teh@vai.org; mrs@sanger.ac.uk; paf@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; Lee Foundation; International Human Frontier Science Program Organization; Cancer Research UK; University of Cambridge; Van Andel Research Institute
NR 30
TC 1022
Z9 1277
U1 1
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 27
PY 2011
VL 469
IS 7331
BP 539
EP 542
DI 10.1038/nature09639
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500034
PM 21248752
DA 2026-03-09
ER

PT J
AU Anthony, RM
   Kobayashi, T
   Wermeling, F
   Ravetch, JV
AF Anthony, Robert M.
   Kobayashi, Toshihiko
   Wermeling, Fredrik
   Ravetch, Jeffrey V.
TI Intravenous gammaglobulin suppresses inflammation through a novel TH2 pathway
SO NATURE
LA English
DT Article
ID dc-sign; antiinflammatory activity; dendritic cell; in-vivo; bone-marrow; immune-responses; il-4; interleukin-4; antibody; receptors
AB High-dose intravenous immunoglobulin is a widely used therapeutic preparation of highly purified immunoglobulin G (IgG) antibodies. It is administered at high doses (1-2 grams per kilogram) for the suppression of autoantibody-triggered inflammation in a variety of clinical settings'. This anti-inflammatory activity of intravenous immunoglobulin is triggered by a minor population of IgG crystallizable fragments (Fcs), with glycans terminating in alpha 2,6 sialic acids (sFc) that target myeloid regulatory cells expressing the lectin dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN; also known as CD209)(2-4). Here, to characterize this response in detail, we generated humanized DC-SIGN mice (hDC-SIGN), and demonstrate that the anti-inflammatory activity of intravenous immunoglobulin can be recapitulated by the transfer of bone-marrow-derived sFc-treated hDC-SIGN(+) macrophages or dendritic cells into naive recipients. Furthermore, sFc administration results in the production of IL-33, which, in turn, induces expansion of IL-4-producing basophils that promote increased expression of the inhibitory Fc receptor Fc gamma RIIB on effector macrophages. Systemic administration of the T(H)2 cytokines IL-33 or IL-4 upregulates Fc gamma RIIB on macrophages, and suppresses serum-induced arthritis. Consistent with these results, transfer of IL-33-treated basophils suppressed induced arthritic inflammation. This novel DC-SIGN-T(H)2 pathway initiated by an endogenous ligand, sFc, provides an intrinsic mechanism for maintaining immune homeostasis that could be manipulated to provide therapeutic benefit in autoimmune diseases.
C1 [Anthony, Robert M.; Kobayashi, Toshihiko; Wermeling, Fredrik; Ravetch, Jeffrey V.] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10065 USA.
C3 Rockefeller University
RP Ravetch, JV (corresponding author), Rockefeller Univ, Lab Mol Genet & Immunol, 1230 York Ave, New York, NY 10065 USA.
EM ravetch@rockefeller.edu
FU Wenner-Gren Foundations, Sweden; Virdante Pharmaceuticals; NIH
NR 41
TC 505
Z9 582
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 JUL 7
PY 2011
VL 475
IS 7354
BP 110
EP U133
DI 10.1038/nature10134
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300055
PM 21685887
DA 2026-03-09
ER

PT J
AU De Nicola, GM
   Karreth, FA
   Humpton, TJ
   Gopinathan, A
   Wei, C
   Frese, K
   Mangal, D
   Yu, KH
   Yeo, CJ
   Calhoun, ES
   Scrimieri, F
   Winter, JM
   Hruban, RH
   Iacobuzio-Donahue, C
   Kern, SE
   Blair, IA
   Tuveson, DA
AF De Nicola, Gina M.
   Karreth, Florian A.
   Humpton, Timothy J.
   Gopinathan, Aarthi
   Wei, Cong
   Frese, Kristopher
   Mangal, Dipti
   Yu, Kenneth H.
   Yeo, Charles J.
   Calhoun, Eric S.
   Scrimieri, Francesca
   Winter, Jordan M.
   Hruban, Ralph H.
   Iacobuzio-Donahue, Christine
   Kern, Scott E.
   Blair, Ian A.
   Tuveson, David A.
TI Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
SO NATURE
LA English
DT Article
ID pancreatic-cancer; heme oxygenase-1; k-ras; activation; expression; pathway; inhibition; mutations; induction; elements
AB Reactive oxygen species (ROS) are mutagenic and may thereby promote cancer(1). Normally, ROS levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors and is predominantly regulated by the transcription factor Nrf2 (also known as Nfe212) and its repressor protein Keap1 (refs 2-5). In contrast to the acute physiological regulation of Nrf2, in neoplasia there is evidence for increased basal activation of Nrf2. Indeed, somatic mutations that disrupt the Nrf2-Keap1 interaction to stabilize Nrf2 and increase the constitutive transcription of Nrf2 target genes were recently identified, indicating that enhanced ROS detoxification and additional Nrf2 functions may in fact be pro-tumorigenic(6). Here, we investigated ROS metabolism in primary murine cells following the expression of endogenous oncogenic alleles of Kras, Braf and Myc, and found that ROS are actively suppressed by these oncogenes. K-Ras(G12D), B-Raf(V619E) and Myc(ERT2) each increased the transcription of Nrf2 to stably elevate the basal Nrf2, antioxidant program and thereby lower intracellular ROS and confer a more reduced intracellular environment. Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras(G12D) up and B-Raf(V619E), and in human pancreatic cancer. Furthermore, genetic targeting of the Nrf2 pathway impairs K-Ras(G12D)-induced proliferation and tumorigenesis in vivo. Thus, the Nrf2 antioxidant and cellular detoxification program represents a previously unappreciated mediator of oncogenesis.
C1 [De Nicola, Gina M.; Karreth, Florian A.; Humpton, Timothy J.; Gopinathan, Aarthi; Frese, Kristopher; Tuveson, David A.] Cancer Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [De Nicola, Gina M.; Gopinathan, Aarthi] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Karreth, Florian A.] Univ Vienna, A-1030 Vienna, Austria.
   [Wei, Cong; Mangal, Dipti; Yu, Kenneth H.; Blair, Ian A.] Univ Penn, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA.
   [Yeo, Charles J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA.
   [Calhoun, Eric S.] Alma Coll, Dept Biol, Alma, MI 48801 USA.
   [Scrimieri, Francesca; Hruban, Ralph H.; Iacobuzio-Donahue, Christine; Kern, Scott E.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21287 USA.
   [Winter, Jordan M.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21287 USA.
   [Hruban, Ralph H.; Iacobuzio-Donahue, Christine; Kern, Scott E.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21287 USA.
C3 CRUK Cambridge Institute; Cancer Research UK; University of Pennsylvania; University of Vienna; University of Pennsylvania; Thomas Jefferson University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine
RP Tuveson, DA (corresponding author), Cancer Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England.
EM david.tuveson@cancer.org.uk
FU University of Cambridge; Cancer Research UK; The Li Ka Shing Foundation; Hutchison Whampoa Limited; NIHR Cambridge Biomedical Research Centre; NIH [CA101973, CA111294, CA084291, CA105490, CA62924, CA128920, CA106610]; Abramson Cancer Center of the University of Pennsylvania [IRG 78-002-26]; Emerald Foundation; Marjorie Kovler Fund; Ruth L. Kirschstein National Research Service Award [F32CA123887-01]; National Cancer Institute [P50CA062924] Funding Source: NIH RePORTER
NR 31
TC 1872
Z9 2119
U1 2
U2 374
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 106
EP U128
DI 10.1038/nature10189
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300054
PM 21734707
DA 2026-03-09
ER

PT J
AU Zielke, N
   Kim, KJ
   Tran, V
   Shibutani, ST
   Bravo, MJ
   Nagarajan, S
   van Straaten, M
   Woods, B
   von Dassow, G
   Rottig, C
   Lehner, CF
   Grewal, SS
   Duronio, RJ
   Edgar, BA
AF Zielke, Norman
   Kim, Kerry J.
   Vuong Tran
   Shibutani, Shusaku T.
   Bravo, Maria-Jose
   Nagarajan, Sabarish
   van Straaten, Monique
   Woods, Brigitte
   von Dassow, George
   Rottig, Carmen
   Lehner, Christian F.
   Grewal, Savraj S.
   Duronio, Robert J.
   Edgar, Bruce A.
TI Control of Drosophila endocycles by E2F and CRL4CDT2
SO NATURE
LA English
DT Article
ID dependent kinase inhibitor; cyclin-e; cell-proliferation; s-phase; dna-replication; transcriptional program; endoreplication cycles; developmental control; progression; expression
AB Endocycles are variant cell cycles comprised of DNA synthesis (S)- and gap (G)-phases but lacking mitosis(1,2). Such cycles facilitate post-mitotic growth in many invertebrate and plant cells, and are so ubiquitous that they may account for up to half the world's biomass(3,4). DNA replication in endocycling Drosophila cells is triggered by cyclin E/cyclin dependent kinase 2 (CYCE/CDK2), but this kinase must be inactivated during each G-phase to allow the assembly of pre-Replication Complexes (preRCs) for the next S-phase(5,6). How CYCE/CDK2 is periodically silenced to allow re-replication has not been established. Here, using genetic tests in parallel with computational modelling, we show that the endocycles of Drosophila are driven by a molecular oscillator in which the E2F1 transcription factor promotes CycE expression and S-phase initiation, S-phase then activates the CRL4(CDT2) ubiquitin ligase, and this in turn mediates the destruction of E2F1 (ref. 7). We propose that it is the transient loss of E2F1 during S phases that creates the window of low Cdk activity required for preRC formation. In support of this model overexpressed E2F1 accelerated endocycling, whereas a stabilized variant of E2F1 blocked endocycling by de-regulating target genes, including CycE, as well as Cdk1 and mitotic cyclins. Moreover, we find that altering cell growth by changing nutrition or target of rapamycin (TOR) signalling impacts E2F1 translation, thereby making endocycle progression growth-dependent. Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants(1,2,8), indicating that elements of this mechanism act in most growth-dependent cell cycles.
C1 [Zielke, Norman; van Straaten, Monique; Edgar, Bruce A.] Univ Heidelberg ZMBH Alliance, Zentrum Mol Biol, German Canc Res Ctr DKFZ, D-69120 Heidelberg, Germany.
   [Zielke, Norman; Vuong Tran; Bravo, Maria-Jose; Woods, Brigitte; Edgar, Bruce A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Kim, Kerry J.; von Dassow, George] Univ Washington, Friday Harbor Labs, Ctr Cell Dynam, Friday Harbor, WA 98250 USA.
   [Shibutani, Shusaku T.; Duronio, Robert J.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Nagarajan, Sabarish; Grewal, Savraj S.] Univ Calgary, Clark H Smith Brain Tumor Ctr, So Alberta Canc Res Inst, Calgary, AB T2N 4N1, Canada.
   [Nagarajan, Sabarish; Grewal, Savraj S.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada.
   [Rottig, Carmen; Lehner, Christian F.] Univ Zurich, Inst Mol & Life Sci IMLS, CH-8057 Zurich, Switzerland.
C3 Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Fred Hutchinson Cancer Center; University of Washington; University of North Carolina; University of North Carolina Chapel Hill; University of Calgary; University of Calgary; University of Zurich
RP Edgar, BA (corresponding author), Univ Heidelberg ZMBH Alliance, Zentrum Mol Biol, German Canc Res Ctr DKFZ, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
EM b.edgar@dkfz.de
FU NIH [GM51186, GM57859]; DAAD; NIGMS [5 P50 GM66050]; NSF [MCB0090835]; DFG [LE987/5-1]; CIHR [MOP-86622]
NR 45
TC 121
Z9 150
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 123
EP U296
DI 10.1038/nature10579
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900047
PM 22037307
DA 2026-03-09
ER

PT J
AU Allen, AE
   Dupont, CL
   Oborník, M
   Horák, A
   Nunes-Nesi, A
   McCrow, JP
   Zheng, H
   Johnson, DA
   Hu, HH
   Fernie, AR
   Bowler, C
AF Allen, Andrew E.
   Dupont, Christopher L.
   Obornik, Miroslav
   Horak, Ales
   Nunes-Nesi, Adriano
   McCrow, John P.
   Zheng, Hong
   Johnson, Daniel A.
   Hu, Hanhua
   Fernie, Alisdair R.
   Bowler, Chris
TI Evolution and metabolic significance of the urea cycle in photosynthetic diatoms
SO NATURE
LA English
DT Article
ID carbamoyl-phosphate synthetase; phylogenetic analysis; sequence alignment; tree; inference; accurate; insights; history; mrbayes; genome
AB Diatoms dominate the biomass of phytoplankton in nutrient-rich conditions and form the basis of some of the world's most productive marine food webs(1-4). The diatom nuclear genome contains genes with bacterial and plastid origins as well as genes of the secondary endosymbiotic host (the exosymbiont(5))(1,6-10), yet little is known about the relative contribution of each gene group to diatom metabolism. Here we show that the exosymbiont-derived ornithine-urea cycle, which is similar to that of metazoans but is absent in green algae and plants, facilitates rapid recovery from prolonged nitrogen limitation. RNA-interference-mediated knockdown of a mitochondrial carbamoyl phosphate synthase impairs the response of nitrogen-limited diatoms to nitrogen addition. Metabolomic analyses indicate that intermediates in the ornithine-urea cycle are particularly depleted and that both the tricarboxylic acid cycle and the glutamine synthetase/glutamate synthase cycles are linked directly with the ornithine-urea cycle. Several other depleted metabolites are generated from ornithine-urea cycle intermediates by the products of genes laterally acquired from bacteria. This metabolic coupling of bacterial-and exosymbiont-derived proteins seems to be fundamental to diatom physiology because the compounds affected include the major diatom osmolyte proline(12) and the precursors for long-chain polyamines required for silica precipitation during cell wall formation(11). So far, the ornithine-urea cycle is only known for its essential role in the removal of fixed nitrogen in metazoans. In diatoms, this cycle serves as a distribution and repackaging hub for inorganic carbon and nitrogen and contributes significantly to the metabolic response of diatoms to episodic nitrogen availability. The diatom ornithine-urea cycle therefore represents a key pathway for anaplerotic carbon fixation into nitrogenous compounds that are essential for diatom growth and for the contribution of diatoms to marine productivity.
C1 [Allen, Andrew E.; Dupont, Christopher L.; McCrow, John P.; Zheng, Hong; Johnson, Daniel A.] J Craig Venter Inst, San Diego, CA 92121 USA.
   [Allen, Andrew E.; Hu, Hanhua; Bowler, Chris] Ecole Normale Super, Inst Biol, Environm & Evolutionary Genom Sect, CNRS,UMR8197,INSERM,U1024, F-75005 Paris, France.
   [Obornik, Miroslav; Horak, Ales] Biol Ctr ASCR, Inst Parasitol, Ceske Budejovice 37005, Czech Republic.
   [Obornik, Miroslav; Horak, Ales] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
   [Nunes-Nesi, Adriano; Fernie, Alisdair R.] Max Planck Insitut Mol Pfanzenphysiol, D-14476 Potsdam, Germany.
C3 J. Craig Venter Institute; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Czech Academy of Sciences; Biology Centre of the Czech Academy of Sciences; University of South Bohemia Ceske Budejovice; Max Planck Society
RP Allen, AE (corresponding author), J Craig Venter Inst, San Diego, CA 92121 USA.
EM aallen@jcvi.org
FU National Science Foundation [NSF-OCE-0722374, NSF-OCE-0727997, NSF-MCB-1024913]; JCVI; European Commission; Agence Nationale de la Recherche (France); Czech Science Foundation [206/08/1423]
NR 49
TC 403
Z9 467
U1 5
U2 415
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2011
VL 473
IS 7346
BP 203
EP +
DI 10.1038/nature10074
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200036
PM 21562560
DA 2026-03-09
ER

PT J
AU Hessa, T
   Sharma, A
   Mariappan, M
   Eshleman, HD
   Gutierrez, E
   Hegde, RS
AF Hessa, Tara
   Sharma, Ajay
   Mariappan, Malaiyalam
   Eshleman, Heather D.
   Gutierrez, Erik
   Hegde, Ramanujan S.
TI Protein targeting and degradation are coupled for elimination of mislocalized proteins
SO NATURE
LA English
DT Article
ID signal recognition particle; cytosolic prion protein; quality-control pathway; endoplasmic-reticulum; translocation channel; membrane; neurodegeneration; er; contributes; sequence
AB A substantial proportion of the genome encodes membrane proteins that are delivered to the endoplasmic reticulum by dedicated targeting pathways(1). Membrane proteins that fail targeting must be rapidly degraded to avoid aggregation and disruption of cytosolic protein homeostasis(2,3). The mechanisms of mislocalized protein (MLP) degradation are unknown. Here we reconstitute MLP degradation in vitro to identify factors involved in this pathway. We find that nascent membrane proteins tethered to ribosomes are not substrates for ubiquitination unless they are released into the cytosol. Their inappropriate release results in capture by the Bag6 complex, a recently identified ribosome-associating chaperone(4). Bag6-complex-mediated capture depends on the presence of unprocessed or non-inserted hydrophobic domains that distinguish MLPs from potential cytosolic proteins. A subset of these Bag6 complex 'clients' are transferred to TRC40 for insertion into the membrane, whereas the remainder are rapidly ubiquitinated. Depletion of the Bag6 complex selectively impairs the efficient ubiquitination of MLPs. Thus, by its presence on ribosomes that are synthesizing nascent membrane proteins, the Bag6 complex links targeting and ubiquitination pathways. We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery.
C1 [Hessa, Tara; Sharma, Ajay; Mariappan, Malaiyalam; Eshleman, Heather D.; Gutierrez, Erik; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
   [Gutierrez, Erik] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
C3 National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Johns Hopkins University
RP Hegde, RS (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM hegde.science@gmail.com
FU National Institutes of Health; Wenner-Gren Foundations
NR 38
TC 222
Z9 267
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 JUL 21
PY 2011
VL 475
IS 7356
BP 394
EP U154
DI 10.1038/nature10181
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200046
PM 21743475
DA 2026-03-09
ER

PT J
AU Yalcin, B
   Wong, K
   Agam, A
   Goodson, M
   Keane, TM
   Gan, XC
   Nellåker, C
   Goodstadt, L
   Nicod, J
   Bhomra, A
   Hernandez-Pliego, P
   Whitley, H
   Cleak, J
   Dutton, R
   Janowitz, D
   Mott, R
   Adams, DJ
   Flint, J
AF Yalcin, Binnaz
   Wong, Kim
   Agam, Avigail
   Goodson, Martin
   Keane, Thomas M.
   Gan, Xiangchao
   Nellaker, Christoffer
   Goodstadt, Leo
   Nicod, Jerome
   Bhomra, Amarjit
   Hernandez-Pliego, Polinka
   Whitley, Helen
   Cleak, James
   Dutton, Rebekah
   Janowitz, Deborah
   Mott, Richard
   Adams, David J.
   Flint, Jonathan
TI Sequence-based characterization of structural variation in the mouse genome
SO NATURE
LA English
DT Article
ID copy number variation; heterogeneous stock mice; gene-expression; t-cells; disease; rearrangements; mechanism
AB Structural variation is widespread in mammalian genomes(1,2) and is an important cause of disease(3), but just how abundant and important structural variants (SVs) are in shaping phenotypic variation remains unclear(4,5). Without knowing how many SVs there are, and how they arise, it is difficult to discover what they do. Combining experimental with automated analyses, we identified 711,920 SVs at 281,243 sites in the genomes of thirteen classical and four wild-derived inbred mouse strains. The majority of SVs are less than 1 kilobase in size and 98% are deletions or insertions. The breakpoints of 160,000 SVs were mapped to base pair resolution, allowing us to infer that insertion of retrotransposons causes more than half of SVs. Yet, despite their prevalence, SVs are less likely than other sequence variants to cause gene expression or quantitative phenotypic variation. We identified 24 SVs that disrupt coding exons, acting as rare variants of large effect on gene function. One-third of the genes so affected have immunological functions.
C1 [Yalcin, Binnaz; Agam, Avigail; Goodson, Martin; Gan, Xiangchao; Goodstadt, Leo; Nicod, Jerome; Bhomra, Amarjit; Hernandez-Pliego, Polinka; Whitley, Helen; Cleak, James; Dutton, Rebekah; Janowitz, Deborah; Mott, Richard; Flint, Jonathan] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Wong, Kim; Keane, Thomas M.; Adams, David J.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Agam, Avigail; Nellaker, Christoffer] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Janowitz, Deborah] Ernst Moritz Arndt Univ Greifswald, Klinikum Hansestadt Stralsund, Dept Psychiat & Psychotherapy, D-18437 Stralsund, Germany.
C3 University of Oxford; Wellcome Centre for Human Genetics; Wellcome Trust Sanger Institute; University of Oxford; Universitat Greifswald
RP Flint, J (corresponding author), Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM da1@sanger.ac.uk; jf@well.ox.ac.uk
FU Medical Research Council, UK; Wellcome Trust; Cancer Research UK; Medical Research Council [G0800024, MC_U137761446, MC_EX_G0802457] Funding Source: researchfish; MRC [G0800024, MC_U137761446, MC_EX_G0802457] Funding Source: UKRI
NR 29
TC 249
Z9 294
U1 5
U2 29
PU 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 15
PY 2011
VL 477
IS 7364
BP 326
EP 329
DI 10.1038/nature10432
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400030
PM 21921916
DA 2026-03-09
ER

PT J
AU Hiller, DA
   Singh, V
   Zhong, MH
   Strobel, SA
AF Hiller, David A.
   Singh, Vipender
   Zhong, Minghong
   Strobel, Scott A.
TI A two-step chemical mechanism for ribosome-catalysed peptide bond formation
SO NATURE
LA English
DT Article
ID transition-state; transferase reaction; transfer-rna; hydrazinolysis; intermediate; 2'-hydroxyl; aminolysis; reveals; 2'-oh; water
AB The chemical step of natural protein synthesis, peptide bond formation, is catalysed by the large subunit of the ribosome. Crystal structures have shown that the active site for peptide bond formation is composed entirely of RNA(1). Recent work has focused on how an RNA active site is able to catalyse this fundamental biological reaction at a suitable rate for protein synthesis. On the basis of the absence of important ribosomal functional groups(2), lack of a dependence on pH(3), and the dominant contribution of entropy to catalysis(4), it has been suggested that the role of the ribosome is limited to bringing the substrates into close proximity. Alternatively, the importance of the 2'-hydroxyl of the peptidyl-transfer RNA(5) and a Bronsted coefficient near zero(6) have been taken as evidence that the ribosome coordinates a proton-transfer network. Here we report the transition state of peptide bond formation, based on analysis of the kinetic isotope effect at five positions within the reaction centre of a peptidyl-transfer RNA mimic. Our results indicate that in contrast to the uncatalysed reaction, formation of the tetrahedral intermediate and proton transfer from the nucleophilic nitrogen both occur in the rate-limiting step. Unlike in previous proposals, the reaction is not fully concerted; instead, breakdown of the tetrahedral intermediate occurs in a separate fast step. This suggests that in addition to substrate positioning, the ribosome is contributing to chemical catalysis by changing the rate-limiting transition state.
C1 [Hiller, David A.; Singh, Vipender; Zhong, Minghong; Strobel, Scott A.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
C3 Yale University
RP Strobel, SA (corresponding author), Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
EM scott.strobel@yale.edu
FU NIH [GM54839]; Brown-Coxe fellowship
NR 30
TC 65
Z9 90
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 AUG 11
PY 2011
VL 476
IS 7359
BP 236
EP U143
DI 10.1038/nature10248
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900043
PM 21765427
DA 2026-03-09
ER

PT J
AU Okamoto, I
   Patrat, C
   Thépot, D
   Peynot, N
   Fauque, P
   Daniel, N
   Diabangouaya, P
   Wolf, JP
   Renard, JP
   Duranthon, V
   Heard, E
AF Okamoto, Ikuhiro
   Patrat, Catherine
   Thepot, Dominique
   Peynot, Nathalie
   Fauque, Patricia
   Daniel, Nathalie
   Diabangouaya, Patricia
   Wolf, Jean-Philippe
   Renard, Jean-Paul
   Duranthon, Veronique
   Heard, Edith
TI Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development
SO NATURE
LA English
DT Article
ID early mouse development; nuclear transfer; xist expression; cloned rabbits; somatic-cells; gene; embryos; mice; establishment; methylation
AB X-chromosome inactivation (XCI) in female mammals allows dosage compensation for X-linked gene products between the sexes(1). The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript). Paternal XCI is reversed in the inner cell mass of the blastocyst and random XCI subsequently occurs in epiblast cells. Here we show that other eutherian mammals have very different strategies for initiating XCI. In rabbits and humans, the Xist homologue is not subject to imprinting and XCI begins later than in mice. Furthermore, Xist is upregulated on both X chromosomes in a high proportion of rabbit and human embryo cells, even in the inner cell mass. In rabbits, this triggers XCI on both X chromosomes in some cells. In humans, chromosome-wide XCI has not initiated even by the blastocyst stage, despite the upregulation of XIST. The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice. Our study demonstrates the remarkable diversity in XCI regulation and highlights differences between mammals in their requirement for dosage compensation during early embryogenesis.
C1 [Okamoto, Ikuhiro; Patrat, Catherine; Diabangouaya, Patricia; Heard, Edith] Inst Curie, Mammalian Dev Epigenet Grp, CNRS UMR 3215, INSERM,U934, F-75248 Paris, France.
   [Patrat, Catherine] Univ Paris Diderot, Hop Bichat Claude Bernard, Assistance Publ Hop Paris, Serv Biol Reprod, F-75018 Paris, France.
   [Thepot, Dominique; Peynot, Nathalie; Daniel, Nathalie; Renard, Jean-Paul; Duranthon, Veronique] INRA, UMR Biol Dev & Reprod 1198, F-78352 Jouy En Josas, France.
   [Diabangouaya, Patricia] Univ Bourgogne, CHU Dijon, Lab Biol Reprod CECOS, F-21079 Dijon, France.
   [Fauque, Patricia] Inst Curie, INSERM, CNRS UMR 3215, F-75248 Paris, France.
   [Wolf, Jean-Philippe] Univ Paris 05, Unite 1016, INSERM, Assistance Publ Hop Paris,Serv Biol,Hop Cochin, F-75014 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Bichat-Claude Bernard - APHP; Universite Paris Saclay; INRAE; Universite Bourgogne Europe; CHU Dijon Bourgogne; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Cochin - APHP
RP Heard, E (corresponding author), Inst Curie, Mammalian Dev Epigenet Grp, CNRS UMR 3215, INSERM,U934, F-75248 Paris, France.
EM veronique.duranthon@jouy.inra.fr; edith.heard@curie.fr
FU FRM (Equipe FRM); ANR; ERC; Agence de Biomedecine; INRA PHASE department
CR BARLOW P, 1970, NATURE, V226, P961, DOI 10.1038/226961a0
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NR 38
TC 354
Z9 412
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 370
EP U141
DI 10.1038/nature09872
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600044
PM 21471966
DA 2026-03-09
ER

PT J
AU Larschan, E
   Bishop, EP
   Kharchenko, PV
   Core, LJ
   Lis, JT
   Park, PJ
   Kuroda, MI
AF Larschan, Erica
   Bishop, Eric P.
   Kharchenko, Peter V.
   Core, Leighton J.
   Lis, John T.
   Park, Peter J.
   Kuroda, Mitzi I.
TI X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila
SO NATURE
LA English
DT Article
ID msl complex; h4-k16 acetylation; analysis reveals; rna-polymerase; genes; genome; melanogaster; initiation; yeast; mof
AB The evolution of sex chromosomes has resulted innumerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes(1). The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed(2) that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 39 ends(3-7). However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) 8 to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.
C1 [Larschan, Erica; Kuroda, Mitzi I.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Larschan, Erica; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Larschan, Erica] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
   [Bishop, Eric P.; Kharchenko, Peter V.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Bishop, Eric P.; Kharchenko, Peter V.; Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Bishop, Eric P.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
   [Core, Leighton J.; Lis, John T.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Brown University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Boston University; Cornell University
RP Kuroda, MI (corresponding author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM peter_park@harvard.edu; mkuroda@genetics.med.harvard.edu
FU NIH [GM45744, GM082798, HG4845]; Medical Foundation
NR 28
TC 148
Z9 187
U1 1
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 115
EP U139
DI 10.1038/nature09757
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100045
PM 21368835
DA 2026-03-09
ER

PT J
AU Chapman, HN
   Fromme, P
   Barty, A
   White, TA
   Kirian, RA
   Aquila, A
   Hunter, MS
   Schulz, J
   DePonte, DP
   Weierstall, U
   Doak, RB
   Maia, FRNC
   Martin, AV
   Schlichting, I
   Lomb, L
   Coppola, N
   Shoeman, RL
   Epp, SW
   Hartmann, R
   Rolles, D
   Rudenko, A
   Foucar, L
   Kimmel, N
   Weidenspointner, G
   Holl, P
   Liang, MN
   Barthelmess, M
   Caleman, C
   Boutet, S
   Bogan, MJ
   Krzywinski, J
   Bostedt, C
   Bajt, S
   Gumprecht, L
   Rudek, B
   Erk, B
   Schmidt, C
   Hömke, A
   Reich, C
   Pietschner, D
   Strüder, L
   Hauser, G
   Gorke, H
   Ullrich, J
   Herrmann, S
   Schaller, G
   Schopper, F
   Soltau, H
   Kühnel, KU
   Messerschmidt, M
   Bozek, JD
   Hau-Riege, SP
   Frank, M
   Hampton, CY
   Sierra, RG
   Starodub, D
   Williams, GJ
   Hajdu, J
   Timneanu, N
   Seibert, MM
   Andreasson, J
   Rocker, A
   Jönsson, O
   Svenda, M
   Stern, S
   Nass, K
   Andritschke, R
   Schröter, CD
   Krasniqi, F
   Bott, M
   Schmidt, KE
   Wang, XY
   Grotjohann, I
   Holton, JM
   Barends, TRM
   Neutze, R
   Marchesini, S
   Fromme, R
   Schorb, S
   Rupp, D
   Adolph, M
   Gorkhover, T
   Andersson, I
   Hirsemann, H
   Potdevin, G
   Graafsma, H
   Nilsson, B
   Spence, JCH
AF Chapman, Henry N.
   Fromme, Petra
   Barty, Anton
   White, Thomas A.
   Kirian, Richard A.
   Aquila, Andrew
   Hunter, Mark S.
   Schulz, Joachim
   DePonte, Daniel P.
   Weierstall, Uwe
   Doak, R. Bruce
   Maia, Filipe R. N. C.
   Martin, Andrew V.
   Schlichting, Ilme
   Lomb, Lukas
   Coppola, Nicola
   Shoeman, Robert L.
   Epp, Sascha W.
   Hartmann, Robert
   Rolles, Daniel
   Rudenko, Artem
   Foucar, Lutz
   Kimmel, Nils
   Weidenspointner, Georg
   Holl, Peter
   Liang, Mengning
   Barthelmess, Miriam
   Caleman, Carl
   Boutet, Sebastien
   Bogan, Michael J.
   Krzywinski, Jacek
   Bostedt, Christoph
   Bajt, Sasa
   Gumprecht, Lars
   Rudek, Benedikt
   Erk, Benjamin
   Schmidt, Carlo
   Hoemke, Andre
   Reich, Christian
   Pietschner, Daniel
   Strueder, Lothar
   Hauser, Guenter
   Gorke, Hubert
   Ullrich, Joachim
   Herrmann, Sven
   Schaller, Gerhard
   Schopper, Florian
   Soltau, Heike
   Kuehnel, Kai-Uwe
   Messerschmidt, Marc
   Bozek, John D.
   Hau-Riege, Stefan P.
   Frank, Matthias
   Hampton, Christina Y.
   Sierra, Raymond G.
   Starodub, Dmitri
   Williams, Garth J.
   Hajdu, Janos
   Timneanu, Nicusor
   Seibert, M. Marvin
   Andreasson, Jakob
   Rocker, Andrea
   Joensson, Olof
   Svenda, Martin
   Stern, Stephan
   Nass, Karol
   Andritschke, Robert
   Schroeter, Claus-Dieter
   Krasniqi, Faton
   Bott, Mario
   Schmidt, Kevin E.
   Wang, Xiaoyu
   Grotjohann, Ingo
   Holton, James M.
   Barends, Thomas R. M.
   Neutze, Richard
   Marchesini, Stefano
   Fromme, Raimund
   Schorb, Sebastian
   Rupp, Daniela
   Adolph, Marcus
   Gorkhover, Tais
   Andersson, Inger
   Hirsemann, Helmut
   Potdevin, Guillaume
   Graafsma, Heinz
   Nilsson, Bjoern
   Spence, John C. H.
TI Femtosecond X-ray protein nanocrystallography
SO NATURE
LA English
DT Article
ID refinement
AB X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded(1-3). It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source(4). We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes(5). More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (similar to 200 nm to 2 mm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes(6). This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
C1 [Chapman, Henry N.; Barty, Anton; White, Thomas A.; Aquila, Andrew; Schulz, Joachim; DePonte, Daniel P.; Martin, Andrew V.; Coppola, Nicola; Liang, Mengning; Caleman, Carl; Gumprecht, Lars; Stern, Stephan] DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Chapman, Henry N.; Nass, Karol] Univ Hamburg, D-22761 Hamburg, Germany.
   [Fromme, Petra; Hunter, Mark S.; Grotjohann, Ingo; Fromme, Raimund] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Kirian, Richard A.; Weierstall, Uwe; Doak, R. Bruce; Schmidt, Kevin E.; Wang, Xiaoyu; Spence, John C. H.] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA.
   [Maia, Filipe R. N. C.; Hajdu, Janos; Timneanu, Nicusor; Seibert, M. Marvin; Andreasson, Jakob; Rocker, Andrea; Joensson, Olof; Svenda, Martin] Uppsala Univ, Dept Cell & Mol Biol, Lab Mol Biophys, SE-75124 Uppsala, Sweden.
   [Schlichting, Ilme; Epp, Sascha W.; Rolles, Daniel; Rudenko, Artem; Foucar, Lutz; Rudek, Benedikt; Erk, Benjamin; Schmidt, Carlo; Hoemke, Andre; Strueder, Lothar; Ullrich, Joachim; Krasniqi, Faton] Max Planck Adv Study Grp, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Schlichting, Ilme; Lomb, Lukas; Shoeman, Robert L.; Rolles, Daniel; Foucar, Lutz; Krasniqi, Faton; Bott, Mario; Barends, Thomas R. M.] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [Epp, Sascha W.; Rudenko, Artem; Rudek, Benedikt; Erk, Benjamin; Schmidt, Carlo; Hoemke, Andre; Ullrich, Joachim; Kuehnel, Kai-Uwe; Schroeter, Claus-Dieter] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Hartmann, Robert; Holl, Peter; Reich, Christian; Soltau, Heike] PNSensor GmbH, D-81739 Munich, Germany.
   [Kimmel, Nils; Weidenspointner, Georg; Pietschner, Daniel; Strueder, Lothar; Hauser, Guenter; Herrmann, Sven; Schaller, Gerhard; Schopper, Florian; Andritschke, Robert] Max Planck Inst Halbleiterlab, D-81739 Munich, Germany.
   [Weidenspointner, Georg] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Boutet, Sebastien; Krzywinski, Jacek; Bostedt, Christoph; Messerschmidt, Marc; Bozek, John D.; Williams, Garth J.] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Bogan, Michael J.; Hampton, Christina Y.; Sierra, Raymond G.; Starodub, Dmitri] SLAC Natl Accelerator Lab, PULSE Inst, Menlo Pk, CA 94025 USA.
   [Gorke, Hubert] Forschungszentrum Julich, Inst ZEL, D-52425 Julich, Germany.
   [Hau-Riege, Stefan P.; Frank, Matthias] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Holton, James M.; Marchesini, Stefano] Lawrence Berkeley Natl Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Neutze, Richard] Univ Gothenburg, Dept Chem Biochem & Biophys, SE-40530 Gothenburg, Sweden.
   [Schorb, Sebastian; Rupp, Daniela; Adolph, Marcus; Gorkhover, Tais] Tech Univ Berlin, Inst Opt & Atomare Phys, D-10623 Berlin, Germany.
   [Andersson, Inger] Swedish Univ Agr Sci, Uppsala Biomed Ctr, Dept Mol Biol, S-75124 Uppsala, Sweden.
C3 Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Hamburg; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Uppsala University; Max Planck Society; Max Planck Society; Max Planck Society; PNSensor GmbH; Max Planck Society; Max Planck Society; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Helmholtz Association; Julich Research Centre; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Gothenburg; Technical University of Berlin; Swedish University of Agricultural Sciences
RP Chapman, HN (corresponding author), DESY, Ctr Free Electron Laser Sci, Notkestr 85, D-22607 Hamburg, Germany.
EM henry.chapman@desy.de
FU DOE through the PULSE Institute at the SLAC National Accelerator Laboratory; Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Center for Bio-Inspired Solar Fuel Production; DOE, Office of Basic Energy Sciences [DE-SC0001016]; Hamburg Ministry of Science and Research; Joachim Herz Stiftung; Hamburg Initiative for Excellence in Research (LEXI); Hamburg School for Structure and Dynamics; Max Planck Society; US National Science Foundation [0417142, MCB-1021557]; US National Institutes of Health [1R01GM095583-01, 1U54GM094625-01]; Swedish Research Council; Swedish Foundation for International Cooperation in Research and Higher Education; Stiftelsen Olle Engkvist Byggmastare; DFG Cluster of Excellence at the Munich Centre for Advanced Photonics; CBST at the University of California [PHY 0120999]; U.S. Department of Energy (DOE) [DE-SC0001016] Funding Source: U.S. Department of Energy (DOE); National Institute of General Medical Sciences [R01GM095583] Funding Source: NIH RePORTER; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1021557] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0919195, 0417142] Funding Source: National Science Foundation
NR 35
TC 1782
Z9 2042
U1 4
U2 636
PU NATURE PUBLISHING 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 3
PY 2011
VL 470
IS 7332
BP 73
EP U81
DI 10.1038/nature09750
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400036
PM 21293373
DA 2026-03-09
ER

PT J
AU Valouev, A
   Johnson, SM
   Boyd, SD
   Smith, CL
   Fire, AZ
   Sidow, A
AF Valouev, Anton
   Johnson, Steven M.
   Boyd, Scott D.
   Smith, Cheryl L.
   Fire, Andrew Z.
   Sidow, Arend
TI Determinants of nucleosome organization in primary human cells
SO NATURE
LA English
DT Article
ID high-resolution; human genome; saccharomyces-cerevisiae; c. elegans; in-vivo; chromatin; dna; sequence; yeast; methylations
AB Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodelling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome(1). Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions(2-4). To identify major determinants of nucleosome organization in the human genome, we used deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome showed substantial flexibility of nucleosome positions, whereas a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells.
C1 [Valouev, Anton; Boyd, Scott D.; Smith, Cheryl L.; Fire, Andrew Z.; Sidow, Arend] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
   [Johnson, Steven M.] Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA.
   [Fire, Andrew Z.; Sidow, Arend] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
C3 Stanford University; Brigham Young University; Stanford University
RP Sidow, A (corresponding author), Stanford Univ, Dept Pathol, Sch Med, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM afire@stanford.edu; arend@stanford.edu
FU NIGMS [R01GM37706]; NHGRI [U01HG004695, T32HG00044]; National Human Genome Research Institute [T32HG000044] Funding Source: NIH RePORTER
NR 34
TC 508
Z9 613
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 JUN 23
PY 2011
VL 474
IS 7352
BP 516
EP U148
DI 10.1038/nature10002
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700050
PM 21602827
DA 2026-03-09
ER

PT J
AU Baker, DJ
   Wijshake, T
   Tchkonia, T
   LeBrasseur, NK
   Childs, BG
   van de Sluis, B
   Kirkland, JL
   van Deursen, JM
AF Baker, Darren J.
   Wijshake, Tobias
   Tchkonia, Tamar
   LeBrasseur, Nathan K.
   Childs, Bennett G.
   van de Sluis, Bart
   Kirkland, James L.
   van Deursen, Jan M.
TI Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
SO NATURE
LA English
DT Article
ID tumor-suppressor; bubr1 insufficiency; oncogenic ras; mutant mice; expression; mouse; fibroblasts; phenotypes; inhibitor; biomarker
AB Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells(1,2). Senescent cells accumulate in various tissues and organs with ageing(3) and have been hypothesized to disrupt tissue structure and function because of the components they secrete(4,5). However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues-such as adipose tissue, skeletal muscle and eye-in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
C1 [Baker, Darren J.; Wijshake, Tobias; Childs, Bennett G.; van Deursen, Jan M.] Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
   [Baker, Darren J.; Tchkonia, Tamar; LeBrasseur, Nathan K.; Kirkland, James L.; van Deursen, Jan M.] Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN 55905 USA.
   [Wijshake, Tobias; van de Sluis, Bart] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9700 RB Groningen, Netherlands.
C3 Mayo Clinic; Mayo Clinic; University of Groningen
RP van Deursen, JM (corresponding author), Mayo Clin, Coll Med, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
EM vandeursen.jan@mayo.edu
FU Ellison Medical Foundation; Noaber Foundation; Robert and Arlene Kogod Center on Aging; National Institutes of Health [CA96985, AG13925]; National Cancer Institute [R01CA096985] Funding Source: NIH RePORTER; National Institute on Aging [R37AG013925] Funding Source: NIH RePORTER
NR 30
TC 2905
Z9 3398
U1 15
U2 418
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 232
EP U112
DI 10.1038/nature10600
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800043
PM 22048312
DA 2026-03-09
ER

PT J
AU Franosch, T
   Grimm, M
   Belushkin, M
   Mor, FM
   Foffi, G
   Forró, L
   Jeney, S
AF Franosch, Thomas
   Grimm, Matthias
   Belushkin, Maxim
   Mor, Flavio M.
   Foffi, Giuseppe
   Forro, Laszlo
   Jeney, Sylvia
TI Resonances arising from hydrodynamic memory in Brownian motion
SO NATURE
LA English
DT Article
ID optical-tweezers; complex fluids; actin networks; single cells; technology
AB Observation of the Brownian motion of a small probe interacting with its environment provides one of the main strategies for characterizing soft matter(1-4). Essentially, two counteracting forces govern the motion of the Brownian particle. First, the particle is driven by rapid collisions with the surrounding solvent molecules, referred to as thermal noise. Second, the friction between the particle and the viscous solvent damps its motion. Conventionally, the thermal force is assumed to be random and characterized by a Gaussian white noise spectrum. The friction is assumed to be given by the Stokes drag, suggesting that motion is overdamped at long times in particle tracking experiments, when inertia becomes negligible. However, as the particle receives momentum from the fluctuating fluid molecules, it also displaces the fluid in its immediate vicinity. The entrained fluid acts back on the particle and gives rise to long-range correlations(5,6). This hydrodynamic 'memory' translates to thermal forces, which have a coloured, that is, non-white, noise spectrum. One hundred years after Perrin's pioneering experiments on Brownian motion(7-9), direct experimental observation of this colour is still elusive(10). Here we measure the spectrum of thermal noise by confining the Brownian fluctuations of a microsphere in a strong optical trap. We show that hydrodynamic correlations result in a resonant peak in the power spectral density of the sphere's positional fluctuations, in strong contrast to overdamped systems. Furthermore, we demonstrate different strategies to achieve peak amplification. By analogy with microcantilever-based sensors(11,12), our results reveal that the particle-fluid-trap system can be considered a nanomechanical resonator in which the intrinsic hydrodynamic backflow enhances resonance. Therefore, instead of being treated as a disturbance, details in thermal noise could be exploited for the development of new types of sensor and particle-based assay in lab-on-a-chip applications(13,14).
C1 [Grimm, Matthias; Jeney, Sylvia] Univ Basel, Biozentrum, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland.
   [Franosch, Thomas] Univ Erlangen Nurnberg, Inst Theoret Phys, D-91058 Erlangen, Germany.
   [Grimm, Matthias; Mor, Flavio M.; Forro, Laszlo; Jeney, Sylvia] Ecole Polytech Fed Lausanne, Lab Phys Complex Matter, CH-1015 Lausanne, Switzerland.
   [Belushkin, Maxim; Foffi, Giuseppe] Ecole Polytech Fed Lausanne, Inst Theoret Phys, CH-1015 Lausanne, Switzerland.
C3 University of Basel; University of Erlangen Nuremberg; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Jeney, S (corresponding author), Univ Basel, Biozentrum, ME Muller Inst Struct Biol, Klingelbergstr 70, CH-4056 Basel, Switzerland.
EM sylvia.jeney@epfl.ch
FU Swiss National Science Foundation (SNF) [200021-113529, 206021-121396]; NCCR Nanoscale Science; German Academic Exchange Service (DAAD); National Competence Center in Biomedical Imaging (NCCBI); SNF [PP0022_119006]; Swiss National Science Foundation (SNF) [206021_121396] Funding Source: Swiss National Science Foundation (SNF)
NR 31
TC 323
Z9 356
U1 1
U2 242
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 85
EP 88
DI 10.1038/nature10498
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400039
PM 21979048
DA 2026-03-09
ER

PT J
AU Schreiber, A
   Stengel, F
   Zhang, ZG
   Enchev, RI
   Kong, EH
   Morris, EP
   Robinson, CV
   da Fonseca, PCA
   Barford, D
AF Schreiber, Anne
   Stengel, Florian
   Zhang, Ziguo
   Enchev, Radoslav I.
   Kong, Eric H.
   Morris, Edward P.
   Robinson, Carol V.
   da Fonseca, Paula C. A.
   Barford, David
TI Structural basis for the subunit assembly of the anaphase-promoting complex
SO NATURE
LA English
DT Article
ID crystal-structure; evolutionary conservation; saccharomyces-cerevisiae; protein; complex/cyclosome; expression; insights; cyclin; visualization; purification
AB The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. Information on how its 13 constituent proteins are assembled, and how they interact with co-activators, substrates and regulatory proteins is limited. Here, we describe a recombinant expression system that allows the reconstitution of holo APC/C and its sub-complexes that, when combined with electron microscopy, mass spectrometry and docking of crystallographic and homology-derived coordinates, provides a precise definition of the organization and structure of all essential APC/C subunits, resulting in a pseudo-atomic model for 70% of the APC/C. A lattice-like appearance of the APC/C is generated by multiple repeat motifs of most APC/C subunits. Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates.
C1 [Schreiber, Anne; Zhang, Ziguo; Enchev, Radoslav I.; Kong, Eric H.; Morris, Edward P.; da Fonseca, Paula C. A.; Barford, David] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England.
   [Stengel, Florian; Robinson, Carol V.] Univ Oxford, Dept Chem, Oxford OX1 3TA, England.
C3 University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; University of Oxford
RP Barford, D (corresponding author), Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, 237 Fulham Rd, London SW3 6JB, England.
EM david.barford@icr.ac.uk
FU Cancer Research UK; EU [HEALTH-F4-2008-201648]
NR 56
TC 142
Z9 177
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 227
EP +
DI 10.1038/nature09756
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200037
PM 21307936
DA 2026-03-09
ER

PT J
AU Moussion, C
   Girard, JP
AF Moussion, Christine
   Girard, Jean-Philippe
TI Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules
SO NATURE
LA English
DT Article
ID vascular addressin expression; selectin ligand biosynthesis; tumor-necrosis-factor; cd8(+) t-cells; in-vivo; bone-marrow; trafficking; vessels; proliferation; modulation
AB While patrolling the body in search of foreign antigens, naive lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood(1,2). This process, called lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body's own cells. However, the mechanisms that regulate lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T lymphocytes(3), control the entry of naive lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in lymphocyte recruitment(2,4,5). We found that in vivo depletion of CD11c(+) DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-beta-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of lymphocyte recirculation during immune surveillance.
C1 [Moussion, Christine; Girard, Jean-Philippe] CNRS, Inst Pharmacol & Biol Struct, F-31077 Toulouse, France.
   [Moussion, Christine; Girard, Jean-Philippe] Univ Toulouse, UPS, Inst Pharmacol & Biol Struct, F-31077 Toulouse, France.
C3 Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS)
RP Girard, JP (corresponding author), CNRS, Inst Pharmacol & Biol Struct, 205 Route Narbonne, F-31077 Toulouse, France.
EM Jean-Philippe.Girard@ipbs.fr
FU Ligue Nationale Contre le Cancer; Association pour la Recherche contre le Cancer (ARC) [8505]; French Ministry of Research; Fondation RITC
NR 37
TC 264
Z9 295
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 24
PY 2011
VL 479
IS 7374
BP 542
EP U273
DI 10.1038/nature10540
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600054
PM 22080953
DA 2026-03-09
ER

PT J
AU De Fazio, S
   Bartonicek, N
   Di Giacomo, M
   Abreu-Goodger, C
   Sankar, A
   Funaya, C
   Antony, C
   Moreira, PN
   Enright, AJ
   O'Carroll, D
AF De Fazio, Serena
   Bartonicek, Nenad
   Di Giacomo, Monica
   Abreu-Goodger, Cei
   Sankar, Aditya
   Funaya, Charlotta
   Antony, Claude
   Moreira, Pedro N.
   Enright, Anton J.
   O'Carroll, Donal
TI The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements
SO NATURE
LA English
DT Article
ID dna methylation; piwi proteins; gene; pathway; risc; retrotransposon; transposons; argonaute2; expression; rnas
AB Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing(1). The murine Piwi proteins Mili and Miwi2 (also called Piwil2 and Piwil4, respectively) direct epigenetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line(2-4). Piwi proteins are proposed to be piRNA-guided endonucleases that initiate secondary piRNA biogenesis(5-7); however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the Mili(DAH) and Miwi2(DAH) alleles, respectively. Analysis of Mili-bound piRNAs from homozygous Mili(DAH) fetal gonadocytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in Mili(DAH) mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2(DAH) mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing.
C1 [De Fazio, Serena; Di Giacomo, Monica; Sankar, Aditya; Moreira, Pedro N.; O'Carroll, Donal] European Mol Biol Lab, Mouse Biol Unit, I-00015 Monterotondo, Italy.
   [Bartonicek, Nenad; Abreu-Goodger, Cei; Enright, Anton J.] European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Funaya, Charlotta; Antony, Claude] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; European Molecular Biology Laboratory (EMBL)
RP O'Carroll, D (corresponding author), European Mol Biol Lab, Mouse Biol Unit, Via Ramarini 32, I-00015 Monterotondo, Italy.
EM ocarroll@embl.it
NR 40
TC 287
Z9 317
U1 4
U2 37
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 259
EP U148
DI 10.1038/nature10547
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200055
PM 22020280
DA 2026-03-09
ER

PT J
AU Murakoshi, H
   Wang, H
   Yasuda, R
AF Murakoshi, Hideji
   Wang, Hong
   Yasuda, Ryohei
TI Local, persistent activation of Rho GTPases during plasticity of single dendritic spines
SO NATURE
LA English
DT Article
ID long-term potentiation; kinase; proteins; dynamics; actin; cultures; binding
AB The Rho family of GTPases have important roles in the morphogenesis of the dendritic spines(1-3) of neurons in the brain and synaptic plasticity(4-9) by modulating the organization of the actin cytoskeleton(10). Here we used two-photon fluorescence lifetime imaging microscopy(11-13) to monitor the activity of two Rho GTPases-RhoA and Cdc42-in single dendritic spines undergoing structural plasticity associated with long-term potentiation in CA1 pyramidal neurons in cultured slices of rat hippocampus. When long-term volume increase was induced in a single spine using two-photon glutamate uncaging(14,15), RhoA and Cdc42 were rapidly activated in the stimulated spine. These activities decayed over about five minutes, and were then followed by a phase of persistent activation lasting more than half an hour. Although active RhoA and Cdc42 were similarly mobile, their activity patterns were different. RhoA activation diffused out of the stimulated spine and spread over about 5 mm along the dendrite. In contrast, Cdc42 activation was restricted to the stimulated spine, and exhibited a steep gradient at the spine necks. Inhibition of the Rho-Rock pathway preferentially inhibited the initial spine growth, whereas the inhibition of the Cdc42-Pak pathway blocked the maintenance of sustained structural plasticity. RhoA and Cdc42 activation depended on Ca2+/calmodulin-dependent kinase (CaMKII). Thus, RhoA and Cdc42 relay transient CaMKII activation(13) to synapse-specific, long-term signalling required for spine structural plasticity.
C1 [Murakoshi, Hideji; Wang, Hong; Yasuda, Ryohei] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
   [Yasuda, Ryohei] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
C3 Duke University; Duke University; Howard Hughes Medical Institute
RP Yasuda, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
EM yasuda@neuro.duke.edu
FU Howard Hughes Medical Institute; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Drug Abuse; Alzheimer's Association; Japan Society for the Promotion of Science; National Institute of Mental Health [R01MH080047] Funding Source: NIH RePORTER
NR 40
TC 441
Z9 555
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 APR 7
PY 2011
VL 472
IS 7341
BP 100
EP U132
DI 10.1038/nature09823
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400045
PM 21423166
DA 2026-03-09
ER

PT J
AU Sahay, A
   Scobie, KN
   Hill, AS
   O'Carroll, CM
   Kheirbek, MA
   Burghardt, NS
   Fenton, AA
   Dranovsky, A
   Hen, R
AF Sahay, Amar
   Scobie, Kimberly N.
   Hill, Alexis S.
   O'Carroll, Colin M.
   Kheirbek, Mazen A.
   Burghardt, Nesha S.
   Fenton, Andre A.
   Dranovsky, Alex
   Hen, Rene
TI Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation
SO NATURE
LA English
DT Article
ID dentate gyrus; synaptic plasticity; fluoxetine; maturation; neurons; brain; depression; disorder; models; memory
AB Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life(1,2). Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation(3) and can account for up to ten per cent of the entire granule cell population(4). Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning(5), environmental enrichment(6), exercise(6) and chronic treatment with antidepressants(7-10). Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions(11), as well as some of the behavioural effects of antidepressants(8-10,12,13), it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing(14,15).
C1 [Sahay, Amar; Scobie, Kimberly N.; Hill, Alexis S.; O'Carroll, Colin M.; Kheirbek, Mazen A.; Burghardt, Nesha S.; Dranovsky, Alex; Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY 10032 USA.
   [Sahay, Amar; Scobie, Kimberly N.; Hill, Alexis S.; O'Carroll, Colin M.; Kheirbek, Mazen A.; Burghardt, Nesha S.; Dranovsky, Alex; Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Sahay, Amar; Scobie, Kimberly N.; Hill, Alexis S.; O'Carroll, Colin M.; Kheirbek, Mazen A.; Burghardt, Nesha S.; Dranovsky, Alex; Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA.
   [Fenton, Andre A.] SUNY, Downstate Med Ctr, Robert F Furchgott Ctr Neural & Behav Sci, Dept Physiol, Brooklyn, NY 11203 USA.
   [Fenton, Andre A.] SUNY, Downstate Med Ctr, Dept Pharmacol & Neurol, Brooklyn, NY 11203 USA.
   [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; New York State Psychiatry Institute; State University of New York (SUNY) System; SUNY Downstate Health Sciences University; SUNY Maritime College; State University of New York (SUNY) System; SUNY Downstate Health Sciences University; SUNY Maritime College; Columbia University
RP Sahay, A (corresponding author), Columbia Univ, Dept Neurosci, New York, NY 10032 USA.
EM as2619@columbia.edu; rh95@columbia.edu
FU National Institute of Mental Health [1K99MH86615-01]; National Alliance for Research on Schizophrenia and Depression (NARSAD); Sackler Institute of Columbia University; Ruth L. Kirschstein National Research Service Award [F31]; New York Stem Cell Initiative (NYSTEM); National Institutes of Health [R01 MH068542]; National Institute of Mental Health [R01MH068542] Funding Source: NIH RePORTER
NR 36
TC 1224
Z9 1528
U1 2
U2 281
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 466
EP U539
DI 10.1038/nature09817
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600033
PM 21460835
DA 2026-03-09
ER

PT J
AU Schwanhäusser, B
   Busse, D
   Li, N
   Dittmar, G
   Schuchhardt, J
   Wolf, J
   Chen, W
   Selbach, M
AF Schwanhaeusser, Bjoern
   Busse, Dorothea
   Li, Na
   Dittmar, Gunnar
   Schuchhardt, Johannes
   Wolf, Jana
   Chen, Wei
   Selbach, Matthias
TI Global quantification of mammalian gene expression control
SO NATURE
LA English
DT Article
ID quantitative proteomics; nucleotide resolution; regulatory networks; in-vivo; protein; dynamics; translation; transcription; stability; cells
AB Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.
C1 [Schwanhaeusser, Bjoern; Busse, Dorothea; Li, Na; Dittmar, Gunnar; Wolf, Jana; Chen, Wei; Selbach, Matthias] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
   [Schuchhardt, Johannes] MicroDiscovery GmbH, D-10405 Berlin, Germany.
C3 Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Wolf, J (corresponding author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13092 Berlin, Germany.
EM jana.wolf@mdc-berlin.de; wei.chen@mdc-berlin.de; matthias.selbach@mdc-berlin.de
FU Helmholtz Association; German Ministry of Education and Research (BMBF); Senate of Berlin by Berlin Institute of Medical Systems Biology (BIMSB) [315362A]; German Ministry of Education and Research [315289]; Helmholtz Alliance on Systems Biology/MSBN; China Scholarship Council CSC
NR 44
TC 5049
Z9 5957
U1 8
U2 752
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 337
EP 342
DI 10.1038/nature10098
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400040
PM 21593866
DA 2026-03-09
ER

PT J
AU Fawcett, PJ
   Werne, JP
   Anderson, RS
   Heikoop, JM
   Brown, ET
   Berke, MA
   Smith, SJ
   Goff, F
   Donohoo-Hurley, L
   Cisneros-Dozal, LM
   Schouten, S
   Damsté, JSS
   Huang, YS
   Toney, J
   Fessenden, J
   WoldeGabriel, G
   Atudorei, V
   Geissman, JW
   Allen, CD
AF Fawcett, Peter J.
   Werne, Josef P.
   Anderson, R. Scott
   Heikoop, Jeffrey M.
   Brown, Erik T.
   Berke, Melissa A.
   Smith, Susan J.
   Goff, Fraser
   Donohoo-Hurley, Linda
   Cisneros-Dozal, Luz M.
   Schouten, Stefan
   Damste, Jaap S. Sinninghe
   Huang, Yongsong
   Toney, Jaime
   Fessenden, Julianna
   WoldeGabriel, Giday
   Atudorei, Viorel
   Geissman, John W.
   Allen, Craig D.
TI Extended megadroughts in the southwestern United States during Pleistocene interglacials
SO NATURE
LA English
DT Article
ID climate variability; drought; reconstructions; monsoon; africa; mexico; record
AB The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern(1). Multi-year droughts during the instrumental period(2) and decadal-length droughts of the past two millennia(1,3) were shorter and climatically different from the future permanent, 'dust-bowl-like' mega-drought conditions, lasting decades to a century, that are predicted as a consequence of warming(4). So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeo-temperature proxies(5) to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C-4 plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles similar to 2 degrees C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6 degrees C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.
C1 [Fawcett, Peter J.; Goff, Fraser; Donohoo-Hurley, Linda; Atudorei, Viorel; Geissman, John W.] Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
   [Werne, Josef P.] Univ Minnesota, Dept Chem & Biochem, Duluth, MN 55812 USA.
   [Werne, Josef P.; Brown, Erik T.; Berke, Melissa A.] Univ Minnesota, Large Lakes Observ, Duluth, MN 55812 USA.
   [Brown, Erik T.; Berke, Melissa A.] Univ Minnesota, Dept Geol Sci, Duluth, MN 55812 USA.
   [Werne, Josef P.] Univ Western Australia, Ctr Water Res, Crawley, WA 6009, Australia.
   [Werne, Josef P.] Curtin Univ Technol, WA Organ & Isotope Geochem Ctr, Bentley, WA 6845, Australia.
   [Anderson, R. Scott; Fessenden, Julianna; WoldeGabriel, Giday] Univ Arizona, Sch Earth Sci & Environm Sustainabil, Flagstaff, AZ 86011 USA.
   [Anderson, R. Scott; Smith, Susan J.] Univ Arizona, Bilby Res Ctr, Lab Paleoecol, Flagstaff, AZ 86011 USA.
   [Heikoop, Jeffrey M.; Cisneros-Dozal, Luz M.; Toney, Jaime] Los Alamos Natl Lab, Div Earth & Environm Sci, Los Alamos, NM 87545 USA.
   [Schouten, Stefan; Damste, Jaap S. Sinninghe] NIOZ Royal Netherlands Inst Sea Res, Dept Marine Organ Biogeochem, NL-1790 AB Den Burg, Netherlands.
   [Huang, Yongsong] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Allen, Craig D.] USGS Ft Collins Sci Ctr, Jemez Mt Field Stn, Los Alamos, NM 87544 USA.
C3 University of New Mexico; University of Minnesota System; University of Minnesota Duluth; University of Minnesota System; University of Minnesota Duluth; Large Lakes Observatory; University of Minnesota System; University of Minnesota Duluth; University of Western Australia; Curtin University; University of Arizona; University of Arizona; United States Department of Energy (DOE); Los Alamos National Laboratory; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Brown University; United States Department of the Interior; United States Geological Survey
RP Fawcett, PJ (corresponding author), Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
EM fawcett@unm.edu
FU NSF; IGPP LANL; USGS Western Mountain Initiative; Gledden Fellowship; Directorate For Geosciences; Division Of Earth Sciences [0902888] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0903016] Funding Source: National Science Foundation
NR 28
TC 113
Z9 139
U1 12
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 FEB 24
PY 2011
VL 470
IS 7335
BP 518
EP 521
DI 10.1038/nature09839
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900038
PM 21350483
DA 2026-03-09
ER

PT J
AU Johnson, MW
   Amin, MHS
   Gildert, S
   Lanting, T
   Hamze, F
   Dickson, N
   Harris, R
   Berkley, AJ
   Johansson, J
   Bunyk, P
   Chapple, EM
   Enderud, C
   Hilton, JP
   Karimi, K
   Ladizinsky, E
   Ladizinsky, N
   Oh, T
   Perminov, I
   Rich, C
   Thom, MC
   Tolkacheva, E
   Truncik, CJS
   Uchaikin, S
   Wang, J
   Wilson, B
   Rose, G
AF Johnson, M. W.
   Amin, M. H. S.
   Gildert, S.
   Lanting, T.
   Hamze, F.
   Dickson, N.
   Harris, R.
   Berkley, A. J.
   Johansson, J.
   Bunyk, P.
   Chapple, E. M.
   Enderud, C.
   Hilton, J. P.
   Karimi, K.
   Ladizinsky, E.
   Ladizinsky, N.
   Oh, T.
   Perminov, I.
   Rich, C.
   Thom, M. C.
   Tolkacheva, E.
   Truncik, C. J. S.
   Uchaikin, S.
   Wang, J.
   Wilson, B.
   Rose, G.
TI Quantum annealing with manufactured spins
SO NATURE
LA English
DT Article
ID state
AB Many interesting but practically intractable problems can be reduced to that of finding the ground state of a system of interacting spins; however, finding such a ground state remains computationally difficult(1). It is believed that the ground state of some naturally occurring spin systems can be effectively attained through a process called quantum annealing(2,3). If it could be harnessed, quantum annealing might improve on known methods for solving certain types of problem(4,5). However, physical investigation of quantum annealing has been largely confined to microscopic spins in condensed-matter systems(6-12). Here we use quantum annealing to find the ground state of an artificial Ising spin system comprising an array of eight superconducting flux quantum bits with programmable spin-spin couplings. We observe a clear signature of quantum annealing, distinguishable from classical thermal annealing through the temperature dependence of the time at which the system dynamics freezes. Our implementation can be configured in situ to realize a wide variety of different spin networks, each of which can be monitored as it moves towards a low-energy configuration(13,14). This programmable artificial spin network bridges the gap between the theoretical study of ideal isolated spin networks and the experimental investigation of bulk magnetic samples. Moreover, with an increased number of spins, such a system may provide a practical physical means to implement a quantum algorithm, possibly allowing more-effective approaches to solving certain classes of hard combinatorial optimization problems.
C1 [Johnson, M. W.; Amin, M. H. S.; Gildert, S.; Lanting, T.; Hamze, F.; Dickson, N.; Harris, R.; Berkley, A. J.; Bunyk, P.; Chapple, E. M.; Enderud, C.; Hilton, J. P.; Karimi, K.; Ladizinsky, E.; Ladizinsky, N.; Oh, T.; Perminov, I.; Rich, C.; Thom, M. C.; Tolkacheva, E.; Uchaikin, S.; Wang, J.; Wilson, B.; Rose, G.] D Wave Syst Inc, Burnaby, BC V5C 6G9, Canada.
   [Johansson, J.] Univ Agder, Dept Nat Sci, NO-4604 Kristiansand, Norway.
   [Truncik, C. J. S.] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada.
C3 University of Agder; Simon Fraser University
RP Johnson, MW (corresponding author), D Wave Syst Inc, 100-4401 Still Creek Dr, Burnaby, BC V5C 6G9, Canada.
EM mwjohnson@dwavesys.com
NR 33
TC 1409
Z9 1621
U1 3
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 MAY 12
PY 2011
VL 473
IS 7346
BP 194
EP 198
DI 10.1038/nature10012
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200034
PM 21562559
DA 2026-03-09
ER

PT J
AU Langford, NK
   Ramelow, S
   Prevedel, R
   Munro, WJ
   Milburn, GJ
   Zeilinger, A
AF Langford, N. K.
   Ramelow, S.
   Prevedel, R.
   Munro, W. J.
   Milburn, G. J.
   Zeilinger, A.
TI Efficient quantum computing using coherent photon conversion
SO NATURE
LA English
DT Article
ID linear optics; computation; scheme; fiber
AB Single photons are excellent quantum information carriers: they were used in the earliest demonstrations of entanglement(1) and in the production of the highest-quality entanglement reported so far(2,3). However, current schemes for preparing, processing and measuring them are inefficient. For example, down-conversion provides heralded, but randomly timed, single photons(4), and linear optics gates are inherently probabilistic(5). Here we introduce a deterministic process-coherent photon conversion (CPC)-that provides a new way to generate and process complex, multiquanta states for photonic quantum information applications. The technique uses classically pumped nonlinearities to induce coherent oscillations between orthogonal states of multiple quantum excitations. One example of CPC, based on a pumped four-wave-mixing interaction, is shown to yield a single, versatile process that provides a full set of photonic quantum processing tools. This set satisfies the DiVincenzo criteria for a scalable quantum computing architecture(6), including deterministic multiqubit entanglement gates (based on a novel form of photon-photon interaction), high-quality heralded single-and multiphoton states free from higher-order imperfections, and robust, high-efficiency detection. It can also be used to produce heralded multiphoton entanglement, create optically switchable quantum circuits and implement an improved form of down-conversion with reduced higher-order effects. Such tools are valuable building blocks for many quantum-enabled technologies. Finally, using photonic crystal fibres we experimentally demonstrate quantum correlations arising from a four-colour nonlinear process suitable for CPC and use these measurements to study the feasibility of reaching the deterministic regime with current technology(4,7). Our scheme, which is based on interacting bosonic fields, is not restricted to optical systems but could also be implemented in optomechanical, electromechanical and superconducting systems(8-12) with extremely strong intrinsic nonlinearities. Furthermore, exploiting higher-order nonlinearities with multiple pump fields yields a mechanism for multiparty mediation of the complex, coherent dynamics.
C1 [Langford, N. K.; Ramelow, S.; Prevedel, R.; Milburn, G. J.; Zeilinger, A.] Univ Vienna, Vienna Ctr Quantum Sci & Technol, Fac Phys, A-1090 Vienna, Austria.
   [Langford, N. K.; Ramelow, S.; Zeilinger, A.] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-1090 Vienna, Austria.
   [Langford, N. K.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Prevedel, R.] Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
   [Munro, W. J.] Natl Inst Informat, Chiyoda Ku, Tokyo 1018430, Japan.
   [Munro, W. J.] NTT Corp, NTT Basic Res Labs, Kanagawa 2430198, Japan.
   [Milburn, G. J.] Univ Queensland, Ctr Engn Quantum Syst, St Lucia, Qld 4072, Australia.
C3 University of Vienna; Austrian Academy of Sciences; University of Oxford; University of Waterloo; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan; NTT, Inc; University of Queensland
RP Langford, NK (corresponding author), Univ Vienna, Vienna Ctr Quantum Sci & Technol, Fac Phys, Boltzmanngasse 5, A-1090 Vienna, Austria.
EM nathan.langford@univie.ac.at; anton.zeilinger@univie.ac.at
FU ERC [QIT4QAD]; Austrian Science Fund [F4007]; EC (QU-ESSENCE and QAP); Vienna Doctoral Program on Complex Quantum Systems; John Templeton Foundation; Japanese FIRST programme; Ontario Ministry of Research and Innovation; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 30
TC 121
Z9 138
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 360
EP 363
DI 10.1038/nature10463
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100040
PM 21993627
DA 2026-03-09
ER

PT J
AU Lee, JM
   Lee, YK
   Mamrosh, JL
   Busby, SA
   Griffin, PR
   Pathak, MC
   Ortlund, EA
   Moore, DD
AF Lee, Jae Man
   Lee, Yoon Kwang
   Mamrosh, Jennifer L.
   Busby, Scott A.
   Griffin, Patrick R.
   Pathak, Manish C.
   Ortlund, Eric A.
   Moore, David D.
TI A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects
SO NATURE
LA English
DT Article
ID orphan receptors; liver; identification; lrh-1; phospholipids; homolog-1; binding; deficiency; activation; promoter
AB Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis(1,2). Structural studies have identified phospholipids as potential LRH-1 ligands(3-5), but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.
C1 [Lee, Jae Man; Moore, David D.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
   [Lee, Yoon Kwang; Mamrosh, Jennifer L.; Moore, David D.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Lee, Yoon Kwang] Northeastern Ohio Univ Coll Med & Pharm, Dept Integrat Med Sci, Coll Med, Rootstown, OH 44272 USA.
   [Lee, Yoon Kwang] Northeastern Ohio Univ Coll Med & Pharm, Coll Pharm, Rootstown, OH 44272 USA.
   [Busby, Scott A.; Griffin, Patrick R.] Scripps Res Inst, Scripps Res Mol Screening Ctr, Jupiter, FL 33458 USA.
   [Pathak, Manish C.; Ortlund, Eric A.] Emory Univ, Dept Biochem, Sch Med, Atlanta, GA 30322 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; University System of Ohio; Northeast Ohio Medical University (NEOMED); University System of Ohio; Northeast Ohio Medical University (NEOMED); State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Emory University
RP Moore, DD (corresponding author), Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
EM moore@bcm.edu
FU NIH [DK-079638, DK068804, R01 CA134873]; USDA [ARS 6250-52000-055]; Alkek Foundation; Robert R. P. Doherty Jr-Welch Chair in Science
NR 32
TC 202
Z9 227
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2011
VL 474
IS 7352
BP 506
EP U135
DI 10.1038/nature10111
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700048
PM 21614002
DA 2026-03-09
ER

PT J
AU Cissé, M
   Halabisky, B
   Harris, J
   Devidze, N
   Dubal, DB
   Sun, BG
   Orr, A
   Lotz, G
   Kim, DH
   Hamto, P
   Ho, K
   Yu, GQ
   Mucke, L
AF Cisse, Moustapha
   Halabisky, Brian
   Harris, Julie
   Devidze, Nino
   Dubal, Dena B.
   Sun, Binggui
   Orr, Anna
   Lotz, Gregor
   Kim, Daniel H.
   Hamto, Patricia
   Ho, Kaitlyn
   Yu, Gui-Qiu
   Mucke, Lennart
TI Reversing EphB2 depletion rescues cognitive functions in Alzheimer model
SO NATURE
LA English
DT Article
ID amyloid-beta-protein; dependent synaptic plasticity; transgenic mouse model; long-term potentiation; precursor protein; calcium influx; behavioral impairments; cellular prion; in-vitro; disease
AB Amyloid-beta oligomers may cause cognitive deficits in Alzheimer's disease by impairing neuronal NMDA-type glutamate receptors, whose function is regulated by the receptor tyrosine kinase EphB2. Here we show that amyloid-beta oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. To determine the pathogenic importance of EphB2 depletions in Alzheimer's disease and related models, we used lentiviral constructs to reduce or increase neuronal expression of EphB2 in memory centres of the mouse brain. In nontransgenic mice, knockdown of EphB2 mediated by short hairpin RNA reduced NMDA receptor currents and impaired long-term potentiation in the dentate gyrus, which are important for memory formation. Increasing EphB2 expression in the dentate gyrus of human amyloid precursor protein transgenic mice reversed deficits in NMDA receptor-dependent long-term potentiation and memory impairments. Thus, depletion of EphB2 is critical in amyloid-beta-induced neuronal dysfunction. Increasing EphB2 levels or function could be beneficial in Alzheimer's disease.
C1 [Cisse, Moustapha; Halabisky, Brian; Harris, Julie; Devidze, Nino; Dubal, Dena B.; Sun, Binggui; Orr, Anna; Lotz, Gregor; Kim, Daniel H.; Hamto, Patricia; Ho, Kaitlyn; Yu, Gui-Qiu; Mucke, Lennart] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA.
   [Cisse, Moustapha; Halabisky, Brian; Harris, Julie; Dubal, Dena B.; Sun, Binggui; Orr, Anna; Lotz, Gregor; Mucke, Lennart] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco
RP Mucke, L (corresponding author), Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA.
EM lmucke@gladstone.ucsf.edu
FU NIH [AG011385, AG022074, NS041787]; McBean Family Foundation; National Center for Research Resources [RR18928-01]
NR 50
TC 352
Z9 422
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 47
EP 52
DI 10.1038/nature09635
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600028
PM 21113149
DA 2026-03-09
ER

PT J
AU Gracheva, EO
   Cordero-Morales, JF
   González-Carcacía, JA
   Ingolia, NT
   Manno, C
   Aranguren, CI
   Weissman, JS
   Julius, D
AF Gracheva, Elena O.
   Cordero-Morales, Julio F.
   Gonzalez-Carcacia, Jose A.
   Ingolia, Nicholas T.
   Manno, Carlo
   Aranguren, Carla I.
   Weissman, Jonathan S.
   Julius, David
TI Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats
SO NATURE
LA English
DT Article
ID capsaicin receptor; cold; warm
AB Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle(1-3). Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation(1,4). In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal's face(5-10). Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector(6). Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to about 30 degrees C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, thereby maintaining a role for TRPV1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat Trpv1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs and moles), supporting a close phylogenetic relationship with bats. These findings reveal a novel molecular mechanism for physiological tuning of thermosensory nerve fibres.
C1 [Gracheva, Elena O.; Cordero-Morales, Julio F.; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Gonzalez-Carcacia, Jose A.; Aranguren, Carla I.] Inst Venezolano Invest Cient, Ctr Ecol, Lab Biol Organismos, Caracas 1020A, Venezuela.
   [Ingolia, Nicholas T.] Carnegie Inst, Dept Embryol, Baltimore, MD 21218 USA.
   [Manno, Carlo] Inst Venezolano Invest Cient, Ctr Biofis & Bioquim, Lab Fisiol Celular, Caracas 1020A, Venezuela.
   [Weissman, Jonathan S.; Julius, David] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Weissman, Jonathan S.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
   [Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; Venezuelan Institute Science Research; Carnegie Institution for Science; Venezuelan Institute Science Research; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM ingolia@ciwemb.edu; david.julius@ucsf.edu
FU Ruth L. Kirschstein National Research Service Award [GM080853]; UCSF CVRI; Howard Hughes Medical Institute; NIH [P01 AG010770, NS047723, NS055299]
NR 30
TC 193
Z9 242
U1 3
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 AUG 4
PY 2011
VL 476
IS 7358
BP 88
EP +
DI 10.1038/nature10245
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300035
PM 21814281
DA 2026-03-09
ER

PT J
AU Nomura, R
   Ozawa, H
   Tateno, S
   Hirose, K
   Hernlund, J
   Muto, S
   Ishii, H
   Hiraoka, N
AF Nomura, Ryuichi
   Ozawa, Haruka
   Tateno, Shigehiko
   Hirose, Kei
   Hernlund, John
   Muto, Shunsuke
   Ishii, Hirofumi
   Hiraoka, Nozomu
TI Spin crossover and iron-rich silicate melt in the Earth's deep mantle
SO NATURE
LA English
DT Article
ID ultralow-velocity zone; high-pressure; magma ocean; perovskite; dynamics; density; gpa; fe; geochemistry; spectroscopy
AB A melt has greater volume than a silicate solid of the same composition. But this difference diminishes at high pressure, and the possibility that a melt sufficiently enriched in the heavy element iron might then become more dense than solids at the pressures in the interior of the Earth (and other terrestrial bodies) has long been a source of considerable speculation(1,2). The occurrence of such dense silicate melts in the Earth's lowermost mantle would carry important consequences for its physical and chemical evolution and could provide a unifying model for explaining a variety of observed features in the core-mantle boundary region(3). Recent theoretical calculations(4) combined with estimates of iron partitioning between (Mg,Fe)SiO3 perovskite and melt at shallower mantle conditions(5-7) suggest that melt is more dense than solids at pressures in the Earth's deepest mantle, consistent with analysis of shockwave experiments(8). Here we extend measurements of iron partitioning over the entire mantle pressure range, and find a precipitous change at pressures greater than similar to 76 GPa, resulting in strong iron enrichment in melts. Additional X-ray emission spectroscopy measurements on (Mg0.95Fe0.05)SiO3 glass indicate a spin collapse around 70 GPa, suggesting that the observed change in iron partitioning could be explained by a spin crossover of iron (from high-spin to low-spin) in silicate melt. These results imply that (Mg,Fe)SiO3 liquid becomes more dense than coexisting solid at similar to 1,800 km depth in the lower mantle. Soon after the Earth's formation, the heat dissipated by accretion and internal differentiation could have produced a dense melt layer up to similar to 1,000 km in thickness underneath the solid mantle. We also infer that (Mg,Fe)SiO3 perovskite is on the liquidus at deep mantle conditions, and predict that fractional crystallization of dense magma would have evolved towards an iron-rich and silicon-poor composition, consistent with seismic inferences of structures in the core-mantle boundary region.
C1 [Nomura, Ryuichi; Ozawa, Haruka; Tateno, Shigehiko; Hirose, Kei] Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, Tokyo 1528551, Japan.
   [Nomura, Ryuichi] Univ Tokyo, Dept Earth & Planetary Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Ozawa, Haruka; Hirose, Kei] Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Yokosuka, Kanagawa 2370061, Japan.
   [Hernlund, John] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
   [Muto, Shunsuke] Nagoya Univ, Dept Mat Phys & Energy Engn, Chikusa Ku, Nagoya, Aichi 4648603, Japan.
   [Ishii, Hirofumi; Hiraoka, Nozomu] Natl Synchrotron Radiat Res Ctr, Hsinchu 30076, Taiwan.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; University of Tokyo; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); University of California System; University of California Berkeley; Nagoya University; National Synchrotron Radiation Research Center
RP Hirose, K (corresponding author), Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, Tokyo 1528551, Japan.
EM kei@geo.titech.ac.jp
FU National Science Foundation [NSFEAR0855737]; Grants-in-Aid for Scientific Research [19053004] Funding Source: KAKEN
NR 41
TC 231
Z9 260
U1 4
U2 138
PU 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 12
PY 2011
VL 473
IS 7346
BP 199
EP +
DI 10.1038/nature09940
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200035
PM 21516105
DA 2026-03-09
ER

PT J
AU Wu, YH
   Vendome, J
   Shapiro, L
   Ben-Shaul, A
   Honig, B
AF Wu, Yinghao
   Vendome, Jeremie
   Shapiro, Lawrence
   Ben-Shaul, Avinoam
   Honig, Barry
TI Transforming binding affinities from three dimensions to two with application to cadherin clustering
SO NATURE
LA English
DT Article
ID cell-adhesion molecules; specificity; macromolecules; cd2
AB Membrane-bound receptors often form large assemblies resulting from binding to soluble ligands, cell-surface molecules on other cells and extracellular matrix proteins(1). For example, the association of membrane proteins with proteins on different cells (trans-interactions) can drive the oligomerization of proteins on the same cell(2) (cis-interactions). A central problem in understanding the molecular basis of such phenomena is that equilibrium constants are generally measured in three-dimensional solution and are thus difficult to relate to the two-dimensional environment of a membrane surface. Here we present a theoretical treatment that converts three-dimensional affinities to two dimensions, accounting directly for the structure and dynamics of the membrane-bound molecules. Using a multiscale simulation approach, we apply the theory to explain the formation of ordered, junction-like clusters by classical cadherin adhesion proteins. The approach features atomic-scale molecular dynamics simulations to determine interdomain flexibility, Monte Carlo simulations of multidomain motion and lattice simulations of junction formation(3). A finding of general relevance is that changes in interdomain motion on trans-binding have a crucial role in driving the lateral, cis-, clustering of adhesion receptors.
C1 [Ben-Shaul, Avinoam] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
   [Ben-Shaul, Avinoam] Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel.
   [Wu, Yinghao; Vendome, Jeremie; Shapiro, Lawrence; Honig, Barry] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Wu, Yinghao; Vendome, Jeremie; Honig, Barry] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Wu, Yinghao; Vendome, Jeremie; Honig, Barry] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Shapiro, Lawrence] Columbia Univ, Edward S Harkness Eye Inst, New York, NY 10032 USA.
C3 Hebrew University of Jerusalem; Hebrew University of Jerusalem; Columbia University; Columbia University; Howard Hughes Medical Institute; Columbia University; Columbia University
RP Ben-Shaul, A (corresponding author), Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
EM abs@fh.huji.ac.il; bh6@columbia.edu
FU National Science Foundation [MCB-0918535]; National Institutes of Health [R01 GM062270-07]; US-Israel Binational Science Foundation [2006-401]; Israel Science Foundation (ISF) [1448/10, 695/06]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0918535] Funding Source: National Science Foundation
NR 23
TC 189
Z9 216
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 510
EP U107
DI 10.1038/nature10183
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900043
PM 21796210
DA 2026-03-09
ER

PT J
AU Huang, WD
   Ghisletti, S
   Saijo, KR
   Gandhi, M
   Aouadi, M
   Tesz, GJ
   Zhang, DX
   Yao, J
   Czech, MP
   Goode, BL
   Rosenfeld, MG
   Glass, CK
AF Huang, Wendy
   Ghisletti, Serena
   Saijo, Kaoru
   Gandhi, Meghal
   Aouadi, Myriam
   Tesz, Greg J.
   Zhang, Dawn X.
   Yao, Joyee
   Czech, Michael P.
   Goode, Bruce L.
   Rosenfeld, Michael G.
   Glass, Christopher K.
TI Coronin 2A mediates actin-dependent de-repression of inflammatory response genes
SO NATURE
LA English
DT Article
ID ppar-gamma; nuclear; receptor; pathways; transrepression; integration; activation; checkpoint; expression; roles
AB Toll-like receptors (TLRs) function as initiators of inflammation through their ability to sense pathogen-associated molecular patterns and products of tissue damage(1,2). Transcriptional activation of many TLR-responsive genes requires an initial de-repression step in which nuclear receptor co-repressor (NCoR) complexes are actively removed from the promoters of target genes to relieve basal repression(3,4). Ligand-dependent SUMOylation of liver X receptors (LXRs) has been found to suppress TLR4-induced transcription potently by preventing the NCoR clearance step(5-7), but the underlying mechanisms remain enigmatic. Here we provide evidence that coronin 2A (CORO2A), a component of the NCoR complex of previously unknown function(8,9), mediates TLR-induced NCoR turnover by a mechanism involving interaction with oligomeric nuclear actin. SUMOylated LXRs block NCoR turnover by binding to a conserved SUMO2/SUMO3-interaction motif in CORO2A and preventing actin recruitment. Intriguingly, the LXR transrepression pathway can itself be inactivated by inflammatory signals that induce calcium/calmodulin-dependent protein kinase II gamma (CaMKII gamma)-dependent phosphorylation of LXRs, leading to their deSUMOylation by the SUMO protease SENP3 and release from CORO2A. These findings uncover a CORO2A-actin-dependent mechanism for the de-repression of inflammatory response genes that can be differentially regulated by phosphorylation and by nuclear receptor signalling pathways that control immunity and homeostasis.
C1 [Huang, Wendy; Ghisletti, Serena; Saijo, Kaoru; Zhang, Dawn X.; Yao, Joyee; Glass, Christopher K.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Huang, Wendy; Zhang, Dawn X.] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Gandhi, Meghal; Goode, Bruce L.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biol, Waltham, MA 02454 USA.
   [Aouadi, Myriam; Tesz, Greg J.; Czech, Michael P.] Univ Massachusetts, Program Mol Med, Sch Med, Worcester, MA 01605 USA.
   [Czech, Michael P.; Glass, Christopher K.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Rosenfeld, Michael G.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Brandeis University; University of Massachusetts System; University of Massachusetts Worcester; University of California System; University of California San Diego; 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 NRSA [1F31DK083913]; National Institutes of Health [CA52599, DK074868, HC088093, DK085853]; Leducq Foundation Transatlantic Network; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK091183] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007198] Funding Source: NIH RePORTER
NR 30
TC 131
Z9 159
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 FEB 17
PY 2011
VL 470
IS 7334
BP 414
EP U25
DI 10.1038/nature09703
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100046
PM 21331046
DA 2026-03-09
ER

PT J
AU Günther, C
   Martini, E
   Wittkopf, N
   Amann, K
   Weigmann, B
   Neumann, H
   Waldner, MJ
   Hedrick, SM
   Tenzer, S
   Neurath, MF
   Becker, C
AF Guenther, Claudia
   Martini, Eva
   Wittkopf, Nadine
   Amann, Kerstin
   Weigmann, Benno
   Neumann, Helmut
   Waldner, Maximilian J.
   Hedrick, Stephen M.
   Tenzer, Stefan
   Neurath, Markus F.
   Becker, Christoph
TI Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
SO NATURE
LA English
DT Article
ID inflammatory-bowel-disease; cell-death; innate immunity; crohns-disease; apoptosis; necrosis; gut; expression; intestine; integrity
AB Dysfunction of the intestinal epithelium is believed to result in the excessive translocation of commensal bacteria into the bowel wall that drives chronic mucosal inflammation in Crohn's disease, an incurable inflammatory bowel disease in humans characterized by inflammation of the terminal ileum(1). In healthy individuals, the intestinal epithelium maintains a physical barrier, established by the tight contact of cells. Moreover, specialized epithelial cells such as Paneth cells and goblet cells provide innate immune defence functions by secreting mucus and antimicrobial peptides, which hamper access and survival of bacteria adjacent to the epithelium(2). Epithelial cell death is a hallmark of intestinal inflammation and has been discussed as a possible pathogenic mechanism driving Crohn's disease in humans(3). However, the regulation of epithelial cell death and its role in intestinal homeostasis remain poorly understood. Here we demonstrate a critical role for caspase-8 in regulating necroptosis of intestinal epithelial cells (IECs) and terminal ileitis. Mice with a conditional deletion of caspase-8 in the intestinal epithelium (Casp8(Delta IEC)) spontaneously developed inflammatory lesions in the terminal ileum and were highly susceptible to colitis. Casp8(Delta IEC) mice lacked Paneth cells and showed reduced numbers of goblet cells, indicating dysregulated antimicrobial immune cell functions of the intestinal epithelium. Casp8(Delta IEC) mice showed increased cell death in the Paneth cell area of small intestinal crypts. Epithelial cell death was induced by tumour necrosis factor (TNF)-alpha, was associated with increased expression of receptor-interacting protein 3 (Rip3; also known as Ripk3) and could be inhibited on blockade of necroptosis. Lastly, we identified high levels of RIP3 in human Paneth cells and increased necroptosis in the terminal ileum of patients with Crohn's disease, suggesting a potential role of necroptosis in the pathogenesis of this disease. Together, our data demonstrate a critical function of caspase-8 in regulating intestinal homeostasis and in protecting IECs from TNF-alpha-induced necroptotic cell death.
C1 [Guenther, Claudia; Martini, Eva; Wittkopf, Nadine; Weigmann, Benno; Neumann, Helmut; Waldner, Maximilian J.; Neurath, Markus F.; Becker, Christoph] Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany.
   [Amann, Kerstin] Univ Erlangen Nurnberg, Dept Nephropathol, D-91054 Erlangen, Germany.
   [Hedrick, Stephen M.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Tenzer, Stefan] Johannes Gutenberg Univ Mainz, Inst Immunol, D-55131 Mainz, Germany.
C3 University of Erlangen Nuremberg; University of Erlangen Nuremberg; University of California System; University of California San Diego; Johannes Gutenberg University of Mainz
RP Becker, C (corresponding author), Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany.
EM christoph.becker@uk-erlangen.de
FU Interdisciplinary Center for Clinical Research (IZKF) of the University Erlangen-Nuremberg; European Community [202230]; Welcome Trust [WT087768MA]; NIH [AI037988]
NR 30
TC 767
Z9 876
U1 5
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 335
EP U108
DI 10.1038/nature10400
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400032
PM 21921917
DA 2026-03-09
ER

PT J
AU Ringel, R
   Sologub, M
   Morozov, YI
   Litonin, D
   Cramer, P
   Temiakov, D
AF Ringel, Rieke
   Sologub, Marina
   Morozov, Yaroslav I.
   Litonin, Dmitry
   Cramer, Patrick
   Temiakov, Dmitry
TI Structure of human mitochondrial RNA polymerase
SO NATURE
LA English
DT Article
ID transcription factor-a; yeast mitochondrial; promoter recognition; crystal-structure; initiation; elongation; complex; translation; specificity; transition
AB Transcription of the mitochondrial genome is performed by a single-subunit RNA polymerase (mtRNAP) that is distantly related to the RNAP of bacteriophage T7, the pol I family of DNA polymerases, and single-subunit RNAPs from chloroplasts(1-4). Whereas T7 RNAP can initiate transcription by itself, mtRNAP requires the factors TFAM and TFB2M for binding and melting promoter DNA(5-7). TFAM is an abundant protein that binds and bends promoter DNA 15-40 base pairs upstream of the transcription start site, and stimulates the recruitment of mtRNAP and TFB2M to the promoter(8,9). TFB2M assists mtRNAP in promoter melting and reaches the active site of mtRNAP to interact with the first base pair of the RNA-DNA hybrid(10). Here we report the X-ray structure of human mtRNAP at 2.5 angstrom resolution, which reveals a T7-like catalytic carboxy-terminal domain, an amino-terminal domain that remotely resembles the T7 promoter-binding domain, a novel pentatricopeptide repeat domain, and a flexible N-terminal extension. The pentatricopeptide repeat domain sequesters an AT-rich recognition loop, which binds promoter DNA in T7 RNAP, probably explaining the need for TFAM during promoter binding. Consistent with this, substitution of a conserved arginine residue in the AT-rich recognition loop, or release of this loop by deletion of the N-terminal part of mtRNAP, had no effect on transcription. The fingers domain and the intercalating hairpin, which melts DNA in phage RNAPs, are repositioned, explaining the need for TFB2M during promoter melting. Our results provide a new venue for the mechanistic analysis of mitochondrial transcription. They also indicate how an early phage-like mtRNAP lost functions in promoter binding and melting, which were provided by initiation factors in trans during evolution, to enable mitochondrial gene regulation and the adaptation of mitochondrial function to changes in the environment.
C1 [Ringel, Rieke; Litonin, Dmitry; Cramer, Patrick] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Ringel, Rieke; Litonin, Dmitry; Cramer, Patrick] Univ Munich, Dept Biochem, CIPSM, D-81377 Munich, Germany.
   [Sologub, Marina; Morozov, Yaroslav I.; Litonin, Dmitry; Temiakov, Dmitry] Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Cell Biol, Stratford, NJ 08084 USA.
C3 University of Munich; University of Munich; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rowan University; Rowan University School of Osteopathic Medicine
RP Cramer, P (corresponding author), Univ Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM cramer@lmb.uni-muenchen.de; d.temiakov@umdnj.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Deutsche Forschungsgemeinschaft [SFB646, TR5, FOR1068]; Nanosystems Initiative Munich NIM; European Research Council ERC; Jung-Stiftung; UMDNJ Foundation [PC25-11]
NR 30
TC 164
Z9 203
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 13
PY 2011
VL 478
IS 7368
BP 269
EP 273
DI 10.1038/nature10435
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800056
PM 21947009
DA 2026-03-09
ER

PT J
AU Planavsky, NJ
   McGoldrick, P
   Scott, CT
   Li, C
   Reinhard, CT
   Kelly, AE
   Chu, XL
   Bekker, A
   Love, GD
   Lyons, TW
AF Planavsky, Noah J.
   McGoldrick, Peter
   Scott, Clinton T.
   Li, Chao
   Reinhard, Christopher T.
   Kelly, Amy E.
   Chu, Xuelei
   Bekker, Andrey
   Love, Gordon D.
   Lyons, Timothy W.
TI Widespread iron-rich conditions in the mid-Proterozoic ocean
SO NATURE
LA English
DT Article
ID ferruginous conditions; sulfur; sulfate; carbon; chemistry; evolution; seawater; deposits; model
AB The chemical composition of the ocean changed markedly with the oxidation of the Earth's surface(1), and this process has profoundly influenced the evolutionary and ecological history of life(2,3). The early Earth was characterized by a reducing ocean-atmosphere system, whereas the Phanerozoic eon (less than 542 million years ago) is known for a stable and oxygenated biosphere conducive to the radiation of animals. The redox characteristics of surface environments during Earth's middle age (1.8-1 billion years ago) are less well known, but it is generally assumed that the mid-Proterozoic was home to a globally sulphidic (euxinic) deep ocean(2,3). Here we present iron data from a suite of mid-Proterozoic marine mudstones. Contrary to the popular model, our results indicate that ferruginous (anoxic and Fe2+-rich) conditions were both spatially and temporally extensive across diverse palaeogeographic settings in the mid-Proterozoic ocean, inviting new models for the temporal distribution of iron formations and the availability of bioessential trace elements during a critical window for eukaryotic evolution.
C1 [Planavsky, Noah J.; Scott, Clinton T.; Li, Chao; Reinhard, Christopher T.; Kelly, Amy E.; Love, Gordon D.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [McGoldrick, Peter] Univ Tasmania, CODES ARC Ctr Excellence Ore Deposits, Hobart, Tas 7001, Australia.
   [Li, Chao] China Univ Geosci, State Key Lab Biogeol & Environm Geol, Wuhan 430074, Peoples R China.
   [Chu, Xuelei] Chinese Acad Sci, Inst Geol & Geophys, Beijing 100029, Peoples R China.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
C3 University of California System; University of California Riverside; University of Tasmania; China University of Geosciences; Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; University of Manitoba
RP Lyons, TW (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM timothy.lyons@ucr.edu
FU National Science Foundation (NSF); Geological Society of America; American Philosophical Society; NSF Division of Earth Sciences; NASA; Astrobiology Institute; UTAS Visiting Fellows programme; Agouron Institute; Natural Sciences and Engineering Research Council of Canada; Australian Research Council; Directorate For Geosciences; Division Of Earth Sciences [0951998, 0745605] Funding Source: National Science Foundation
NR 33
TC 420
Z9 492
U1 16
U2 285
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 448
EP U95
DI 10.1038/nature10327
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500037
PM 21900895
DA 2026-03-09
ER

PT J
AU Agakishiev, H
   Aggarwal, MM
   Ahammed, Z
   Alakhverdyants, AV
   Alekseev, I
   Alford, J
   Anderson, BD
   Anson, CD
   Arkhipkin, D
   Averichev, GS
   Balewski, J
   Beavis, DR
   Behera, NK
   Bellwied, R
   Betancourt, MJ
   Betts, RR
   Bhasin, A
   Bhati, AK
   Bichsel, H
   Bielcik, J
   Bielcikova, J
   Biritz, B
   Bland, LC
   Bordyuzhin, IG
   Borowski, W
   Bouchet, J
   Braidot, E
   Brandin, AV
   Bridgeman, A
   Brovko, SG
   Bruna, E
   Bueltmann, S
   Bunzarov, I
   Burton, TP
   Cai, XZ
   Caines, H
   Calderon, M
   Cebra, D
   Cendejas, R
   Cervantes, MC
   Chajecki, Z
   Chaloupka, P
   Chattopadhyay, S
   Chen, HF
   Chen, JH
   Chen, JY
   Chen, L
   Cheng, J
   Cherney, M
   Chikanian, A
   Choi, KE
   Christie, W
   Chung, P
   Codrington, MJM
   Corliss, R
   Cramer, JG
   Crawford, HJ
   Leyva, AD
   De Silva, LC
   Debbe, RR
   Dedovich, TG
   Derevschikov, AA
   de Souza, RD
   Didenko, L
   Djawotho, P
   Dogra, SM
   Dong, X
   Drachenberg, JL
   Draper, JE
   Dunlop, C
   Efimov, LG
   Elnimr, M
   Engelage, J
   Eppley, G
   Estienne, M
   Eun, L
   Evdokimov, O
   Fatemi, R
   Fedorisin, J
   Fersch, RG
   Filip, P
   Finch, E
   Fine, V
   Fisyak, Y
   Gagliardi, CA
   Gangadharan, DR
   Geurts, F
   Ghosh, P
   Gorbunov, YN
   Gordon, A
   Grebenyuk, OG
   Grosnick, D
   Guertin, SM
   Gupta, A
   Gupta, S
   Guryn, W
   Haag, B
   Hajkova, O
   Hamed, A
   Han, LX
   Harris, JW
   Hays-Wehle, JP
   Heinz, M
   Heppelmann, S
   Hirsch, A
   Hjort, E
   Hoffmann, GW
   Hofman, DJ
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   Huang, HZ
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   Huo, L
   Igo, G
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   Jacobs, W
   Jena, C
   Jin, F
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   Judd, EG
   Kabana, S
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   Kumar, L
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   Hamed, A.
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TI Observation of the antimatter helium-4 nucleus
SO NATURE
LA English
DT Article
ID quark-gluon plasma; antiprotons; collisions; electron
AB High-energy nuclear collisions create an energy density similar to that of the Universe microseconds after the Big Bang(1); in both cases, matter and antimatter are formed with comparable abundance. However, the relatively short-lived expansion in nuclear collisions allows antimatter to decouple quickly from matter, and avoid annihilation. Thus, a high-energy accelerator of heavy nuclei provides an efficient means of producing and studying antimatter. The antimatter helium-4 nucleus ((4)(He) over bar), also known as the anti-alpha ((alpha) over bar), consists of two antiprotons and two antineutrons (baryon number B = -4). It has not been observed previously, although the alpha-particle was identified a century ago by Rutherford and is present in cosmic radiation at the ten per cent level(2). Antimatter nuclei with B -1 have been observed only as rare products of interactions at particle accelerators, where the rate of antinucleus production in high-energy collisions decreases by a factor of about 1,000 with each additional antinucleon(3-5). Here we report the observation of (4)<(He) over bar, the heaviest observed antinucleus to date. In total, 18 (4)(He) over bar counts were detected at the STAR experiment at the Relativistic Heavy Ion Collider (RHIC; ref. 6) in 10(9) recorded gold-on-gold (Au+Au) collisions at centre-of-mass energies of 200 GeV and 62 GeV per nucleon-nucleon pair. The yield is consistent with expectations from thermodynamic(7) and coalescent nucleosynthesis(8) models, providing an indication of the production rate of even heavier antimatter nuclei and a benchmark for possible future observations of (4)(He) over bar in cosmic radiation.
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   [Braidot, E.; Peitzmann, T.] Univ Utrecht, NL-1098 XG Amsterdam, Netherlands.
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   [Bueltmann, S.; Koralt, I.; Plyku, D.] Old Dominion Univ, Norfolk, VA 23529 USA.
   [Cai, X. Z.; Chen, J. H.; Han, L-X.; Jin, F.; Li, W.; Ma, G. L.; Ma, Y. G.; Shou, Q. Y.; Tian, J.; Xue, L.; Zhang, S.; Zhao, J.; Zhong, C.; Zhu, Y. H.] Shanghai Inst Appl Phys, Shanghai 201800, Peoples R China.
   [Bhasin, A.; Cervantes, M. C.; Codrington, M. J. M.; Djawotho, P.; Drachenberg, J. L.; Gagliardi, C. A.; Hamed, A.; Huo, L.; Mioduszewski, S.; Mohammed, Y.; Pal, S. K.; Tribble, R. E.] Texas A&M Univ, College Stn, TX 77843 USA.
   [Bhasin, A.; Chattopadhyay, S.; Ghosh, P.; Mohanty, B.; Mondal, M. M.; Nayak, T. K.; Sahoo, N. R.; Singaraju, R. N.; Tribedy, P.; Viyogi, Y. P.] Variable Energy Cyclotron Ctr, Kolkata 700064, India.
   [Chen, H. F.; Huang, B.; Li, C.; Lu, Y.; Luo, X.; Shao, M.; Sun, Y.; Tang, Z.; Wang, X. L.; Xu, Y.; Zhang, Z. P.] Univ Sci & Technol China, Hefei 230026, Peoples R China.
   [Chen, J. Y.; Chen, L.; Ke, H. W.; Li, N.; Li, Z. M.; Liu, F.; Shi, S. S.; Wu, Y. F.; Xu, N.; Yang, Y.; Zhang, J. B.] CCNU HZNU, Inst Particle Phys, Wuhan 430079, Peoples R China.
   [Cheng, J.; Kang, K.; Li, Y.; Wang, Y.; Xiao, Z.; Zhang, X. P.; Zhu, X.] Tsinghua Univ, Beijing 100084, Peoples R China.
   [Cherney, M.; Gorbunov, Y. N.; McShane, T. S.; Seger, J.] Creighton Univ, Omaha, NE 68178 USA.
   [Choi, K. E.; Oh, K.; Yoo, I-K.] Pusan Natl Univ, Pusan 609735, South Korea.
   [Leyva, A. Davila; Hoffmann, G. W.; Li, L.; Markert, C.; Oldag, E. W.; Ray, R. L.; Schambach, J.; Thein, D.; Wada, M.] Univ Texas Austin, Austin, TX 78712 USA.
   [Derevschikov, A. A.; Matulenko, Yu A.; Meschanin, A.; Minaev, N. G.; Morozov, D. A.; Nogach, L. V.; Nurushev, S. B.; Vasiliev, A. N.] Inst High Energy Phys, Protvino 142281, Russia.
   [Derradi de Souza, R.; Takahashi, J.; Vasconcelos, G. M. S.] Univ Estadual Campinas, BR-13083859 Sao Paulo, Brazil.
   [Elnimr, M.; LaPointe, S.; Pruneau, C.; Sharma, M.; Tarini, L. H.; Voloshin, S. A.] Wayne State Univ, Detroit, MI 48201 USA.
   [Eppley, G.; Geurts, F.; Llope, W. J.; McDonald, D.; Roberts, J. B.; Yepes, P.] Rice Univ, Houston, TX 77251 USA.
   [Eun, L.; Heppelmann, S.] Penn State Univ, University Pk, PA 16802 USA.
   [Fatemi, R.; Fersch, R. G.; Korsch, W.; Webb, G.; Witzke, W.] Univ Kentucky, Lexington, KY 40506 USA.
   [Grosnick, D.; Koetke, D. D.; Manweiler, R.; Stanislaus, T. D. S.] Valparaiso Univ, Valparaiso, IN 46383 USA.
   [Hirsch, A.; Kikola, D. P.; Konzer, J.; Li, X.; Mustafa, M. K.; Netrakanti, P. K.; Scharenberg, R. P.; Skoby, M. J.; Srivastava, B.; Stringfellow, B.; Wang, F.; Wang, Q.; Xie, W.] Purdue Univ, W Lafayette, IN 47907 USA.
   [Jacobs, W.; Page, B. S.; Selyuzhenkov, I.; Stevens, J. R.; Wissink, S. W.] Indiana Univ, Bloomington, IN 47408 USA.
   [Jena, C.; Mahapatra, D. P.] Inst Phys, Bhubaneswar 751005, Orissa, India.
   [Kisiel, A.; Pawlak, T.; Peryt, W.; Pluta, J.; Zawisza, M.; Zbroszczyk, H.] Warsaw Univ Technol, PL-00661 Warsaw, Poland.
   [Kollegger, T.; Schuster, T. R.; Stock, R.; Zhou, W.] Goethe Univ Frankfurt, D-60325 Frankfurt, Germany.
   [Li, X.; Xu, Q. H.] Shandong Univ, Jinan 250100, Shandong, Peoples R China.
   [Munhoz, M. G.; Suaide, A. A. P.; Szanto de Toledo, A.] Univ Sao Paulo, BR-05508090 Sao Paulo, Brazil.
   [Planinic, M.; Poljak, N.] Univ Zagreb, HR-10002 Zagreb, Croatia.
   [Qiu, H.; Sun, Z.; Wang, J. S.; Xu, H.; Yang, Y.; Zhan, W.] Inst Modern Phys, Lanzhou 730000, Peoples R China.
   [Raniwala, R.; Raniwala, S.; Solanki, D.] Univ Rajasthan, Jaipur 302004, Rajasthan, India.
   [Schmitz, N.; Seyboth, P.; Simon, F.] Max Planck Inst Phys & Astrophys, D-80805 Munich, Germany.
   [Tarnowsky, T.; Wang, H.; Westfall, G. D.] Michigan State Univ, E Lansing, MI 48824 USA.
   [Witt, R.] USN Acad, Annapolis, MD 21402 USA.
C3 Joint Institute for Nuclear Research - Russia; Panjab University; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; National Research Centre - Kurchatov Institute; Alikhanov Institute for Theoretical & Experimental Physics; University System of Ohio; Kent State University; Kent State University Salem; Kent State University Kent; University System of Ohio; Ohio State University; United States Department of Energy (DOE); Brookhaven National Laboratory; Massachusetts Institute of Technology (MIT); Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Bombay; University of Houston System; University of Houston; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Jammu; University of Washington; University of Washington Seattle; Czech Technical University Prague; Czech Academy of Sciences; Nuclear Physics Institute of the Czech Academy of Sciences; University of California System; University of California Los Angeles; IMT - Institut Mines-Telecom; IMT Atlantique; FOM National Institute for Subatomic Physics; Utrecht University; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); United States Department of Energy (DOE); Argonne National Laboratory; University of California System; University of California Davis; Yale University; Old Dominion University; Chinese Academy of Sciences; Shanghai Institute of Applied Physics, CAS; Texas A&M University System; Texas A&M University College Station; Variable Energy Cyclotron Centre; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Central China Normal University; Tsinghua University; Creighton University; Pusan National University; University of Texas System; University of Texas Austin; National Research Centre - Kurchatov Institute; Institute of High Energy Physics - IHEP; Universidade Estadual de Campinas; Wayne State University; Rice University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Kentucky; Valparaiso University; Purdue University System; Purdue University; Indiana University System; Indiana University Bloomington; Institute of Physics Bhubaneswar (IOPB); Warsaw University of Technology; Goethe University Frankfurt; Shandong University; Universidade de Sao Paulo; University of Zagreb; Chinese Academy of Sciences; Institute of Modern Physics, CAS; University of Rajasthan; Max Planck Society; Michigan State University; United States Department of Defense; United States Navy; United States Naval Academy
FU RHIC Operations Group; RACF at BNL; NERSC Center at LBNL; Open Science Grid consortium; Offices of NP and HEP within the US DOE Office of Science; US NSF; Sloan Foundation; DFG cluster of excellence 'Origin and Structure of the Universe' of Germany; CNRS/IN2P3; FAPESP; CNPq of Brazil; Ministry of Education and Science of the Russian Federation; NNSFC; CAS; MoST; MoE of China; GA and MSMT of the Czech Republic; FOM and NWO of the Netherlands; DAE, DST and CSIR of India; Polish Ministry of Science and Higher Education; Korea Research Foundation; Ministry of Science, Education and Sports of Croatia; RosAtom of Russia
NR 30
TC 148
Z9 165
U1 0
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 353
EP 356
DI 10.1038/nature10079
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400043
PM 21516103
DA 2026-03-09
ER

PT J
AU West, AP
   Brodsky, IE
   Rahner, C
   Woo, DK
   Erdjument-Bromage, H
   Tempst, P
   Walsh, MC
   Choi, Y
   Shadel, GS
   Ghosh, S
AF West, A. Phillip
   Brodsky, Igor E.
   Rahner, Christoph
   Woo, Dong Kyun
   Erdjument-Bromage, Hediye
   Tempst, Paul
   Walsh, Matthew C.
   Choi, Yongwon
   Shadel, Gerald S.
   Ghosh, Sankar
TI TLR signalling augments macrophage bactericidal activity through mitochondrial ROS
SO NATURE
LA English
DT Article
ID salmonella-typhimurium; reactive oxygen; phagosome maturation; ecsit; association; homeostasis; ubiquitin; membrane; complex; protein
AB Reactive oxygen species (ROS) are essential components of the innate immune response against intracellular bacteria and it is thought that professional phagocytes generate ROS primarily via the phagosomal NADPH oxidase machinery(1). However, recent studies have suggested that mitochondrial ROS (mROS) also contribute to mouse macrophage bactericidal activity, although the mechanisms linking innate immune signalling to mitochondria for mROS generation remain unclear(2-4). Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly(5). Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation. ECSIT-and TRAF6-depleted macrophages have decreased levels of TLR-induced ROS and are significantly impaired in their ability to kill intracellular bacteria. Additionally, reducing macrophage mROS levels by expressing catalase in mitochondria results in defective bacterial killing, confirming the role of mROS in bactericidal activity. These results reveal a novel pathway linking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling.
C1 [Ghosh, Sankar] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
   [West, A. Phillip; Brodsky, Igor E.] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06520 USA.
   [Rahner, Christoph] Yale Univ, Dept Cell Biol, Sch Med, New Haven, CT 06520 USA.
   [Woo, Dong Kyun; Shadel, Gerald S.] Yale Univ, Dept Pathol, Sch Med, New Haven, CT 06520 USA.
   [Erdjument-Bromage, Hediye; Tempst, Paul] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA.
   [Walsh, Matthew C.; Choi, Yongwon] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
C3 Columbia University; Yale University; Yale University; Yale University; Memorial Sloan Kettering Cancer Center; University of Pennsylvania
RP Ghosh, S (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
EM sg2715@columbia.edu
FU NIH [R37-AI33443, NS-056206]
NR 36
TC 1367
Z9 1554
U1 2
U2 311
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 476
EP U543
DI 10.1038/nature09973
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600035
PM 21525932
DA 2026-03-09
ER

PT J
AU Walsh, KJ
   Morbidelli, A
   Raymond, SN
   O'Brien, DP
   Mandell, AM
AF Walsh, Kevin J.
   Morbidelli, Alessandro
   Raymond, Sean N.
   O'Brien, David P.
   Mandell, Avi M.
TI A low mass for Mars from Jupiter's early gas-driven migration
SO NATURE
LA English
DT Article
ID protoplanetary disk; planet migration; solar-system; evolution; dynamics; water; belt
AB Jupiter and Saturn formed in a few million years (ref. 1) from a gas-dominated protoplanetary disk, and were susceptible to gas-driven migration of their orbits on timescales of only similar to 100,000 years (ref. 2). Hydrodynamic simulations show that these giant planets can undergo a two-stage, inward-then-outward, migration(3-5). The terrestrial planets finished accreting much later(6), and their characteristics, including Mars' small mass, are best reproduced by starting from a planetesimal disk with an outer edge at about one astronomical unit from the Sun(7,8) (1 AU is the Earth-Sun distance). Here we report simulations of the early Solar System that show how the inward migration of Jupiter to 1.5 AU, and its subsequent outward migration, lead to a planetesimal disk truncated at 1 AU; the terrestrial planets then form from this disk over the next 30-50 million years, with an Earth/Mars mass ratio consistent with observations. Scattering by Jupiter initially empties but then repopulates the asteroid belt, with inner-belt bodies originating between 1 and 3 AU and outer-belt bodies originating between and beyond the giant planets. This explains the significant compositional differences across the asteroid belt. The key aspect missing from previous models of terrestrial planet formation is the substantial radial migration of the giant planets, which suggests that their behaviour is more similar to that inferred for extrasolar planets than previously thought.
C1 [Walsh, Kevin J.; Morbidelli, Alessandro] Univ Nice Sophia Antipolis, CNRS, Observ Cote Azur, F-06304 Nice 4, France.
   [Walsh, Kevin J.] SW Res Inst, Dept Space Studies, Boulder, CO 80302 USA.
   [Raymond, Sean N.] Univ Bordeaux, Observ Aquitain Sci Univers, F-33270 Floirac, France.
   [Raymond, Sean N.] CNRS, UMR 5804, Lab Astrophys Bordeaux, F-33270 Floirac, France.
   [O'Brien, David P.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Mandell, Avi M.] NASA Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
C3 Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Observatoire de la Cote d'Azur; Universite de Bordeaux; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Walsh, KJ (corresponding author), Univ Nice Sophia Antipolis, CNRS, Observ Cote Azur, BP 4229, F-06304 Nice 4, France.
EM kwalsh@boulder.swri.edu
FU Helmholtz Alliances; CNRS; NASA; Goddard Center for Astrobiology
NR 30
TC 972
Z9 1078
U1 6
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 14
PY 2011
VL 475
IS 7355
BP 206
EP 209
DI 10.1038/nature10201
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500045
PM 21642961
DA 2026-03-09
ER

PT J
AU Mishra, SK
   Ammon, T
   Popowicz, GM
   Krajewski, M
   Nagel, RJ
   Ares, M
   Holak, TA
   Jentsch, S
AF Mishra, Shravan Kumar
   Ammon, Tim
   Popowicz, Grzegorz M.
   Krajewski, Marcin
   Nagel, Roland J.
   Ares, Manuel, Jr.
   Holak, Tad A.
   Jentsch, Stefan
TI Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing
SO NATURE
LA English
DT Article
ID gene-expression; messenger-rnas; yeast genes; modifier; intron; sensitivity; design; src1; step; ubl5
AB Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1-HIND interaction, cannot use certain non-canonical 59 splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier.
C1 [Mishra, Shravan Kumar; Ammon, Tim; Jentsch, Stefan] Max Planck Inst Biochem, Dept Mol Cell Biol, D-82152 Martinsried, Germany.
   [Popowicz, Grzegorz M.; Krajewski, Marcin; Holak, Tad A.] Max Planck Inst Biochem, NMR Spect, D-82152 Martinsried, Germany.
   [Nagel, Roland J.; Ares, Manuel, Jr.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
C3 Max Planck Society; Max Planck Society; University of California System; University of California Santa Cruz
RP Jentsch, S (corresponding author), Max Planck Inst Biochem, Dept Mol Cell Biol, Klopferspitz 18, D-82152 Martinsried, Germany.
EM Jentsch@biochem.mpg.de
FU Max Planck Society; Deutsche Forschungsgemeinschaft; Fonds der chemischen Industrie; Center for Integrated Protein Science Munich; RUBICON EU Network of Excellence; NIH [GM040478]; National Institute of General Medical Sciences [R01GM040478] Funding Source: NIH RePORTER
NR 44
TC 79
Z9 97
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 JUN 9
PY 2011
VL 474
IS 7350
BP 173
EP U205
DI 10.1038/nature10143
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800041
PM 21614000
DA 2026-03-09
ER

PT J
AU Pellegrino, M
   Steinbach, N
   Stensmyr, MC
   Hansson, BS
   Vosshall, LB
AF Pellegrino, Maurizio
   Steinbach, Nicole
   Stensmyr, Marcus C.
   Hansson, Bill S.
   Vosshall, Leslie B.
TI A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor
SO NATURE
LA English
DT Article
ID aedes-aegypti; drosophila-melanogaster; repellent deet; cellular basis; mosquitos; diptera; superfamily; attraction; inhibition; culicidae
AB Blood-feeding insects such as mosquitoes are efficient vectors of human infectious diseases because they are strongly attracted by body heat, carbon dioxide and odours produced by their vertebrate hosts. Insect repellents containing DEET (N,N-diethyl-meta-toluamide) are highly effective, but the mechanism by which this chemical wards off biting insects remains controversial despite decades of investigation(1-11). DEET seems to act both at close range as a contact chemo-repellent, by affecting insect gustatory receptors(12), and at long range, by affecting the olfactory system(1-11). Two opposing mechanisms for the observed behavioural effects of DEET in the gas phase have been proposed: that DEET interferes with the olfactory system to block host odour recognition(1-7) and that DEET actively repels insects by activating olfactory neurons that elicit avoidance behaviour(8-11). Here we show that DEET functions as a modulator of the odour-gated ion channel formed by the insect odorant receptor complex(13,14). The functional insect odorant receptor complex consists of a common co-receptor, ORCO (ref. 15) (formerly called OR83B; ref. 16), and one or more variable odorant receptor subunits that confer odour selectivity(17). DEET acts on this complex to potentiate or inhibit odour-evoked activity or to inhibit odour-evoked suppression of spontaneous activity. This modulation depends on the specific odorant receptor and the concentration and identity of the odour ligand. We identify a single amino-acid polymorphism in the second transmembrane domain of receptor OR59B in a Drosophila melanogaster strain from Brazil that renders OR59B insensitive to inhibition by the odour ligand and modulation by DEET. Our data indicate that natural variation can modify the sensitivity of an odour-specific insect odorant receptor to odour ligands and DEET. Furthermore, they support the hypothesis that DEET acts as a molecular 'confusant' that scrambles the insect odour code, and provide a compelling explanation for the broad-spectrum efficacy of DEET against multiple insect species.
C1 [Pellegrino, Maurizio; Steinbach, Nicole; Vosshall, Leslie B.] Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
   [Vosshall, Leslie B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Stensmyr, Marcus C.; Hansson, Bill S.] Max Planck Inst Chem Ecol, Dept Evolutionary Neuroethol, D-07745 Jena, Germany.
C3 Rockefeller University; Howard Hughes Medical Institute; Rockefeller University; Max Planck Society
RP Vosshall, LB (corresponding author), Rockefeller Univ, Lab Neurogenet & Behav, 1230 York Ave,Box 63, 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; NIH [RO1 DC008600]; Max Planck Society
NR 36
TC 152
Z9 183
U1 2
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 511
EP U106
DI 10.1038/nature10438
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200042
PM 21937991
DA 2026-03-09
ER

PT J
AU Sumi, T
   Kamiya, K
   Bennett, DP
   Bond, IA
   Abe, F
   Botzler, CS
   Fukui, A
   Furusawa, K
   Hearnshaw, JB
   Itow, Y
   Kilmartin, PM
   Korpela, A
   Lin, W
   Ling, CH
   Masuda, K
   Matsubara, Y
   Miyake, N
   Motomura, M
   Muraki, Y
   Nagaya, M
   Nakamura, S
   Ohnishi, K
   Okumura, T
   Perrott, YC
   Rattenbury, N
   Saito, T
   Sako, T
   Sullivan, DJ
   Sweatman, WL
   Tristram, PJ
   Yock, PCM
   Udalski, A
   Szymanski, MK
   Kubiak, M
   Pietrzynski, G
   Poleski, R
   Soszynski, I
   Wyrzykowski, L
   Ulaczyk, K
AF Sumi, T.
   Kamiya, K.
   Bennett, D. P.
   Bond, I. A.
   Abe, F.
   Botzler, C. S.
   Fukui, A.
   Furusawa, K.
   Hearnshaw, J. B.
   Itow, Y.
   Kilmartin, P. M.
   Korpela, A.
   Lin, W.
   Ling, C. H.
   Masuda, K.
   Matsubara, Y.
   Miyake, N.
   Motomura, M.
   Muraki, Y.
   Nagaya, M.
   Nakamura, S.
   Ohnishi, K.
   Okumura, T.
   Perrott, Y. C.
   Rattenbury, N.
   Saito, To
   Sako, T.
   Sullivan, D. J.
   Sweatman, W. L.
   Tristram, P. J.
   Yock, P. C. M.
   Udalski, A.
   Szymanski, M. K.
   Kubiak, M.
   Pietrzynski, G.
   Poleski, R.
   Soszynski, I.
   Wyrzykowski, L.
   Ulaczyk, K.
TI Unbound or distant planetary mass population detected by gravitational microlensing
SO NATURE
LA English
DT Article
ID difference image-analysis; galactic bulge; optical depth; lensing experiment; macho project; brown dwarfs; star; neptunes; jupiters; systems
AB Since 1995, more than 500 exoplanets have been detected using different techniques(1,2), of which 12 were detected with gravitational microlensing(3,4). Most of these are gravitationally bound to their host stars. There is some evidence of free-floating planetary-mass objects in young star-forming regions(5-8), but these objects are limited to massive objects of 3 to 15 Jupiter masses with large uncertainties in photometric mass estimates and their abundance. Here, we report the discovery of a population of unbound or distant Jupiter-mass objects, which are almost twice (1.8(-0.8)(+1.7)) as common as main-sequence stars, based on two years of gravitational microlensing survey observations towards the Galactic Bulge. These planetary-mass objects have no host stars that can be detected within about ten astronomical units by gravitational microlensing. However, a comparison with constraints from direct imaging(9) suggests that most of these planetary-mass objects are not bound to any host star. An abrupt change in the mass function at about one Jupiter mass favours the idea that their formation process is different from that of stars and brown dwarfs. They may have formed in proto-planetary disks and subsequently scattered into unbound or very distant orbits.
C1 [Sumi, T.] Osaka Univ, Dept Earth & Space Sci, Osaka 5600043, Japan.
   [Sumi, T.; Kamiya, K.; Abe, F.; Fukui, A.; Furusawa, K.; Itow, Y.; Masuda, K.; Matsubara, Y.; Miyake, N.; Motomura, M.; Nagaya, M.; Nakamura, S.; Okumura, T.; Sako, T.] Nagoya Univ, Solar Terr Environm Lab, Nagoya, Aichi 4648601, Japan.
   [Bennett, D. P.] Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA.
   [Bond, I. A.; Lin, W.; Ling, C. H.; Sweatman, W. L.] Massey Univ, N Shore Mail Ctr, Inst Informat & Math Sci, Auckland 0745, New Zealand.
   [Botzler, C. S.; Rattenbury, N.; Tristram, P. J.; Yock, P. C. M.] Univ Auckland, Dept Phys, Auckland 1142, New Zealand.
   [Hearnshaw, J. B.] Univ Canterbury, Dept Phys & Astron, Christchurch 8140, New Zealand.
   [Kilmartin, P. M.] Univ Canterbury, Mt John Univ Observ, Lake Tekapo 8770, New Zealand.
   [Korpela, A.; Sullivan, D. J.] Victoria Univ, Sch Chem & Phys Sci, Wellington 6140, New Zealand.
   [Muraki, Y.] Konan Univ, Dept Phys, Kobe, Hyogo 6588501, Japan.
   [Ohnishi, K.] Nagano Natl Coll Technol, Nagano 3818550, Japan.
   [Perrott, Y. C.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Saito, To] Tokyo Metropolitan Coll Ind Technol, Tokyo 1168523, Japan.
   [Udalski, A.; Szymanski, M. K.; Kubiak, M.; Pietrzynski, G.; Poleski, R.; Soszynski, I.; Ulaczyk, K.] Univ Warsaw Observ, PL-00478 Warsaw, Poland.
   [Pietrzynski, G.] Univ Concepcion, Dept Astron, Concepcion, Chile.
   [Wyrzykowski, L.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
C3 University of Osaka; Nagoya University; University of Notre Dame; Massey University; University of Auckland; University of Canterbury; University of Canterbury; Victoria University Wellington; Konan University; University of Cambridge; University of Warsaw; Warsaw University Observatory; Universidad de Concepcion; University of Cambridge
RP Sumi, T (corresponding author), Osaka Univ, Dept Earth & Space Sci, Osaka 5600043, Japan.
EM sumi@ess.sci.osaka-u.ac.jp
FU Marsden Fund of New Zealand; NSF; NASA; European Research Council; Grants-in-Aid for Scientific Research [23103002, 10J07272, 23540339, 23654082, 23340044, 22403003, 23340064] Funding Source: KAKEN; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1009621] Funding Source: National Science Foundation
NR 29
TC 411
Z9 462
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 349
EP 352
DI 10.1038/nature10092
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400042
PM 21593867
DA 2026-03-09
ER

PT J
AU Kurian, L
   Palanimurugan, R
   Gödderz, D
   Dohmen, RJ
AF Kurian, Leo
   Palanimurugan, R.
   Goedderz, Daniela
   Dohmen, R. Juergen
TI Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA
SO NATURE
LA English
DT Article
ID translation; yeast; ribosome; degradation; pathway; protein; stress; tunnel
AB Polyamines are essential organic polycations with multiple cellular functions relevant for cell division, cancer and ageing(1-3). Regulation of polyamine synthesis is mainly achieved by controlling the activity of ornithine decarboxylase (ODC) through an unusual mechanism involving ODC antizyme(1,4), the binding of which disrupts homodimeric ODC and targets it for ubiquitin-independent degradation by the 26S proteasome(5). Whereas mammals express several antizyme genes(6), we have identified a single orthologue, termed OAZ1, in Saccharomyces cerevisiae(7). Similar to its mammalian counterparts, OAZ1 synthesis is induced with rising intracellular polyamine concentrations, which also inhibit ubiquitin-dependent degradation of the OAZ1 protein(7). Together, these mechanisms contribute to a homeostatic feedback regulation of polyamines(1,7,8). Antizyme synthesis involves a conserved +1 ribosomal frameshifting (RFS) event at an internal STOP codon during decoding of its messenger RNA(6-10). Here we used S. cerevisiae OAZ1 to dissect the enigmatic mechanism underlying polyamine regulation of RFS. In contrast with previous assumptions, we report here that the nascent antizyme polypeptide is the relevant polyamine sensor that operates in cis to negatively regulate upstream RFS on the polysomes, where its own mRNA is being translated. At low polyamine levels, the emerging antizyme polypeptide inhibits completion of its synthesis causing a ribosome pile-up on antizyme mRNA, whereas polyamine binding to nascent antizyme promotes completion of its synthesis. Thus, our study reveals a novel autoregulatory mechanism, in which binding of a small metabolite to a nascent sensor protein stimulates the latter's synthesis co-translationally.
C1 [Kurian, Leo; Palanimurugan, R.; Goedderz, Daniela; Dohmen, R. Juergen] Univ Cologne, Cologne Bioctr, Inst Genet, D-50674 Cologne, Germany.
C3 University of Cologne
RP Dohmen, RJ (corresponding author), Univ Cologne, Cologne Bioctr, Inst Genet, Zulpicher Str 47A, D-50674 Cologne, Germany.
EM j.dohmen@uni-koeln.de
FU NRW Graduate School in Genetics and Functional Genomics; Deutsche Forschungsgemeinschaft [Do 649/4]
NR 22
TC 85
Z9 109
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 490
EP U147
DI 10.1038/nature10393
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500046
PM 21900894
DA 2026-03-09
ER

PT J
AU Dauphas, N
   Pourmand, A
AF Dauphas, N.
   Pourmand, A.
TI Hf-W-Th evidence for rapid growth of Mars and its status as a planetary embryo
SO NATURE
LA English
DT Article
ID core formation; early differentiation; isotope geochemistry; terrestrial planets; oligarchic growth; giant impact; todga resin; lu-hf; moon; chondrites
AB Terrestrial planets are thought to have formed through collisions between large planetary embryos(1) of diameter similar to 1,000-5,000 km. For Earth, the last of these collisions involved an impact by a Mars-size embryo that formed the Moon 50-150 million years (Myr) after the birth of the Solar System(2,3). Although model simulations of the growth of terrestrial planets can reproduce the mass and dynamical parameters of the Earth and Venus, they fall short of explaining the small size of Mars(4,5). One possibility is that Mars was a planetary embryo that escaped collision and merging with other embryos(1). To assess this idea, it is crucial to know Mars' accretion timescale(6), which can be investigated using the Hf-182-W-182 decay system in shergottite-nakhlite-chassignite meteorites(6-10). Nevertheless, this timescale remains poorly constrained owing to a large uncertainty associated with the Hf/W ratio of the Martian mantle(6) and as a result, contradicting timescales have been reported that range between 0 and 15 Myr (refs 6-10). Here we show that Mars accreted very rapidly and reached about half of its present size in only 1.8(-1.0)(+0.9) Myr or less, which is consistent with a stranded planetary embryo origin. We have found a well-defined correlation between the Th/Hf and Hf-176/Hf-177 ratios in chondrites that reflects remobilization of Lu and Th during parent-body processes. Using this relationship, we estimate the Hf/W ratio in Mars' mantle to be 3.51 +/- 0.45. This value is much more precise than previous estimates, which ranged between 2.6 and 5.0 (ref. 6), and lifts the large uncertainty that plagued previous estimates of the age of Mars. Our results also demonstrate that Mars grew before dissipation of the nebular gas when similar to 100-km planetesimals, such as the parent bodies of chondrites, were still being formed. Mars' accretion occurred early enough to allow establishment of a magma ocean powered by decay of Al-26.
C1 [Dauphas, N.; Pourmand, A.] Univ Chicago, Dept Geophys Sci, Origins Lab, Chicago, IL 60637 USA.
   [Dauphas, N.; Pourmand, A.] Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA.
   [Pourmand, A.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Geol & Geophys, Miami, FL 33149 USA.
C3 University of Chicago; University of Chicago; University of Miami
RP Dauphas, N (corresponding author), Univ Chicago, Dept Geophys Sci, Origins Lab, 5734 S Ellis Ave, Chicago, IL 60637 USA.
EM dauphas@uchicago.edu
FU Packard fellowship; NASA; NSF [NNX09AG59G, EAR-0820807]
NR 39
TC 371
Z9 405
U1 1
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 MAY 26
PY 2011
VL 473
IS 7348
BP 489
EP U227
DI 10.1038/nature10077
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300035
PM 21614076
DA 2026-03-09
ER

PT J
AU Lin, JZ
   Lai, SM
   Jia, R
   Xu, AB
   Zhang, LM
   Lu, J
   Ye, KQ
AF Lin, Jinzhong
   Lai, Shaomei
   Jia, Ru
   Xu, Anbi
   Zhang, Liman
   Lu, Jing
   Ye, Keqiong
TI Structural basis for site-specific ribose methylation by box C/D RNA protein complexes
SO NATURE
LA English
DT Article
ID crystal-structure; soluble-rna; core; 2'-o-methylation; requirement; rnps
AB Box C/D RNA protein complexes (RNPs) direct site-specific 2'-O-methylation of RNA and ribosome assembly(1-4). The guide RNA in C/D RNP forms base pairs with complementary substrates and selects the modification site using a molecular ruler(5-7). Despite many studies of C/D RNP structure(8-25), the fundamental questions of how C/D RNAs assemble into RNPs and how they guide modification remain unresolved. Here we report the crystal structure of an entire catalytically active archaeal C/D RNP consisting of a bipartite C/D RNA associated with two substrates and two copies each of Nop5, L7Ae and fibrillarin at 3.15-angstrom resolution. The substrate pairs with the second through the eleventh nucleotide of the 12-nucleotide guide, and the resultant duplex is bracketed in a channel with flexible ends. The methyltransferase fibrillarin binds to an undistorted A-form structure of the guide-substrate duplex and specifically loads the target ribose into the active site. Because interaction with the RNA duplex alone does not determine the site specificity, fibrillarin is further positioned by non-specific and specific protein interactions. Compared with the structure of the inactive C/D RNP, extensive domain movements are induced by substrate loading. Our results reveal the organization of a monomeric C/D RNP and the mechanism underlying its site-specific methylation activity.
C1 [Lin, Jinzhong; Lai, Shaomei; Jia, Ru; Xu, Anbi; Zhang, Liman; Lu, Jing; Ye, Keqiong] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Zhang, Liman; Lu, Jing] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China.
   [Zhang, Liman; Lu, Jing] Peking Union Med Coll, Beijing 100730, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
RP Ye, KQ (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM yekeqiong@nibs.ac.cn
FU Chinese Ministry of Science and Technology [2008AA022310]; Beijing Municipal Government
NR 37
TC 112
Z9 128
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 JAN 27
PY 2011
VL 469
IS 7331
BP 559
EP U140
DI 10.1038/nature09688
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500038
PM 21270896
DA 2026-03-09
ER

PT J
AU Lucanic, M
   Held, JM
   Vantipalli, MC
   Klang, IM
   Graham, JB
   Gibson, BW
   Lithgow, GJ
   Gill, MS
AF Lucanic, Mark
   Held, Jason M.
   Vantipalli, Maithili C.
   Klang, Ida M.
   Graham, Jill B.
   Gibson, Bradford W.
   Lithgow, Gordon J.
   Gill, Matthew S.
TI N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID restriction-induced longevity; c-elegans; endocannabinoid system; evolutionary origins; dauer formation; food-intake; extension; acid; mechanisms; expression
AB Dietary restriction is a robust means of extending adult lifespan and postponing age-related disease in many species, including yeast, nematode worms, flies and rodents(1,2). Studies of the genetic requirements for lifespan extension by dietary restriction in the nematode Caenorhabditis elegans have implicated a number of key molecules in this process(3-5), including the nutrient-sensing target of rapamycin (TOR) pathway(6) and the Foxa transcription factor PHA-4 (ref. 7). However, little is known about the metabolic signals that coordinate the organismal response to dietary restriction and maintain homeostasis when nutrients are limited. The endocannabinoid system is an excellent candidate for such a role given its involvement in regulating nutrient intake and energy balance(8). Despite this, a direct role for endocannabinoid signalling in dietary restriction or lifespan determination has yet to be demonstrated, in part due to the apparent absence of endocannabinoid signalling pathways in model organisms that are amenable to lifespan analysis(9). N-acylethanolamines (NAEs) are lipid-derived signalling molecules, which include the mammalian endocannabinoid arachidonoyl ethanolamide. Here we identify NAEs in C. elegans, show that NAE abundance is reduced under dietary restriction and that NAE deficiency is sufficient to extend lifespan through a dietary restriction mechanism requiring PHA-4. Conversely, dietary supplementation with the nematode NAE eicosapentaenoyl ethanolamide not only inhibits dietary-restriction-induced lifespan extension in wild-type worms, but also suppresses lifespan extension in a TOR pathway mutant. This demonstrates a role for NAE signalling in ageing and indicates that NAEs represent a signal that coordinates nutrient status with metabolic changes that ultimately determine lifespan.
C1 [Lucanic, Mark; Held, Jason M.; Vantipalli, Maithili C.; Klang, Ida M.; Graham, Jill B.; Gibson, Bradford W.; Lithgow, Gordon J.; Gill, Matthew S.] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Klang, Ida M.] Karolinska Inst, Ctr Biosci, Novum, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
C3 Buck Institute for Research on Aging; Karolinska Institutet
RP Gill, MS (corresponding author), Scripps Res Inst Scripps Florida, 130 Scripps Way,3B3, Jupiter, FL 33458 USA.
EM mgill@scripps.edu
FU NIH National Center for Research Resources (NCRR); NIH [T32 AG000266, R01 AG029631, PL1-AG032118, UL1 DE019608, R21 AG030192, R01 AG036992]; Larry L. Hillblom Foundation; National Institute on Aging [T32AG000266] Funding Source: NIH RePORTER
NR 39
TC 127
Z9 162
U1 2
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 MAY 12
PY 2011
VL 473
IS 7346
BP 226
EP +
DI 10.1038/nature10007
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200041
PM 21562563
DA 2026-03-09
ER

PT J
AU Kollatschny, W
   Zetzl, M
AF Kollatschny, Wolfram
   Zetzl, Matthias
TI Broad-line active galactic nuclei rotate faster than narrow-line ones
SO NATURE
LA English
DT Article
ID supermassive black-holes; galaxy; profile; region; reverberation; quasars; masses
AB The super-massive black holes of 10(6)M(circle dot) to 10(9)M(circle dot) that reside in the nuclei of active galaxies(1) (AGN) are surrounded by a region emitting broad lines, probably associated with an accretion disk. The diameters of the broad-line regions range from a few light-days to more than a hundred light-days(1), and cannot be resolved spatially. The relative significance of inflow, outflow, rotational or turbulent motions in the broad-line regions as well as their structure (spherical, thin or thick accretion disk) are unknown despite intensive studies over more than thirty years(2,3). Here we report a fundamental relation between the observed emission linewidth full-width at half-maximum (FWHM) and the emission line shape FWHM/sigma(line) in AGN spectra. From this relation we infer that the predominant motion in the broad-line regions is Keplerian rotation in combination with turbulence. The geometry of the inner region varies systematically with the rotation velocity: it is flattest for the fast-rotating broad-line objects, whereas slow-rotating narrow-line AGN have a more spherical structure. Superimposed is the trend that the line-emitting region becomes geometrically thicker towards the centre within individual galaxies. Knowing the rotational velocities, we can derive the central black-hole masses more accurately; they are two to ten times smaller than has been estimated previously.
C1 [Kollatschny, Wolfram; Zetzl, Matthias] Univ Gottingen, Inst Astrophys, D-37077 Gottingen, Germany.
C3 University of Gottingen
RP Kollatschny, W (corresponding author), Univ Gottingen, Inst Astrophys, Friedrich Hund Pl 1, D-37077 Gottingen, Germany.
EM wkollat@astro.physik.uni-goettingen.de
FU Niedersachsen-Israel Research Cooperation Program [ZN2318]
NR 19
TC 70
Z9 73
U1 0
U2 2
PU 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 17
PY 2011
VL 470
IS 7334
BP 366
EP 368
DI 10.1038/nature09761
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100035
PM 21331037
DA 2026-03-09
ER

PT J
AU Miyamichi, K
   Amat, F
   Moussavi, F
   Wang, C
   Wickersham, I
   Wall, NR
   Taniguchi, H
   Tasic, B
   Huang, ZJ
   He, ZG
   Callaway, EM
   Horowitz, MA
   Luo, LQ
AF Miyamichi, Kazunari
   Amat, Fernando
   Moussavi, Farshid
   Wang, Chen
   Wickersham, Ian
   Wall, Nicholas R.
   Taniguchi, Hiroki
   Tasic, Bosiljka
   Huang, Z. Josh
   He, Zhigang
   Callaway, Edward M.
   Horowitz, Mark A.
   Luo, Liqun
TI Cortical representations of olfactory input by trans-synaptic tracing
SO NATURE
LA English
DT Article
ID piriform cortex; rabies virus; topographic organization; gene-expression; mosaic analysis; bulb glomeruli; double markers; pars externa; drosophila; nucleus
AB In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.
C1 [Miyamichi, Kazunari; Tasic, Bosiljka; Luo, Liqun] Stanford Univ, Dept Biol, HHMI, Stanford, CA 94305 USA.
   [Amat, Fernando; Moussavi, Farshid; Horowitz, Mark A.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Wang, Chen; He, Zhigang] Childrens Hosp, Dept Neurosci, Boston, MA 02115 USA.
   [Wickersham, Ian; Wall, Nicholas R.; Callaway, Edward M.] Univ Calif San Diego, Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
   [Wickersham, Ian; Wall, Nicholas R.; Callaway, Edward M.] Univ Calif San Diego, Grad Program Neurosci, La Jolla, CA 92037 USA.
   [Taniguchi, Hiroki; Huang, Z. Josh] Cold Spring Harbor Lab, New York, NY 11724 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Salk Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Cold Spring Harbor Laboratory
RP Luo, LQ (corresponding author), Stanford Univ, Dept Biol, HHMI, Stanford, CA 94305 USA.
EM lluo@stanford.edu
FU JSPS; NIH; National Institute of Neurological Disorders and Stroke [R01NS050835] Funding Source: NIH RePORTER
NR 58
TC 406
Z9 502
U1 1
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 APR 14
PY 2011
VL 472
IS 7342
BP 191
EP 196
DI 10.1038/nature09714
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100036
PM 21179085
DA 2026-03-09
ER

PT J
AU Liu, JN
   Steiner, M
   Dunlop, JA
   Keupp, H
   Shu, DG
   Ou, QA
   Han, JA
   Zhang, ZF
   Zhang, XL
AF Liu, Jianni
   Steiner, Michael
   Dunlop, Jason A.
   Keupp, Helmut
   Shu, Degan
   Ou, Qiang
   Han, Jian
   Zhang, Zhifei
   Zhang, Xingliang
TI An armoured Cambrian lobopodian from China with arthropod-like appendages
SO NATURE
LA English
DT Article
ID chengjiang lagerstatte; anomalocaris; evolution; origin; fauna
AB Cambrian fossil Lagerstatten preserving soft-bodied organisms have contributed much towards our understanding of metazoan origins(1-3). Lobopodians are a particularly interesting group that diversified and flourished in the Cambrian seas. Resembling 'worms with legs', they have long attracted much attention in that they may have given rise to both Onychophora (velvet worms)(4-6) and Tardigrada (water bears)(7,8), as well as to arthropods in general(9-12). Here we describe Diania cactiformis gen. et sp. nov. as an 'armoured' lobopodian from the Chengjiang fossil Lagerstatte (Cambrian Stage 3), Yunnan, southwestern China. Although sharing features with other typical lobopodians, it is remarkable for possessing robust and probably sclerotized appendages, with what appear to be articulated elements. In terms of limb morphology it is therefore closer to the arthropod condition, to our knowledge, than any lobopodian recorded until now. Phylogenetic analysis recovers it in a derived position, close to Arthropoda; thus, it seems to belong to a grade of organization close to the point of becoming a true arthropod. Further, D. cactiformis could imply that arthropodization (sclerotization of the limbs) preceded arthrodization (sclerotization of the body). Comparing our fossils with other lobopodian appendage morphologies-see Kerygmachela(9,10), Jianshanopodia(13) and Megadictyon(12)-reinforces the hypothesis that the group as a whole is paraphyletic, with different taxa expressing different grades of arthropodization.
C1 [Liu, Jianni; Shu, Degan; Han, Jian; Zhang, Zhifei; Zhang, Xingliang] NW Univ Xian, Dept Geol, State Key Lab Continental Dynam, Early Life Inst, Xian 710069, Peoples R China.
   [Liu, Jianni; Steiner, Michael; Keupp, Helmut] Free Univ Berlin, Dept Earth Sci, D-12249 Berlin, Germany.
   [Dunlop, Jason A.] Humboldt Univ, Leibniz Inst Res Evolut & Biodivers, Museum Nat Kunde, D-10115 Berlin, Germany.
   [Shu, Degan; Ou, Qiang] China Univ Geosci, Sch Earth Sci & Resources, Beijing 100083, Peoples R China.
C3 Northwest University Xi'an; Free University of Berlin; Leibniz Institut fur Evolutions und Biodiversitatsforschung; Humboldt University of Berlin; China University of Geosciences
RP Liu, JN (corresponding author), NW Univ Xian, Dept Geol, State Key Lab Continental Dynam, Early Life Inst, Xian 710069, Peoples R China.
EM liujianni@126.com
FU Alexander von Humboldt Foundation at the Freie Universitat Berlin; National Science Foundation of China [40802011, 40830208]; State Key Laboratory of Continental Dynamics, Northwest University; DFG [Forschergruppe 736]
NR 24
TC 56
Z9 74
U1 5
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 FEB 24
PY 2011
VL 470
IS 7335
BP 526
EP 530
DI 10.1038/nature09704
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900040
PM 21350485
DA 2026-03-09
ER

PT J
AU Takahashi, S
   Tupitsyn, IS
   van Tol, J
   Beedle, CC
   Hendrickson, DN
   Stamp, PCE
AF Takahashi, S.
   Tupitsyn, I. S.
   van Tol, J.
   Beedle, C. C.
   Hendrickson, D. N.
   Stamp, P. C. E.
TI Decoherence in crystals of quantum molecular magnets
SO NATURE
LA English
DT Article
ID coherent dynamics; electron; state; gravity
AB Quantum decoherence is a central concept in physics. Applications such as quantum information processing depend on understanding it; there are even fundamental theories proposed that go beyond quantum mechanics(1-3), in which the breakdown of quantum theory would appear as an 'intrinsic' decoherence, mimicking the more familiar environmental decoherence processes(4). Such applications cannot be optimized, and such theories cannot be tested, until we have a firm handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate and testable predictions for environmental decoherence in molecular-based quantum magnets(5). Experiments on molecular magnets have successfully demonstrated quantum-coherent phenomena(6-8) but the decoherence processes that ultimately limit such behaviour were not well constrained. For molecular magnets, theory predicts three principal contributions to environmental decoherence: from phonons, from nuclear spins and from intermolecular dipolar interactions. We use high magnetic fields on single crystals of Fe-8 molecular magnets (in which the Fe ions are surrounded by organic ligands) to suppress dipolar and nuclear-spin decoherence. In these high-field experiments, we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally, and there are no other visible decoherence sources. In these high fields, we obtain a maximum decoherence quality-factor of 1.49 x 10(6); our investigation suggests that the environmental decoherence time can be extended up to about 500 microseconds, with a decoherence quality factor of similar to 6 x 10(7), by optimizing the temperature, magnetic field and nuclear isotopic concentrations.
C1 [Takahashi, S.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Takahashi, S.] Univ Calif Santa Barbara, Inst Terahertz Sci & Technol, Santa Barbara, CA 93106 USA.
   [Takahashi, S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Tupitsyn, I. S.; Stamp, P. C. E.] Univ British Columbia, Pacific Inst Theoret Phys, Vancouver, BC V6T 1Z1, Canada.
   [Tupitsyn, I. S.; Stamp, P. C. E.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [van Tol, J.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Beedle, C. C.; Hendrickson, D. N.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
C3 University of Southern California; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of British Columbia; University of British Columbia; State University System of Florida; Florida State University; University of California System; University of California San Diego
RP Takahashi, S (corresponding author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
EM susumuta@usc.edu; stamp@phas.ubc.ca
FU NSF [DMR-0520481, DMR-0703925, DMR-0654118]; Keck Foundation; NSERC; CIFAR; PITP; John E. Fetzer Memorial Trust [D21-C62]; Center for Philosophy and the Natural Sciences, California State University, Sacramento; State of Florida; DOE
NR 30
TC 166
Z9 188
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 76
EP 79
DI 10.1038/nature10314
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300032
PM 21775988
DA 2026-03-09
ER

PT J
AU Thöne, CC
   Postigo, AD
   Fryer, CL
   Page, KL
   Gorosabel, J
   Aloy, MA
   Perley, DA
   Kouveliotou, C
   Janka, HT
   Mimica, P
   Racusin, JL
   Krimm, H
   Cummings, J
   Oates, SR
   Holland, ST
   Siegel, MH
   De Pasquale, M
   Sonbas, E
   Im, M
   Park, WK
   Kann, DA
   Guziy, S
   García, LH
   Llorente, A
   Bundy, K
   Choi, C
   Jeong, H
   Korhonen, H
   Kubànek, P
   Lim, J
   Moskvitin, A
   Muñoz-Darias, T
   Pak, S
   Parrish, I
AF Thoene, C. C.
   Postigo, A. de Ugarte
   Fryer, C. L.
   Page, K. L.
   Gorosabel, J.
   Aloy, M. A.
   Perley, D. A.
   Kouveliotou, C.
   Janka, H. T.
   Mimica, P.
   Racusin, J. L.
   Krimm, H.
   Cummings, J.
   Oates, S. R.
   Holland, S. T.
   Siegel, M. H.
   De Pasquale, M.
   Sonbas, E.
   Im, M.
   Park, W. -K.
   Kann, D. A.
   Guziy, S.
   Hernandez Garcia, L.
   Llorente, A.
   Bundy, K.
   Choi, C.
   Jeong, H.
   Korhonen, H.
   Kubanek, P.
   Lim, J.
   Moskvitin, A.
   Munoz-Darias, T.
   Pak, S.
   Parrish, I.
TI The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33
SO NATURE
LA English
DT Article
ID supernova; grb-060218; galaxy; swift; hole
AB Long gamma-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae(1). They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium(2). Here we report observations of the unusual GRB 101225A. Its gamma-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy(3).
C1 [Thoene, C. C.; Gorosabel, J.; Guziy, S.; Hernandez Garcia, L.; Kubanek, P.] IAA CSIC, Granada 18008, Spain.
   [Thoene, C. C.] Niels Bohr Int Acad, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Postigo, A. de Ugarte] Univ Copenhagen, Dark Cosmol Ctr, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Fryer, C. L.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Page, K. L.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Aloy, M. A.; Mimica, P.] Univ Valencia, Dept Astron & Astrofis, E-46100 Burjassot, Spain.
   [Perley, D. A.; Bundy, K.; Parrish, I.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Kouveliotou, C.] NASA, George C Marshall Space Flight Ctr, Sci & Technol Off, Huntsville, AL 35812 USA.
   [Janka, H. T.] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Racusin, J. L.; Krimm, H.; Cummings, J.; Holland, S. T.; Sonbas, E.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Krimm, H.; Holland, S. T.; Sonbas, E.] Univ Space Res Assoc, Columbia, MD 21044 USA.
   [Krimm, H.; Holland, S. T.] CRESST, Columbia, MD 21044 USA.
   [Oates, S. R.; De Pasquale, M.] Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Siegel, M. H.] Penn State Univ, Dept Astron & Astrophys, Davey Lab 104, University Pk, PA 16802 USA.
   [Sonbas, E.] Univ Adiyaman, Dept Phys, TR-02040 Adiyaman, Turkey.
   [Im, M.; Park, W. -K.; Choi, C.] Seoul Natl Univ, Dept Phys & Astron, Ctr Explorat Origin Universe, Seoul, South Korea.
   [Kann, D. A.] Thuringer Landessternwarte Tautenburg, D-07778 Tautenburg, Germany.
   [Guziy, S.] Nikolaev Natl Univ, UA-54030 Nikolayev, Ukraine.
   [Llorente, A.] ESAC, INSA, Herschel Sci Operat Ctr, Madrid 28080, Spain.
   [Jeong, H.; Pak, S.] Kyung Hee Univ, Sch Space Res, Yongin 446701, Gyeonggi Do, South Korea.
   [Korhonen, H.] Univ Turku, Finnish Ctr Astron ESO FINCA, Piikkio 21500, Finland.
   [Kubanek, P.] Inst Phys, Prague 18000 8, Czech Republic.
   [Lim, J.] Kyung Hee Univ, Dept Astron & Space Sci, Yongin 446701, Gyeonggi Do, South Korea.
   [Moskvitin, A.] Russian Acad Sci, Special Astrophys Observ, Nizhnii Arkhyz 369167, Russia.
   [Munoz-Darias, T.] INAF Osservatorio Astron Brera, I-23807 Merate, Italy.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); University of Copenhagen; Niels Bohr Institute; University of Copenhagen; Niels Bohr Institute; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Leicester; University of Valencia; University of California System; University of California Berkeley; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; Max Planck Society; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Universities Space Research Association (USRA); University of London; University College London; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Adiyaman University; Seoul National University (SNU); V.O. Sukhomlynskyi Mykolaiv National University; European Space Agency; European Space Astronomy Center; Kyung Hee University; University of Turku; Kyung Hee University; Russian Academy of Sciences; Special Astrophysics Observatory of the Russian Academy of Sciences; Istituto Nazionale Astrofisica (INAF)
RP Thöne, CC (corresponding author), IAA CSIC, Glorieta Astron S-N, Granada 18008, Spain.
EM cthoene@iaa.es
FU DNRF; UK Space Agency; MICINN; ERC; DFG; CRI/NRF/MEST of Korea; Russian government; STFC [ST/H00260X/1, ST/G009465/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H00260X/1, ST/G009465/1] Funding Source: researchfish
NR 21
TC 112
Z9 121
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 DEC 1
PY 2011
VL 480
IS 7375
BP 72
EP 74
DI 10.1038/nature10611
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900035
PM 22129726
DA 2026-03-09
ER

PT J
AU Mackelprang, R
   Waldrop, MP
   DeAngelis, KM
   David, MM
   Chavarria, KL
   Blazewicz, SJ
   Rubin, EM
   Jansson, JK
AF Mackelprang, Rachel
   Waldrop, Mark P.
   DeAngelis, Kristen M.
   David, Maude M.
   Chavarria, Krystle L.
   Blazewicz, Steven J.
   Rubin, Edward M.
   Jansson, Janet K.
TI Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw
SO NATURE
LA English
DT Article
ID bacterial community; r-package; diversity; carbon; soil; rna; discovery; alignment; search; genes
AB Permafrost contains an estimated 1672 Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere(1-3). This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw(2). During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions(4,5). Despite recent advances in the use of molecular tools to study permafrost microbial communities(6-9), their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 degrees C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost.
C1 [Mackelprang, Rachel; Rubin, Edward M.; Jansson, Janet K.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Mackelprang, Rachel] Calif State Univ Northridge, Dept Biol, Northridge, CA 91330 USA.
   [Waldrop, Mark P.] US Geol Survey, Menlo Pk, CA 94025 USA.
   [DeAngelis, Kristen M.; David, Maude M.; Chavarria, Krystle L.; Jansson, Janet K.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Earth Sci, Berkeley, CA 94720 USA.
   [Blazewicz, Steven J.] Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA.
   [Rubin, Edward M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
C3 United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; California State University System; California State University Northridge; United States Department of the Interior; United States Geological Survey; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Jansson, JK (corresponding author), US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
EM jrjansson@lbl.gov
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Venture Capital; United States Geological Survey
NR 44
TC 545
Z9 638
U1 21
U2 916
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 368
EP U120
DI 10.1038/nature10576
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000051
PM 22056985
DA 2026-03-09
ER

PT J
AU Payandeh, J
   Scheuer, T
   Zheng, N
   Catterall, WA
AF Payandeh, Jian
   Scheuer, Todd
   Zheng, Ning
   Catterall, William A.
TI The crystal structure of a voltage-gated sodium channel
SO NATURE
LA English
DT Article
ID molecular determinants; ionic selectivity; na+ channels; local-anesthetics; potassium channel; skeletal-muscle; k+ selectivity; block; ca2+; proteins
AB Voltage-gated sodium (Na-V) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na+ channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 angstrom resolution. The arginine gating charges make multiple hydrophilic interactions within the voltage sensor, including unanticipated hydrogen bonds to the protein backbone. Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. The NavAb selectivity filter is short, similar to 4.6 angstrom wide, and water filled, with four acidic side chains surrounding the narrowest part of the ion conduction pathway. This unique structure presents a high-field-strength anionic coordination site, which confers Na+ selectivity through partial dehydration via direct interaction with glutamate side chains. Fenestrations in the sides of the pore module are unexpectedly penetrated by fatty acyl chains that extend into the central cavity, and these portals are large enough for the entry of small, hydrophobic pore-blocking drugs. This structure provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level.
C1 [Payandeh, Jian; Scheuer, Todd; Zheng, Ning; Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Zheng, N (corresponding author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
EM nzheng@uw.edu; wcatt@uw.edu
FU Canadian Institutes of Health Research; National Institutes of Health [R01 NS15751, U01 NS058039]; Howard Hughes Medical Institute
NR 66
TC 1184
Z9 1385
U1 9
U2 532
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 353
EP U104
DI 10.1038/nature10238
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200037
PM 21743477
DA 2026-03-09
ER

PT J
AU Jezek, K
   Henriksen, EJ
   Treves, A
   Moser, EI
   Moser, MB
AF Jezek, Karel
   Henriksen, Espen J.
   Treves, Alessandro
   Moser, Edvard I.
   Moser, May-Britt
TI Theta-paced flickering between place-cell maps in the hippocampus
SO NATURE
LA English
DT Article
ID path-integration; attractor dynamics; neural networks; environment; ca1; model; representations; information; assembly; discharge
AB The ability to recall discrete memories is thought to depend on the formation of attractor states in recurrent neural networks(1-4). In such networks, representations can be reactivated reliably from subsets of the cues that were present when the memory was encoded, at the same time as interference from competing representations is minimized. Theoretical studies have pointed to the recurrent CA3 system of the hippocampus as a possible attractor network(3,4). Consistent with predictions from these studies, experiments have shown that place representations in CA3 and downstream CA1 tolerate small changes in the configuration of the environment but switch to uncorrelated representations when dissimilarities become larger(5-9). However, the kinetics supporting such network transitions, at the subsecond timescale, is poorly understood. Here we show in rats that instantaneous transformation of the spatial context does not change the hippocampal representation all at once but is followed by temporary bistability in the discharge activity of CA3 ensembles. Rather than sliding through a continuum of intermediate activity states, the CA3 network undergoes a short period of competitive flickering between preformed representations of the past and present environment before settling on the latter. Network flickers are extremely fast, often with complete replacement of the active ensemble from one theta cycle to the next. Within individual cycles, segregation is stronger towards the end, when firing starts to decline, pointing to the theta cycle as a temporal unit for expression of attractor states in the hippocampus. Repetition of pattern-completion processes across successive theta cycles may facilitate error correction and enhance discriminative power in the presence of weak and ambiguous input cues.
C1 [Jezek, Karel; Henriksen, Espen J.; Treves, Alessandro; Moser, Edvard I.; Moser, May-Britt] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, MTFS, N-7489 Trondheim, Norway.
   [Jezek, Karel; Henriksen, Espen J.; Treves, Alessandro; Moser, Edvard I.; Moser, May-Britt] Norwegian Univ Sci & Technol, Ctr Biol Memory, MTFS, N-7489 Trondheim, Norway.
   [Jezek, Karel] Acad Sci Czech Republic, Inst Physiol, Dept Physiol Memory, CR-14220 Prague 4, Krc, Czech Republic.
   [Treves, Alessandro] SISSA Int Sch Adv Studies, Cognit Neurosci Sect, I-34136 Trieste, Italy.
C3 Norwegian University of Science & Technology (NTNU); Norwegian University of Science & Technology (NTNU); Czech Academy of Sciences; Institute of Physiology of the Czech Academy of Sciences; International School for Advanced Studies (SISSA)
RP Jezek, K (corresponding author), Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, MTFS, Olav Kyrres Gate 9, N-7489 Trondheim, Norway.
EM karel.jezek@biomed.cas.cz; edvard.moser@ntnu.no
FU European Commission [200873]; European Research Council ('ENSEMBLE'); Kavli Foundation; Norwegian Research Council; Academy of Sciences of the Czech Republic [MSMT CR LC554, 1M0517, AV0Z50110509]
NR 30
TC 235
Z9 297
U1 0
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 OCT 13
PY 2011
VL 478
IS 7368
BP 246
EP U136
DI 10.1038/nature10439
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800051
PM 21964339
DA 2026-03-09
ER

PT J
AU Venditti, C
   Meade, A
   Pagel, M
AF Venditti, Chris
   Meade, Andrew
   Pagel, Mark
TI Multiple routes to mammalian diversity
SO NATURE
LA English
DT Article
ID body-size; evolutionary patterns; climate-change; fossil record; phylogeny; disparity; rates; mass
AB The radiation of the mammals provides a 165-million-year test case for evolutionary theories of how species occupy and then fill ecological niches. It is widely assumed that species often diverge rapidly early in their evolution, and that this is followed by a longer, drawn-out period of slower evolutionary fine-tuning as natural selection fits organisms into an increasingly occupied niche space(1,2). But recent studies have hinted that the process may not be so simple(3-5). Here we apply statistical methods that automatically detect temporal shifts in the rate of evolution through time to a comprehensive mammalian phylogeny(6) and data set(7) of body sizes of 3,185 extant species. Unexpectedly, the majority of mammal species, including two of the most speciose orders (Rodentia and Chiroptera), have no history of substantial and sustained increases in the rates of evolution. Instead, a subset of the mammals has experienced an explosive increase (between 10- and 52-fold) in the rate of evolution along the single branch leading to the common ancestor of their monophyletic group (for example Chiroptera), followed by a quick return to lower or background levels. The remaining species are a taxonomically diverse assemblage showing a significant, sustained increase or decrease in their rates of evolution. These results necessarily decouple morphological diversification from speciation and suggest that the processes that give rise to the morphological diversity of a class of animals are far more free to vary than previously considered. Niches do not seem to fill up, and diversity seems to arise whenever, wherever and at whatever rate it is advantageous.
C1 [Venditti, Chris] Univ Hull, Dept Biol Sci, Kingston Upon Hull HU6 7RX, N Humberside, England.
   [Meade, Andrew; Pagel, Mark] Univ Reading, Sch Biol Sci, Reading RG6 6BX, Berks, England.
   [Pagel, Mark] Santa Fe Inst, Santa Fe, NM 87501 USA.
C3 University of Hull; University of Reading; The Santa Fe Institute
RP Venditti, C (corresponding author), Univ Hull, Dept Biol Sci, Kingston Upon Hull HU6 7RX, N Humberside, England.
EM c.venditti@hull.ac.uk; m.pagel@reading.ac.uk
FU Leverhulme Trust [ECF/2009/0029]; Natural Environment Research Council, UK; European Research Council; Natural Environment Research Council [NE/C51992X/1] Funding Source: researchfish
NR 25
TC 262
Z9 281
U1 0
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 NOV 17
PY 2011
VL 479
IS 7373
BP 393
EP 396
DI 10.1038/nature10516
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700044
PM 22012260
DA 2026-03-09
ER

PT J
AU Temme, K
   Osborne, TJ
   Vollbrecht, KG
   Poulin, D
   Verstraete, F
AF Temme, K.
   Osborne, T. J.
   Vollbrecht, K. G.
   Poulin, D.
   Verstraete, F.
TI Quantum Metropolis sampling
SO NATURE
LA English
DT Article
ID computation; algorithms; complexity; systems
AB The original motivation to build a quantum computer came from Feynman(1), who imagined a machine capable of simulating generic quantum mechanical systems-a task that is believed to be intractable for classical computers. Such a machine could have far-reaching applications in the simulation of many-body quantum physics in condensed-matter, chemical and high-energy systems. Part of Feynman's challenge was met by Lloyd(2), who showed how to approximately decompose the time evolution operator of interacting quantum particles into a short sequence of elementary gates, suitable for operation on a quantum computer. However, this left open the problem of how to simulate the equilibrium and static properties of quantum systems. This requires the preparation of ground and Gibbs states on a quantum computer. For classical systems, this problem is solved by the ubiquitous Metropolis algorithm(3), a method that has basically acquired a monopoly on the simulation of interacting particles. Here we demonstrate how to implement a quantum version of the Metropolis algorithm. This algorithm permits sampling directly from the eigenstates of the Hamiltonian, and thus evades the sign problem present in classical simulations. A small-scale implementation of this algorithm should be achievable with today's technology.
C1 [Temme, K.; Verstraete, F.] Univ Vienna, Fak Phys, Vienna Ctr Quantum Sci & Technol, A-1090 Vienna, Austria.
   [Osborne, T. J.] Leibniz Univ Hannover, Inst Theoret Phys, D-30167 Hannover, Germany.
   [Vollbrecht, K. G.] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Poulin, D.] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
C3 University of Vienna; Leibniz University Hannover; Max Planck Society; University of Sherbrooke
RP Verstraete, F (corresponding author), Univ Vienna, Fak Phys, Vienna Ctr Quantum Sci & Technol, Waehringer Guertel 18, A-1090 Vienna, Austria.
EM fverstraete@gmail.com
FU FWF; EPSRC; DFG [FG 635]; NSERC; MITACS; FQRNT; European grant QUEVADIS; ERC; EPSRC [EP/G045771/1] Funding Source: UKRI; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF); Engineering and Physical Sciences Research Council [EP/G045771/1] Funding Source: researchfish
NR 30
TC 234
Z9 272
U1 0
U2 26
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 87
EP 90
DI 10.1038/nature09770
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100039
PM 21368829
DA 2026-03-09
ER

PT J
AU Li, F
   Martienssen, R
   Cande, WZ
AF Li, Fei
   Martienssen, Rob
   Cande, W. Zacheus
TI Coordination of DNA replication and histone modification by the Rik1-Dos2 complex
SO NATURE
LA English
DT Article
ID fission yeast; schizosaccharomyces-pombe; polymerase-epsilon; rna interference; s-phase; heterochromatin formation; chromosomal replication; epigenetic inheritance; cell-cycle; chromatin
AB Histone modification marks have an important role in many chromatin processes(1,2). During DNA replication, both heterochromatin and euchromatin are disrupted ahead of the replication fork and are then reassembled into their original epigenetic states behind the fork(3,4). How histone marks are accurately inherited from generation to generation is still poorly understood. In fission yeast (Schizosaccharomyces pombe), RNA interference (RNAi)-mediated histone methylation is cell cycle regulated. Centromeric repeats are transiently transcribed in the S phase of the cell cycle and are processed into short interfering RNAs (siRNAs) by the complexes RITS (RNA-induced initiation of transcriptional gene silencing) and RDRC (RNA-directed RNA polymerase complex)(5-7). The small RNAs together with silencing factors-including Dos1 (also known as Clr8 and Raf1), Dos2 (also known as Clr7 and Raf2), Rik1 and Lid2-promote heterochromatic methylation of histone H3 at lysine 9 (H3K9) by a histone methyltransferase, Clr4 (refs 8-13). The methylation of H3K9 provides a binding site for Swi6, a structural and functional homologue of metazoan heterochromatin protein 1 (HP1)(14). Here we characterize a silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the catalytic subunit of DNA polymerase-e). This complex regulates RNA polymerase II (RNA Pol II) activity in heterochromatin and is required for DNA replication and heterochromatin assembly. Our findings provide a molecular link between DNA replication and histone methylation, shedding light on how epigenetic marks are transmitted during each cell cycle.
C1 [Li, Fei] NYU, Dept Biol, New York, NY 10003 USA.
   [Martienssen, Rob] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Cande, W. Zacheus] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
C3 New York University; Cold Spring Harbor Laboratory; University of California System; University of California Berkeley
RP Li, F (corresponding author), NYU, Dept Biol, New York, NY 10003 USA.
EM fl43@nyu.edu
FU National Institutes of Health [RO1GM076396]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1025830] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0963400] Funding Source: National Science Foundation
NR 32
TC 95
Z9 102
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 244
EP U2562
DI 10.1038/nature10161
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500054
PM 21725325
DA 2026-03-09
ER

PT J
AU Choi, M
   Lee, SH
   Kim, Y
   Kang, SB
   Shin, J
   Kwak, MH
   Kang, KY
   Lee, YH
   Park, N
   Min, B
AF Choi, Muhan
   Lee, Seung Hoon
   Kim, Yushin
   Kang, Seung Beom
   Shin, Jonghwa
   Kwak, Min Hwan
   Kang, Kwang-Young
   Lee, Yong-Hee
   Park, Namkyoo
   Min, Bumki
TI A terahertz metamaterial with unnaturally high refractive index
SO NATURE
LA English
DT Article
ID negative-index; cloak; frequency
AB Controlling the electromagnetic properties of materials, going beyond the limit that is attainable with naturally existing substances, has become a reality with the advent of metamaterials(1-3). The range of various structured artificial 'atoms' has promised a vast variety of otherwise unexpected physical phenomena(3-17), among which the experimental realization of a negative refractive index has been one of the main foci thus far. Expanding the refractive index into a high positive regime will complete the spectrum of achievable refractive index and provide more design flexibility for transformation optics(9-14). Naturally existing transparent materials possess small positive indices of refraction, except for a few semiconductors and insulators, such as lead sulphide or strontium titanate, that exhibit a rather high peak refractive index at mid- and far-infrared frequencies(18). Previous approaches using metamaterials were not successful in realizing broadband high refractive indices(19-21). A broadband high-refractive-index metamaterial structure was theoretically investigated only recently(22), but the proposed structure does not lend itself to easy implementation. Here we demonstrate that a broadband, extremely high index of refraction can be realized from large-area, free-standing, flexible terahertz metamaterials composed of strongly coupled unit cells. By drastically increasing the effective permittivity through strong capacitive coupling and decreasing the diamagnetic response with a thin metallic structure in the unit cell, a peak refractive index of 38.6 along with a low-frequency quasi-static value of over 20 were experimentally realized for a single-layer terahertz metamaterial, while maintaining low losses. As a natural extension of these single-layer metamaterials, we fabricated quasi-three-dimensional high-refractive-index metamaterials, and obtained a maximum bulk refractive index of 33.2 along with a value of around 8 at the quasi-static limit.
C1 [Choi, Muhan; Lee, Seung Hoon; Kim, Yushin; Min, Bumki] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305751, South Korea.
   [Kang, Seung Beom; Kwak, Min Hwan; Kang, Kwang-Young] Elect & Telecommun Res Inst, Convergence Components & Mat Res Lab, Taejon 305700, South Korea.
   [Shin, Jonghwa; Lee, Yong-Hee] Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305751, South Korea.
   [Park, Namkyoo] Seoul Natl Univ, Sch Elect Engn & Comp Sci, Seoul 151744, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST); Electronics & Telecommunications Research Institute - Korea (ETRI); Korea Advanced Institute of Science & Technology (KAIST); Seoul National University (SNU)
RP Min, B (corresponding author), Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305751, South Korea.
EM bmin@kaist.ac.kr
FU Korean government [2009-0069459, 2008-0062235, 2010-0012058, GRL K20815000003, 2010-0001859]; MKE/KEIT [2006-S-005-04]; National Research Foundation of Korea [2007-0093863]; National Research Foundation of Korea [2007-0093863] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NR 25
TC 554
Z9 608
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 FEB 17
PY 2011
VL 470
IS 7334
BP 369
EP 373
DI 10.1038/nature09776
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100036
PM 21331038
DA 2026-03-09
ER

PT J
AU Higham, T
   Compton, T
   Stringer, C
   Jacobi, R
   Shapiro, B
   Trinkaus, E
   Chandler, B
   Gröning, F
   Collins, C
   Hillson, S
   O'Higgins, P
   FitzGerald, C
   Fagan, M
AF Higham, Tom
   Compton, Tim
   Stringer, Chris
   Jacobi, Roger
   Shapiro, Beth
   Trinkaus, Erik
   Chandler, Barry
   Groening, Flora
   Collins, Chris
   Hillson, Simon
   O'Higgins, Paul
   FitzGerald, Charles
   Fagan, Michael
TI The earliest evidence for anatomically modern humans in northwestern Europe
SO NATURE
LA English
DT Article
ID oxford ams system; radiocarbon-dates; bone; age; ancient; middle
AB The earliest anatomically modern humans in Europe are thought to have appeared around 43,000-42,000 calendar years before present (43-42 kyr cal BP), by association with Aurignacian sites and lithic assemblages assumed to have been made by modern humans rather than by Neanderthals. However, the actual physical evidence for modern humans is extremely rare, and direct dates reach no farther back than about 41-39 kyr cal BP, leaving a gap. Here we show, using stratigraphic, chronological and archaeological data, that a fragment of human maxilla from the Kent's Cavern site, UK, dates to the earlier period. The maxilla (KC4), which was excavated in 1927, was initially diagnosed as Upper Palaeolithic modern human(1). In 1989, it was directly radiocarbon dated by accelerator mass spectrometry to 36.4-34.7 kyr cal BP2. Using a Bayesian analysis of new ultrafiltered bone collagen dates in an ordered stratigraphic sequence at the site, we show that this date is a considerable underestimate. Instead, KC4 dates to 44.2-41.5 kyr cal BP. This makes it older than any other equivalently dated modern human specimen and directly contemporary with the latest European Neanderthals, thus making its taxonomic attribution crucial. We also show that in 13 dental traits KC4 possesses modern human rather than Neanderthal characteristics; three other traits show Neanderthal affinities and a further seven are ambiguous. KC4 therefore represents the oldest known anatomically modern human fossil in northwestern Europe, fills a key gap between the earliest dated Aurignacian remains and the earliest human skeletal remains, and demonstrates the wide and rapid dispersal of early modern humans across Europe more than 40 kyr ago.
C1 [Higham, Tom] Univ Oxford, Res Lab Archaeol & Hist Art, Oxford Radiocarbon Accelerator Unit, Oxford OX1 3QY, England.
   [Compton, Tim; Stringer, Chris; Jacobi, Roger; Collins, Chris] Nat Hist Museum, London SW7 5BD, England.
   [Jacobi, Roger] British Museum, Dept Prehist & Europe, Quaternary Sect, London N1 5QJ, England.
   [Shapiro, Beth] Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA.
   [Trinkaus, Erik] Washington Univ, Dept Anthropol, St Louis, MO 63130 USA.
   [Chandler, Barry] Torquay Museum, Torquay TQ1 1HG, Devon, England.
   [Groening, Flora; Fagan, Michael] Univ Hull, Dept Engn, Kingston Upon Hull HU6 7RX, Yorks, England.
   [Hillson, Simon] UCL, Inst Archaeol, London WC1H 0PY, England.
   [O'Higgins, Paul] Univ York, Hull York Med Sch, Ctr Anat & Human Sci, York YO10 5DD, N Yorkshire, England.
   [FitzGerald, Charles] McMaster Univ, Dept Anthropol, Hamilton, ON L8S 4L9, Canada.
C3 University of Oxford; Natural History Museum London; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Washington University (WUSTL); University of Hull; University of London; University College London; University of Hull; University of York - UK; McMaster University
RP Higham, T (corresponding author), Univ Oxford, Res Lab Archaeol & Hist Art, Oxford Radiocarbon Accelerator Unit, S Parks Rd, Oxford OX1 3QY, England.
EM thomas.higham@rlaha.ox.ac.uk; c.stringer@nhm.ac.uk
FU NERC [NE/D014077/1]; Leverhulme Trust; NERC [NE/D014077/1, NE/E015905/1] Funding Source: UKRI; Natural Environment Research Council [NE/D014077/1, NE/E015905/1] Funding Source: researchfish
NR 25
TC 221
Z9 256
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 NOV 24
PY 2011
VL 479
IS 7374
BP 521
EP 524
DI 10.1038/nature10484
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600049
PM 22048314
DA 2026-03-09
ER

PT J
AU Moore, EB
   Molinero, V
AF Moore, Emily B.
   Molinero, Valeria
TI Structural transformation in supercooled water controls the crystallization rate of ice
SO NATURE
LA English
DT Article
ID molecular-dynamics; glassy water; stability; singularity; nucleation; behavior; density; growth; liquid; phase
AB One of water's unsolved puzzles is the question of what determines the lowest temperature to which it can be cooled before freezing to ice. The supercooled liquid has been probed experimentally to near the homogeneous nucleation temperature, T approximate to 232 K, yet the mechanism of ice crystallization-including the size and structure of critical nuclei-has not yet been resolved. The heat capacity and compressibility of liquid water anomalously increase on moving into the supercooled region, according to power laws that would diverge ( that is, approach infinity) at similar to 225K (refs 1, 2), so there may be a link between water's thermodynamic anomalies and the crystallization rate of ice. But probing this link is challenging because fast crystallization prevents experimental studies of the liquid below T-H. And although atomistic studies have captured water crystallization(3), high computational costs have so far prevented an assessment of the rates and mechanism involved. Here we report coarse-grained molecular simulations with the mW water model(4) in the supercooled regime around TH which reveal that a sharp increase in the fraction of four-coordinated molecules in supercooled liquid water explains its anomalous thermodynamics and also controls the rate and mechanisms of ice formation. The results of the simulations and classical nucleation theory using experimental data suggest that the crystallization rate of water reaches a maximum around 225 K, below which ice nuclei form faster than liquid water can equilibrate. This implies a lower limit of metastability of liquid water just below TH and well above its glass transition temperature, 136 K. By establishing a relationship between the structural transformation in liquid water and its anomalous thermodynamics and crystallization rate, our findings also provide mechanistic insight into the observed(5) dependence of homogeneous ice nucleation rates on the thermodynamics of water.
C1 [Moore, Emily B.; Molinero, Valeria] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah
RP Molinero, V (corresponding author), Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
EM Valeria.Molinero@utah.edu
FU Arnold and Mabel Beckman Foundation
CR Angell CA, 2008, SCIENCE, V319, P582, DOI 10.1126/science.1131939
   de la Llave E, 2010, J CHEM PHYS, V133, P0, DOI 10.1063/1.3462964
   Finney JL, 2002, PHYS REV LETT, V88, P0, DOI 10.1103/PhysRevLett.88.225503
   Huang CC, 2010, J CHEM PHYS, V133, P0, DOI 10.1063/1.3495974
   Jacobson LC, 2009, J PHYS CHEM B, V113, P10298, DOI 10.1021/jp903439a
   Jähnert S, 2008, PHYS CHEM CHEM PHYS, V10, P6039, DOI 10.1039/b809438c
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   KAUZMANN W, 1948, CHEM REV, V43, P219, DOI 10.1021/cr60135a002
   Kiselev SB, 2001, INT J THERMOPHYS, V22, P1421, DOI 10.1023/A:1012893020651
   Kohl I, 2000, PHYS CHEM CHEM PHYS, V2, P1579, DOI 10.1039/a908688i
   Koop T, 2000, NATURE, V406, P611, DOI 10.1038/35020537
   Limmer DT, 2011, J CHEM PHYS, V135, P0, DOI 10.1063/1.3643333
   Liu J, 2007, LANGMUIR, V23, P7286, DOI 10.1021/la063650a
   Liu Y, 2009, J CHEM PHYS, V131, P0, DOI 10.1063/1.3229892
   Mallamace F, 2007, P NATL ACAD SCI USA, V104, P18387, DOI 10.1073/pnas.0706504104
   Matsumoto M, 2002, NATURE, V416, P409, DOI 10.1038/416409a
   Mishima O, 2005, J CHEM PHYS, V123, P0, DOI 10.1063/1.2085144
   Mishima O, 1998, NATURE, V396, P329, DOI 10.1038/24540
   Molinero V, 2009, J PHYS CHEM B, V113, P4008, DOI 10.1021/jp805227c
   Moore EB, 2010, J CHEM PHYS, V132, P0, DOI 10.1063/1.3451112
   Moore EB, 2010, PHYS CHEM CHEM PHYS, V12, P4124, DOI 10.1039/b919724a
   Moore EB, 2009, J CHEM PHYS, V130, P0, DOI 10.1063/1.3158470
   PLIMPTON S, 1995, J COMPUT PHYS, V117, P1, DOI 10.1006/jcph.1995.1039
   POOLE PH, 1992, NATURE, V360, P324, DOI 10.1038/360324a0
   Sastry S, 1996, PHYS REV E, V53, P6144, DOI 10.1103/PhysRevE.53.6144
   SPEEDY RJ, 1976, J CHEM PHYS, V65, P851, DOI 10.1063/1.433153
   SPEEDY RJ, 1982, J PHYS CHEM-US, V86, P982, DOI 10.1021/j100395a030
   Stevenson JD, 2011, J PHYS CHEM A, V115, P3713, DOI 10.1021/jp1060057
   Tanaka H, 2003, PHYS REV E, V68, P0, DOI 10.1103/PhysRevE.68.011505
   Tombari E, 1999, CHEM PHYS LETT, V300, P749, DOI 10.1016/S0009-2614(98)01392-X
   Wedekind J, 2007, J CHEM PHYS, V126, P0, DOI 10.1063/1.2713401
   Xu LM, 2009, NAT PHYS, V5, P565, DOI 10.1038/NPHYS1328
NR 32
TC 652
Z9 726
U1 17
U2 612
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 506
EP U226
DI 10.1038/nature10586
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600045
PM 22113691
DA 2026-03-09
ER

PT J
AU Mullighan, CG
   Zhang, JH
   Kasper, LH
   Lerach, S
   Payne-Turner, D
   Phillips, LA
   Heatley, SL
   Holmfeldt, L
   Collins-Underwood, JR
   Ma, J
   Buetow, KH
   Pui, CH
   Baker, SD
   Brindle, PK
   Downing, JR
AF Mullighan, Charles G.
   Zhang, Jinghui
   Kasper, Lawryn H.
   Lerach, Stephanie
   Payne-Turner, Debbie
   Phillips, Letha A.
   Heatley, Sue L.
   Holmfeldt, Linda
   Collins-Underwood, J. Racquel
   Ma, Jing
   Buetow, Kenneth H.
   Pui, Ching-Hon
   Baker, Sharyn D.
   Brindle, Paul K.
   Downing, James R.
TI CREBBP mutations in relapsed acute lymphoblastic leukaemia
SO NATURE
LA English
DT Article
ID genetic alterations; binding protein; genomic analysis; p300; cbp; reveals; childhood; deletions; cbp/p300; database
AB Relapsed acute lymphoblastic leukaemia (ALL) is a leading cause of death due to disease in young people, but the biological determinants of treatment failure remain poorly understood. Recent genome-wide profiling of structural DNA alterations in ALL have identified multiple submicroscopic somatic mutations targeting key cellular pathways(1,2), and have demonstrated substantial evolution in genetic alterations from diagnosis to relapse(3). However, DNA sequence mutations in ALL have not been analysed in detail. To identify novel mutations in relapsed ALL, we resequenced 300 genes in matched diagnosis and relapse samples from 23 patients with ALL. This identified 52 somatic non-synonymous mutations in 32 genes, many of which were novel, including the transcriptional coactivators CREBBP and NCOR1, the transcription factors ERG, SPI1, TCF4 and TCF7L2, components of the Ras signalling pathway, histone genes, genes involved in histone modification (CREBBP and CTCF), and genes previously shown(1,2) to be targets of recurring DNA copy number alteration in ALL. Analysis of an extended cohort of 71 diagnosis-relapse cases and 270 acute leukaemia cases that did not relapse found that 18.3% of relapse cases had sequence or deletion mutations of CREBBP, which encodes the transcriptional coactivator and histone acetyltransferase CREB-binding protein (CREBBP, also known as CBP)(4). The mutations were either present at diagnosis or acquired at relapse, and resulted in truncated alleles or deleterious substitutions in conserved residues of the histone acetyltransferase domain. Functionally, the mutations impaired histone acetylation and transcriptional regulation of CREBBP targets, including glucocorticoid responsive genes. Several mutations acquired at relapse were detected in subclones at diagnosis, suggesting that the mutations may confer resistance to therapy. These results extend the landscape of genetic alterations in leukaemia, and identify mutations targeting transcriptional and epigenetic regulation as a mechanism of resistance in ALL.
C1 [Mullighan, Charles G.; Payne-Turner, Debbie; Phillips, Letha A.; Heatley, Sue L.; Holmfeldt, Linda; Collins-Underwood, J. Racquel; Downing, James R.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Zhang, Jinghui] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.
   [Kasper, Lawryn H.; Lerach, Stephanie; Brindle, Paul K.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA.
   [Ma, Jing] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [Buetow, Kenneth H.] NCI, Ctr Bioinformat, Rockville, MD 20892 USA.
   [Buetow, Kenneth H.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
   [Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Baker, Sharyn D.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Tennessee System; University of Tennessee Health Science Center
RP Mullighan, CG (corresponding author), St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
EM charles.mullighan@stjude.org
FU ALSAC of St Jude and Cancer Center [P30 CA021765, DE018183]; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER
NR 42
TC 500
Z9 582
U1 0
U2 50
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 235
EP U127
DI 10.1038/nature09727
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200041
PM 21390130
DA 2026-03-09
ER

PT J
AU Tripodi, M
   Stepien, AE
   Arber, S
AF Tripodi, Marco
   Stepien, Anna E.
   Arber, Silvia
TI Motor antagonism exposed by spatial segregation and timing of neurogenesis
SO NATURE
LA English
DT Article
ID functionally complex muscles; spinal-cord; modular organization; fluorescent protein; locomotor-activity; gene-expression; cat hindlimb; neurons; pattern; motoneurons
AB Walking is a key motor behaviour of limbed animals, executed by contraction of functionally antagonistic muscle groups during swing and stance phases. Nevertheless, neuronal circuits regulating the activation of antagonistic extensor-flexor muscles remain poorly understood. Here we use monosynaptically restricted trans-synaptic viruses to elucidate premotor anatomical substrates for extensor-flexor control in mice. We observe a medio-lateral spatial segregation between extensor and flexor premotor interneurons in the dorsal spinal cord. These premotor interneuron populations are derived from common progenitor domains, but segregate by timing of neurogenesis. We find that proprioceptive sensory feedback from the periphery is targeted to medial extensor premotor populations and is required for extensor-specific connectivity profiles during development. Our findings provide evidence for a discriminating anatomical basis of antagonistic circuits at the level of premotor interneurons, and point to synaptic input and developmental ontogeny as key factors in the establishment of circuits regulating motor behavioural dichotomy.
C1 [Tripodi, Marco; Stepien, Anna E.; Arber, Silvia] Univ Basel, Biozentrum, Dept Cell Biol, CH-4056 Basel, Switzerland.
   [Tripodi, Marco; Stepien, Anna E.; Arber, Silvia] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
C3 University of Basel; Friedrich Miescher Institute for Biomedical Research
RP Arber, S (corresponding author), Univ Basel, Biozentrum, Dept Cell Biol, CH-4056 Basel, Switzerland.
EM silvia.arber@unibas.ch
FU EMBO long-term fellowship; ERC Advanced Grant; Swiss National Science Foundation; Kanton Basel-Stadt; EU Framework Program 7; Novartis Research Foundation
NR 63
TC 137
Z9 170
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 61
EP U84
DI 10.1038/nature10538
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600032
PM 22012263
DA 2026-03-09
ER

PT J
AU Ishizuka, K
   Kamiya, A
   Oh, EC
   Kanki, H
   Seshadri, S
   Robinson, JF
   Murdoch, H
   Dunlop, AJ
   Kubo, K
   Furukori, K
   Huang, B
   Zeledon, M
   Hayashi-Takagi, A
   Okano, H
   Nakajima, K
   Houslay, MD
   Katsanis, N
   Sawa, A
AF Ishizuka, Koko
   Kamiya, Atsushi
   Oh, Edwin C.
   Kanki, Hiroaki
   Seshadri, Saurav
   Robinson, Jon F.
   Murdoch, Hannah
   Dunlop, Allan J.
   Kubo, Ken-ichiro
   Furukori, Keiko
   Huang, Beverly
   Zeledon, Mariela
   Hayashi-Takagi, Akiko
   Okano, Hideyuki
   Nakajima, Kazunori
   Houslay, Miles D.
   Katsanis, Nicholas
   Sawa, Akira
TI DISC1-dependent switch from progenitor proliferation to migration in the developing cortex
SO NATURE
LA English
DT Article
ID developing mouse-brain; neuronal migration; disc1; protein; adult; gene; mice; differentiation; visualization; defects
AB Regulatory mechanisms governing the sequence from progenitor cell proliferation to neuronal migration during corticogenesis are poorly understood(1-10). Here we report that phosphorylation of DISC1, a major susceptibility factor for several mental disorders, acts as a molecular switch from maintaining proliferation of mitotic progenitor cells to activating migration of postmitotic neurons in mice. Unphosphorylated DISC1 regulates canonical Wnt signalling via an interaction with GSK3 beta, whereas specific phosphorylation at serine 710 (S710) triggers the recruitment of Bardet-Biedl syndrome (BBS) proteins to the centrosome. In support of this model, loss of BBS1 leads to defects in migration, but not proliferation, whereas DISC1 knockdown leads to deficits in both. A phospho-dead mutant can only rescue proliferation, whereas a phospho-mimic mutant rescues exclusively migration defects. These data highlight a dual role for DISC1 in corticogenesis and indicate that phosphorylation of this protein at S710 activates a key developmental switch.
C1 [Ishizuka, Koko; Kamiya, Atsushi; Seshadri, Saurav; Furukori, Keiko; Huang, Beverly; Zeledon, Mariela; Hayashi-Takagi, Akiko; Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
   [Oh, Edwin C.; Robinson, Jon F.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA.
   [Oh, Edwin C.; Robinson, Jon F.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA.
   [Oh, Edwin C.; Robinson, Jon F.; Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA.
   [Kanki, Hiroaki; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan.
   [Kubo, Ken-ichiro; Nakajima, Kazunori] Keio Univ, Sch Med, Dept Anat, Tokyo 1608582, Japan.
   [Murdoch, Hannah; Dunlop, Allan J.; Houslay, Miles D.] Univ Glasgow, CMVLS, Inst Neurosci & Psychol, Mol Pharmacol Grp, Glasgow G12 8QQ, Lanark, Scotland.
   [Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
C3 Johns Hopkins University; Duke University; Duke University; Duke University; Keio University; Keio University; University of Glasgow; Johns Hopkins University
RP Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
EM katsanis@cellbio.duke.edu; asawa1@jhmi.edu
FU USPHS [MH-084018, MH-069853, MH-085226, MH-088753, MH-091230, HD-04260, DK-072301, DK-075972]; Stanley foundation; RUSK foundation; Maryland Stem Cell Research Fund; NARSAD; Macular Vision Research Foundation; Foundation for Fighting Blindness; Health Labor Sciences; MEXT; Takeda; PMAC-PSJ; Fight for Sight Postdoctoral Fellowship; Medical Research Council, UK [G0600765]; Strategic Research Program for Brain Sciences; MRC [G0600765] Funding Source: UKRI; Medical Research Council [G0600765] Funding Source: researchfish; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD042601] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK072301] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007814] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [21591425, 23700417, 22240041] Funding Source: KAKEN
NR 38
TC 162
Z9 193
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 MAY 5
PY 2011
VL 473
IS 7345
BP 92
EP U107
DI 10.1038/nature09859
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300037
PM 21471969
DA 2026-03-09
ER

PT J
AU Fricke, HC
   Hencecroth, J
   Hoerner, ME
AF Fricke, Henry C.
   Hencecroth, Justin
   Hoerner, Marie E.
TI Lowland-upland migration of sauropod dinosaurs during the Late Jurassic epoch
SO NATURE
LA English
DT Article
ID isotope compositions; hydrogen isotopes; oxygen; enamel
AB Sauropod dinosaurs were the largest vertebrates ever to walk the Earth, and as mega-herbivores they were important parts of terrestrial ecosystems. In the Late Jurassic-aged Morrison depositional basin of western North America, these animals occupied lowland river-floodplain settings characterized by a seasonally dry climate(1,2). Massive herbivores with high nutritional and water needs could periodically experience nutritional and water stress under these conditions, and thus the common occurrence of sauropods in this basin has remained a paradox. Energetic arguments and mammalian analogues have been used to suggest that migration allowed sauropods access to food and water resources over a wide region or during times of drought or both(3,4), but there has been no direct support for these hypotheses. Here we compare oxygen isotope ratios (delta O-18) of tooth-enamel carbonate from the sauropod Camarasaurus with those of ancient soil, lake and wetland (that is, 'authigenic') carbonates that formed in lowland settings. We demonstrate that certain populations of these animals did in fact undertake seasonal migrations of several hundred kilometres from lowland to upland environments. This ability to describe patterns of sauropod movement will help to elucidate the role that migration played in the ecology and evolution of gigantism of these and associated dinosaurs.
C1 [Fricke, Henry C.; Hencecroth, Justin; Hoerner, Marie E.] Colorado Coll, Dept Geol, Colorado Springs, CO 80903 USA.
C3 Colorado College
RP Fricke, HC (corresponding author), Colorado Coll, Dept Geol, Colorado Springs, CO 80903 USA.
EM hfricke@coloradocollege.edu
FU National Science Foundation [EAR-0319041, EAR 0923831]; Colorado College
NR 19
TC 38
Z9 48
U1 7
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 513
EP 515
DI 10.1038/nature10570
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000058
PM 22031326
DA 2026-03-09
ER

PT J
AU Beardmore, RE
   Gudelj, I
   Lipson, DA
   Hurst, LD
AF Beardmore, Robert E.
   Gudelj, Ivana
   Lipson, David A.
   Hurst, Laurence D.
TI Metabolic trade-offs and the maintenance of the fittest and the flattest
SO NATURE
LA English
DT Article
ID lethal mutagenesis; escherichia-coli; periodic selection; growth-rate; evolution; yield; populations; mechanisms; transport; diversity
AB How is diversity maintained? Environmental heterogeneity is considered to be important(1), yet diversity in seemingly homogeneous environments is nonetheless observed(2). This, it is assumed, must either be owing to weak selection, mutational input or a fitness advantage to genotypes when rare(1). Here we demonstrate the possibility of a new general mechanism of stable diversity maintenance, one that stems from metabolic and physiological trade-offs(3). The model requires that such trade-offs translate into a fitness landscape in which the most fit has unfit near-mutational neighbours, and a lower fitness peak also exists that is more mutationally robust. The 'survival of the fittest' applies at low mutation rates, giving way to 'survival of the flattest'(4-6) at high mutation rates. However, as a consequence of quasispecies-level negative frequency-dependent selection and differences in mutational robustness we observe a transition zone in which both fittest and flattest coexist. Although diversity maintenance is possible for simple organisms in simple environments, the more trade-offs there are, the wider the maintenance zone becomes. The principle may be applied to lineages within a species or species within a community, potentially explaining why competitive exclusion need not be observed in homogeneous environments. This principle predicts the enigmatic richness of metabolic strategies in clonal bacteria(7) and questions the safety of lethal mutagenesis(8,9) as an antimicrobial treatment.
C1 [Hurst, Laurence D.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England.
   [Beardmore, Robert E.; Gudelj, Ivana] Univ London Imperial Coll Sci Technol & Med, Dept Math, London SW7 2A7, England.
   [Lipson, David A.] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
C3 University of Bath; Imperial College London; California State University System; San Diego State University
RP Hurst, LD (corresponding author), Univ Bath, Dept Biol & Biochem, Claverton Down, Bath BA2 7AY, Avon, England.
EM l.d.hurst@bath.ac.uk
FU Royal Society; EPSRC; NERC; EPSRC [EP/I018263/1, EP/F037856/1] Funding Source: UKRI; MRC [G0802611] Funding Source: UKRI; NERC [NE/E013007/1, NE/E013007/2, NE/E013007/3] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F037856/1, EP/I018263/1] Funding Source: researchfish; Medical Research Council [G0802611] Funding Source: researchfish; Natural Environment Research Council [NE/E013007/1, NE/E013007/3, NE/E013007/2] Funding Source: researchfish
NR 27
TC 92
Z9 106
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 342
EP 346
DI 10.1038/nature09905
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600038
PM 21441905
DA 2026-03-09
ER

PT J
AU Togan, E
   Chu, Y
   Imamoglu, A
   Lukin, MD
AF Togan, E.
   Chu, Y.
   Imamoglu, A.
   Lukin, M. D.
TI Laser cooling and real-time measurement of the nuclear spin environment of a solid-state qubit
SO NATURE
LA English
DT Article
ID diamond spins; coherent; magnetometry; photon; media; field
AB Control over quantum dynamics of open systems is one of the central challenges in quantum science and engineering. Coherent optical techniques, such as coherent population trapping involving dark resonances(1,2), are widely used to control quantum states of isolated atoms and ions. In conjunction with spontaneous emission, they allow for laser cooling of atomic motion(3), preparation and manipulation of atomic states(4), and rapid quantum optical measurements that are essential for applications in metrology(5-7). Here we show that these techniques can be applied to monitor and control individual atom-like impurities, and their local environment(8-11), in the solid state. Using all-optical manipulation of the electronic spin of an individual nitrogen-vacancy colour centre in diamond, we demonstrate optical cooling, real-time measurement and conditional preparation of its nuclear spin environment by post-selection. These methods offer potential applications ranging from all-optical nanomagnetometry to quantum feedback control of solid-state qubits, and may lead to new approaches for quantum information storage and processing
C1 [Togan, E.; Chu, Y.; Lukin, M. D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Imamoglu, A.] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Harvard University; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM lukin@fas.harvard.edu
FU NSF; CUA; DARPA; ARO MURI; NDSEG Fellowship; Packard Foundation; ERC; Direct For Mathematical & Physical Scien; Division Of Physics [0969816] Funding Source: National Science Foundation
NR 30
TC 87
Z9 105
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 OCT 27
PY 2011
VL 478
IS 7370
BP 497
EP 501
DI 10.1038/nature10528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200039
PM 22031442
DA 2026-03-09
ER

PT J
AU Geller, AM
   Mathieu, RD
AF Geller, Aaron M.
   Mathieu, Robert D.
TI A mass transfer origin for blue stragglers in NGC 188 as revealed by half-solar-mass companions
SO NATURE
LA English
DT Article
ID wiyn open cluster; giant branch stars; spectroscopic binary; globular-clusters; main-sequence; evolution; population; systems; orbits; m67
AB In open star clusters, where all members formed at about the same time, blue straggler stars are typically observed to be brighter and bluer than hydrogen-burning main-sequence stars, and therefore should already have evolved into giant stars and stellar remnants. Correlations between blue straggler frequency and cluster binary star fraction(1), core mass(2) and radial position(3) suggest that mass transfer or mergers in binary stars dominates the production of blue stragglers in open clusters. Analytic models(4,5), detailed observations(6) and sophisticated N-body simulations(7), however, argue in favour of stellar collisions. Here we report that the blue stragglers in long-period binaries in the old(8) (7x10(9)-year) open cluster NGC 188 have companions with masses of about half a solar mass, with a surprisingly narrow mass distribution. This conclusively rules out a collisional origin, as the collision hypothesis predicts a companion mass distribution with significantly higher masses. Mergers in hierarchical triple stars(9) are marginally permitted by the data, but the observations do not favour this hypothesis. The data are highly consistent with a mass transfer origin for the long-period blue straggler binaries in NGC 188, in which the companions would be white dwarfs of about half a solar mass.
C1 [Geller, Aaron M.; Mathieu, Robert D.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [Geller, Aaron M.] Northwestern Univ, CIERA, Evanston, IL 60208 USA.
   [Geller, Aaron M.] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Northwestern University; Northwestern University
RP Geller, AM (corresponding author), Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
EM a-geller@northwestern.edu
FU National Science Foundation; US National Science Foundation [AST-0908082]; Wisconsin Space Grant Consortium; Northwestern University
NR 30
TC 99
Z9 108
U1 0
U2 6
PU 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 20
PY 2011
VL 478
IS 7369
BP 356
EP 359
DI 10.1038/nature10512
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100039
PM 22012393
DA 2026-03-09
ER

PT J
AU Brawand, D
   Soumillon, M
   Necsulea, A
   Julien, P
   Csárdi, G
   Harrigan, P
   Weier, M
   Liechti, A
   Aximu-Petri, A
   Kircher, M
   Albert, FW
   Zeller, U
   Khaitovich, P
   Grützner, F
   Bergmann, S
   Nielsen, R
   Pääbo, S
   Kaessmann, H
AF Brawand, David
   Soumillon, Magali
   Necsulea, Anamaria
   Julien, Philippe
   Csardi, Gabor
   Harrigan, Patrick
   Weier, Manuela
   Liechti, Angelica
   Aximu-Petri, Ayinuer
   Kircher, Martin
   Albert, Frank W.
   Zeller, Ulrich
   Khaitovich, Philipp
   Gruetzner, Frank
   Bergmann, Sven
   Nielsen, Rasmus
   Paeaebo, Svante
   Kaessmann, Henrik
TI The evolution of gene expression levels in mammalian organs
SO NATURE
LA English
DT Article
ID sex-chromosm; humans; conservation; platypus; transcriptm; sequences; primates; reveals; model
AB Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.
C1 [Brawand, David; Soumillon, Magali; Necsulea, Anamaria; Julien, Philippe; Weier, Manuela; Liechti, Angelica; Kaessmann, Henrik] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Brawand, David; Soumillon, Magali; Necsulea, Anamaria; Julien, Philippe; Csardi, Gabor; Bergmann, Sven; Kaessmann, Henrik] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Csardi, Gabor; Bergmann, Sven] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Harrigan, Patrick; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Aximu-Petri, Ayinuer; Kircher, Martin; Albert, Frank W.; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
   [Zeller, Ulrich] Humboldt Univ, Chair Systemat Zool, D-10099 Berlin, Germany.
   [Khaitovich, Philipp] CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China.
   [Gruetzner, Frank] Univ Adelaide, Robinson Inst, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia.
   [Nielsen, Rasmus] Univ Copenhagen, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
C3 University of Lausanne; Swiss Institute of Bioinformatics; University of Lausanne; University of California System; University of California Berkeley; Max Planck Society; Humboldt University of Berlin; Chinese Academy of Sciences; Max Planck Society; Robinson Research Institute; Adelaide University; University of Adelaide; University of Copenhagen
RP Kaessmann, H (corresponding author), Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
EM henrik.kaessmann@unil.ch
FU European Research Council [242597]; Swiss National Science Foundation [31003A_130287, 31003A_130691/1]; Swiss Institute of Bioinformatics; Max Planck Society; FEBS postdoctoral fellowship; European Research Council (ERC) [242597] Funding Source: European Research Council (ERC); Swiss National Science Foundation (SNF) [31003A_130287] Funding Source: Swiss National Science Foundation (SNF)
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NR 59
TC 912
Z9 1077
U1 2
U2 292
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 343
EP +
DI 10.1038/nature10532
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100037
PM 22012392
DA 2026-03-09
ER

PT J
AU Yang, XJ
   Ren, Z
   Kuk, J
   Moffat, K
AF Yang, Xiaojing
   Ren, Zhong
   Kuk, Jane
   Moffat, Keith
TI Temperature-scan cryocrystallography reveals reaction intermediates in bacteriophytochrome
SO NATURE
LA English
DT Article
ID pseudomonas-aeruginosa bacteriophytochrome; chromophore-binding domain; ground-state; midinfrared spectroscopy; crystal-structure; gaf domain; phytochrome; light; photoconversion; pfr
AB Light is a fundamental signal that regulates important physiological processes such as development and circadian rhythm in living organisms. Phytochromes form a major family of photoreceptors responsible for red light perception in plants, fungi and bacteria(1). They undergo reversible photoconversion between red-absorbing (Pr) and far-red-absorbing (Pfr) states, thereby ultimately converting a light signal into a distinct biological signal that mediates subsequent cellular responses(2). Several structures of microbial phytochromes have been determined in their dark-adapted Pr or Pfr states(3-7). However, the structural nature of initial photochemical events has not been characterized by crystallography. Here we report the crystal structures of three intermediates in the photoreaction of Pseudomonas aeruginosa bacteriophytochrome (PaBphP). We used cryotrapping crystallography to capture intermediates, and followed structural changes by scanning the temperature at which the photoreaction proceeded. Light-induced conformational changes in PaBphP originate in ring D of the biliverdin (BV) chromophore, and E-to-Z isomerization about the C-15 = C-16 double bond between rings C and D is the initial photochemical event. As the chromophore relaxes, the twist of the C-15 methine bridge about its two dihedral angles is reversed. Structural changes extend further to rings B and A, and to the surrounding protein regions. These data indicate that absorption of a photon by the Pfr state of PaBphP converts a light signal into a structural signal via twisting and untwisting of the methine bridges in the linear tetrapyrrole within the confined protein cavity.
C1 [Yang, Xiaojing; Kuk, Jane; Moffat, Keith] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Ren, Zhong; Moffat, Keith] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
   [Moffat, Keith] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago
RP Yang, XJ (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 929 E 57th St, Chicago, IL 60637 USA.
EM xiaojingyang@uchicago.edu; moffat@cars.uchicago.edu
FU National Institutes of Health [GM036452, RR07707]
NR 35
TC 154
Z9 175
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 NOV 17
PY 2011
VL 479
IS 7373
BP 428
EP U190
DI 10.1038/nature10506
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700052
PM 22002602
DA 2026-03-09
ER

PT J
AU Cande, SC
   Stegman, DR
AF Cande, Steven C.
   Stegman, Dave R.
TI Indian and African plate motions driven by the push force of the Reunion plume head
SO NATURE
LA English
DT Article
ID flood basalts; melt production; deccan traps; evolution; ocean; constraints; atlantic; ridge; age; collision
AB Mantle plumes are thought to play an important part in the Earth's tectonics, yet it has been difficult to isolate the effect that plumes have on plate motions. Here we analyse the plate motions involved in two apparently disparate events-the unusually rapid motion of India between 67 and 52 million years ago and a contemporaneous, transitory slowing of Africa's motion-and show that the events are coupled, with the common element being the position of the Indian and African plates relative to the location of the Reunion plume head. The synchroneity of these events suggests that they were both driven by the force of the Reunion plume head. The recognition of this plume force has substantial tectonic implications: the speed-up and slowdown of India, the possible cessation of convergence between Africa and Eurasia in the Palaeocene epoch and the enigmatic bends of the fracture zones on the Southwest Indian Ridge can all be attributed to the Reunion plume.
C1 [Cande, Steven C.; Stegman, Dave R.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Cande, SC (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
EM scande@ucsd.edu
FU NSF [ANT-0944345]; Office of Polar Programs (OPP); Directorate For Geosciences [0944345] Funding Source: National Science Foundation
NR 49
TC 265
Z9 291
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 JUL 7
PY 2011
VL 475
IS 7354
BP 47
EP 52
DI 10.1038/nature10174
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300042
PM 21734702
DA 2026-03-09
ER

PT J
AU Yokoyama, S
   Woods, SL
   Boyle, GM
   Aoude, LG
   MacGregor, S
   Zismann, V
   Gartside, M
   Cust, AE
   Haq, R
   Harland, M
   Taylor, JC
   Duffy, DL
   Holohan, K
   Dutton-Regester, K
   Palmer, JM
   Bonazzi, V
   Stark, MS
   Symmons, J
   Law, MH
   Schmidt, C
   Lanagan, C
   O'Connor, L
   Holland, EA
   Schmid, H
   Maskiell, JA
   Jetann, J
   Ferguson, M
   Jenkins, MA
   Kefford, RF
   Giles, G
   Armstrong, BK
   Aitken, JF
   Hopper, JL
   Whiteman, DC
   Pharoah, PD
   Easton, DF
   Dunning, AM
   Newton-Bishop, JA
   Montgomery, GW
   Martin, NG
   Mann, GJ
   Bishop, DT
   Tsao, H
   Trent, JM
   Fisher, DE
   Hayward, NK
   Brown, KM
AF Yokoyama, Satoru
   Woods, Susan L.
   Boyle, Glen M.
   Aoude, Lauren G.
   MacGregor, Stuart
   Zismann, Victoria
   Gartside, Michael
   Cust, Anne E.
   Haq, Rizwan
   Harland, Mark
   Taylor, John C.
   Duffy, David L.
   Holohan, Kelly
   Dutton-Regester, Ken
   Palmer, Jane M.
   Bonazzi, Vanessa
   Stark, Mitchell S.
   Symmons, Judith
   Law, Matthew H.
   Schmidt, Christopher
   Lanagan, Cathy
   O'Connor, Linda
   Holland, Elizabeth A.
   Schmid, Helen
   Maskiell, Judith A.
   Jetann, Jodie
   Ferguson, Megan
   Jenkins, Mark A.
   Kefford, Richard F.
   Giles, GrahamG.
   Armstrong, Bruce K.
   Aitken, Joanne F.
   Hopper, John L.
   Whiteman, David C.
   Pharoah, Paul D.
   Easton, Douglas F.
   Dunning, Alison M.
   Newton-Bishop, Julia A.
   Montgomery, Grant W.
   Martin, Nicholas G.
   Mann, Graham J.
   Bishop, D. Timothy
   Tsao, Hensin
   Trent, Jeffrey M.
   Fisher, David E.
   Hayward, Nicholas K.
   Brown, Kevin M.
TI A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma
SO NATURE
LA English
DT Article
ID genome-wide association; cutaneous melanoma; phenotypic characteristics; transcription factor; germline mutations; melanocytic nevi; sun exposure; risk; variants; linkage
AB So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases(1), and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds(2). Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c. G1075A; protein sequence p. E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log of odds (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case-control sample. Likewise, it was similarly associated in an independent case-control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility.
C1 [Zismann, Victoria; Trent, Jeffrey M.; Brown, Kevin M.] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
   [Yokoyama, Satoru; Haq, Rizwan; Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02114 USA.
   [Woods, Susan L.; Boyle, Glen M.; Aoude, Lauren G.; MacGregor, Stuart; Gartside, Michael; Duffy, David L.; Holohan, Kelly; Dutton-Regester, Ken; Palmer, Jane M.; Bonazzi, Vanessa; Stark, Mitchell S.; Symmons, Judith; Law, Matthew H.; Schmidt, Christopher; Lanagan, Cathy; O'Connor, Linda; Whiteman, David C.; Montgomery, Grant W.; Martin, Nicholas G.; Hayward, Nicholas K.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
   [Cust, Anne E.; Armstrong, Bruce K.] Univ Sydney, Sydney Med Sch, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
   [Harland, Mark; Taylor, John C.; Newton-Bishop, Julia A.; Bishop, D. Timothy] St James Univ Hosp, Canc Res UK Clin Ctr Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds LS9 7TF, W Yorkshire, England.
   [Holland, Elizabeth A.; Schmid, Helen; Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia.
   [Holland, Elizabeth A.; Schmid, Helen; Kefford, Richard F.; Mann, Graham J.] Melanoma Inst Australia, Westmead, NSW 2145, Australia.
   [Maskiell, Judith A.; Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia.
   [Jetann, Jodie; Ferguson, Megan; Aitken, Joanne F.] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld 4004, Australia.
   [Giles, GrahamG.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia.
   [Pharoah, Paul D.; Easton, Douglas F.; Dunning, Alison M.] Univ Cambridge, Cambridge CB1 8RN, England.
   [Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Brown, Kevin M.] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20892 USA.
C3 Translational Genomics Research Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; QIMR Berghofer Medical Research Institute; University of Sydney; Saint James's University Hospital; University of Leeds; Cancer Research UK; University of Sydney; Westmead Institute for Medical Research; Melanoma Institute Australia; University of Melbourne; Cancer Council Queensland; Cancer Council Victoria; University of Cambridge; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics
RP Brown, KM (corresponding author), Translat Genom Res Inst, Phoenix, AZ 85004 USA.
EM brownkm2@mail.nih.gov
FU Melanoma Research Alliance; American Cancer Society [RSG-08-200-01]; National Institutes of Health (NIH) [AR043369-14, CA88363, K24CA149202, P50CA93683, R01 CA83115, CA-83115-01A2]; Doris Duke Medical Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; US-Israel Binational Science Foundation; Division of Cancer Epidemiology and Genetics of the National Cancer Institute; National Health and Medical Research Council of Australia (NHMRC); Cancer Australia [1011143]; Cancer Research UK [C8216/A6129, C588/A4994, C588/A10589, C490/A11021, C8197/A10123]; NHMRC [566946, 107359, 211172, 402761, 520018]; Cancer Council New South Wales [77/00, 06/10]; Cancer Council Victoria; Cancer Council Queensland [371]; Cancer Institute NSW [10/ECF/2-06]; University of Sydney Medical Foundation; Cancer Research UK [10118, 10589, 11022] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [520018, 107359, 211172, 566946, 402761] Funding Source: National Health and Medical Research Council (NHMRC); National Cancer Institute [ZIACP010201] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR043369] Funding Source: NIH RePORTER
NR 46
TC 353
Z9 392
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 99
EP U266
DI 10.1038/nature10630
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900042
PM 22080950
DA 2026-03-09
ER

PT J
AU Chen, CF
   Park, CH
   Boudouris, BW
   Horng, J
   Geng, BS
   Girit, C
   Zettl, A
   Crommie, MF
   Segalman, RA
   Louie, SG
   Wang, F
AF Chen, Chi-Fan
   Park, Cheol-Hwan
   Boudouris, Bryan W.
   Horng, Jason
   Geng, Baisong
   Girit, Caglar
   Zettl, Alex
   Crommie, Michael F.
   Segalman, Rachel A.
   Louie, Steven G.
   Wang, Feng
TI Controlling inelastic light scattering quantum pathways in graphene
SO NATURE
LA English
DT Article
ID gel gate dielectrics; carbon nanotubes; raman-spectroscopy; transistors; electrons
AB Inelastic light scattering spectroscopy has, since its first discovery(1,2), been an indispensable tool in physical science for probing elementary excitations, such as phonons(3), magnons(4) and plasmons(5) in both bulk and nanoscale materials. In the quantum mechanical picture of inelastic light scattering, incident photons first excite a set of intermediate electronic states, which then generate crystal elementary excitations and radiate energy-shifted photons(6). The intermediate electronic excitations therefore have a crucial role as quantum pathways in inelastic light scattering, and this is exemplified by resonant Raman scattering(6) and Raman interference(7,8). The ability to control these excitation pathways can open up new opportunities to probe, manipulate and utilize inelastic light scattering. Here we achieve excitation pathway control in graphene with electrostatic doping. Our study reveals quantum interference between different Raman pathways in graphene: when some of the pathways are blocked, the one-phonon Raman intensity does not diminish, as commonly expected, but increases dramatically. This discovery sheds new light on the understanding of resonance Raman scattering in graphene. In addition, we demonstrate hot-electron luminescence9 in graphene as the Fermi energy approaches half the laser excitation energy. This hot luminescence, which is another form of inelastic light scattering, results from excited-state relaxation channels that become available only in heavily doped graphene.
C1 [Chen, Chi-Fan; Park, Cheol-Hwan; Horng, Jason; Geng, Baisong; Girit, Caglar; Zettl, Alex; Crommie, Michael F.; Louie, Steven G.; Wang, Feng] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Boudouris, Bryan W.; Segalman, Rachel A.] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA.
   [Boudouris, Bryan W.; Zettl, Alex; Crommie, Michael F.; Segalman, Rachel A.; Louie, Steven G.; Wang, Feng] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Wang, F (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM fengwang76@berkeley.edu
FU US Department of Energy, Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; Office of Basic Energy Sciences [DE-AC02-05CH11231, DE-AC03-76SF0098]; ONR MURI [N00014-09-1-1066]; National Science Council; National Tsing Hua University, Taiwan [NSC98-2811-M-007-008, NSC98-2120-M-007-004]
NR 30
TC 513
Z9 590
U1 2
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 MAR 31
PY 2011
VL 471
IS 7340
BP 617
EP 620
DI 10.1038/nature09866
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200038
PM 21412234
DA 2026-03-09
ER

PT J
AU Hu, J
   Xue, Y
   Lee, S
   Ha, Y
AF Hu, Jian
   Xue, Yi
   Lee, Sangwon
   Ha, Ya
TI The crystal structure of GXGD membrane protease FlaK
SO NATURE
LA English
DT Article
ID signal peptide peptidase; gamma-secretase; pseudomonas-aeruginosa; catalytic pore; ii secretion; presenilin; domain; identification; conformation; topology
AB The GXGD proteases are polytopic membrane proteins with catalytic activities against membrane-spanning substrates that require a pair of aspartyl residues(1-4). Representative members of the family include preflagellin peptidase, type 4 prepilin peptidase, presenilin and signal peptide peptidase. Many GXGD proteases are important in medicine. For example, type 4 prepilin peptidase may contribute to bacterial pathogenesis(5-7), and mutations in presenilin are associated with Alzheimer's disease(8-10). As yet, there is no atomic-resolution structure in this protease family. Here we report the crystal structure of FlaK, a preflagellin peptidase from Methanococcus maripaludis, solved at 3.6 angstrom resolution. The structure contains six transmembrane helices. The GXGD motif and a short transmembrane helix, helix 4, are positioned at the centre, surrounded by other transmembrane helices. The crystal structure indicates that the protease must undergo conformational changes to bring the GXGD motif and a second essential aspartyl residue from transmembrane helix 1 into close proximity for catalysis. A comparison of the crystal structure with models of presenilin derived from biochemical analysis reveals three common transmembrane segments that are similarly arranged around the active site. This observation reinforces the idea that the prokaryotic and human proteases are evolutionarily related(11,12). The crystal structure presented here provides a framework for understanding the mechanism of the GXGD proteases, and may facilitate the rational design of inhibitors that target specific members of the family.
C1 [Hu, Jian; Xue, Yi; Lee, Sangwon; Ha, Ya] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
C3 Yale University
RP Ha, Y (corresponding author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
EM ya.ha@yale.edu
FU US Department of Energy; National Institutes of Health; Ellison Medical Foundation; Yale's programme in Cellular Neuroscience, Neurodegeneration, and Repair (CNNR)
NR 41
TC 63
Z9 72
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 528
EP U130
DI 10.1038/nature10218
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900047
PM 21765428
DA 2026-03-09
ER

PT J
AU McDermott-Roe, C
   Ye, JM
   Ahmed, R
   Sun, XM
   Serafín, A
   Ware, J
   Bottolo, L
   Muckett, P
   Cañas, X
   Zhang, JS
   Rowe, GC
   Buchan, R
   Lu, H
   Braithwaite, A
   Mancini, M
   Hauton, D
   Martí, R
   García-Arumí, E
   Hubner, N
   Jacob, H
   Serikawa, T
   Zidek, V
   Papousek, F
   Kolar, F
   Cardona, M
   Ruiz-Meana, M
   García-Dorado, D
   Comella, JX
   Felkin, LE
   Barton, PJR
   Arany, Z
   Pravenec, M
   Petretto, E
   Sanchis, D
   Cook, SA
AF McDermott-Roe, Chris
   Ye, Junmei
   Ahmed, Rizwan
   Sun, Xi-Ming
   Serafin, Anna
   Ware, James
   Bottolo, Leonardo
   Muckett, Phil
   Canas, Xavier
   Zhang, Jisheng
   Rowe, Glenn C.
   Buchan, Rachel
   Lu, Han
   Braithwaite, Adam
   Mancini, Massimiliano
   Hauton, David
   Marti, Ramon
   Garcia-Arumi, Elena
   Hubner, Norbert
   Jacob, Howard
   Serikawa, Tadao
   Zidek, Vaclav
   Papousek, Frantisek
   Kolar, Frantisek
   Cardona, Maria
   Ruiz-Meana, Marisol
   Garcia-Dorado, David
   Comella, Joan X.
   Felkin, Leanne E.
   Barton, Paul J. R.
   Arany, Zoltan
   Pravenec, Michal
   Petretto, Enrico
   Sanchis, Daniel
   Cook, Stuart A.
TI Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function
SO NATURE
LA English
DT Article
ID left-ventricular mass; oxidative stress; cardiomyopathy; disease; death; pathogenesis; replication; biogenesis; mechanisms; expression
AB Left ventricular mass (LVM) is a highly heritable trait(1) and an independent risk factor for all-cause mortality(2). So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation(3), and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood(4,5). Unbiased systems genetics approaches in the rat(6,7) now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis(8) but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-alpha and PGC1 alpha (which are master regulators of mitochondrial and cardiac function)(9-11), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.
C1 [McDermott-Roe, Chris; Ahmed, Rizwan; Sun, Xi-Ming; Ware, James; Bottolo, Leonardo; Muckett, Phil; Buchan, Rachel; Lu, Han; Braithwaite, Adam; Petretto, Enrico; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Med Res Council Clin Sci Ctr, London W12 0NN, England.
   [Ye, Junmei; Zhang, Jisheng; Cardona, Maria; Sanchis, Daniel] Univ Lleida, Biomed Res Inst Lleida IRBLLEIDA, Cell Signaling & Apoptosis Grp, Lleida 25198, Spain.
   [Serafin, Anna; Canas, Xavier] Platform Appl Res Lab Anim, Barcelona 08028, Spain.
   [Rowe, Glenn C.; Arany, Zoltan] Beth Israel Deaconess Med Inst, Cardiovasc Inst, Boston, MA 02215 USA.
   [Mancini, Massimiliano] Univ Rome, Dept Radiol Oncol & Anatomopathol Sci, I-00161 Sapienza, Italy.
   [Hauton, David] Univ Birmingham, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
   [Marti, Ramon; Garcia-Arumi, Elena] Univ Autonoma Barcelona, Inst Recerca Hosp Univ Vall dHebron, Unitat Patol Mitocondrial & Neuromuscular CIBERER, Barcelona 08035, Spain.
   [Hubner, Norbert] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Hubner, Norbert] Charite Univ Med Berlin, Campus Charite Mitte, CC4, D-10117 Berlin, Germany.
   [Jacob, Howard] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
   [Serikawa, Tadao] Kyoto Univ, Grad Sch Med, Inst Lab Anim, Sakyo Ku, Kyoto 6068501, Japan.
   [Zidek, Vaclav; Papousek, Frantisek; Kolar, Frantisek; Pravenec, Michal] Acad Sci Czech Republic, Inst Physiol, CR-14220 Prague 4, Czech Republic.
   [Ruiz-Meana, Marisol; Garcia-Dorado, David] Univ Autonoma Barcelona, Inst Recerca Hosp Univ Vall dHebron, Grp Patol Cardiovasc, Barcelona 08035, Spain.
   [Comella, Joan X.] CIBERNED, Cell Signaling & Apoptosis Grp, Barcelona 08035, Spain.
   [Comella, Joan X.] VHIR, Barcelona 08035, Spain.
   [Comella, Joan X.] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Barcelona 08035, Spain.
   [Comella, Joan X.] Univ Autonoma Barcelona, Inst Neurociencies, Barcelona 08035, Spain.
   [Felkin, Leanne E.; Barton, Paul J. R.] Harefield Hosp, Imperial Coll London, Natl Heart & Lung Inst, Heart Sci Ctr, Harefield UB9 6JH, Middx, England.
   [Barton, Paul J. R.; Cook, Stuart A.] Royal Brompton & Harefield NHS Trust, Cardiovasc Biomed Res Unit, London SW3 6NP, England.
   [Petretto, Enrico] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, London W2 1PG, England.
C3 Imperial College London; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); Universitat de Lleida; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Sapienza University Rome; University of Birmingham; Autonomous University of Barcelona; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Medical College of Wisconsin; Kyoto University; Czech Academy of Sciences; Institute of Physiology of the Czech Academy of Sciences; Autonomous University of Barcelona; CIBERNED; Autonomous University of Barcelona; Hospital Universitari Vall d'Hebron; Vall d'Hebron Institut de Recerca (VHIR); Autonomous University of Barcelona; Autonomous University of Barcelona; Royal Brompton & Harefield NHS Foundation Trust; Harefield Hospital; Imperial College London; Royal Brompton Hospital; Royal Brompton & Harefield NHS Foundation Trust; Imperial College London
RP Cook, SA (corresponding author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Med Res Council Clin Sci Ctr, Du Cane Rd, London W12 0NN, England.
EM daniel.sanchis@cmb.udl.cat; stuart.cook@imperial.ac.uk
FU Medical Research Council (UK); National Institute for Health Research (UK); Royal Brompton and Harefield Cardiovascular Biomedical Research Unit; Imperial College Healthcare Biomedical Research Centre; British Heart Foundation; Fondation Leducq; Wellcome Trust; Grant Agency of the Czech Republic [301/08/0166]; Ministry of Education of the Czech Republic [1M0520]; Ministerio de Ciencia e Innovacion (Spain) [PTQ-08-03-07880, SAF2008-02271, SAF2008-03067, SAF2010-19125]; Agencia de Gestio d'Ajuts Universitaris i Recerca (Spain) [2009-SGR-346]; Fondo de Investigaciones Sanitarias (Spain) [PS09/02034, PS09/01602, PS09/01591]; European Community [HEALTH-F4-2010-241504]; German National Genome Research Network (NGFN-Plus) Heart Failure; British Heart Foundation [SP/10/10/28431] Funding Source: researchfish; Medical Research Council [MC_U120097112, MC_U120085815] Funding Source: researchfish; National Institute for Health Research [ACF-2007-21-004] Funding Source: researchfish; MRC [MC_U120097112, MC_U120085815] Funding Source: UKRI
NR 30
TC 131
Z9 155
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 OCT 6
PY 2011
VL 478
IS 7367
BP 114
EP 118
DI 10.1038/nature10490
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400045
PM 21979051
DA 2026-03-09
ER

PT J
AU Fawzi, NL
   Ying, JF
   Ghirlando, R
   Torchia, DA
   Clore, GM
AF Fawzi, Nicolas L.
   Ying, Jinfa
   Ghirlando, Rodolfo
   Torchia, Dennis A.
   Clore, G. Marius
TI Atomic-resolution dynamics on the surface of amyloid-β protofibrils probed by solution NMR
SO NATURE
LA English
DT Article
ID alzheimers-disease; experimental constraints; chemical-exchange; fibril formation; protein; oligomers; mechanism; state; a-beta(1-40); aggregation
AB Exchange dynamics between molecules free in solution and bound to the surface of a large supramolecular structure, a polymer, a membrane or solid support are important in many phenomena in biology and materials science. Here we present a novel and generally applicable solution NMR technique, known as dark-state exchange saturation transfer (DEST), to probe such exchange phenomena with atomic resolution. This is illustrated by the exchange reaction between amyloid-beta (A beta) monomers and polydisperse, NMR-invisible ('dark') protofibrils, a process of significant interest because the accumulation of toxic, aggregated forms of A beta, from small oligomers to very large assemblies, has been implicated in the aetiology of Alzheimer's disease(1-6). The (15)N-DEST experiment imprints with single-residue-resolution dynamic information on the protofibril-bound species in the form of (15)N transverse relaxation rates ((15)N-R(2)) and exchange kinetics between monomers and protofibrils onto the easily observed two-dimensional (1)H-(15)N correlation spectrum of the monomer. The exchanging species on the protofibril surface comprise an ensemble of sparsely populated states where each residue is either tethered to (through other residues) or in direct contact with the surface. The first eight residues exist predominantly in a mobile tethered state, whereas the largely hydrophobic central region and part of the carboxy (C)-terminal hydrophobic region are in direct contact with the protofibril surface for a significant proportion of the time. The C-terminal residues of both A beta 40 and A beta 42 display lower affinity for the protofibril surface, indicating that they are likely to be surface exposed rather than buried as in structures of A beta fibrils(7-10), and might therefore comprise the critical nucleus for fibril formation(11,12). The (15)N-R(2)(tethered) values, however, are significantly larger for the C-terminal residues of A beta 42 than A beta 40, which might explain the former's higher propensity for rapid aggregation and fibril formation(13,14).
C1 [Fawzi, Nicolas L.; Ying, Jinfa; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Torchia, Dennis A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR)
RP Clore, GM (corresponding author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health; Office of the Director of the National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK033007] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK029023] Funding Source: NIH RePORTER
NR 32
TC 356
Z9 398
U1 1
U2 224
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 268
EP U161
DI 10.1038/nature10577
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200057
PM 22037310
DA 2026-03-09
ER

PT J
AU Huybers, P
AF Huybers, Peter
TI Combined obliquity and precession pacing of late Pleistocene deglaciations
SO NATURE
LA English
DT Article
ID glacial terminations; climate-change; insolation; paleoclimate; temperature; southern; cycles; co2
AB Milankovitch(1) proposed that Earth resides in an interglacial state when its spin axis both tilts to a high obliquity and precesses to align the Northern Hemisphere summer with Earth's nearest approach to the Sun. This general concept has been elaborated into hypotheses that precession(2), obliquity(3,4) or combinations of both(5-8) could pace deglaciations during the late Pleistocene(9,10). Earlier tests have shown that obliquity paces the late Pleistocene glacial cycles(4,11) but have been inconclusive with regard to precession, whose shorter period of about 20,000 years makes phasing more sensitive to timing errors(4,11,12). No quantitative test has provided firm evidence for a dual effect. Here I show that both obliquity and precession pace late Pleistocene glacial cycles. Deficiencies in time control that have long stymied efforts to establish orbital effects on deglaciation are overcome using a new statistical test that focuses on maxima in orbital forcing. The results are fully consistent with Milankovitch's proposal but also admit the possibility that long Southern Hemisphere summers contribute to deglaciation.
C1 Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Harvard University
RP Huybers, P (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM phuybers@fas.harvard.edu
NR 30
TC 118
Z9 146
U1 5
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 229
EP 232
DI 10.1038/nature10626
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200048
PM 22158246
DA 2026-03-09
ER

PT J
AU Burdette, DL
   Monroe, KM
   Sotelo-Troha, K
   Iwig, JS
   Eckert, B
   Hyodo, M
   Hayakawa, Y
   Vance, RE
AF Burdette, Dara L.
   Monroe, Kathryn M.
   Sotelo-Troha, Katia
   Iwig, Jeff S.
   Eckert, Barbara
   Hyodo, Mamoru
   Hayakawa, Yoshihiro
   Vance, Russell E.
TI STING is a direct innate immune sensor of cyclic di-GMP
SO NATURE
LA English
DT Article
ID i interferon response; cytosolic dna; pseudomonas-aeruginosa; intracellular dna; bis-(3'-5')-cyclic-gmp; diguanylate; reveals; adapter
AB The innate immune system detects infection by using germline-encoded receptors that are specific for conserved microbial molecules. The recognition of microbial ligands leads to the production of cytokines, such as type I interferons (IFNs), that are essential for successful pathogen elimination. Cytosolic detection of pathogen-derived DNA is one major mechanism of inducing IFN production(1,2), and this process requires signalling through TANK binding kinase 1 (TBK1) and its downstream transcription factor, IFN-regulatory factor 3 (IRF3). In addition, a transmembrane protein called STING (stimulator of IFN genes; also known as MITA, ERIS, MPYS and TMEM173) functions as an essential signalling adaptor, linking the cytosolic detection of DNA to the TBK1-IRF3 signalling axis(3-7). Recently, unique nucleic acids called cyclic dinucleotides, which function as conserved signalling molecules in bacteria(8), have also been shown to induce a STING-dependent type I IFN response(9-12). However, a mammalian sensor of cyclic dinucleotides has not been identified. Here we report evidence that STING itself is an innate immune sensor of cyclic dinucleotides. We demonstrate that STING binds directly to radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids, compete with c-di-GMP for binding to STING. Furthermore, we identify mutations in STING that selectively affect the response to cyclic dinucleotides without affecting the response to DNA. Thus, STING seems to function as a direct sensor of cyclic dinucleotides, in addition to its established role as a signalling adaptor in the IFN response to cytosolic DNA. Cyclic dinucleotides have shown promise as novel vaccine adjuvants and immunotherapeutics(9,13), and our results provide insight into the mechanism by which cyclic dinucleotides are sensed by the innate immune system.
C1 [Burdette, Dara L.; Monroe, Kathryn M.; Sotelo-Troha, Katia; Iwig, Jeff S.; Eckert, Barbara; Vance, Russell E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Iwig, Jeff S.] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Chem, Berkeley, CA 94720 USA.
   [Hyodo, Mamoru] Hokkaido Univ, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan.
   [Hayakawa, Yoshihiro] Aichi Inst Technol, Fac Engn, Dept Appl Chem, Toyota 4700392, Japan.
C3 University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Hokkaido University; Aichi Institute of Technology
RP Vance, RE (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM rvance@berkeley.edu
FU Burroughs Wellcome Fund; Cancer Research Institute; National Institutes of Health (NIH) [AI075039, AI080749, AI063302, F32 (AI091100)]; National Institute of Allergy and Infectious Diseases [P01AI063302] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [23700552] Funding Source: KAKEN
NR 26
TC 1318
Z9 1611
U1 8
U2 329
PU 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 27
PY 2011
VL 478
IS 7370
BP 515
EP U111
DI 10.1038/nature10429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200043
PM 21947006
DA 2026-03-09
ER

PT J
AU Deriano, L
   Chaumeil, J
   Coussens, M
   Multani, A
   Chou, YF
   Alekseyenko, AV
   Chang, S
   Skok, JA
   Roth, DB
AF Deriano, Ludovic
   Chaumeil, Julie
   Coussens, Marc
   Multani, Asha
   Chou, Yifan
   Alekseyenko, Alexander V.
   Chang, Sandy
   Skok, Jane A.
   Roth, David B.
TI The RAG2 C terminus suppresses genomic instability and lymphomagenesis
SO NATURE
LA English
DT Article
ID double-strand breaks; atm-deficient mice; v(d)j recombination; lymphocyte development; gene amplification; thymic lymphoma; b-cell; repair; roles; translocations
AB Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans(1) and in mice(2-7). Defects in DNA damage response factors such as ataxia telangiectasia mutated (ATM) protein and combined deficiencies in classical non-homologous end joining and p53 predispose to RAG-initiated genomic rearrangements and lymphomagenesis(2-11). Although we showed previously that RAG1/RAG2 shepherd the broken DNA ends to classical non-homologous end joining for proper repair(12,13), roles for the RAG proteins in preserving genomic stability remain poorly defined. Here we show that the RAG2 carboxy (C) terminus, although dispensable for recombination(14,15), is critical for maintaining genomic stability. Thymocytes from 'core' Rag2 homozygotes (Rag2(c/c) mice) show dramatic disruption of Tcr alpha/delta locus integrity. Furthermore, all Rag2(c/c) p53(-/-) mice, unlike Rag1(c/c) p53(-/-) and p53(-/-) animals, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcra/delta and Igh loci. We also find these features in lymphomas from Atm(-/-) mice. We show that, like ATM-deficiency(3), core RAG2 severely destabilizes the RAG post-cleavage complex. These results reveal a novel genome guardian role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2(c/c) p53(-/-) and Atm(-/-) mice.
C1 [Deriano, Ludovic; Chaumeil, Julie; Coussens, Marc; Chou, Yifan; Skok, Jane A.; Roth, David B.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Multani, Asha] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
   [Alekseyenko, Alexander V.] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, Div Clin Pharmacol,Dept Med, New York, NY 10016 USA.
   [Chang, Sandy] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Skok, Jane A.] UCL, Div Infect & Immun, Dept Immunol & Mol Pathol, London W1T 4JF, England.
C3 New York University; University of Texas System; UTMD Anderson Cancer Center; New York University; Yale University; University of London; University College London
RP Roth, DB (corresponding author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
EM david.roth@nyumc.org
FU National Institutes of Health Roadmap Initiative in Nanomedicine through a Nanomedicine Development Center [1PN2EY018244]; National Institutes of Health [CA104588, R01GM086852]; Irene Diamond Fund; National Center for Research Resources, National Institutes of Health [1UL1RR029893]; NCI [R01CA145746-01]; Leukemia and Lymphoma Scholar Award; Wellcome trust [085096]
NR 39
TC 82
Z9 96
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 119
EP U145
DI 10.1038/nature09755
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100046
PM 21368836
DA 2026-03-09
ER

PT J
AU Ospelkaus, C
   Warring, U
   Colombe, Y
   Brown, KR
   Amini, JM
   Leibfried, D
   Wineland, DJ
AF Ospelkaus, C.
   Warring, U.
   Colombe, Y.
   Brown, K. R.
   Amini, J. M.
   Leibfried, D.
   Wineland, D. J.
TI Microwave quantum logic gates for trapped ions
SO NATURE
LA English
DT Article
ID states
AB Control over physical systems at the quantum level is important in fields as diverse as metrology, information processing, simulation and chemistry. For trapped atomic ions, the quantized motional and internal degrees of freedom can be coherently manipulated with laser light(1,2). Similar control is difficult to achieve with radio-frequency or microwave radiation: the essential coupling between internal degrees of freedom and motion requires significant field changes over the extent of the atoms' motion(2,3), but such changes are negligible at these frequencies for freely propagating fields. An exception is in the near field of microwave currents in structures smaller than the free-space wavelength(4,5), where stronger gradients can be generated. Here we first manipulate coherently (on time-scales of 20 nanoseconds) the internal quantum states of ions held in a microfabricated trap. The controlling magnetic fields are generated by microwave currents in electrodes that are integrated into the trap structure. We also generate entanglement between the internal degrees of freedom of two atoms with a gate operation(4,6-8) suitable for general quantum computation(9); the entangled state has a fidelity of 0.76(3), where the uncertainty denotes standard error of the mean. Our approach, which involves integrating the quantum control mechanism into the trapping device in a scalable manner, could be applied to quantum information processing(4), simulation(5,10) and spectroscopy(3,11).
C1 [Ospelkaus, C.; Warring, U.; Colombe, Y.; Brown, K. R.; Amini, J. M.; Leibfried, D.; Wineland, D. J.] Natl Inst Stand & Technol, Time & Frequency Div, Boulder, CO 80305 USA.
C3 National Institute of Standards & Technology (NIST) - USA
RP Ospelkaus, C (corresponding author), Leibniz Univ Hannover, Inst Quantum Opt, Welfengarten 1, D-30167 Hannover, Germany.
EM christian.ospelkaus@iqo.uni-hannover.de
FU IARPA; ONR; DARPA; NSA; Sandia National Laboratories; NIST
NR 33
TC 283
Z9 335
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 AUG 11
PY 2011
VL 476
IS 7359
BP 181
EP U77
DI 10.1038/nature10290
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900030
PM 21833084
DA 2026-03-09
ER

PT J
AU Cheung, ACM
   Cramer, P
AF Cheung, Alan C. M.
   Cramer, Patrick
TI Structural basis of RNA polymerase II backtracking, arrest and reactivation
SO NATURE
LA English
DT Article
ID cleavage factor tfiis; transcript-cleavage; elongation complex; dna hybrid; angstrom resolution; trigger loop; mechanism; site; translocation; architecture
AB During gene transcription, RNA polymerase (Pol) II moves forwards along DNA and synthesizes messenger RNA. However, at certain DNA sequences, Pol II moves backwards, and such backtracking can arrest transcription. Arrested Pol II is reactivated by transcription factor IIS (TFIIS), which induces RNA cleavage that is required for cell viability(1). Pol II arrest and reactivation are involved in transcription through nucleosomes(2,3) and in promoter-proximal gene regulation(4-6). Here we present X-ray structures at 3.3 angstrom resolution of an arrested Saccharomyces cerevisiae Pol II complex with DNA and RNA, and of a reactivation intermediate that additionally contains TFIIS. In the arrested complex, eight nucleotides of backtracked RNA bind a conserved 'backtrack site' in the Pol II pore and funnel, trapping the active centre trigger loop and inhibiting mRNA elongation. In the reactivation intermediate, TFIIS locks the trigger loop away from backtracked RNA, displaces RNA from the backtrack site, and complements the polymerase active site with a basic and two acidic residues that may catalyse proton transfers during RNA cleavage. The active site is demarcated from the backtrack site by a 'gating tyrosine' residue that probably delimits backtracking. These results establish the structural basis of Pol II backtracking, arrest and reactivation, and provide a framework for analysing gene regulation during transcription elongation.
C1 [Cheung, Alan C. M.; Cramer, Patrick] Univ Munich, Ctr Integrated Prot Sci Munich, Gene Ctr, D-81377 Munich, Germany.
   [Cheung, Alan C. M.; Cramer, Patrick] Univ Munich, Ctr Integrated Prot Sci Munich, Dept Biochem, D-81377 Munich, Germany.
C3 University of Munich; University of Munich
RP Cramer, P (corresponding author), Univ Munich, Ctr Integrated Prot Sci Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM cramer@lmb.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft [SFB646, TR5, FOR1068]; NIM; Bioimaging Network BIN; Jung-Stiftung
NR 30
TC 294
Z9 349
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 249
EP 253
DI 10.1038/nature09785
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200044
PM 21346759
DA 2026-03-09
ER

PT J
AU Ferraccioli, F
   Finn, CA
   Jordan, TA
   Bell, RE
   Anderson, LM
   Damaske, D
AF Ferraccioli, Fausto
   Finn, Carol A.
   Jordan, Tom A.
   Bell, Robin E.
   Anderson, Lester M.
   Damaske, Detlef
TI East Antarctic rifting triggers uplift of the Gamburtsev Mountains
SO NATURE
LA English
DT Article
ID transantarctic mountains; subglacial mountains; crustal; strength; southern; delamination; deformation; lithosphere; intraplate; evolution
AB The Gamburtsev Subglacial Mountains are the least understood tectonic feature on Earth, because they are completely hidden beneath the East Antarctic Ice Sheet. Their high elevation and youthful Alpine topography, combined with their location on the East Antarctic craton, creates a paradox that has puzzled researchers since the mountains were discovered in 1958(1). The preservation of Alpine topography in the Gamburtsevs(2) may reflect extremely low long-term erosion rates beneath the ice sheet(3), but the mountains' origin remains problematic. Here we present the first comprehensive view of the crustal architecture and uplift mechanisms for the Gamburtsevs, derived from radar, gravity and magnetic data. The geophysical data define a 2,500-km-long rift system in East Antarctica surrounding the Gamburtsevs, and a thick crustal root(4) beneath the range. We propose that the root formed during the Proterozoic assembly of interior East Antarctica (possibly about 1 Gyr ago), was preserved as in some old orogens(5,6) and was rejuvenated during much later Permian (roughly 250 Myr ago) and Cretaceous (roughly 100 Myr ago) rifting. Much like East Africa(7), the interior of East Antarctica is a mosaic of Precambrian provinces affected by rifting processes. Our models show that the combination of rift-flank uplift, root buoyancy and the isostatic response to fluvial and glacial erosion explains the high elevation and relief of the Gamburtsevs. The evolution of the Gamburtsevs demonstrates that rifting and preserved orogenic roots can produce broad regions of high topography in continental interiors without significantly modifying the underlying Precambrian lithosphere.
C1 [Ferraccioli, Fausto; Jordan, Tom A.; Anderson, Lester M.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Finn, Carol A.] US Geol Survey, Denver, CO 80225 USA.
   [Bell, Robin E.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Damaske, Detlef] Bundesanstalt Geowissensch & Rohstoffe, D-30655 Hannover, Germany.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; United States Department of the Interior; United States Geological Survey; Columbia University
RP Ferraccioli, F (corresponding author), British Antarctic Survey, Madingley Rd, Cambridge CB3 0ET, England.
EM ffe@bas.ac.uk
FU AGAP International Polar Year; Federal Institute for Geosciences and Resources; Australian Antarctic Division; NERC [bas0100026] Funding Source: UKRI; Natural Environment Research Council [bas0100026] Funding Source: researchfish; Office of Polar Programs (OPP); Directorate For Geosciences [0636883] Funding Source: National Science Foundation
NR 56
TC 206
Z9 224
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 NOV 17
PY 2011
VL 479
IS 7373
BP 388
EP U139
DI 10.1038/nature10566
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700043
PM 22094700
DA 2026-03-09
ER

PT J
AU Vitari, AC
   Leong, KG
   Newton, K
   Yee, C
   O'Rourke, K
   Liu, JF
   Phu, LL
   Vij, R
   Ferrando, R
   Couto, SS
   Mohan, S
   Pandita, A
   Hongo, JA
   Arnott, D
   Wertz, IE
   Gao, WQ
   French, DM
   Dixit, VM
AF Vitari, Alberto C.
   Leong, Kevin G.
   Newton, Kim
   Yee, Cindy
   O'Rourke, Karen
   Liu, Jinfeng
   Phu, Lilian
   Vij, Rajesh
   Ferrando, Ronald
   Couto, Suzana S.
   Mohan, Sankar
   Pandita, Ajay
   Hongo, Jo-Anne
   Arnott, David
   Wertz, Ingrid E.
   Gao, Wei-Qiang
   French, Dorothy M.
   Dixit, Vishva M.
TI COP1 is a tumour suppressor that causes degradation of ETS transcription factors
SO NATURE
LA English
DT Article
ID ubiquitin ligase; prostate-cancer; gene fusions; c-myc; burkitts-lymphoma; regulated gene; mouse models; pea3 group; in-vivo; mutations
AB The proto-oncogenes ETV1, ETV4 and ETV5 encode transcription factors in the E26 transformation-specific (ETS) family, which includes the most frequently rearranged and overexpressed genes in prostate cancer(1-4). Despite being critical regulators of development, little is known about their post-translational regulation. Here we identify the ubiquitin ligase COP1 (also known as RFWD2) as a tumour suppressor that negatively regulates ETV1, ETV4 and ETV5. ETV1, which is mutated in prostate cancer more often, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs and was 50-fold more stable than wild-type ETV1. Almost all patient translocations render ETV1 insensitive to COP1, implying that this confers a selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. Combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein, and elevated ETV1 protein while lacking a translocation event. These findings identify COP1 as a tumour suppressor whose downregulation promotes prostatic epithelial cell proliferation and tumorigenesis.
C1 [Vitari, Alberto C.; Newton, Kim; O'Rourke, Karen; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
   [Leong, Kevin G.] Genentech Inc, Dept Res Oncol, San Francisco, CA 94080 USA.
   [Yee, Cindy; Gao, Wei-Qiang] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Liu, Jinfeng] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
   [Phu, Lilian; Arnott, David] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Vij, Rajesh; Hongo, Jo-Anne] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
   [Ferrando, Ronald; Couto, Suzana S.; French, Dorothy M.] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Mohan, Sankar; Pandita, Ajay] Genentech Inc, Dept Mol Diagnost & Canc Cell Biol, San Francisco, CA 94080 USA.
   [Wertz, Ingrid E.] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
RP Dixit, VM (corresponding author), Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA.
EM dixit@gene.com
NR 44
TC 151
Z9 170
U1 0
U2 35
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 403
EP +
DI 10.1038/nature10005
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100051
PM 21572435
DA 2026-03-09
ER

PT J
AU Jutzi, M
   Asphaug, E
AF Jutzi, M.
   Asphaug, E.
TI Forming the lunar farside highlands by accretion of a companion moon
SO NATURE
LA English
DT Article
ID origin; impact; simulations; asymmetry; evolution; mantle
AB The most striking geological feature of the Moon is the terrain and elevation dichotomy(1) between the hemispheres: the nearside is low and flat, dominated by volcanic maria, whereas the farside is mountainous and deeply cratered. Associated with this geological dichotomy is a compositional and thermal variation(2,3), with the nearside Procellarum KREEP (potassium/rare-earth element/phosphorus) Terrane and environs interpreted as having thin, compositionally evolved crust in comparison with the massive feldspathic highlands. The lunar dichotomy may have been caused by internal effects (for example spatial variations in tidal heating(4), asymmetric convective processes(5) or asymmetric crystallization of the magma ocean(6)) or external effects (such as the event that formed the South Pole/Aitken basin(1) or asymmetric cratering(7)). Here we consider its origin as a late carapace added by the accretion of a companion moon. Companion moons are a common outcome of simulations(8) of Moon formation from a protolunar disk resulting from a giant impact, and although most coplanar configurations are unstable(9), a similar to 1,200-km-diameter moon located at one of the Trojan points could be dynamically stable for tens of millions of years after the giant impact(10). Most of the Moon's magma ocean would solidify on this timescale(11,12), whereas the companion moon would evolve more quickly into a crust and a solid mantle derived from similar disk material, and would presumably have little or no core. Its likely fate would be to collide with the Moon at similar to 2-3 km s(-1), well below the speed of sound in silicates. According to our simulations, a large moon/Moon size ratio (similar to 0.3) and a subsonic impact velocity lead to an accretionary pile rather than a crater, contributing a hemispheric layer of extent and thickness consistent with the dimensions of the farside highlands(1,13) and in agreement with the degree-two crustal thickness profile(4). The collision furthermore displaces the KREEP-rich layer to the opposite hemisphere, explaining the observed concentration(2,3).
C1 [Jutzi, M.; Asphaug, E.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95060 USA.
   [Jutzi, M.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
C3 University of California System; University of California Santa Cruz; University of Bern
RP Jutzi, M (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, 1156 Highst, Santa Cruz, CA 95060 USA.
EM martin.jutzi@space.unibe.ch
FU NASA; NSF-MRI
NR 24
TC 61
Z9 71
U1 1
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 69
EP 72
DI 10.1038/nature10289
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300030
PM 21814278
DA 2026-03-09
ER

PT J
AU Shimamura, T
   Shiroishi, M
   Weyand, S
   Tsujimoto, H
   Winter, G
   Katritch, V
   Abagyan, R
   Cherezov, V
   Liu, W
   Han, GW
   Kobayashi, T
   Stevens, RC
   Iwata, S
AF Shimamura, Tatsuro
   Shiroishi, Mitsunori
   Weyand, Simone
   Tsujimoto, Hirokazu
   Winter, Graeme
   Katritch, Vsevolod
   Abagyan, Ruben
   Cherezov, Vadim
   Liu, Wei
   Han, Gye Won
   Kobayashi, Takuya
   Stevens, Raymond C.
   Iwata, So
TI Structure of the human histamine H1 receptor complex with doxepin
SO NATURE
LA English
DT Article
ID site-directed mutagenesis; structure-based discovery; crystal-structure; binding-site; mutational analysis; antidepressants; purification; membrane; affinity; models
AB The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H-1 receptor (H1R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H1R complex with. doxepin, a first-generation H1R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 428(6,48), a highly conserved key residue G -protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H1R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys191(5.39) and/or Lys 179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H1R antagonist specificity against H1R.
C1 [Shimamura, Tatsuro; Cherezov, Vadim; Liu, Wei; Han, Gye Won; Stevens, Raymond C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Shimamura, Tatsuro; Shiroishi, Mitsunori; Weyand, Simone; Tsujimoto, Hirokazu; Kobayashi, Takuya; Iwata, So] Japan Sci & Technol Agcy, ERATO, Human Receptor Crystallog Project, Sakyo Ku, Kyoto 6068501, Japan.
   [Shimamura, Tatsuro; Shiroishi, Mitsunori; Tsujimoto, Hirokazu; Kobayashi, Takuya; Iwata, So] Kyoto Univ, Grad Sch Med, Dept Cell Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Shiroishi, Mitsunori] Kyushu Univ, Grad Sch Pharmaceut Sci, Higashi Ku, Fukuoka 8128582, Japan.
   [Weyand, Simone; Iwata, So] Univ London Imperial Coll Sci Technol & Med, Membrane Prot Crystallog Grp, Div Mol Biosci, London SW7 2AZ, England.
   [Weyand, Simone; Winter, Graeme; Iwata, So] Diamond Light Source, Didcot OX11 0DE, Oxon, England.
   [Katritch, Vsevolod; Abagyan, Ruben] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
   [Katritch, Vsevolod; Abagyan, Ruben] Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA.
   [Iwata, So] RIKEN, Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
C3 Scripps Research Institute; Japan Science & Technology Agency (JST); Kyoto University; Kyushu University; Imperial College London; Diamond Light Source; University of California System; University of California San Diego; University of California System; University of California San Diego; RIKEN
RP Stevens, RC (corresponding author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM t-coba@mfour.med.kyoto-u.ac.jp; stevens@scripps.edu; so_iwata@me.com
FU Japan Science and Technology Agency; MEXT, Japan; NIH [P50 GM073197, R01 GM071872, GM075915]; NIH PSI [U54 GM094618]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/G023425/1]; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Scientific Foundation; Sumitomo Foundation; Wellcome Trust at the Diamond Light Source Limited [062164/7/00/Z]; Scripps Research Institute; National Science Foundation [HS0308078]; Science Foundation Ireland [02-IN1-B266]; Biotechnology and Biological Sciences Research Council [BB/G023425/1] Funding Source: researchfish; Grants-in-Aid for Scientific Research [23657074, 22659059] Funding Source: KAKEN; BBSRC [BB/G023425/1] Funding Source: UKRI
NR 59
TC 678
Z9 768
U1 3
U2 174
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 65
EP U82
DI 10.1038/nature10236
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300045
PM 21697825
DA 2026-03-09
ER

PT J
AU Barreiro, JT
   Müller, M
   Schindler, P
   Nigg, D
   Monz, T
   Chwalla, M
   Hennrich, M
   Roos, CF
   Zoller, P
   Blatt, R
AF Barreiro, Julio T.
   Mueller, Markus
   Schindler, Philipp
   Nigg, Daniel
   Monz, Thomas
   Chwalla, Michael
   Hennrich, Markus
   Roos, Christian F.
   Zoller, Peter
   Blatt, Rainer
TI An open-system quantum simulator with trapped ions
SO NATURE
LA English
DT Article
ID multiparticle entanglement; information; states; computation; physics; driven; spins
AB The control of quantum systems is of fundamental scientific interest and promises powerful applications and technologies. Impressive progress has been achieved in isolating quantum systems from the environment and coherently controlling their dynamics, as demonstrated by the creation and manipulation of entanglement in various physical systems. However, for open quantum systems, engineering the dynamics of many particles by a controlled coupling to an environment remains largely unexplored. Here we realize an experimental toolbox for simulating an open quantum system with up to five quantum bits (qubits). Using a quantum computing architecture with trapped ions, we combine multi-qubit gates with optical pumping to implement coherent operations and dissipative processes. We illustrate our ability to engineer the open-system dynamics through the dissipative preparation of entangled states, the simulation of coherent many-body spin interactions, and the quantum non-demolition measurement of multi-qubit observables. By adding controlled dissipation to coherent operations, this work offers novel prospects for open-system quantum simulation and computation.
C1 [Mueller, Markus; Chwalla, Michael; Roos, Christian F.; Zoller, Peter; Blatt, Rainer] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Barreiro, Julio T.; Schindler, Philipp; Nigg, Daniel; Monz, Thomas; Chwalla, Michael; Hennrich, Markus; Roos, Christian F.; Blatt, Rainer] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Mueller, Markus; Zoller, Peter] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
C3 Austrian Academy of Sciences; University of Innsbruck; University of Innsbruck
RP Zoller, P (corresponding author), Austrian Acad Sci, Inst Quantenopt & Quanteninformat, Technikerstr 21A, A-6020 Innsbruck, Austria.
EM Peter.Zoller@uibk.ac.at; Rainer.Blatt@uibk.ac.at
FU Austrian Science Fund; European Commission; Institut fur Quanteninformation GmbH; European Community
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NR 48
TC 882
Z9 959
U1 3
U2 177
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 486
EP 491
DI 10.1038/nature09801
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900032
PM 21350481
DA 2026-03-09
ER

PT J
AU Pei, YZ
   Shi, XY
   LaLonde, A
   Wang, H
   Chen, LD
   Snyder, GJ
AF Pei, Yanzhong
   Shi, Xiaoya
   LaLonde, Aaron
   Wang, Heng
   Chen, Lidong
   Snyder, G. Jeffrey
TI Convergence of electronic bands for high performance bulk thermoelectrics
SO NATURE
LA English
DT Article
ID transport phenomena; lead-chalcogenides; pbte; telluride; alloys; figure; merit; power
AB Thermoelectric generators, which directly convert heat into electricity, have long been relegated to use in space-based or other niche applications, but are now being actively considered for a variety of practical waste heat recovery systems-such as the conversion of car exhaust heat into electricity. Although these devices can be very reliable and compact, the thermoelectric materials themselves are relatively inefficient: to facilitate widespread application, it will be desirable to identify or develop materials that have an intensive thermoelectric materials figure of merit, zT, above 1.5 (ref. 1). Many different concepts have been used in the search for new materials with high thermoelectric efficiency, such as the use of nanostructuring to reduce phonon thermal conductivity(2-4), which has led to the investigation of a variety of complex material systems(5). In this vein, it is well known(6,7) that a high valley degeneracy (typically <= 6 for known thermoelectrics) in the electronic bands is conducive to high zT, and this in turn has stimulated attempts to engineer such degeneracy by adopting low-dimensional nanostructures(8-10). Here we demonstrate that it is possible to direct the convergence of many valleys in a bulk material by tuning the doping and composition. By this route, we achieve a convergence of at least 12 valleys in doped PbTe(1-x)Se(x) alloys, leading to an extraordinary zT value of 1.8 at about 850 kelvin. Band engineering to converge the valence (or conduction) bands to achieve high valley degeneracy should be a general strategy in the search for and improvement of bulk thermoelectric materials, because it simultaneously leads to a high Seebeck coefficient and high electrical conductivity.
C1 [Pei, Yanzhong; LaLonde, Aaron; Wang, Heng; Snyder, G. Jeffrey] CALTECH, Pasadena, CA 91125 USA.
   [Shi, Xiaoya; Chen, Lidong] Chinese Acad Sci, Shanghai Inst Ceram, CAS Key Lab Mat Energy Convers, Shanghai 200050, Peoples R China.
C3 California Institute of Technology; Chinese Academy of Sciences; Shanghai Institute of Ceramics, CAS
RP Snyder, GJ (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM jsnyder@caltech.edu
FU NASA-JPL; DARPA; CAS
NR 30
TC 3780
Z9 4062
U1 45
U2 2272
PU 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 5
PY 2011
VL 473
IS 7345
BP 66
EP 69
DI 10.1038/nature09996
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300031
PM 21544143
DA 2026-03-09
ER

PT J
AU Fushinobu, S
   Nishimasu, H
   Hattori, D
   Song, HJ
   Wakagi, T
AF Fushinobu, Shinya
   Nishimasu, Hiroshi
   Hattori, Daiki
   Song, Hyun-Jin
   Wakagi, Takayoshi
TI Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase/phosphatase
SO NATURE
LA English
DT Article
ID aldolase; catalysis; archaea
AB Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity(1). Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose-1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P)(2). Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-angstrom resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form(3) revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction.
C1 [Fushinobu, Shinya; Hattori, Daiki; Song, Hyun-Jin; Wakagi, Takayoshi] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biotechnol, Bunkyo Ku, Tokyo 1138657, Japan.
   [Nishimasu, Hiroshi] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.
C3 University of Tokyo; University of Tokyo
RP Wakagi, T (corresponding author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Biotechnol, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan.
EM atwakag@mail.ecc.u-tokyo.ac.jp
FU Grants-in-Aid for Scientific Research [23687014] Funding Source: KAKEN
NR 15
TC 60
Z9 74
U1 1
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 OCT 27
PY 2011
VL 478
IS 7370
BP 538
EP U139
DI 10.1038/nature10457
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200048
PM 21983966
DA 2026-03-09
ER

PT J
AU Burguillos, MA
   Deierborg, T
   Kavanagh, E
   Persson, A
   Hajji, N
   Garcia-Quintanilla, A
   Cano, J
   Brundin, P
   Englund, E
   Venero, JL
   Joseph, B
AF Burguillos, Miguel A.
   Deierborg, Tomas
   Kavanagh, Edel
   Persson, Annette
   Hajji, Nabil
   Garcia-Quintanilla, Albert
   Cano, Josefina
   Brundin, Patrik
   Englund, Elisabet
   Venero, Jose L.
   Joseph, Bertrand
TI Caspase signalling controls microglia activation and neurotoxicity
SO NATURE
LA English
DT Article
ID kinase-c-delta; nf-kappa-b; necrosis-factor-alpha; blood-brain-barrier; parkinsons-disease; dopaminergic-neurons; alzheimers-disease; endotoxic-shock; nitric-oxide; cell-death
AB Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-delta-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves.
C1 [Burguillos, Miguel A.; Kavanagh, Edel; Hajji, Nabil; Joseph, Bertrand] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden.
   [Burguillos, Miguel A.; Cano, Josefina; Venero, Jose L.] Univ Seville, Dept Bioquim & Biol Mol, Fac Farm, E-41012 Seville, Spain.
   [Burguillos, Miguel A.; Cano, Josefina; Venero, Jose L.] Inst Biomed Sevilla, Seville 41012, Spain.
   [Burguillos, Miguel A.; Deierborg, Tomas; Brundin, Patrik] Wallenberg Neurosci Ctr, Dept Expt Med Sci, Neuronal Survival Unit, S-22184 Lund, Sweden.
   [Persson, Annette; Englund, Elisabet] Univ Lund Hosp, Div Neuropathol, Dept Pathol, S-22185 Lund, Sweden.
   [Garcia-Quintanilla, Albert] Univ Seville, Serv Biol, CITIUS, Ctr Invest Tecnol & Innovac, E-41012 Seville, Spain.
C3 Karolinska Institutet; University of Sevilla; Consejo Superior de Investigaciones Cientificas (CSIC); University of Sevilla; CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS); Lund University; Skane University Hospital; University of Sevilla
RP Joseph, B (corresponding author), Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden.
EM jlvenero@us.es; bertrand.joseph@ki.se
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2006-04119, 2009-13778]; Swedish Research Council; Parkinson Foundation of Sweden; Swedish Alzheimer Foundation; Swedish Cancer Society; Medical Research Council [G0801056B] Funding Source: researchfish
NR 47
TC 498
Z9 605
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 APR 21
PY 2011
VL 472
IS 7343
BP 319
EP U214
DI 10.1038/nature09788
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600033
PM 21389984
DA 2026-03-09
ER

PT J
AU Sievers, SA
   Karanicolas, J
   Chang, HW
   Zhao, A
   Jiang, L
   Zirafi, O
   Stevens, JT
   Münch, J
   Baker, D
   Eisenberg, D
AF Sievers, Stuart A.
   Karanicolas, John
   Chang, Howard W.
   Zhao, Anni
   Jiang, Lin
   Zirafi, Onofrio
   Stevens, Jason T.
   Muench, Jan
   Baker, David
   Eisenberg, David
TI Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation
SO NATURE
LA English
DT Article
ID paired helical filaments; tau-protein; peptide inhibitors; alzheimers-disease; aggregation; binding; mechanism; toxicity; model
AB Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies(1) as well as with normal cellular functions(2,3), and frequently form during protein denaturation(4,5). Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-D-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural L.-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-beta-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.
C1 [Sievers, Stuart A.; Chang, Howard W.; Zhao, Anni; Jiang, Lin; Eisenberg, David] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Biol Chem, Los Angeles, CA 90095 USA.
   [Sievers, Stuart A.; Chang, Howard W.; Zhao, Anni; Jiang, Lin; Eisenberg, David] Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Karanicolas, John; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Karanicolas, John; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Karanicolas, John; Stevens, Jason T.] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA.
   [Karanicolas, John; Stevens, Jason T.] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
   [Zirafi, Onofrio; Muench, Jan] Univ Hosp Ulm, Inst Mol Virol, D-89081 Ulm, Germany.
C3 Howard Hughes Medical Institute; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Kansas; University of Kansas; Ulm University
RP Eisenberg, D (corresponding author), Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Biol Chem, Los Angeles, CA 90095 USA.
EM david@mbi.ucla.edu
FU Damon Runyon Cancer Research Foundation; Ruth L. Kirschstein National Research Service Award; Ministry of Science, Baden-Wurttemberg; UCLA-IGERT; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0958111] Funding Source: National Science Foundation
NR 49
TC 408
Z9 495
U1 7
U2 294
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 96
EP U117
DI 10.1038/nature10154
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300052
PM 21677644
DA 2026-03-09
ER

PT J
AU Krüger, M
   Schenk, M
   Hommelhoff, P
AF Krueger, Michael
   Schenk, Markus
   Hommelhoff, Peter
TI Attosecond control of electrons emitted from a nanoscale metal tip
SO NATURE
LA English
DT Article
ID above-threshold ionization; spectroscopy; dynamics; pulses; fields; light
AB Attosecond science is based on steering electrons with the electric field of well controlled femtosecond laser pulses(1). It has led to the generation of extreme-ultraviolet pulses(2) with a duration of less than 100 attoseconds (ref. 3; 1 as = 10(-18) s), to the measurement of intramolecular dynamics (by diffraction of an electron taken from the molecule under scrutiny(4,5)) and to ultrafast electron holography(6). All these effects have been observed with atoms or molecules in the gas phase. Electrons liberated from solids by few-cycle laser pulses are also predicted(7,8) to show a strong light-phase sensitivity, but only very small effects have been observed(14). Here we report that the spectra of electrons undergoing photoemission from a nanometre-scale tungsten tip show a dependence on the carrier-envelope phase of the laser, with a current modulation of up to 100 per cent. Depending on the carrier-envelope phase, electrons are emitted either from a single sub-500-attosecond interval of the 6-femtosecond laser pulse, or from two such intervals; the latter case leads to spectral interference. We also show that coherent elastic re-scattering of liberated electrons takes place at the metal surface. Owing to field enhancement at the tip, a simple laser oscillator reaches the peak electric field strengths required for attosecond experiments at 100-megahertz repetition rates, rendering complex amplified laser systems dispensable. Practically, this work represents a simple, extremely sensitive carrier-envelope phase sensor, which could be shrunk in volume to about one cubic centimetre. Our results indicate that the attosecond techniques developed with (and for) atoms and molecules can also be used with solids. In particular, we foresee subfemtosecond, subnanometre probing of collective electron dynamics (such as plasmon polaritons(9)) in solid-state systems ranging in scale from mesoscopic solids to clusters and to single protruding atoms.
C1 [Krueger, Michael; Schenk, Markus; Hommelhoff, Peter] Max Planck Inst Quantum Opt, Ultrafast Quantum Opt Grp, D-85748 Garching, Germany.
C3 Max Planck Society
RP Hommelhoff, P (corresponding author), Max Planck Inst Quantum Opt, Ultrafast Quantum Opt Grp, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM peter.hommelhoff@mpq.mpg.de
FU European Union
NR 30
TC 539
Z9 594
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 JUL 7
PY 2011
VL 475
IS 7354
BP 78
EP 81
DI 10.1038/nature10196
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300048
PM 21734706
DA 2026-03-09
ER

PT J
AU Kho, C
   Lee, A
   Jeong, D
   Oh, JG
   Chaanine, AH
   Kizana, E
   Park, WJ
   Hajjar, RJ
AF Kho, Changwon
   Lee, Ahyoung
   Jeong, Dongtak
   Oh, Jae Gyun
   Chaanine, Antoine H.
   Kizana, Eddy
   Park, Woo Jin
   Hajjar, Roger J.
TI SUMO1-dependent modulation of SERCA2a in heart failure
SO NATURE
LA English
DT Article
ID sarcoplasmic-reticulum ca2+-atpase; serum response factor; gene-transfer; ventricular-function; protein; sumo-1; cardiomyocytes; sumoylation; expression; cells
AB The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling. Impaired Ca(2+) uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure(1). Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients(2), as well as in animal models(3). The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins(4), and is involved in many cellular processes(5). Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene delivery maintained the protein abundance of SERCA2a and markedly improved cardiac function in mice with heart failure. This effect was comparable to SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay. Transgene-mediated SUMO1 overexpression rescued cardiac dysfunction induced by pressure overload concomitantly with increased SERCA2a function. By contrast, downregulation of SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced deterioration of cardiac function and was accompanied by decreased SERCA2a function. However, knockdown of SERCA2a resulted in severe contractile dysfunction both in vitro and in vivo, which was not rescued by overexpression of SUMO1. Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure.
C1 [Kho, Changwon; Lee, Ahyoung; Jeong, Dongtak; Chaanine, Antoine H.; Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY 10029 USA.
   [Oh, Jae Gyun; Park, Woo Jin] Gwangju Inst Sci & Technol, Coll Life Sci, Kwangju 500712, South Korea.
   [Kizana, Eddy] Westmead Hosp, Westmead Millennium Inst, Sydney Med Sch, Westmead, NSW 2145, Australia.
   [Kizana, Eddy] Westmead Hosp, Dept Cardiol, Westmead, NSW 2145, Australia.
C3 Icahn School of Medicine at Mount Sinai; Gwangju Institute of Science & Technology (GIST); NSW Health; Westmead Hospital; University of Sydney; Westmead Institute for Medical Research; NSW Health; Westmead Hospital; University of Sydney
RP Hajjar, RJ (corresponding author), Mt Sinai Sch Med, Cardiovasc Res Ctr, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA.
EM roger.hajjar@mssm.edu
FU NIH [RO1 HL083156, HL080498, HL093183, P20HL100396]; Global Research Laboratory of the Korean Ministry of Science and Technology [M6-0605-00-0001]; National Heart Lung and Blood Institute [T32HL007824] Funding Source: NIH RePORTER
NR 32
TC 317
Z9 352
U1 0
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 SEP 29
PY 2011
VL 477
IS 7366
BP 601
EP U263
DI 10.1038/nature10407
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900042
PM 21900893
DA 2026-03-09
ER

PT J
AU Chen, HN
   Gu, XY
   Liu, YH
   Wang, J
   Wirt, SE
   Bottino, R
   Schorle, H
   Sage, J
   Kim, SK
AF Chen, Hainan
   Gu, Xueying
   Liu, Yinghua
   Wang, Jing
   Wirt, Stacey E.
   Bottino, Rita
   Schorle, Hubert
   Sage, Julien
   Kim, Seung K.
TI PDGF signalling controls age-dependent proliferation in pancreatic β-cells
SO NATURE
LA English
DT Article
ID growth-factor; transgenic mice; dna-synthesis; rat islets; mass; receptor; expression; replication; expansion; ezh2
AB Determining the signalling pathways that direct tissue expansion is a principal goal of regenerative biology. Vigorous pancreatic beta-cell replication in juvenile mice and humans declines with age, and elucidating the basis for this decay may reveal strategies for inducing beta-cell expansion, a long-sought goal for diabetes therapy. Here we show that platelet-derived growth factor receptor (Pdgfr) signalling controls age-dependent beta-cell proliferation in mouse and human pancreatic islets. With age, declining beta-cell Pdgfr levels were accompanied by reductions in beta-cell enhancer of zeste homologue 2 (Ezh2) levels and beta-cell replication. Conditional inactivation of the Pdgfra gene in beta-cells accelerated these changes, preventing mouse neonatal beta-cell expansion and adult beta-cell regeneration. Targeted human PDGFR-a activation in mouse beta-cells stimulated Erk1/2 phosphorylation, leading to Ezh2-dependent expansion of adult beta-cells. Adult human islets lack PDGF signalling competence, but exposure of juvenile human islets to PDGF-AA stimulated beta-cell proliferation. The discovery of a conserved pathway controlling age-dependent beta-cell proliferation indicates new strategies for beta-cell expansion.
C1 [Chen, Hainan; Gu, Xueying; Liu, Yinghua; Wang, Jing; Kim, Seung K.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Wirt, Stacey E.; Sage, Julien] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Wirt, Stacey E.; Sage, Julien] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Bottino, Rita] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Div Immunogenet,Dept Pediat, Pittsburgh, PA 15213 USA.
   [Schorle, Hubert] Univ Bonn, Sch Med, Inst Pathol, Dept Dev Biol, D-53127 Bonn, Germany.
   [Kim, Seung K.] Stanford Univ, Sch Med, Dept Med Oncol, Stanford, CA 94305 USA.
   [Kim, Seung K.] Howard Hughes Med Inst, Dept Dev Biol, Beckman Ctr B300, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Bonn; Stanford University; Howard Hughes Medical Institute
RP Kim, SK (corresponding author), Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
EM seungkim@stanford.edu
FU NIH; NIH-NCI [RO1 CA114102]; Stem Cell Network NRW; Deutsche Krebshilfe; Dewey family fund; Juvenile Diabetes Research Foundation; Snyder Foundation; Stinehart Foundation; NIH Beta Cell Biology Consortium [UO1 DK89532, UO1 DK89572]; Howard Hughes Medical Institute (HHMI); National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER
NR 43
TC 238
Z9 295
U1 0
U2 39
PU 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 20
PY 2011
VL 478
IS 7369
BP 349
EP +
DI 10.1038/nature10502
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100038
PM 21993628
DA 2026-03-09
ER

PT J
AU Sato, T
   Katagiri, K
   Gohbara, A
   Inoue, K
   Ogonuki, N
   Ogura, A
   Kubota, Y
   Ogawa, T
AF Sato, Takuya
   Katagiri, Kumiko
   Gohbara, Ayako
   Inoue, Kimiko
   Ogonuki, Narumi
   Ogura, Atsuo
   Kubota, Yoshinobu
   Ogawa, Takehiko
TI In vitro production of functional sperm in cultured neonatal mouse testes
SO NATURE
LA English
DT Article
ID rat spermatogenic cells; transmeiotic differentiation; organ-culture; germ-cells; protein; nuclei; marker
AB Spermatogenesis is one of the most complex and longest processes of sequential cell proliferation and differentiation in the body, taking more than a month from spermatogonial stem cells, through meiosis, to sperm formation(1,2). The whole process, therefore, has never been reproduced in vitro in mammals(3-5), nor in any other species with a very few exceptions in some particular types of fish(6,7). Here we show that neonatal mouse testes which contain only gonocytes or primitive spermatogonia as germ cells can produce spermatids and sperm in vitro with serum-free culture media. Spermatogenesis was maintained over 2 months in tissue fragments positioned at the gas-liquid interphase. The obtained spermatids and sperm resulted in healthy and reproductively competent offspring through microinsemination. In addition, neonatal testis tissues were cryopreserved and, after thawing, showed complete spermatogenesis in vitro. Our organ culture method could be applicable through further refinements to a variety of mammalian species, which will serve as a platform for future clinical application as well as mechanistic understanding of spermatogenesis.
C1 [Sato, Takuya; Katagiri, Kumiko; Gohbara, Ayako; Kubota, Yoshinobu; Ogawa, Takehiko] Yokohama City Univ, Grad Sch Med, Dept Urol, Yokohama, Kanagawa 2360004, Japan.
   [Inoue, Kimiko; Ogonuki, Narumi; Ogura, Atsuo] RIKEN, Bioresource Ctr, Ibaraki 3050074, Japan.
   [Ogawa, Takehiko] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 2360004, Japan.
C3 Yokohama City University; RIKEN; Yokohama City University
RP Ogawa, T (corresponding author), Yokohama City Univ, Grad Sch Med, Dept Urol, Yokohama, Kanagawa 2360004, Japan.
EM ogawa@med.yokohama-cu.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan [20116005, 21592080]; Yokohama Foundation for Advancement of Medical Science; Yokohama City University, Japan [S2116]; Grants-in-Aid for Scientific Research [20116005, 23220011, 21592080] Funding Source: KAKEN
NR 28
TC 564
Z9 630
U1 6
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 504
EP +
DI 10.1038/nature09850
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200060
PM 21430778
DA 2026-03-09
ER

PT J
AU Poulikakos, PI
   Persaud, Y
   Janakiraman, M
   Kong, XJ
   Ng, C
   Moriceau, G
   Shi, HB
   Atefi, M
   Titz, B
   Gabay, MT
   Salton, M
   Dahlman, KB
   Tadi, M
   Wargo, JA
   Flaherty, KT
   Kelley, MC
   Misteli, T
   Chapman, PB
   Sosman, JA
   Graeber, TG
   Ribas, A
   Lo, RS
   Rosen, N
   Solit, DB
AF Poulikakos, Poulikos I.
   Persaud, Yogindra
   Janakiraman, Manickam
   Kong, Xiangju
   Ng, Charles
   Moriceau, Gatien
   Shi, Hubing
   Atefi, Mohammad
   Titz, Bjoern
   Gabay, May Tal
   Salton, Maayan
   Dahlman, Kimberly B.
   Tadi, Madhavi
   Wargo, Jennifer A.
   Flaherty, Keith T.
   Kelley, Mark C.
   Misteli, Tom
   Chapman, Paul B.
   Sosman, Jeffrey A.
   Graeber, Thomas G.
   Ribas, Antoni
   Lo, Roger S.
   Rosen, Neal
   Solit, David B.
TI RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
SO NATURE
LA English
DT Article
ID braf; pathway; mek
AB Activated RAS promotes dimerization of members of the RAF kinase family(1-3). ATP-competitive RAF inhibitors activate ERK signalling(4-7) by transactivating RAF dimers(4). In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E)(8). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.
C1 [Persaud, Yogindra; Janakiraman, Manickam; Solit, David B.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Poulikakos, Poulikos I.; Gabay, May Tal; Tadi, Madhavi; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10065 USA.
   [Kong, Xiangju; Moriceau, Gatien; Shi, Hubing; Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA.
   [Ng, Charles; Atefi, Mohammad; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Titz, Bjoern; Graeber, Thomas G.; Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
   [Salton, Maayan; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
   [Dahlman, Kimberly B.; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37232 USA.
   [Wargo, Jennifer A.] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Boston, MA 02114 USA.
   [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
   [Kelley, Mark C.] Vanderbilt Ingram Canc Ctr, Dept Surg, Nashville, TN 37232 USA.
   [Chapman, Paul B.; Rosen, Neal; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Vanderbilt University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Vanderbilt University; Memorial Sloan Kettering Cancer Center
RP Solit, DB (corresponding author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
EM solitd@mskcc.org
FU Vanderbilt-Ingram Cancer Center; T. J. Martell Foundation; National Institutes of Health (NIH); Beene Foundation; Melanoma Research Alliance; STARR Foundation; Burroughs Wellcome Fund; American Skin Association; Joint Center for Translational Medicine; Sidney Kimmel Foundation; Stand Up to Cancer; NIH, NCI, Center for Cancer Research; Danny Federici Melanoma Fund;  [T32 CACA062948-15]; National Cancer Institute [P30CA008748, ZIABC010309] Funding Source: NIH RePORTER
NR 22
TC 1190
Z9 1404
U1 0
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 387
EP U144
DI 10.1038/nature10662
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000056
PM 22113612
DA 2026-03-09
ER

PT J
AU Mack, MC
   Bret-Harte, MS
   Hollingsworth, TN
   Jandt, RR
   Schuur, EAG
   Shaver, GR
   Verbyla, DL
AF Mack, Michelle C.
   Bret-Harte, M. Syndonia
   Hollingsworth, Teresa N.
   Jandt, Randi R.
   Schuur, Edward A. G.
   Shaver, Gaius R.
   Verbyla, David L.
TI Carbon loss from an unprecedented Arctic tundra wildfire
SO NATURE
LA English
DT Article
ID climate-change; north-america; fire; vegetation; soils; vulnerability; ecosystems; severity; storage; forests
AB Arctic tundra soils store large amounts of carbon (C) in organic soil layers hundreds to thousands of years old that insulate, and in some cases maintain, permafrost soils(1,2). Fire has been largely absent from most of this biome since the early Holocene epoch(3), but its frequency and extent are increasing, probably in response to climate warming(4). The effect of fires on the C balance of tundra landscapes, however, remains largely unknown. The Anaktuvuk River fire in 2007 burned 1,039 square kilometres of Alaska's Arctic slope, making it the largest fire on record for the tundra biome and doubling the cumulative area burned since 1950 (ref. 5). Here we report that tundra ecosystems lost 2,016 +/- 435 g C m(-2) in the fire, an amount two orders of magnitude larger than annual net C exchange in undisturbed tundra(6). Sixty per cent of this C loss was from soil organic matter, and radiocarbon dating of residual soil layers revealed that the maximum age of soil C lost was 50 years. Scaled to the entire burned area, the fire released approximately 2.1 teragrams of C to the atmosphere, an amount similar in magnitude to the annual net C sink for the entire Arctic tundra biome averaged over the last quarter of the twentieth century(7). The magnitude of ecosystem C lost by fire, relative to both ecosystem and biome-scale fluxes, demonstrates that a climate-driven increase in tundra fire disturbance may represent a positive feedback, potentially offsetting Arctic greening(8) and influencing the net C balance of the tundra biome.
C1 [Mack, Michelle C.; Schuur, Edward A. G.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Bret-Harte, M. Syndonia] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA.
   [Hollingsworth, Teresa N.] Univ Alaska Fairbanks, Boreal Ecol Cooperat Res Unit, PNW Res Stn USDA Forest Serv, Fairbanks, AK 99775 USA.
   [Jandt, Randi R.] Bur Land Management, Alaska Fire Serv, Ft Wainwright, AK 99703 USA.
   [Shaver, Gaius R.] Marine Biol Lab, Ctr Ecosyst, Woods Hole, MA 02543 USA.
   [Verbyla, David L.] Univ Alaska Fairbanks, Dept Forest Sci, Fairbanks, AK USA.
C3 State University System of Florida; University of Florida; University of Alaska System; University of Alaska Fairbanks; United States Department of Agriculture (USDA); United States Forest Service; University of Alaska System; University of Alaska Fairbanks; Marine Biological Laboratory - Woods Hole; University of Alaska System; University of Alaska Fairbanks
RP Mack, MC (corresponding author), Univ Florida, Dept Biol, POB 118525, Gainesville, FL 32611 USA.
EM mcmack@ufl.edu
FU US NSF Division of Environmental Biology; Division of Biological Infrastructure and Office of Polar Programs; US National Center for Ecological Analysis and Synthesis; US Bureau of Land Management Alaska Fire Service and Arctic Field Office; Direct For Biological Sciences; Division Of Environmental Biology [1026415] Funding Source: National Science Foundation; Direct For Biological Sciences; Emerging Frontiers [1065587] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0856853, 0806271, 1107707] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1107892, 0807639] Funding Source: National Science Foundation
NR 32
TC 365
Z9 428
U1 2
U2 344
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 489
EP 492
DI 10.1038/nature10283
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900038
PM 21796209
DA 2026-03-09
ER

PT J
AU Kasturi, SP
   Skountzou, I
   Albrecht, RA
   Koutsonanos, D
   Hua, T
   Nakaya, HI
   Ravindran, R
   Stewart, S
   Alam, M
   Kwissa, M
   Villinger, F
   Murthy, N
   Steel, J
   Jacob, J
   Hogan, RJ
   García-Sastre, A
   Compans, R
   Pulendran, B
AF Kasturi, Sudhir Pai
   Skountzou, Ioanna
   Albrecht, Randy A.
   Koutsonanos, Dimitrios
   Hua, Tang
   Nakaya, Helder I.
   Ravindran, Rajesh
   Stewart, Shelley
   Alam, Munir
   Kwissa, Marcin
   Villinger, Francois
   Murthy, Niren
   Steel, John
   Jacob, Joshy
   Hogan, Robert J.
   Garcia-Sastre, Adolfo
   Compans, Richard
   Pulendran, Bali
TI Programming the magnitude and persistence of antibody responses with innate immunity
SO NATURE
LA English
DT Article
ID memory b-cells; yellow-fever vaccine; dermal dendritic cells; toll-like receptors; germinal center; in-vivo; t-cells; langerhans cells; expression; antigen
AB Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs)(1,2). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed(3), activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines(4,5). Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines(6), which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.
C1 [Kasturi, Sudhir Pai; Skountzou, Ioanna; Hua, Tang; Nakaya, Helder I.; Ravindran, Rajesh; Kwissa, Marcin; Villinger, Francois; Jacob, Joshy; Compans, Richard; Pulendran, Bali] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
   [Kasturi, Sudhir Pai; Hua, Tang; Nakaya, Helder I.; Ravindran, Rajesh; Kwissa, Marcin; Villinger, Francois; Jacob, Joshy; Pulendran, Bali] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Skountzou, Ioanna; Koutsonanos, Dimitrios; Jacob, Joshy; Compans, Richard] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
   [Albrecht, Randy A.; Steel, John; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
   [Stewart, Shelley; Alam, Munir] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
   [Villinger, Francois; Pulendran, Bali] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
   [Murthy, Niren] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Hogan, Robert J.] Univ Georgia, Dept Anat & Radiol, Coll Vet Med, Athens, GA 30602 USA.
   [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Dept Med, New York, NY 10029 USA.
   [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
C3 Emory University; Emory University; Emory University; Icahn School of Medicine at Mount Sinai; Duke University; Emory University; University System of Georgia; Georgia Institute of Technology; University System of Georgia; University of Georgia; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Pulendran, B (corresponding author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
EM bpulend@emory.edu
FU National Institutes of Health [U54AI057157, R37AI48638, R01DK057665, U19AI057266, HHSN266200700006C, NO1 AI50025, U19AI090023, HHSN266200700010C, U54AI57158, U01AI070469]; Bill & Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [R01AI048638, U19AI090023, U19AI057266] Funding Source: NIH RePORTER
NR 56
TC 803
Z9 973
U1 2
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 24
PY 2011
VL 470
IS 7335
BP 543
EP U136
DI 10.1038/nature09737
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900044
PM 21350488
DA 2026-03-09
ER

PT J
AU Pasqualucci, L
   Dominguez-Sola, D
   Chiarenza, A
   Fabbri, G
   Grunn, A
   Trifonov, V
   Kasper, LH
   Lerach, S
   Tang, HY
   Ma, J
   Rossi, D
   Chadburn, A
   Murty, VV
   Mullighan, CG
   Gaidano, G
   Rabadan, R
   Brindle, PK
   Dalla-Favera, R
AF Pasqualucci, Laura
   Dominguez-Sola, David
   Chiarenza, Annalisa
   Fabbri, Giulia
   Grunn, Adina
   Trifonov, Vladimir
   Kasper, Lawryn H.
   Lerach, Stephanie
   Tang, Hongyan
   Ma, Jing
   Rossi, Davide
   Chadburn, Amy
   Murty, Vundavalli V.
   Mullighan, Charles G.
   Gaidano, Gianluca
   Rabadan, Raul
   Brindle, Paul K.
   Dalla-Favera, Riccardo
TI Inactivating mutations of acetyltransferase genes in B-cell lymphoma
SO NATURE
LA English
DT Article
ID creb-binding-protein; acute myeloid-leukemia; cycle arrest; cbp; p300; p53; transcription; coactivator; acetylation; hematopoiesis
AB B-cell non-Hodgkin's lymphoma comprises biologically and clinically distinct diseases the pathogenesis of which is associated with genetic lesions affecting oncogenes and tumour-suppressor genes. We report here that the two most common types-follicular lymphoma and diffuse large B-cell lymphoma-harbour frequent structural alterations inactivating CREBBP and, more rarely, EP300, two highly related histone and non-histone acetyltransferases (HATs) that act as transcriptional co-activators in multiple signalling pathways. Overall, about 39% of diffuse large B-cell lymphoma and 41% of follicular lymphoma cases display genomic deletions and/or somatic mutations that remove or inactivate the HAT coding domain of these two genes. These lesions usually affect one allele, suggesting that reduction in HAT dosage is important for lymphomagenesis. We demonstrate specific defects in acetylation-mediated inactivation of the BCL6 oncoprotein and activation of the p53 tumour suppressor. These results identify CREBBP/EP300 mutations as a major pathogenetic mechanism shared by common forms of B-cell non-Hodgkin's lymphoma, with direct implications for the use of drugs targeting acetylation/deacetylation mechanisms.
C1 [Pasqualucci, Laura; Dominguez-Sola, David; Chiarenza, Annalisa; Fabbri, Giulia; Grunn, Adina; Tang, Hongyan; Murty, Vundavalli V.; Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
   [Pasqualucci, Laura; Dominguez-Sola, David; Chiarenza, Annalisa; Fabbri, Giulia; Grunn, Adina; Tang, Hongyan; Murty, Vundavalli V.; Dalla-Favera, Riccardo] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
   [Pasqualucci, Laura; Murty, Vundavalli V.; Dalla-Favera, Riccardo] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Trifonov, Vladimir; Rabadan, Raul] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
   [Trifonov, Vladimir; Rabadan, Raul] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Kasper, Lawryn H.; Lerach, Stephanie; Brindle, Paul K.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA.
   [Ma, Jing] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [Rossi, Davide; Gaidano, Gianluca] Amedeo Avogadro Univ Eastern Piedmont, Div Hematol, Dept Clin & Expt Med, I-28100 Novara, Italy.
   [Rossi, Davide; Gaidano, Gianluca] Amedeo Avogadro Univ Eastern Piedmont, IRCAD, I-28100 Novara, Italy.
   [Chadburn, Amy] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
   [Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Dalla-Favera, Riccardo] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Eastern Piedmont Amedeo Avogadro; University of Eastern Piedmont Amedeo Avogadro; Northwestern University; Feinberg School of Medicine; St Jude Children's Research Hospital; Columbia University
RP Pasqualucci, L (corresponding author), Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
EM lp171@columbia.edu; rd10@columbia.edu
FU NIH [PO1-CA092625, RO1-CA37295, DE018183]; Leukemia and Lymphoma Society; Cancer Center (CORE) [P30 CA021765]; American Lebanese Syrian Associated Charities of St Jude Children's Research Hospital; Northeast Biodefence Center [U54-AI057158]; National Library of Medicine [1R01LM010140-01]; AIRC [10007]; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER
NR 49
TC 747
Z9 876
U1 0
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 189
EP U75
DI 10.1038/nature09730
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200031
PM 21390126
DA 2026-03-09
ER

PT J
AU Tokunaga, F
   Nakagawa, T
   Nakahara, M
   Saeki, Y
   Taniguchi, M
   Sakata, S
   Tanaka, K
   Nakano, H
   Iwai, K
AF Tokunaga, Fuminori
   Nakagawa, Tomoko
   Nakahara, Masaki
   Saeki, Yasushi
   Taniguchi, Masami
   Sakata, Shin-ichi
   Tanaka, Keiji
   Nakano, Hiroyasu
   Iwai, Kazuhiro
TI SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
SO NATURE
LA English
DT Article
ID chronic proliferative dermatitis; incontinentia pigmenti; immune-deficiency; signaling pathway; mutations; nemo; protein; ligase; identification; alpha
AB Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM(1-3), symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-kappa B essential modulator; also known as IKBKG)(4-6). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density)(7) gene are responsible for the cpdm phenotype in mice(8). SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1)(8,9), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-kappa B activation through conjugation of linear polyubiquitin chains to NEMO10-13. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-kappa B. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-alpha- and CD40-mediated activation of NF-kappa B in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-kappa B activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-kappa B activation in various disorders.
C1 [Tokunaga, Fuminori; Nakagawa, Tomoko; Nakahara, Masaki; Taniguchi, Masami; Sakata, Shin-ichi; Iwai, Kazuhiro] Osaka Univ, Grad Sch Med, Dept Biophys & Biochem, Suita, Osaka 5650871, Japan.
   [Saeki, Yasushi; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 1568506, Japan.
   [Nakano, Hiroyasu] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1138421, Japan.
   [Iwai, Kazuhiro] Osaka Univ, Grad Sch Frontier Biosci, Cell Biol & Metab Grp, Suita, Osaka 5650871, Japan.
C3 University of Osaka; Tokyo Metropolitan Institute of Medical Science; Juntendo University; University of Osaka
RP Iwai, K (corresponding author), Osaka Univ, Grad Sch Med, Dept Biophys & Biochem, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM kiwai@cellbio.med.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan; Grants-in-Aid for Scientific Research [21000012, 23659404, 23657075, 22117006] Funding Source: KAKEN
NR 26
TC 530
Z9 588
U1 1
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 633
EP U113
DI 10.1038/nature09815
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200042
PM 21455180
DA 2026-03-09
ER

PT J
AU Rios, AC
   Serralbo, O
   Salgado, D
   Marcelle, C
AF Rios, Anne C.
   Serralbo, Olivier
   Salgado, David
   Marcelle, Christophe
TI Neural crest regulates myogenesis through the transient activation of NOTCH
SO NATURE
LA English
DT Article
ID dermomyotome dorsomedial lip; progenitor cells; gene-expression; muscle; differentiation; maintenance; population; inhibition; movements; mechanism
AB How dynamic signalling and extensive tissue rearrangements interact to generate complex patterns and shapes during embryogenesis is poorly understood(1-3). Here we characterize the signalling events taking place during early morphogenesis of chick skeletal muscles. We show that muscle progenitors present in somites require the transient activation of NOTCH signalling to undergo terminal differentiation. The NOTCH ligand Delta1 is expressed in a mosaic pattern in neural crest cells that migrate past the somites. Gain and loss of Delta1 function in neural crest modifies NOTCH signalling in somites, which results in delayed or premature myogenesis. Our results indicate that the neural crest regulates early muscle formation by a unique mechanism that relies on the migration of Delta1-expressing neural crest cells to trigger the transient activation of NOTCH signalling in selected muscle progenitors. This dynamic signalling guarantees a balanced and progressive differentiation of the muscle progenitor pool.
C1 [Rios, Anne C.; Serralbo, Olivier; Salgado, David; Marcelle, Christophe] Monash Univ, EMBL Australia, Clayton, Vic 3800, Australia.
   [Rios, Anne C.; Serralbo, Olivier; Salgado, David; Marcelle, Christophe] Monash Univ, ARMI, Clayton, Vic 3800, Australia.
C3 European Molecular Biology Laboratory (EMBL); EMBL Australia; Monash University; Monash University; Australian Regenerative Medicine Institute
RP Marcelle, C (corresponding author), Monash Univ, EMBL Australia, Bldg 75, Clayton, Vic 3800, Australia.
EM christophe.marcelle@monash.edu
FU Agence Nationale pour le Recherche (ANR); EU
NR 41
TC 125
Z9 151
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 532
EP U279
DI 10.1038/nature09970
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300045
PM 21572437
DA 2026-03-09
ER

PT J
AU Peça, J
   Feliciano, C
   Ting, JT
   Wang, WT
   Wells, MF
   Venkatraman, TN
   Lascola, CD
   Fu, ZY
   Feng, GP
AF Peca, Joao
   Feliciano, Catia
   Ting, Jonathan T.
   Wang, Wenting
   Wells, Michael F.
   Venkatraman, Talaignair N.
   Lascola, Christopher D.
   Fu, Zhanyan
   Feng, Guoping
TI Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
SO NATURE
LA English
DT Article
ID 22q13 deletion syndrome; spectrum disorders; synaptic-transmission; mutations; protein; brain; gene; neuroligins; sapaps; family
AB Autismspectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.
C1 [Peca, Joao; Feliciano, Catia; Ting, Jonathan T.; Wang, Wenting; Wells, Michael F.; Lascola, Christopher D.; Fu, Zhanyan; Feng, Guoping] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
   [Peca, Joao] Univ Coimbra, Ctr Neurosci & Cell Biol, PhD Programme Biomed & Expt Biol, Coimbra, Portugal.
   [Feliciano, Catia] Gulbenkian Inst Sci, Gulbenkian PhD Programme Biomed, P-2781901 Oeiras, Portugal.
   [Venkatraman, Talaignair N.; Lascola, Christopher D.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
   [Venkatraman, Talaignair N.; Lascola, Christopher D.] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA.
   [Fu, Zhanyan] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
   [Fu, Zhanyan; Feng, Guoping] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Feng, Guoping] Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02142 USA.
C3 Duke University; Universidade de Coimbra; Duke University; Duke University; Duke University; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Feng, GP (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
EM fengg@mit.edu
FU NIMH/NIH [R01MH081201]; Hartwell Foundation; Simons Foundation Autism Research Initiative (SFARI); NARSAD; NIH [F32MH084460, R03MH085224]; Portuguese Foundation for Science and Technology [SFRH/BD/15231/2004, SFRH/BD/15855/2005]; "Programa Gulbenkian de Doutoramento em Biomedicina'' (PGDB, Oeiras, Portugal); "Programa Doutoral em Biologia Experimental e Biomedicina'' (CNC, Coimbra, Portugal); Fundação para a Ciência e a Tecnologia [SFRH/BD/15231/2004, SFRH/BD/15855/2005] Funding Source: FCT
NR 42
TC 1206
Z9 1459
U1 7
U2 164
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 437
EP U534
DI 10.1038/nature09965
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600027
PM 21423165
DA 2026-03-09
ER

PT J
AU Venkatachalam, V
   Yacoby, A
   Pfeiffer, L
   West, K
AF Venkatachalam, Vivek
   Yacoby, Amir
   Pfeiffer, Loren
   West, Ken
TI Local charge of the v = 5/2 fractional quantum Hall state
SO NATURE
LA English
DT Article
ID localization
AB Electrons moving in two dimensions under the influence of strong magnetic fields effectively lose their kinetic energy and display exotic behaviour dominated by Coulomb forces. When the ratio of electrons to magnetic flux quanta in the system (nu) is near 5/2, the electrons are predicted to condense into a correlated phase with fractionally charged quasiparticles and a ground-state degeneracy that grows exponentially as these quasiparticles are introduced(1). The only way for electrons to transform between the many ground states would be to braid the fractional excitations around each other. This property has been proposed as the basis of a fault-tolerant quantum computer(2). Here we present observations of localized quasiparticles at nu = 5/2, confined to puddles by disorder. Using a local electrometer to compare how quasiparticles at nu = 5/2 and nu = 7/3 charge these puddles, we were able to extract the ratio of local charges for these states. Averaged over several disorder configurations and samples, we found the ratio to be 4/3, suggesting that the local charges are e(7/3)* = e/3 and e(5/2)* = e/4, where e is the charge of an electron. This is in agreement with theoretical predictions for a paired state at nu = 5/2. Confirming the existence of localized e/4 quasiparticles shows that proposed interferometry experiments to test statistics and computational ability of the state at nu = 5/2 would be possible.
C1 [Venkatachalam, Vivek; Yacoby, Amir] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Pfeiffer, Loren; West, Ken] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
C3 Harvard University; Princeton University
RP Yacoby, A (corresponding author), Harvard Univ, Dept Phys, 11 Oxford St, Cambridge, MA 02138 USA.
EM yacoby@physics.harvard.edu
FU Microsoft Corporation; National Science Foundation
NR 16
TC 84
Z9 105
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 185
EP 188
DI 10.1038/nature09680
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400032
PM 21228871
DA 2026-03-09
ER

PT J
AU McLean, CY
   Reno, PL
   Pollen, AA
   Bassan, AI
   Capellini, TD
   Guenther, C
   Indjeian, VB
   Lim, XH
   Menke, DB
   Schaar, BT
   Wenger, AM
   Bejerano, G
   Kingsley, DM
AF McLean, Cory Y.
   Reno, Philip L.
   Pollen, Alex A.
   Bassan, Abraham I.
   Capellini, Terence D.
   Guenther, Catherine
   Indjeian, Vahan B.
   Lim, Xinhong
   Menke, Douglas B.
   Schaar, Bruce T.
   Wenger, Aaron M.
   Bejerano, Gill
   Kingsley, David M.
TI Human-specific loss of regulatory DNA and the evolution of human-specific traits
SO NATURE
LA English
DT Article
ID human genome; gene; testosterone; chimpanzees; expression; patterns; thalamus; sequence; enhancer; area
AB Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown(1). Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes(2-5). Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species(6-8). Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage(9,10). Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G)(11,12), a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations(6-8) and inactivation events(13) long proposed to have an important role in human evolutionary divergence.
C1 [McLean, Cory Y.; Wenger, Aaron M.; Bejerano, Gill] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
   [Reno, Philip L.; Pollen, Alex A.; Bassan, Abraham I.; Capellini, Terence D.; Guenther, Catherine; Indjeian, Vahan B.; Lim, Xinhong; Menke, Douglas B.; Schaar, Bruce T.; Bejerano, Gill; Kingsley, David M.] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA.
   [Reno, Philip L.; Guenther, Catherine; Indjeian, Vahan B.; Menke, Douglas B.; Kingsley, David M.] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Bejerano, G (corresponding author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
EM bejerano@stanford.edu; kingsley@stanford.edu
FU Bio-X graduate fellowship; Ruth L. Kirschstein NRSA [1 F32 HD062137-01]; National Defense Science and Engineering; Agency of Science, Technology, and Research, Singapore; Stanford Graduate Fellowship; Edward Mallinckrodt, Jr. Foundation; National Institute of Health [R01 HD059862, R01 HG005058, P50 HG002568]
NR 30
TC 368
Z9 466
U1 2
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 216
EP 219
DI 10.1038/nature09774
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200037
PM 21390129
DA 2026-03-09
ER

PT J
AU Snyder, SA
   Gollner, A
   Chiriac, MI
AF Snyder, Scott A.
   Gollner, Andreas
   Chiriac, Maria I.
TI Regioselective reactions for programmable resveratrol oligomer synthesis
SO NATURE
LA English
DT Article
ID caragana-sinica; stem bark; 4-hydroxystilbenes; oligostilbenes; products; dimers; plants
AB Although much attention has been devoted to resveratrol, a unique polyphenol produced by plants and credited as potentially being responsible for the 'French paradox'-the observation that French people have a relatively low incidence of coronary heart disease, even though their diet is high in saturated fats-the oligomers of resveratrol have been largely ignored despite their high biological activity. Challenges in achieving their isolation in sufficient quantity from natural sources, coupled with an inability to prepare them easily synthetically, are seen as the main obstacles. Here we report a programmable, controlled and potentially scalable synthesis of the resveratrol family via a three-stage design. The synthetic approach requires strategy- and reagent-guided chemical functionalizations to differentiate two distinct cores possessing multiple sites with the same or similar reactivity, ultimately leading to five higher-order natural products. This work demonstrates that challenging, positionally selective functionalizations of complex materials are possible where biosynthetic studies have indicated otherwise, it provides materials and tools with which to unlock the full biochemical potential of this family of natural products, and it affords an intellectual framework within which other oligomeric families could potentially be accessed.
C1 [Snyder, Scott A.; Gollner, Andreas; Chiriac, Maria I.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
C3 Columbia University
RP Snyder, SA (corresponding author), Columbia Univ, Dept Chem, Havemeyer Hall,3000 Broadway, New York, NY 10027 USA.
EM sas2197@columbia.edu
FU Columbia University; National Institutes of Health [R01-GM84994]; Bristol-Myers Squibb; Eli Lilly; Research Corporation for Science Advancement; Austrian Science Fund (FWF) [J2986-N19]
NR 45
TC 178
Z9 207
U1 1
U2 92
PU 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 23
PY 2011
VL 474
IS 7352
BP 461
EP 466
DI 10.1038/nature10197
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700038
PM 21697944
DA 2026-03-09
ER

PT J
AU Hermelin, S
   Takada, S
   Yamamoto, M
   Tarucha, S
   Wieck, AD
   Saminadayar, L
   Bäuerle, C
   Meunier, T
AF Hermelin, Sylvain
   Takada, Shintaro
   Yamamoto, Michihisa
   Tarucha, Seigo
   Wieck, Andreas D.
   Saminadayar, Laurent
   Baeuerle, Christopher
   Meunier, Tristan
TI Electrons surfing on a sound wave as a platform for quantum optics with flying electrons
SO NATURE
LA English
DT Article
ID teleportation; interference; transport; spin; dots
AB Electrons in a metal are indistinguishable particles that interact strongly with other electrons and their environment. Isolating and detecting a single flying electron after propagation, in a similar manner to quantum optics experiments with single photons(1,2), is therefore a challenging task. So far only a few experiments have been performed in a high-mobility two-dimensional electron gas in which the electron propagates almost ballistically(3-5). In these previous works, flying electrons were detected by means of the current generated by an ensemble of electrons, and electron correlations were encrypted in the current noise. Here we demonstrate the experimental realization of high-efficiency single-electron source and detector for a single electron propagating isolated from the other electrons through a one-dimensional channel. The moving potential is excited by a surface acoustic wave, which carries the single electron along the one-dimensional channel at a speed of 3 mu m ns(-1). When this quantum channel is placed between two quantum dots several micrometres apart, a single electron can be transported from one quantum dot to the other with quantum efficiencies of emission and detection of 96% and 92%, respectively. Furthermore, the transfer of the electron can be triggered on a timescale shorter than the coherence time T-2* of GaAs spin qubits(6). Our work opens new avenues with which to study the teleportation of a single electron spin and the distant interaction between spatially separated qubits in a condensed-matter system.
C1 [Hermelin, Sylvain; Saminadayar, Laurent; Baeuerle, Christopher; Meunier, Tristan] CNRS, Inst Neel, F-38042 Grenoble, France.
   [Hermelin, Sylvain; Saminadayar, Laurent; Baeuerle, Christopher; Meunier, Tristan] Univ Grenoble 1, F-38042 Grenoble, France.
   [Takada, Shintaro; Yamamoto, Michihisa; Tarucha, Seigo] Univ Tokyo, Dept Appl Phys, Tokyo 1138656, Japan.
   [Yamamoto, Michihisa] ERATO JST, Kawaguchi, Saitama 3310012, Japan.
   [Tarucha, Seigo] ICORP Int Cooperat Res Project Quantum Spin Infor, Atsugi, Kanagawa 2430198, Japan.
   [Wieck, Andreas D.] Ruhr Univ Bochum, Lehrstuhl Angew Festkorperphys, D-44780 Bochum, Germany.
   [Saminadayar, Laurent] Inst Univ France, F-75005 Paris, France.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); University of Tokyo; Japan Science & Technology Agency (JST); Ruhr University Bochum; Institut Universitaire de France
RP Bäuerle, C (corresponding author), CNRS, Inst Neel, F-38042 Grenoble, France.
EM bauerle@grenoble.cnrs.fr; tristan.meunier@grenoble.cnrs.fr
FU ERATO-JST [080300000477]; Special Coordination Funds for Promoting Science and Technology (NanoQuine); Japan Science and Technology Agency Strategic International Cooperative Program; Japanese Ministry of Education, Culture, Sports, Science, and Technology; Harvard University; Deutsche Forschungsgemeinschaft [SPP1285]; Bundesministerium fur Bildung und Forschung [QuaHLRep 01BQ1035]; Centre National de la Recherche Scientifique (DREI) - Japan Society for the Promotion of Science [PRC 424, L08519]; Marie-Curie European Reintegration Grant [224786]; Nanoscience Foundation of Grenoble;  [20684011]; Grants-in-Aid for Scientific Research [11J09061, 21102003] Funding Source: KAKEN
NR 24
TC 272
Z9 292
U1 1
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 435
EP 438
DI 10.1038/nature10416
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500034
PM 21938064
DA 2026-03-09
ER

PT J
AU Chan, J
   Alegre, TPM
   Safavi-Naeini, AH
   Hill, JT
   Krause, A
   Gröblacher, S
   Aspelmeyer, M
   Painter, O
AF Chan, Jasper
   Mayer Alegre, T. P.
   Safavi-Naeini, Amir H.
   Hill, Jeff T.
   Krause, Alex
   Groeblacher, Simon
   Aspelmeyer, Markus
   Painter, Oskar
TI Laser cooling of a nanomechanical oscillator into its quantum ground state
SO NATURE
LA English
DT Article
ID radiation-pressure; optomechanical crystals; mechanical resonator; cavity; motion; micromirror
AB The simple mechanical oscillator, canonically consisting of a coupled mass-spring system, is used in a wide variety of sensitive measurements, including the detection of weak forces(1) and small masses(2). On the one hand, a classical oscillator has a well-defined amplitude of motion; a quantum oscillator, on the other hand, has a lowest-energy state, or ground state, with a finite-amplitude uncertainty corresponding to zero-point motion. On the macroscopic scale of our everyday experience, owing to interactions with its highly fluctuating thermal environment a mechanical oscillator is filled with many energy quanta and its quantum nature is all but hidden. Recently, in experiments performed at temperatures of a few hundredths of a kelvin, engineered nanomechanical resonators coupled to electrical circuits have been measured to be oscillating in their quantum ground state(3,4). These experiments, in addition to providing a glimpse into the underlying quantum behaviour of mesoscopic systems consisting of billions of atoms, represent the initial steps towards the use of mechanical devices as tools for quantum metrology(5,6) or as a means of coupling hybrid quantum systems(7-9). Here we report the development of a coupled, nanoscale optical and mechanical resonator(10) formed in a silicon microchip, in which radiation pressure from a laser is used to cool the mechanical motion down to its quantum ground state (reaching an average phonon occupancy number of 0.85 +/- 0.08). This cooling is realized at an environmental temperature of 20 K, roughly one thousand times larger than in previous experiments and paves the way for optical control of mesoscale mechanical oscillators in the quantum regime.
C1 [Chan, Jasper; Mayer Alegre, T. P.; Safavi-Naeini, Amir H.; Hill, Jeff T.; Krause, Alex; Groeblacher, Simon; Painter, Oskar] CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
   [Groeblacher, Simon; Aspelmeyer, Markus] Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol VCQ, A-1090 Vienna, Austria.
C3 California Institute of Technology; University of Vienna
RP Painter, O (corresponding author), CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
EM opainter@caltech.edu
FU DARPA/MTO through the AFOSR; European Commission (MINOS, QUESSENCE); European Research Council (ERC QOM); Austrian Science Fund (CoQuS, FOQUS, START); Kavli Nanoscience Institute at the California Institute of Technology; NSERC; Austrian Science Fund (FWF) [Y 414] Funding Source: researchfish; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 30
TC 1972
Z9 2230
U1 8
U2 496
PU 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 6
PY 2011
VL 478
IS 7367
BP 89
EP 92
DI 10.1038/nature10461
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400040
PM 21979049
DA 2026-03-09
ER

PT J
AU Joron, M
   Frezal, L
   Jones, RT
   Chamberlain, NL
   Lee, SF
   Haag, CR
   Whibley, A
   Becuwe, M
   Baxter, SW
   Ferguson, L
   Wilkinson, PA
   Salazar, C
   Davidson, C
   Clark, R
   Quail, MA
   Beasley, H
   Glithero, R
   Lloyd, C
   Sims, S
   Jones, MC
   Rogers, J
   Jiggins, CD
   Ffrench-Constant, RH
AF Joron, Mathieu
   Frezal, Lise
   Jones, Robert T.
   Chamberlain, Nicola L.
   Lee, Siu F.
   Haag, Christoph R.
   Whibley, Annabel
   Becuwe, Michel
   Baxter, Simon W.
   Ferguson, Laura
   Wilkinson, Paul A.
   Salazar, Camilo
   Davidson, Claire
   Clark, Richard
   Quail, Michael A.
   Beasley, Helen
   Glithero, Rebecca
   Lloyd, Christine
   Sims, Sarah
   Jones, Matthew C.
   Rogers, Jane
   Jiggins, Chris D.
   Ffrench-Constant, Richard H.
TI Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry
SO NATURE
LA English
DT Article
ID gene flow; papilio-dardanus; evolution; sequence; inversions; linkage; vista
AB Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes(1). Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for 'pin' and 'thrum' floral types in Primula(1) and Fagopyrum(2), but classic examples are also found in insect mimicry(3-5) and snail morphology(6). Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge(7-10). Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species(9-11), with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the P locus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow.
C1 [Joron, Mathieu; Frezal, Lise; Whibley, Annabel] CNRS, Museum Natl Hist Nat, UMR 7205, F-75005 Paris, France.
   [Joron, Mathieu; Becuwe, Michel] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Joron, Mathieu] Leiden Univ, Inst Biol, NL-2300 RA Leiden, Netherlands.
   [Jones, Robert T.; Chamberlain, Nicola L.; Wilkinson, Paul A.; Ffrench-Constant, Richard H.] Univ Exeter, Sch Biosci, Ctr Ecol & Conservat, Penryn TR10 9EZ, Cornwall, England.
   [Lee, Siu F.] Univ Melbourne, Inst Bio21, Dept Genet, Parkville, Vic 3010, Australia.
   [Haag, Christoph R.] Univ Fribourg, Dept Ecol & Evolut Biol, CH-1700 Fribourg, Switzerland.
   [Baxter, Simon W.; Ferguson, Laura; Jiggins, Chris D.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Salazar, Camilo] NAOS Isl, Smithsonian Trop Res Inst, Panama City, Panama.
   [Davidson, Claire; Clark, Richard; Quail, Michael A.; Beasley, Helen; Glithero, Rebecca; Lloyd, Christine; Sims, Sarah; Jones, Matthew C.; Rogers, Jane] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Museum National d'Histoire Naturelle (MNHN); Sorbonne Universite; University of Edinburgh; Leiden University; Leiden University - Excl LUMC; University of Exeter; University of Melbourne; University of Fribourg; University of Cambridge; Smithsonian Institution; Smithsonian Tropical Research Institute; Wellcome Trust Sanger Institute
RP Joron, M (corresponding author), CNRS, Museum Natl Hist Nat, UMR 7205, CP50,45 Rue Buffon, F-75005 Paris, France.
EM joron@mnhn.fr
FU CNRS; EMBO [ALTF-431-2004]; Royal Society [516002.K5917/ROG]; European Research Council; BBSRC [BBE0118451]; Leverhulme Trust [F/00144AY)]; Leverhulme Research Leadership grant; Biotechnology and Biological Sciences Research Council [BB/E006191/1, BB/H014268/1, BB/E008836/1] Funding Source: researchfish; Medical Research Council [G0900740] Funding Source: researchfish; Natural Environment Research Council [NE/D000114/2, NBAF010003] Funding Source: researchfish; BBSRC [BB/E006191/1, BB/H014268/1, BB/E008836/1] Funding Source: UKRI; MRC [G0900740] Funding Source: UKRI; NERC [NBAF010003, NE/D000114/2] Funding Source: UKRI
NR 42
TC 438
Z9 493
U1 2
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 SEP 8
PY 2011
VL 477
IS 7363
BP 203
EP U102
DI 10.1038/nature10341
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900034
PM 21841803
DA 2026-03-09
ER

PT J
AU Van Roy, P
   Briggs, DEG
AF Van Roy, Peter
   Briggs, Derek E. G.
TI A giant Ordovician anomalocaridid
SO NATURE
LA English
DT Article
ID great-appendage arthropod; burgess shale; dinocarida; greenland; evolution; opabinia
AB Anomalocaridids, giant lightly sclerotized invertebrate predators, occur in a number of exceptionally preserved early and middle Cambrian (542-501 million years ago) biotas and have come to symbolize the unfamiliar morphologies displayed by stem organisms in faunas of the Burgess Shale type. They are characterized by a pair of anterior, segmented appendages, a circlet of plates around the mouth, and an elongate segmented trunk lacking true tergites with a pair of flexible lateral lobes per segment(1,2). Disarticulated body parts, such as the anterior appendages and oral circlet, had been assigned to a range of taxonomic groups-but the discovery of complete specimens from the middle Cambrian Burgess Shale showed that these disparate elements all belong to a single kind of animal(3). Phylogenetic analyses support a position of anomalocaridids in the arthropod stem, as a sister group to the euarthropods(4-6). The anomalocaridids were the largest animals in Cambrian communities. The youngest unequivocal examples occur in the middle Cambrian Marjum Formation of Utah(7) but an arthropod retaining some anomalocaridid characteristics is present in the Devonian of Germany(5). Here we report the post-Cambrian occurrence of anomalocaridids, from the Early Ordovician (488-472 million years ago) Fezouata Biota(8) in southeastern Morocco, including specimens larger than any in Cambrian biotas. These giant animals were an important element of some marine communities for about 30 million years longer than previously realized. The Moroccan specimens confirm the presence of a dorsal array of flexible blades attached to a transverse rachis on the trunk segments; these blades probably functioned as gills.
C1 [Van Roy, Peter; Briggs, Derek E. G.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Van Roy, Peter] Univ Ghent, Dept Geol & Soil Sci, Res Unit Palaeontol, B-9000 Ghent, Belgium.
   [Briggs, Derek E. G.] Yale Univ, Yale Peabody Museum Nat Hist, New Haven, CT 06520 USA.
C3 Yale University; Ghent University; Yale University
RP Briggs, DEG (corresponding author), Yale Univ, Dept Geol & Geophys, POB 208109, New Haven, CT 06520 USA.
EM derek.briggs@yale.edu
FU National Geographic Society; Yale University
NR 30
TC 82
Z9 85
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 510
EP 513
DI 10.1038/nature09920
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300040
PM 21614078
DA 2026-03-09
ER

PT J
AU Steidl, C
   Shah, SP
   Woolcock, BW
   Rui, LX
   Kawahara, M
   Farinha, P
   Johnson, NA
   Zhao, YJ
   Telenius, A
   Ben Neriah, S
   McPherson, A
   Meissner, B
   Okoye, UC
   Diepstra, A
   van den Berg, A
   Sun, M
   Leung, G
   Jones, SJ
   Connors, JM
   Huntsman, DG
   Savage, KJ
   Rimsza, LM
   Horsman, DE
   Staudt, LM
   Steidl, U
   Marra, MA
   Gascoyne, RD
AF Steidl, Christian
   Shah, Sohrab P.
   Woolcock, Bruce W.
   Rui, Lixin
   Kawahara, Masahiro
   Farinha, Pedro
   Johnson, Nathalie A.
   Zhao, Yongjun
   Telenius, Adele
   Ben Neriah, Susana
   McPherson, Andrew
   Meissner, Barbara
   Okoye, Ujunwa C.
   Diepstra, Arjan
   van den Berg, Anke
   Sun, Mark
   Leung, Gillian
   Jones, Steven J.
   Connors, Joseph M.
   Huntsman, David G.
   Savage, Kerry J.
   Rimsza, Lisa M.
   Horsman, Douglas E.
   Staudt, Louis M.
   Steidl, Ulrich
   Marra, Marco A.
   Gascoyne, Randy D.
TI MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
SO NATURE
LA English
DT Article
ID b-cell lymphoma; poor patient survival; reed-sternberg cells; hodgkin lymphoma; protein expression; line; jak2; translocation; aberrations; resolution
AB Chromosomal translocations are critically involved in the molecular pathogenesis of B-cell lymphomas, and highly recurrent and specific rearrangements have defined distinct molecular subtypes linked to unique clinicopathological features(1,2). In contrast, several well-characterized lymphoma entities still lack disease-defining translocation events. To identify novel fusion transcripts resulting from translocations, we investigated two Hodgkin lymphoma cell lines by whole-transcriptome paired-end sequencing (RNA-seq). Here we show a highly expressed gene fusion involving the major histocompatibility complex (MHC) class II transactivator CIITA (MHC2TA) in KM-H2 cells. In a subsequent evaluation of 263 B-cell lymphomas, we also demonstrate that genomic CIITA breaks are highly recurrent in primary mediastinal B-cell lymphoma (38%) and classical Hodgkin lymphoma (cHL) (15%). Furthermore, we find that CIITA is a promiscuous partner of various in-frame gene fusions, and we report that CIITA gene alterations impact survival in primary mediastinal B-cell lymphoma (PMBCL). As functional consequences of CIITA gene fusions, we identify downregulation of surface HLA class II expression and overexpression of ligands of the receptor molecule programmed cell death 1 (CD274/PDL1 and CD273/PDL2). These receptor-ligand interactions have been shown to impact anti-tumour immune responses in several cancers(3), whereas decreased MHC class II expression has been linked to reduced tumour cell immunogenicity(4). Thus, our findings suggest that recurrent rearrangements of CIITA may represent a novel genetic mechanism underlying tumour-microenvironment interactions across a spectrum of lymphoid cancers.
C1 [Steidl, Christian; Shah, Sohrab P.; Woolcock, Bruce W.; Farinha, Pedro; Johnson, Nathalie A.; Telenius, Adele; Ben Neriah, Susana; McPherson, Andrew; Meissner, Barbara; Sun, Mark; Leung, Gillian; Huntsman, David G.; Horsman, Douglas E.; Gascoyne, Randy D.] Ctr Lymphoid Cancers, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada.
   [Steidl, Christian; Shah, Sohrab P.; Woolcock, Bruce W.; Farinha, Pedro; Johnson, Nathalie A.; Telenius, Adele; Ben Neriah, Susana; McPherson, Andrew; Meissner, Barbara; Sun, Mark; Leung, Gillian; Huntsman, David G.; Horsman, Douglas E.; Gascoyne, Randy D.] Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada.
   [Rui, Lixin; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Kawahara, Masahiro; Okoye, Ujunwa C.; Steidl, Ulrich] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
   [Kawahara, Masahiro; Okoye, Ujunwa C.; Steidl, Ulrich] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
   [Zhao, Yongjun; Jones, Steven J.; Marra, Marco A.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
   [Diepstra, Arjan; van den Berg, Anke] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9700 AB Groningen, Netherlands.
   [Connors, Joseph M.; Savage, Kerry J.] BC Canc Agcy Ctr Lymphoid Canc, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
   [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
   [Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; British Columbia Cancer Agency; University of Groningen; British Columbia Cancer Agency; University of Arizona; University of British Columbia
RP Gascoyne, RD (corresponding author), Ctr Lymphoid Cancers, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada.
EM rgascoyn@bccancer.bc.ca
FU Cancer Research Society; Michael Smith Foundation for Health Research; Lymphoma Research Foundation; Canadian Breast Cancer Foundation; Canadian Institutes of Health Research [178536]; Terry Fox Foundation [019001]; Genome Canada/Genome BC; National Institutes of Health/National Cancer Institute [R00CA131503]; Leukemia Research Foundation; National Health and Medical Research Council of Australia; National Cancer Institute [ZIABC011006, ZIABC011008] Funding Source: NIH RePORTER
NR 41
TC 478
Z9 537
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 MAR 17
PY 2011
VL 471
IS 7338
BP 377
EP +
DI 10.1038/nature09754
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000045
PM 21368758
DA 2026-03-09
ER

PT J
AU Umena, Y
   Kawakami, K
   Shen, JR
   Kamiya, N
AF Umena, Yasufumi
   Kawakami, Keisuke
   Shen, Jian-Ren
   Kamiya, Nobuo
TI Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å
SO NATURE
LA English
DT Article
ID diffraction data; water; binding; protein; mechanism; oxidation; manganese; channels; cluster; crystallography
AB Photosystem II is the site of photosynthetic water oxidation and contains 20 subunits with a total molecular mass of 350 kDa. The structure of photosystem II has been reported at resolutions from 3.8 to 2.9 angstrom. These resolutions have provided much information on the arrangement of protein subunits and cofactors but are insufficient to reveal the detailed structure of the catalytic centre of water splitting. Here we report the crystal structure of photosystem II at a resolution of 1.9 angstrom. From our electron density map, we located all of the metal atoms of the Mn4CaO5 cluster, together with all of their ligands. We found that five oxygen atoms served as oxo bridges linking the five metal atoms, and that four water molecules were bound to the Mn4CaO5 cluster; some of them may therefore serve as substrates for dioxygen formation. We identified more than 1,300 water molecules in each photosystem II monomer. Some of them formed extensive hydrogen-bonding networks that may serve as channels for protons, water or oxygen molecules. The determination of the high-resolution structure of photosystem II will allow us to analyse and understand its functions in great detail.
C1 [Kawakami, Keisuke; Shen, Jian-Ren] Okayama Univ, Fac Sci, Grad Sch Nat Sci & Technol, Div Biosci, Okayama 7008530, Japan.
   [Umena, Yasufumi; Kamiya, Nobuo] Osaka City Univ, Grad Sch Sci, Dept Chem, Osaka 5588585, Japan.
C3 Okayama University; Osaka Metropolitan University
RP Shen, JR (corresponding author), Okayama Univ, Fac Sci, Grad Sch Nat Sci & Technol, Div Biosci, Okayama 7008530, Japan.
EM shen@cc.okayama-u.ac.jp; nkamiya@sci.osaka-cu.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Yamada Science foundation; Grants-in-Aid for Scientific Research [10J02491] Funding Source: KAKEN
NR 40
TC 3336
Z9 3801
U1 20
U2 1365
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 55
EP U65
DI 10.1038/nature09913
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300029
PM 21499260
DA 2026-03-09
ER

PT J
AU Koch, P
   Breuer, P
   Peitz, M
   Jungverdorben, J
   Kesavan, J
   Poppe, D
   Doerr, J
   Ladewig, J
   Mertens, J
   Tüting, T
   Hoffmann, P
   Klockgether, T
   Evert, BO
   Wüllner, U
   Brüstle, O
AF Koch, Philipp
   Breuer, Peter
   Peitz, Michael
   Jungverdorben, Johannes
   Kesavan, Jaideep
   Poppe, Daniel
   Doerr, Jonas
   Ladewig, Julia
   Mertens, Jerome
   Tueting, Thomas
   Hoffmann, Per
   Klockgether, Thomas
   Evert, Bernd O.
   Wuellner, Ullrich
   Bruestle, Oliver
TI Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease
SO NATURE
LA English
DT Article
ID polyglutamine-expanded ataxin-3; in-vitro; cleavage; expansion; model; neurodegeneration; proteolysis; inclusions; disorders; proteins
AB Machado-Joseph disease (MJD; also called spinocerebellar ataxia type 3) is a dominantly inherited late-onset neurodegenerative disorder caused by expansion of polyglutamine (polyQ)-encoding CAG repeats in the MJD1 gene (also known as ATXN3). Proteolytic liberation of highly aggregation-prone polyQ fragments from the protective sequence of the MJD1 gene product ataxin 3 (ATXN3) has been proposed to trigger the formation of ATXN3-containing aggregates, the neuropathological hallmark of MJD(1-5). ATXN3 fragments are detected in brain tissue of MJD patients and transgenic mice expressing mutant human ATXN3(Q71)(6), and their amount increases with disease severity, supporting a relationship between ATXN3 processing and disease progression. The formation of early aggregation intermediates is thought to have a critical role in disease initiation(7,8), but the precise pathogenic mechanism operating in MJD has remained elusive(9). Here we show that L-glutamate-induced excitation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons initiates Ca2+-dependent proteolysis of ATXN3 followed by the formation of SDS-insoluble aggregates. This phenotype could be abolished by calpain inhibition, confirming a key role of this protease in ATXN3 aggregation. Aggregate formation was further dependent on functional Na+ and K+ channels as well as ionotropic and voltage-gated Ca2+ channels, and was not observed in iPSCs, fibroblasts or glia, thereby providing an explanation for the neuron-specific phenotype of this disease. Our data illustrate that iPSCs enable the study of aberrant protein processing associated with late-onset neurodegenerative disorders in patient-specific neurons.
C1 [Koch, Philipp; Peitz, Michael; Jungverdorben, Johannes; Kesavan, Jaideep; Poppe, Daniel; Doerr, Jonas; Ladewig, Julia; Mertens, Jerome; Bruestle, Oliver] Univ Bonn, Inst Reconstruct Neurobiol, Life & Brain Ctr, D-53127 Bonn, Germany.
   [Koch, Philipp; Peitz, Michael; Jungverdorben, Johannes; Kesavan, Jaideep; Poppe, Daniel; Doerr, Jonas; Ladewig, Julia; Mertens, Jerome; Bruestle, Oliver] Hertie Fdn, D-53127 Bonn, Germany.
   [Breuer, Peter; Klockgether, Thomas; Evert, Bernd O.; Wuellner, Ullrich] Univ Bonn, Med Ctr, Dept Neurol, D-53105 Bonn, Germany.
   [Tueting, Thomas] Univ Bonn, Med Ctr, Dept Dermatol, D-53127 Bonn, Germany.
   [Hoffmann, Per] Univ Bonn, Life & Brain Ctr, Inst Human Genet, D-53127 Bonn, Germany.
   [Hoffmann, Per] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
   [Klockgether, Thomas] German Ctr Neurodegenerat Dis, DZNE, D-53175 Bonn, Germany.
C3 University of Bonn; University of Bonn; University of Bonn; University of Bonn; University of Bonn; Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE)
RP Brüstle, O (corresponding author), Univ Bonn, Inst Reconstruct Neurobiol, Life & Brain Ctr, D-53127 Bonn, Germany.
EM brustle@uni-bonn.de
FU German Federal Ministry for Education and Research (BMBF) [01GNO813, 01GS0860]; European Union [LSHG-CT-2006-018739, HEALTH-F5-2010-266753]; Deutsche Forschungsgemeinschaft [WU 184/6-1, EV143/1-1]; BONFOR; Hertie Foundation
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   Williams AJ, 2008, TRENDS NEUROSCI, V31, P521, DOI 10.1016/j.tins.2008.07.004
   Williams AJ, 2009, NEUROBIOL DIS, V33, P342, DOI 10.1016/j.nbd.2008.10.016
   Yoo SY, 2003, NEURON, V37, P383, DOI 10.1016/S0896-6273(02)01190-X
NR 25
TC 258
Z9 298
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 DEC 22
PY 2011
VL 480
IS 7378
BP 543
EP U170
DI 10.1038/nature10671
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000065
PM 22113611
DA 2026-03-09
ER

PT J
AU Diep, CQ
   Ma, DD
   Deo, RC
   Holm, TM
   Naylor, RW
   Arora, N
   Wingert, RA
   Bollig, F
   Djordjevic, G
   Lichman, B
   Zhu, H
   Ikenaga, T
   Ono, F
   Englert, C
   Cowan, CA
   Hukriede, NA
   Handin, RI
   Davidson, AJ
AF Diep, Cuong Q.
   Ma, Dongdong
   Deo, Rahul C.
   Holm, Teresa M.
   Naylor, Richard W.
   Arora, Natasha
   Wingert, Rebecca A.
   Bollig, Frank
   Djordjevic, Gordana
   Lichman, Benjamin
   Zhu, Hao
   Ikenaga, Takanori
   Ono, Fumihito
   Englert, Christoph
   Cowan, Chad A.
   Hukriede, Neil A.
   Handin, Robert I.
   Davidson, Alan J.
TI Identification of adult nephron progenitors capable of kidney regeneration in zebrafish
SO NATURE
LA English
DT Article
ID transgenic zebrafish; genes; morphogenesis; pronephros; reporter
AB Loss of kidney function underlies many renal diseases(1). Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones(2,3). By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury(4,5), providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.
C1 [Diep, Cuong Q.; Ma, Dongdong; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Ma, Dongdong; Handin, Robert I.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Bollig, Frank; Englert, Christoph] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany.
   [Zhu, Hao] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Ikenaga, Takanori; Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
   [Englert, Christoph] Friedrich Schiller Univ, D-07743 Jena, Germany.
   [Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Hukriede, Neil A.] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA 15260 USA.
   [Diep, Cuong Q.; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Arora, Natasha; Wingert, Rebecca A.; Djordjevic, Gordana; Lichman, Benjamin; Cowan, Chad A.; Davidson, Alan J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Leibniz Association; Leibniz Institut fur Alternsforschung - Fritz-Lipmann-Institut (FLI); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Friedrich Schiller University of Jena; Harvard University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Davidson, AJ (corresponding author), Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1142, New Zealand.
EM a.davidson@auckland.ac.nz
FU Harvard Stem Cell Institute; American Society of Nephrology; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [P50DK074030]
NR 23
TC 229
Z9 278
U1 1
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 FEB 3
PY 2011
VL 470
IS 7332
BP 95
EP U108
DI 10.1038/nature09669
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400041
PM 21270795
DA 2026-03-09
ER

PT J
AU Kriks, S
   Shim, JW
   Piao, JH
   Ganat, YM
   Wakeman, DR
   Xie, Z
   Carrillo-Reid, L
   Auyeung, G
   Antonacci, C
   Buch, A
   Yang, LC
   Beal, MF
   Surmeier, DJ
   Kordower, JH
   Tabar, V
   Studer, L
AF Kriks, Sonja
   Shim, Jae-Won
   Piao, Jinghua
   Ganat, Yosif M.
   Wakeman, Dustin R.
   Xie, Zhong
   Carrillo-Reid, Luis
   Auyeung, Gordon
   Antonacci, Chris
   Buch, Amanda
   Yang, Lichuan
   Beal, M. Flint
   Surmeier, D. James
   Kordower, Jeffrey H.
   Tabar, Viviane
   Studer, Lorenz
TI Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease
SO NATURE
LA English
DT Article
ID stem-cells; floor plate; striatal progenitors; differentiation; transplantation; specification; derivation; tissue; brain
AB Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons(1) or midbrain dopamine (DA) neurons(2) has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease(3,4), DA neurons from human PSCs generally show poor in vivo performance(5). There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth(6,7). Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.
C1 [Kriks, Sonja; Shim, Jae-Won; Piao, Jinghua; Ganat, Yosif M.; Auyeung, Gordon; Antonacci, Chris; Buch, Amanda; Tabar, Viviane; Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, New York, NY 10065 USA.
   [Kriks, Sonja; Shim, Jae-Won; Ganat, Yosif M.; Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Piao, Jinghua; Auyeung, Gordon; Antonacci, Chris; Buch, Amanda; Tabar, Viviane; Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [Wakeman, Dustin R.; Kordower, Jeffrey H.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA.
   [Xie, Zhong; Carrillo-Reid, Luis; Surmeier, D. James] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA.
   [Yang, Lichuan; Beal, M. Flint] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY 10021 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Rush University; Northwestern University; Feinberg School of Medicine; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital
RP Studer, L (corresponding author), Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, 1275 York Ave, New York, NY 10065 USA.
EM studerl@mskcc.org
FU NIH/NINDS [NS052671, P50 NS047085]; European Commission; Starr foundation; NYSTEM [C024414, C024413]; Michael T. McCarthy Foundation; Elkus Family Foundation; Consolidated Anti-Aging Foundation; Falk Medical Research Trust; NYSCF; Starr stem cell scholar fellowship
NR 37
TC 1493
Z9 1780
U1 5
U2 395
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 22
PY 2011
VL 480
IS 7378
BP 547
EP U177
DI 10.1038/nature10648
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000066
PM 22056989
DA 2026-03-09
ER

PT J
AU Grbic, M
   Van Leeuwen, T
   Clark, RM
   Rombauts, S
   Rouzé, P
   Grbic, V
   Osborne, EJ
   Dermauw, W
   Phuong, CTN
   Ortego, F
   Hernández-Crespo, P
   Diaz, I
   Martinez, M
   Navajas, M
   Sucena, É
   Magalhaes, S
   Nagy, L
   Pace, RM
   Djuranovic, S
   Smagghe, G
   Iga, M
   Christiaens, O
   Veenstra, JA
   Ewer, J
   Villalobos, RM
   Hutter, JL
   Hudson, SD
   Velez, M
   Yi, SV
   Zeng, J
   Pires-daSilva, A
   Roch, F
   Cazaux, M
   Navarro, M
   Zhurov, V
   Acevedo, G
   Bjelica, A
   Fawcett, JA
   Bonnet, E
   Martens, C
   Baele, G
   Wissler, L
   Sanchez-Rodriguez, A
   Tirry, L
   Blais, C
   Demeestere, K
   Henz, SR
   Gregory, TR
   Mathieu, J
   Verdon, L
   Farinelli, L
   Schmutz, J
   Lindquist, E
   Feyereisen, R
   Van de Peer, Y
AF Grbic, Miodrag
   Van Leeuwen, Thomas
   Clark, Richard M.
   Rombauts, Stephane
   Rouze, Pierre
   Grbic, Vojislava
   Osborne, Edward J.
   Dermauw, Wannes
   Phuong Cao Thi Ngoc
   Ortego, Felix
   Hernandez-Crespo, Pedro
   Diaz, Isabel
   Martinez, Manuel
   Navajas, Maria
   Sucena, Elio
   Magalhaes, Sara
   Nagy, Lisa
   Pace, Ryan M.
   Djuranovic, Sergej
   Smagghe, Guy
   Iga, Masatoshi
   Christiaens, Olivier
   Veenstra, Jan A.
   Ewer, John
   Mancilla Villalobos, Rodrigo
   Hutter, Jeffrey L.
   Hudson, Stephen D.
   Velez, Marisela
   Yi, Soojin V.
   Zeng, Jia
   Pires-daSilva, Andre
   Roch, Fernando
   Cazaux, Marc
   Navarro, Marie
   Zhurov, Vladimir
   Acevedo, Gustavo
   Bjelica, Anica
   Fawcett, Jeffrey A.
   Bonnet, Eric
   Martens, Cindy
   Baele, Guy
   Wissler, Lothar
   Sanchez-Rodriguez, Aminael
   Tirry, Luc
   Blais, Catherine
   Demeestere, Kristof
   Henz, Stefan R.
   Gregory, T. Ryan
   Mathieu, Johannes
   Verdon, Lou
   Farinelli, Laurent
   Schmutz, Jeremy
   Lindquist, Erika
   Feyereisen, Rene
   Van de Peer, Yves
TI The genome of Tetranychus urticae reveals herbivorous pest adaptations
SO NATURE
LA English
DT Article
ID hox genes; spider; model; mite
AB The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies.
C1 [Rombauts, Stephane; Rouze, Pierre; Phuong Cao Thi Ngoc; Fawcett, Jeffrey A.; Bonnet, Eric; Martens, Cindy; Baele, Guy; Van de Peer, Yves] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Grbic, Miodrag; Grbic, Vojislava; Cazaux, Marc; Navarro, Marie; Zhurov, Vladimir; Acevedo, Gustavo; Bjelica, Anica] Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada.
   [Grbic, Miodrag; Grbic, Vojislava] UR, CSIC, Inst Ciencias Vid & Vino, Logrono 26006, Spain.
   [Van Leeuwen, Thomas; Dermauw, Wannes; Smagghe, Guy; Iga, Masatoshi; Christiaens, Olivier; Tirry, Luc] Univ Ghent, Dept Crop Protect, Fac Biosci Engn, B-9000 Ghent, Belgium.
   [Clark, Richard M.; Osborne, Edward J.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Rombauts, Stephane; Rouze, Pierre; Phuong Cao Thi Ngoc; Fawcett, Jeffrey A.; Bonnet, Eric; Martens, Cindy; Baele, Guy; Van de Peer, Yves] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
   [Ortego, Felix; Hernandez-Crespo, Pedro] CSIC, Ctr Invest Biol, Dept Environm Biol, Madrid 28040, Spain.
   [Diaz, Isabel; Martinez, Manuel] UPM INIA, Ctr Biotecnol & Genom Plantas, Madrid 28223, Spain.
   [Navajas, Maria] Montpellier SupAgro, Cirad, IRD, INRA,UMR CBGP, F-34988 Montferrier Sur Lez, France.
   [Sucena, Elio] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal.
   [Sucena, Elio] Univ Lisbon, Fac Ciencias, Dept Biol Anim, P-1749016 Lisbon, Portugal.
   [Magalhaes, Sara] Univ Lisbon, Fac Ciencias, Ctr Biol Ambiental, P-1749016 Lisbon, Portugal.
   [Nagy, Lisa; Pace, Ryan M.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA.
   [Djuranovic, Sergej] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
   [Veenstra, Jan A.] Univ Bordeaux 1, Inst Neurosci Cognit & Integrat Aquitaine, F-33405 Talence, France.
   [Ewer, John; Mancilla Villalobos, Rodrigo] Univ Valparaiso, Fac Ciencias, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso 2360102, Chile.
   [Hutter, Jeffrey L.; Hudson, Stephen D.] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 5B7, Canada.
   [Velez, Marisela] CSIC, Inst Catalisis & Petroleoquim, E-28040 Madrid, Spain.
   [Velez, Marisela] Univ Autonoma Madrid, Fac Ciencias, IMDEA Nanociencias, Madrid 28050, Spain.
   [Yi, Soojin V.; Zeng, Jia] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Pires-daSilva, Andre] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
   [Roch, Fernando] Univ Toulouse 3, Univ Toulouse, UPS, Ctr Dev Biol, F-31062 Toulouse, France.
   [Roch, Fernando] CNRS, Ctr Dev Biol, UMR 5547, F-31062 Toulouse, France.
   [Wissler, Lothar] Univ Munster, Inst Evolut & Biodivers, Evolutionary Bioinformat Grp, D-48149 Munster, Germany.
   [Sanchez-Rodriguez, Aminael] Katholieke Univ Leuven, Dept Microbial & Mol Syst, CMPG, B-3001 Louvain, Belgium.
   [Blais, Catherine] Univ Paris 06, CNRS, UMR 7622, Equipe Biogenese Signaux Hormonaux, F-75005 Paris, France.
   [Demeestere, Kristof] Univ Ghent, Fac Biosci Engn, Dept Sustainable Organ Chem & Technol, Res Grp EnVOC, B-9000 Ghent, Belgium.
   [Henz, Stefan R.] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Gregory, T. Ryan] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Mathieu, Johannes] Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA.
   [Verdon, Lou] Agr & Agri Food Canada, So Crop Protect & Food Res Ctr, London, ON N5V 4T3, Canada.
   [Farinelli, Laurent] Fasteris SA, CH-1228 Plan Les Ouates, Switzerland.
   [Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Schmutz, Jeremy; Lindquist, Erika] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Feyereisen, Rene] Univ Nice Sophia Antipolis, F-06903 Sophia Antipolis, France.
   [Feyereisen, Rene] CNRS, INRA, UMR 1301, F-06903 Sophia Antipolis, France.
C3 Ghent University; Flanders Institute for Biotechnology (VIB); Western University (University of Western Ontario); Universidad de La Rioja; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-CAR-UR - Instituto de Ciencias de la Vid y del Vino (ICVV); Ghent University; Utah System of Higher Education; University of Utah; Ghent University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigaciones Biologicas (CIB); Universidad Politecnica de Madrid; Institut Agro; Institut Agro Montpellier; INRAE; Institut de Recherche pour le Developpement (IRD); CIRAD; Instituto Gulbenkian de Ciencia; Universidade de Lisboa; Universidade de Lisboa; University of Arizona; Johns Hopkins University; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Universidad de Valparaiso; Western University (University of Western Ontario); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Catalisis y Petroleoquimica (ICP); Autonomous University of Madrid; University System of Georgia; Georgia Institute of Technology; University of Texas System; University of Texas Arlington; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of Munster; KU Leuven; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Ghent University; Max Planck Society; University of Guelph; Cornell University; Boyce Thompson Institute for Plant Research; Agriculture & Agri Food Canada; HudsonAlpha Institute for Biotechnology; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); INRAE
RP Van de Peer, Y (corresponding author), Univ Ghent VIB, Dept Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.
EM mgrbic@uwo.ca; yves.vandepeer@psb.ugent.be
FU NSERC [STPGP 322206-05]; Marie Curie Incoming International Fellowship; OECD [JA00053351]; Ontario Research Fund-Global Leadership in Genomics and Life Sciences [GL2-01-035]; Belgian Federal Science Policy Office IUAP [P6/25]; Fund for Scientific Research Flanders (FWO); Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT); Ghent University (MRP N2N); Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0950896] Funding Source: National Science Foundation
NR 32
TC 898
Z9 1079
U1 20
U2 538
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 487
EP 492
DI 10.1038/nature10640
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600041
PM 22113690
DA 2026-03-09
ER

PT J
AU Gordon, LM
   Joester, D
AF Gordon, Lyle M.
   Joester, Derk
TI Nanoscale chemical tomography of buried organic-inorganic interfaces in the chiton tooth
SO NATURE
LA English
DT Article
ID specimen preparation; radula teeth; protein; matrix; biomineralization; crystals; bone
AB Biological organisms possess an unparalleled ability to control the structure and properties of mineralized tissues. They are able, for example, to guide the formation of smoothly curving single crystals or tough, lightweight, self-repairing skeletal elements(1). In many biominerals, an organic matrix interacts with the mineral as it forms, controls its morphology and polymorph, and is occluded during mineralization(2-4). The remarkable functional properties of the resulting composites-such as outstanding fracture toughness and wear resistance-can be attributed to buried organic-inorganic interfaces at multiple hierarchical levels(5). Analysing and controlling such interfaces at the nanometre length scale is critical also in emerging organic electronic and photovoltaic hybrid materials(6). However, elucidating the structural and chemical complexity of buried organic-inorganic interfaces presents a challenge to state-of-the-art imaging techniques. Here we show that pulsed-laser atom-probe tomography reveals three-dimensional chemical maps of organic fibres with a diameter of 5-10 nm in the surrounding nano-crystalline magnetite (Fe3O4) mineral in the tooth of a marine mollusc, the chiton Chaetopleura apiculata. Remarkably, most fibres co-localize with either sodium or magnesium. Furthermore, clustering of these cations in the fibre indicates a structural level of hierarchy previously undetected. Our results demonstrate that in the chiton tooth, individual organic fibres have different chemical compositions, and therefore probably different functional roles in controlling fibre formation and matrix-mineral interactions. Atom-probe tomography is able to detect this chemical/structural heterogeneity by virtue of its high three-dimensional spatial resolution and sensitivity across the periodic table. We anticipate that the quantitative analysis and visualization of nanometre-scale interfaces by laser-pulsed atom-probe tomography will contribute greatly to our understanding not only of biominerals (such as bone, dentine and enamel), but also of synthetic organic-inorganic composites.
C1 [Gordon, Lyle M.; Joester, Derk] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
C3 Northwestern University
RP Joester, D (corresponding author), Northwestern Univ, Dept Mat Sci & Engn, 2220 Campus Dr, Evanston, IL 60208 USA.
EM d-joester@northwestern.edu
FU Canadian National Sciences and Engineering Research Council; US National Science Foundation [DMR-0805313]; NSF-NSEC; NSF-MRSEC; Keck Foundation; State of Illinois; Northwestern University; NSF-MRI [DMR-0420532]; ONR-DURIP [N00014-0400798, N00014-0610539, N00014-0910781]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0805313] Funding Source: National Science Foundation
NR 40
TC 221
Z9 260
U1 4
U2 317
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 194
EP 197
DI 10.1038/nature09686
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400034
PM 21228873
DA 2026-03-09
ER

PT J
AU Morford, SL
   Houlton, BZ
   Dahlgren, RA
AF Morford, Scott L.
   Houlton, Benjamin Z.
   Dahlgren, Randy A.
TI Increased forest ecosystem carbon and nitrogen storage from nitrogen rich bedrock
SO NATURE
LA English
DT Article
ID mendocino triple junction; fork mountain schist; coast ranges; isotopic composition; northern california; geologic nitrogen; cascadia margin; global patterns; uplift rates; soil
AB Nitrogen (N) limits the productivity of many ecosystems worldwide, thereby restricting the ability of terrestrial ecosystems to offset the effects of rising atmospheric CO2 emissions naturally(1,2). Understanding input pathways of bioavailable N is therefore paramount for predicting carbon (C) storage on land, particularly in temperate and boreal forests(3,4). Paradigms of nutrient cycling and limitation posit that new N enters terrestrial ecosystems solely from the atmosphere. Here we show that bedrock comprises a hitherto overlooked source of ecologically available N to forests. We report that the N content of soils and forest foliage on N-rich metasedimentary rocks (350-950 mg N kg(-1)) is elevated by more than 50% compared with similar temperate forest sites underlain by N-poor igneous parent material (30-70 mg N kg(-1)). Natural abundance N isotopes attribute this difference to rock-derived N: N-15/N-14 values for rock, soils and plants are indistinguishable in sites underlain by N-rich lithology, in marked contrast to sites on N-poor substrates. Furthermore, forests associated with N-rich parent material contain on average 42% more carbon in above-ground tree biomass and 60% more carbon in the upper 30 cm of the soil than similar sites underlain by N-poor rocks. Our results raise the possibility that bedrock N input may represent an important and overlooked component of ecosystem N and C cycling elsewhere.
C1 [Morford, Scott L.; Houlton, Benjamin Z.; Dahlgren, Randy A.] Univ Calif Davis, Dept Land Air & Water Resources, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Morford, SL (corresponding author), Univ Calif Davis, Dept Land Air & Water Resources, Davis, CA 95616 USA.
EM slmorford@ucdavis.edu
FU David and Lucile Packard Foundation; Andrew W. Mellon Foundation; Kearney Foundation of Soil Science
NR 76
TC 137
Z9 181
U1 3
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 SEP 1
PY 2011
VL 477
IS 7362
BP 78
EP U88
DI 10.1038/nature10415
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300034
PM 21886160
DA 2026-03-09
ER

PT J
AU Larsson, J
   Fransson, C
   Östlin, G
   Gröningsson, P
   Jerkstrand, A
   Kozma, C
   Sollerman, J
   Challis, P
   Kirshner, RP
   Chevalier, RA
   Heng, K
   McCray, R
   Suntzeff, NB
   Bouchet, P
   Crotts, A
   Danziger, J
   Dwek, E
   France, K
   Garnavich, PM
   Lawrence, SS
   Leibundgut, B
   Lundqvist, P
   Panagia, N
   Pun, CSJ
   Smith, N
   Sonneborn, G
   Wang, L
   Wheeler, JC
AF Larsson, J.
   Fransson, C.
   Ostlin, G.
   Groningsson, P.
   Jerkstrand, A.
   Kozma, C.
   Sollerman, J.
   Challis, P.
   Kirshner, R. P.
   Chevalier, R. A.
   Heng, K.
   McCray, R.
   Suntzeff, N. B.
   Bouchet, P.
   Crotts, A.
   Danziger, J.
   Dwek, E.
   France, K.
   Garnavich, P. M.
   Lawrence, S. S.
   Leibundgut, B.
   Lundqvist, P.
   Panagia, N.
   Pun, C. S. J.
   Smith, N.
   Sonneborn, G.
   Wang, L.
   Wheeler, J. C.
TI X-ray illumination of the ejecta of supernova 1987A
SO NATURE
LA English
DT Article
ID hubble-space-telescope; sn 1987a; reverse shock; line emission; light-curve; evolution; sn-1987a; remnant; ring
AB When a massive star explodes as a supernova, substantial amounts of radioactive elements-primarily Ni-56, Ni-57 and Ti-44-are produced(1). After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements(2). However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium(3). The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of Ti-44 as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.
C1 [Larsson, J.; Fransson, C.; Ostlin, G.; Groningsson, P.; Jerkstrand, A.; Kozma, C.; Sollerman, J.; Lundqvist, P.] Stockholm Univ, Dept Astron, Oskar Klein Ctr, S-10691 Stockholm, Sweden.
   [Challis, P.; Kirshner, R. P.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Chevalier, R. A.] Univ Virginia, Dept Astron, Charlottesville, VA 22903 USA.
   [Heng, K.] Eidgenossische Tech Hsch, Inst Astron, CH-8093 Zurich, Switzerland.
   [McCray, R.] Univ Colorado, JILA, Boulder, CO USA.
   [Suntzeff, N. B.] Texas A&M Univ, George P & Cynthia Woods Mitchell Inst Fundamenta, Dept Phys & Astron, College Stn, TX 77843 USA.
   [Bouchet, P.] DSM IRFU Serv Astrophys Commissariat Energie Alte, FR-91191 Gif Sur Yvette, France.
   [Crotts, A.] Columbia Univ, Dept Astron, New York, NY 10027 USA.
   [Dwek, E.; Sonneborn, G.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Danziger, J.] Osserv Astron Trieste, I-34131 Trieste, Italy.
   [France, K.] Univ Colorado, Ctr Astrophys & Space Astron, Boulder, CO 80309 USA.
   [Garnavich, P. M.] Univ Notre Dame, Notre Dame, IN 46556 USA.
   [Lawrence, S. S.] Hofstra Univ, Dept Phys & Astron, Hempstead, NY 11549 USA.
   [Leibundgut, B.] ESO, D-85748 Garching, Germany.
   [Panagia, N.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Panagia, N.] Osserv Astrofis Catania, INAF CT, I-95123 Catania, Italy.
   [Pun, C. S. J.] Univ Hong Kong, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
   [Smith, N.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Wheeler, J. C.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
C3 Stockholm University; Oskar Klein Centre; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; University of Virginia; University of Colorado System; University of Colorado Boulder; Texas A&M University System; Texas A&M University College Station; Columbia University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Istituto Nazionale Astrofisica (INAF); University of Colorado System; University of Colorado Boulder; University of Notre Dame; Hofstra University; Space Telescope Science Institute; Istituto Nazionale Astrofisica (INAF); University of Hong Kong; University of Arizona; University of Texas System; University of Texas Austin
RP Larsson, J (corresponding author), Stockholm Univ, Dept Astron, Oskar Klein Ctr, S-10691 Stockholm, Sweden.
EM josefin.larsson@astro.su.se; claes@astro.su.se
FU Swedish Research Council; Swedish National Space Board; Space Telescope Science Institute
NR 24
TC 66
Z9 69
U1 1
U2 12
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2011
VL 474
IS 7352
BP 484
EP 486
DI 10.1038/nature10090
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700042
PM 21654749
DA 2026-03-09
ER

PT J
AU Borgonie, G
   García-Moyano, A
   Litthauer, D
   Bert, W
   Bester, A
   van Heerden, E
   Möller, C
   Erasmus, M
   Onstott, TC
AF Borgonie, G.
   Garcia-Moyano, A.
   Litthauer, D.
   Bert, W.
   Bester, A.
   van Heerden, E.
   Moeller, C.
   Erasmus, M.
   Onstott, T. C.
TI Nematoda from the terrestrial deep subsurface of South Africa
SO NATURE
LA English
DT Article
ID witwatersrand basin; evolution; water
AB Since its discovery over two decades ago, the deep subsurface biosphere has been considered to be the realm of single-cell organisms, extending over three kilometres into the Earth's crust and comprising a significant fraction of the global biosphere(1-4). The constraints of temperature, energy, dioxygen and space seemed to preclude the possibility of more-complex, multicellular organisms from surviving at these depths. Here we report species of the phylum Nematoda that have been detected in or recovered from 0.9-3.6-kilometre-deep fracture water in the deep mines of South Africa but have not been detected in the mining water. These subsurface nematodes, including a new species, Halicephalobus mephisto, tolerate high temperature, reproduce asexually and preferentially feed upon subsurface bacteria. Carbon-14 data indicate that the fracture water in which the nematodes reside is 3,000-12,000-year-old palaeometeoric water. Our data suggest that nematodes should be found in other deep hypoxic settings where temperature permits, and that they may control the microbial population density by grazing on fracture surface biofilm patches. Our results expand the known metazoan biosphere and demonstrate that deep ecosystems are more complex than previously accepted. The discovery of multicellular life in the deep subsurface of the Earth also has important implications for the search for subsurface life on other planets in our Solar System.
C1 [Borgonie, G.; Bert, W.] Univ Ghent, Dept Biol, Nematol Sect, B-9000 Ghent, Belgium.
   [Garcia-Moyano, A.; Litthauer, D.; Bester, A.; van Heerden, E.; Moeller, C.; Erasmus, M.] Univ Free State, Dept Microbial Biochem & Food Biotechnol, ZA-9300 Bloemfontein, South Africa.
   [Bert, W.] Wageningen Univ, Dept Plant Sci, Nematol Lab, NL-6708 Wageningen, Netherlands.
   [Onstott, T. C.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
C3 Ghent University; University of the Free State; Wageningen University & Research; Princeton University
RP Borgonie, G (corresponding author), Univ Ghent, Dept Biol, Nematol Sect, Ledeganckstr 35, B-9000 Ghent, Belgium.
EM gborgonie@gmail.com; tullis@princeton.edu
FU FWO; BOF; UFS; National Science Foundation [EAR 0409605]; BioPAD/UFS; Division Of Earth Sciences; Directorate For Geosciences [0948659] Funding Source: National Science Foundation
NR 29
TC 151
Z9 189
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 JUN 2
PY 2011
VL 474
IS 7349
BP 79
EP 82
DI 10.1038/nature09974
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700041
PM 21637257
DA 2026-03-09
ER

PT J
AU Possemato, R
   Marks, KM
   Shaul, YD
   Pacold, ME
   Kim, D
   Birsoy, K
   Sethumadhavan, S
   Woo, HK
   Jang, HG
   Jha, AK
   Chen, WW
   Barrett, FG
   Stransky, N
   Tsun, ZY
   Cowley, GS
   Barretina, J
   Kalaany, NY
   Hsu, PP
   Ottina, K
   Chan, AM
   Yuan, B
   Garraway, LA
   Root, DE
   Mino-Kenudson, M
   Brachtel, EF
   Driggers, EM
   Sabatini, DM
AF Possemato, Richard
   Marks, Kevin M.
   Shaul, Yoav D.
   Pacold, Michael E.
   Kim, Dohoon
   Birsoy, Kivanc
   Sethumadhavan, Shalini
   Woo, Hin-Koon
   Jang, Hyun G.
   Jha, Abhishek K.
   Chen, Walter W.
   Barrett, Francesca G.
   Stransky, Nicolas
   Tsun, Zhi-Yang
   Cowley, Glenn S.
   Barretina, Jordi
   Kalaany, Nada Y.
   Hsu, Peggy P.
   Ottina, Kathleen
   Chan, Albert M.
   Yuan, Bingbing
   Garraway, Levi A.
   Root, David E.
   Mino-Kenudson, Mari
   Brachtel, Elena F.
   Driggers, Edward M.
   Sabatini, David M.
TI Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
SO NATURE
LA English
DT Article
ID gene-expression signature; neoplastic rat-tissue; embryonic stem-cells; xenograft model; metabolism; identification; dehydrogenase; activation; screen; tumors
AB Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation(1,2). RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes(3). Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of alpha-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent on increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.
C1 [Possemato, Richard; Shaul, Yoav D.; Pacold, Michael E.; Kim, Dohoon; Birsoy, Kivanc; Chen, Walter W.; Barrett, Francesca G.; Tsun, Zhi-Yang; Kalaany, Nada Y.; Hsu, Peggy P.; Ottina, Kathleen; Chan, Albert M.; Yuan, Bingbing; Sabatini, David M.] Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Possemato, Richard; Shaul, Yoav D.; Pacold, Michael E.; Kim, Dohoon; Birsoy, Kivanc; Chen, Walter W.; Tsun, Zhi-Yang; Kalaany, Nada Y.; Hsu, Peggy P.; Ottina, Kathleen; Chan, Albert M.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Possemato, Richard; Shaul, Yoav D.; Pacold, Michael E.; Kim, Dohoon; Birsoy, Kivanc; Chen, Walter W.; Stransky, Nicolas; Cowley, Glenn S.; Barretina, Jordi; Kalaany, Nada Y.; Hsu, Peggy P.; Ottina, Kathleen; Chan, Albert M.; Garraway, Levi A.; Root, David E.; Sabatini, David M.] MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Possemato, Richard; Shaul, Yoav D.; Pacold, Michael E.; Kim, Dohoon; Birsoy, Kivanc; Chen, Walter W.; Barrett, Francesca G.; Stransky, Nicolas; Tsun, Zhi-Yang; Cowley, Glenn S.; Barretina, Jordi; Kalaany, Nada Y.; Hsu, Peggy P.; Ottina, Kathleen; Chan, Albert M.; Garraway, Levi A.; Root, David E.; Sabatini, David M.] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Shaul, Yoav D.; Pacold, Michael E.; Kim, Dohoon; Birsoy, Kivanc; Chen, Walter W.; Tsun, Zhi-Yang; Kalaany, Nada Y.; Hsu, Peggy P.; Ottina, Kathleen; Chan, Albert M.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Marks, Kevin M.; Sethumadhavan, Shalini; Woo, Hin-Koon; Jha, Abhishek K.; Driggers, Edward M.] Agios Pharmaceut, Cambridge, MA 02139 USA.
   [Pacold, Michael E.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02114 USA.
   [Barretina, Jordi; Garraway, Levi A.] Dept Med Oncol, Boston, MA 02115 USA.
   [Barretina, Jordi; Garraway, Levi A.] Ctr Canc Genome Discovery, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Barretina, Jordi; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Mino-Kenudson, Mari; Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Mino-Kenudson, Mari; Brachtel, Elena F.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Agios Pharmaceuticals; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Sabatini, DM (corresponding author), Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU S. G. Komen for the Cure; Life Science Research Foundation; Keck Foundation; David H. Koch Institute for Integrative Cancer Research at MIT; Alexander and Margaret Stewart Trust; NIH [CA103866]; National Cancer Institute [R01CA103866, R01CA129105] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 26
TC 1373
Z9 1602
U1 1
U2 198
PU 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 18
PY 2011
VL 476
IS 7360
BP 346
EP U119
DI 10.1038/nature10350
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500041
PM 21760589
DA 2026-03-09
ER

PT J
AU Voineagu, I
   Wang, XC
   Johnston, P
   Lowe, JK
   Tian, Y
   Horvath, S
   Mill, J
   Cantor, RM
   Blencowe, BJ
   Geschwind, DH
AF Voineagu, Irina
   Wang, Xinchen
   Johnston, Patrick
   Lowe, Jennifer K.
   Tian, Yuan
   Horvath, Steve
   Mill, Jonathan
   Cantor, Rita M.
   Blencowe, Benjamin J.
   Geschwind, Daniel H.
TI Transcriptomic analysis of autistic brain reveals convergent molecular pathology
SO NATURE
LA English
DT Article
ID common genetic-variants; spectrum disorders; network analysis; candidate gene; copy number; association; expression; pathways; package; disease
AB Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity(1-3). Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain(4). Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
C1 [Voineagu, Irina; Lowe, Jennifer K.; Tian, Yuan; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet & Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Voineagu, Irina; Lowe, Jennifer K.; Tian, Yuan; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Los Angeles, CA 90095 USA.
   [Wang, Xinchen; Blencowe, Benjamin J.] Univ Toronto, Donnelly Ctr, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada.
   [Johnston, Patrick; Mill, Jonathan] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Horvath, Steve; Cantor, Rita M.; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of Toronto; University of London; King's College London; University of California System; University of California Los Angeles
RP Geschwind, DH (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet & Neurobehav Genet, Los Angeles, CA 90095 USA.
EM dhg@mednet.ucla.edu
FU CIHR Funding Source: Medline; NIMH NIH HHS [R01 MH081754, R37 MH060233, R01 MH094714, R37MH060233, 5R01MH081754-03] Funding Source: Medline; Medical Research Council [G9817803B] Funding Source: researchfish
NR 37
TC 1450
Z9 1715
U1 4
U2 289
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 380
EP +
DI 10.1038/nature10110
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100046
PM 21614001
DA 2026-03-09
ER

PT J
AU Anderson, K
   Lutz, C
   van Delft, FW
   Bateman, CM
   Guo, YP
   Colman, SM
   Kempski, H
   Moorman, AV
   Titley, I
   Swansbury, J
   Kearney, L
   Enver, T
   Greaves, M
AF Anderson, Kristina
   Lutz, Christoph
   van Delft, Frederik W.
   Bateman, Caroline M.
   Guo, Yanping
   Colman, Susan M.
   Kempski, Helena
   Moorman, Anthony V.
   Titley, Ian
   Swansbury, John
   Kearney, Lyndal
   Enver, Tariq
   Greaves, Mel
TI Genetic variegation of clonal architecture and propagating cells in leukaemia
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; cancer stem-cells; breast-cancer; childhood leukemia; intratumoral heterogeneity; prostate-cancer; tumor-cells; progression; evolution; diversity
AB Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clonemaintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-upto a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2R gamma(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer.
C1 [Anderson, Kristina; van Delft, Frederik W.; Bateman, Caroline M.; Colman, Susan M.; Titley, Ian; Swansbury, John; Kearney, Lyndal; Greaves, Mel] Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England.
   [Lutz, Christoph; Guo, Yanping; Enver, Tariq] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England.
   [Kempski, Helena] Great Ormond St Hosp Sick Children, Paediat Malignancy Unit, London WC1N 3JH, England.
   [Kempski, Helena] UCL Inst Child Hlth, London WC1N 3JH, England.
   [Moorman, Anthony V.] Newcastle Univ, No Inst Canc Res, Leukaemia Res Cytogenet Grp, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
C3 University of London; Institute of Cancer Research - UK; University of Oxford; University of London; University College London; Great Ormond Street Hospital for Children NHS Foundation Trust; University of London; University College London; Newcastle University - UK
RP Greaves, M (corresponding author), Inst Canc Res, Sect Haematooncol, Sutton SM2 5NG, Surrey, England.
EM mel.greaves@icr.ac.uk
FU Kay Kendall Leukaemia Fund; Leukaemia & Lymphoma Research; Deutsche Forschungsgemeinschaft [LU 1474/1-1]; Oxford BRC; Medical Research Council [MC_U137973817] Funding Source: researchfish; MRC [MC_U137973817] Funding Source: UKRI
NR 53
TC 645
Z9 745
U1 0
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 20
PY 2011
VL 469
IS 7330
BP 356
EP +
DI 10.1038/nature09650
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600043
PM 21160474
DA 2026-03-09
ER

PT J
AU Rasmussen, SGF
   DeVree, BT
   Zou, YZ
   Kruse, AC
   Chung, KY
   Kobilka, TS
   Thian, FS
   Chae, PS
   Pardon, E
   Calinski, D
   Mathiesen, JM
   Shah, STA
   Lyons, JA
   Caffrey, M
   Gellman, SH
   Steyaert, J
   Skiniotis, G
   Weis, WI
   Sunahara, RK
   Kobilka, BK
AF Rasmussen, Soren G. F.
   DeVree, Brian T.
   Zou, Yaozhong
   Kruse, Andrew C.
   Chung, Ka Young
   Kobilka, Tong Sun
   Thian, Foon Sun
   Chae, Pil Seok
   Pardon, Els
   Calinski, Diane
   Mathiesen, Jesper M.
   Shah, Syed T. A.
   Lyons, Joseph A.
   Caffrey, Martin
   Gellman, Samuel H.
   Steyaert, Jan
   Skiniotis, Georgios
   Weis, William I.
   Sunahara, Roger K.
   Kobilka, Brian K.
TI Crystal structure of the β2 adrenergic receptor-Gs protein complex
SO NATURE
LA English
DT Article
ID adenylate-cyclase; beta(2)-adrenergic receptor; mediated activation; binding; crystallization; reconstitution; insights; amino
AB G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The beta(2) adrenergic receptor (beta(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric beta(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the beta(2)AR and Gs involve the amino-and carboxy-terminal a-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the beta(2)AR include a 14 angstrom outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an alpha-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the alpha-helical domain of G alpha s relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.
C1 [Rasmussen, Soren G. F.; Zou, Yaozhong; Kruse, Andrew C.; Chung, Ka Young; Kobilka, Tong Sun; Thian, Foon Sun; Mathiesen, Jesper M.; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Dept Mol & Cellular Biol, Sch Med, Stanford, CA 94305 USA.
   [Rasmussen, Soren G. F.] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
   [DeVree, Brian T.; Calinski, Diane; Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Chae, Pil Seok; Gellman, Samuel H.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
   [Pardon, Els; Steyaert, Jan] Vrije Univ Brussel, VIB, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium.
   [Shah, Syed T. A.; Lyons, Joseph A.; Caffrey, Martin] Trinity Coll Dublin, Membrane Struct & Funct Biol Grp, Sch Med, Dublin 2, Ireland.
   [Shah, Syed T. A.; Lyons, Joseph A.; Caffrey, Martin] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin 2, Ireland.
   [Skiniotis, Georgios] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA.
   [Skiniotis, Georgios] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Weis, William I.] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
C3 Stanford University; University of Copenhagen; University of Michigan System; University of Michigan; University of Wisconsin System; University of Wisconsin Madison; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; Trinity College Dublin; Trinity College Dublin; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Stanford University
RP Kobilka, BK (corresponding author), Stanford Univ, Dept Mol & Cellular Biol, Sch Med, Stanford, CA 94305 USA.
EM sunahara@umich.edu; kobilka@stanford.edu
FU National Institutes of Health [NS028471, GM083118, GM56169, P01 GM75913, T32-GM008270, P60DK-20572, GM75915, P50GM073210, U54GM094599]; Science Foundation Ireland [07/IN.1/B1836]; FP7 COST Action [CM0902]; Mathers Foundation; Lundbeck Foundation; University of Michigan; Fund for Scientific Research of Flanders (FWO-Vlaanderen); Institute for the encouragement of Scientific Research and Innovation of Brussels (ISRIB); Danish Council for Independent Research, Medical Sciences; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER; Lundbeck Foundation [R19-2008-2113, R37-2009-3457] Funding Source: researchfish; Science Foundation Ireland (SFI) [07/IN.1/B1836] Funding Source: Science Foundation Ireland (SFI)
NR 48
TC 2529
Z9 3007
U1 8
U2 746
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 549
EP U311
DI 10.1038/nature10361
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900031
PM 21772288
DA 2026-03-09
ER

PT J
AU Müller, J
   Hipsley, CA
   Head, JJ
   Kardjilov, N
   Hilger, A
   Wuttke, M
   Reisz, RR
AF Mueller, Johannes
   Hipsley, Christy A.
   Head, Jason J.
   Kardjilov, Nikolay
   Hilger, Andre
   Wuttke, Michael
   Reisz, Robert R.
TI Eocene lizard from Germany reveals amphisbaenian origins
SO NATURE
LA English
DT Article
ID squamate reptiles; body-form; phylogenetic analysis; middle-eocene; evolution; snakes; systematics; resolution; position
AB Amphisbaenia is a speciose clade of fossorial lizards characterized by a snake-like body and a strongly reinforced skull adapted for head-first burrowing(1,2). The evolutionary origins of amphisbaenians are controversial, with molecular data uniting them with lacertids(3,4), a clade of Old World terrestrial lizards, whereas morphology supports a grouping with snakes and other limbless squamates(5-9). Reports of fossil stem amphisbaenians(10) have been falsified(11), and no fossils have previously tested these competing phylogenetic hypotheses or shed light on ancestral amphisbaenian ecology. Here we report the discovery of a new lacertid-like lizard from the Eocene Messel locality of Germany that provides the first morphological evidence for lacertid-amphisbaenian monophyly on the basis of a reinforced, akinetic skull roof and braincase, supporting the view that body elongation and limblessness in amphisbaenians and snakes evolved independently. Morphometric analysis of body shape and ecology in squamates indicates that the postcranial anatomy of the new taxon is most consistent with opportunistically burrowing habits, which in combination with cranial reinforcement indicates that head-first burrowing evolved before body elongation and may have been a crucial first step in the evolution of amphisbaenian fossoriality.
C1 [Mueller, Johannes; Hipsley, Christy A.] Humboldt Univ, Leibniz Inst Evolut & Biodiversitatsforsch, Museum Nat Kunde, D-10115 Berlin, Germany.
   [Hipsley, Christy A.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
   [Head, Jason J.; Reisz, Robert R.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Kardjilov, Nikolay; Hilger, Andre] Helmholtz Zentrum Berlin Mat & Energie, D-14109 Berlin, Germany.
   [Wuttke, Michael] Gen Direkt Kulturelles Erbe RLP, Direkt Landesarchaol, D-55116 Mainz, Germany.
C3 Humboldt University of Berlin; Leibniz Institut fur Evolutions und Biodiversitatsforschung; University of California System; University of California Santa Cruz; University of Toronto; University Toronto Mississauga; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB)
RP Müller, J (corresponding author), Humboldt Univ, Leibniz Inst Evolut & Biodiversitatsforsch, Museum Nat Kunde, Invalidenstr 43, D-10115 Berlin, Germany.
EM johannes.mueller@mfn-berlin.de
FU Natural Sciences and Engineering Research Council of Canada; Alexander von Humboldt-Stiftung; Office Of Internatl Science &Engineering; Office Of The Director [1028073] Funding Source: National Science Foundation
NR 30
TC 85
Z9 94
U1 4
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 364
EP 367
DI 10.1038/nature09919
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400046
PM 21593869
DA 2026-03-09
ER

PT J
AU Dunn, RA
   Martinez, F
AF Dunn, Robert A.
   Martinez, Fernando
TI Contrasting crustal production and rapid mantle transitions beneath back-arc ridges
SO NATURE
LA English
DT Article
ID lau basin; midocean ridge; mariana trough; morphology; evolution; pacific
AB The opening of back-arc basins behind subduction zones progresses from initial rifting near the volcanic arc to seafloor spreading(1). During this process, the spreading ridge and the volcanic arc separate and lavas erupted at the ridge are predicted to evolve away from being heavily subduction influenced (with high volatile contents derived from the subducting plate)(2-5). Current models(4,6-8) predict gradational, rather than abrupt, changes in the crust formed along the ridge as the inferred broad melting region beneath it migrates away from heavily subduction-influenced mantle. In contrast, here we show that across-strike and along-strike changes in crustal properties at the Eastern Lau spreading centre are large and abrupt, implying correspondingly large discontinuities in the nature of the mantle supplying melt to the ridge axes. With incremental separation of the ridge axis from the volcanic front of as little as 5 km, seafloor morphology changes from shallower complex volcanic landforms to deeper flat sea floor dominated by linear abyssal hills, upper crustal seismic velocities abruptly increase by over 20%, and gravity anomalies and isostasy indicate crustal thinning of more than 1.9 km. We infer that the abrupt changes in crustal properties reflect rapid evolution of the mantle entrained by the ridge, such that stable, broad triangular upwelling regions, as inferred for mid-ocean ridges(9,10), cannot form near the mantle wedge corner. Instead, the observations imply a dynamic process in which the ridge upwelling zone preferentially captures water-rich low-viscosity mantle when it is near the arc. As the ridge moves away from the arc, a tipping point is reached at which that material is rapidly released from the upwelling zone, resulting in rapid changes in the character of the crust formed at the ridge.
C1 [Dunn, Robert A.] Univ Hawaii, Dept Geol & Geophys, Honolulu, HI 96822 USA.
   [Martinez, Fernando] Univ Hawaii, Hawaii Inst Geophys & Planetol, Honolulu, HI 96822 USA.
C3 University of Hawaii System; University of Hawaii System
RP Dunn, RA (corresponding author), Univ Hawaii, Dept Geol & Geophys, Honolulu, HI 96822 USA.
EM dunn@soest.hawaii.edu
FU NSF [OCE0426428, OCE0732536, OCE0727138]; Directorate For Geosciences [0426428] Funding Source: National Science Foundation; Division Of Ocean Sciences [0426428] Funding Source: National Science Foundation
NR 30
TC 63
Z9 69
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 198
EP 202
DI 10.1038/nature09690
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400035
PM 21228874
DA 2026-03-09
ER

PT J
AU Li, QY
   Tullis, TE
   Goldsby, D
   Carpick, RW
AF Li, Qunyang
   Tullis, Terry E.
   Goldsby, David
   Carpick, Robert W.
TI Frictional ageing from interfacial bonding and the origins of rate and state friction
SO NATURE
LA English
DT Article
ID atomic-force microscope; dependent friction; rock friction; slip; stick; indentation; calibration; stability; humidity
AB Earthquakes have long been recognized as being the result of stick-slip frictional instabilities(1,2). Over the past few decades, laboratory studies of rock friction have elucidated many aspects of tectonic fault zone processes and earthquake phenomena(3-5). Typically, the static friction of rocks grows logarithmically with time when they are held in stationary contact(6), but the mechanism responsible for this strengthening is not understood. This time-dependent increase of frictional strength, or frictional ageing, is one manifestation of the 'evolution effect' in rate and state friction theory(5). A prevailing view is that the time dependence of rock friction results from increases in contact area caused by creep of contacting asperities(7,8). Here we present the results of atomic force microscopy experiments that instead show that frictional ageing arises from the formation of interfacial chemical bonds, and the large magnitude of ageing at the nanometre scale is quantitatively consistent with what is required to explain observations in macroscopic rock friction experiments. The relative magnitude of the evolution effect compared with that of the 'direct effect'-the dependence of friction on instantaneous changes in slip velocity-determine whether unstable slip, leading to earthquakes, is possible(9,10). Understanding the mechanism underlying the evolution effect would enable us to formulate physically based frictional constitutive laws, rather than the current empirically based 'laws'(11,12), allowing more confident extrapolation to natural faults.
C1 [Li, Qunyang; Carpick, Robert W.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA.
   [Tullis, Terry E.; Goldsby, David] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
C3 University of Pennsylvania; Brown University
RP Carpick, RW (corresponding author), Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA.
EM carpick@seas.upenn.edu
FU National Science Foundation [EAR0810088, EAR0810192]
NR 29
TC 265
Z9 307
U1 7
U2 255
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 233
EP U112
DI 10.1038/nature10589
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200049
PM 22139421
DA 2026-03-09
ER

PT J
AU Sentürk, A
   Pfennig, S
   Weiss, A
   Burk, K
   Acker-Palmer, A
AF Sentuerk, Aycan
   Pfennig, Sylvia
   Weiss, Alexander
   Burk, Katja
   Acker-Palmer, Amparo
TI Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration
SO NATURE
LA English
DT Article
ID tyrosine kinases; phosphorylation; specification; disabled-1; mechanisms; expression; mutations; caspase-3; preplate; receptor
AB Coordinated migration of neurons in the developing and adult brain is essential for its proper function. The secreted glycoprotein Reelin (also known as RELN) guides migration of neurons by binding to two lipoprotein receptors, the very-low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2, also known as LRP8)(1). Loss of Reelin function in humans results in the severe developmental disorder lissencephaly(2) and it has also been associated with other neurological disorders such as epilepsy, schizophrenia and Alzheimer's disease(3). The molecular mechanisms by which Reelin activates its receptors and controls cellular functions are largely unknown. Here we show that the neuronal guidance cues ephrin B proteins are essential for Reelin signalling during the development of laminated structures in the brain. We show that ephrin Bs genetically interact with Reelin. Notably, compound mouse mutants (Reln(+/-); Efnb3(-/-) or Reln(+/-); Efnb2(-/-)) and triple ephrin B1, B2, B3 knockouts show neuronal migration defects that recapitulate the ones observed in the neocortex, hippocampus and cerebellum of the reeler mouse. Mechanistically, we show that Reelin binds to the extracellular domain of ephrin Bs, which associate at the membrane with VLDLR and ApoER2 in neurons. Clustering of ephrin Bs leads to the recruitment and phosphorylation of Dab1 which is necessary for Reelin signalling. Conversely, loss of function of ephrin Bs severely impairs Reelin-induced Dab1 phosphorylation. Importantly, activation of ephrin Bs can rescue the reeler neuronal migration defects in the absence of Reelin protein. Together, our results identify ephrin Bs as essential components of the Reelin receptor/signalling pathway to control neuronal migration during the development of the nervous system.
C1 [Sentuerk, Aycan; Pfennig, Sylvia; Weiss, Alexander; Burk, Katja; Acker-Palmer, Amparo] Goethe Univ Frankfurt, Frankfurt Inst Mol Life Sci FMLS, D-60438 Frankfurt, Germany.
   [Sentuerk, Aycan; Pfennig, Sylvia; Weiss, Alexander; Burk, Katja; Acker-Palmer, Amparo] Goethe Univ Frankfurt, Inst Cell Biol & Neurosci, D-60438 Frankfurt, Germany.
C3 Goethe University Frankfurt; Goethe University Frankfurt
RP Acker-Palmer, A (corresponding author), Goethe Univ Frankfurt, Frankfurt Inst Mol Life Sci FMLS, Max von Laue Str 9, D-60438 Frankfurt, Germany.
EM Acker-Palmer@bio.uni-frankfurt.de
FU Max Planck Institute of Neurobiology in Martinsried (Germany); Deutsche Forschungsgemeinschaft [AC180/2-1, 2-2]; University Frankfurt [EXC115, EXC147]
NR 34
TC 136
Z9 169
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 356
EP U123
DI 10.1038/nature09874
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600041
PM 21460838
DA 2026-03-09
ER

PT J
AU Tye, KM
   Prakash, R
   Kim, SY
   Fenno, LE
   Grosenick, L
   Zarabi, H
   Thompson, KR
   Gradinaru, V
   Ramakrishnan, C
   Deisseroth, K
AF Tye, Kay M.
   Prakash, Rohit
   Kim, Sung-Yon
   Fenno, Lief E.
   Grosenick, Logan
   Zarabi, Hosniya
   Thompson, Kimberly R.
   Gradinaru, Viviana
   Ramakrishnan, Charu
   Deisseroth, Karl
TI Amygdala circuitry mediating reversible and bidirectional control of anxiety
SO NATURE
LA English
DT Article
ID conditioned fear; central nucleus; rat; disorders; behavior; brain; cat; projections; complex; mice
AB Anxiety-a sustained state of heightened apprehension in the absence of immediate threat-becomes severely debilitating in disease states(1). Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) 2 and contribute to the aetiology of major depression and substance abuse(3,4). Although it has been proposed that the amygdala, a brain region important for emotional processing(5-8), has a role in anxiety(9-13), the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics(14-16) to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)-achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA-exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin(15) (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLACeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
C1 [Tye, Kay M.; Prakash, Rohit; Kim, Sung-Yon; Fenno, Lief E.; Grosenick, Logan; Zarabi, Hosniya; Thompson, Kimberly R.; Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Prakash, Rohit; Kim, Sung-Yon; Fenno, Lief E.; Grosenick, Logan; Gradinaru, Viviana; 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 Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU NIMH [1F32MH088010-01]; NARSAD; Samsung; NSF [0801700]; Defense Advanced Research Projects Agency Reorganization and Plasticity to Accelerate Injury Recovery [N66001-10-C-2010]; Alice Woo Foundation; Albert Yu Foundation; Snyder Foundation; McKnight Foundation; NIDA; NIH
NR 30
TC 993
Z9 1291
U1 4
U2 354
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 17
PY 2011
VL 471
IS 7338
BP 358
EP 362
DI 10.1038/nature09820
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735UE
UT WOS:000288444000041
PM 21389985
DA 2026-03-09
ER

PT J
AU Bajoghli, B
   Guo, P
   Aghaallaei, N
   Hirano, M
   Strohmeier, C
   McCurley, N
   Bockman, DE
   Schorpp, M
   Cooper, MD
   Boehm, T
AF Bajoghli, Baubak
   Guo, Peng
   Aghaallaei, Narges
   Hirano, Masayuki
   Strohmeier, Christine
   McCurley, Nathanael
   Bockman, Dale E.
   Schorpp, Michael
   Cooper, Max D.
   Boehm, Thomas
TI A thymus candidate in lampreys
SO NATURE
LA English
DT Article
ID variable lymphocyte receptors; evolution; diversification; epithelium; responses; hagfish
AB Immunologists and evolutionary biologists have been debating the nature of the immune system of jawless vertebrates-lampreys and hagfish-since the nineteenth century. In the past 50 years, these fish were shown to have antibody-like responses and the capacity to reject allografts(1) but were found to lack the immunoglobulin-based adaptive immune system of jawed vertebrates(2). Recent work has shown that lampreys have lymphocytes that instead express somatically diversified antigen receptors that contain leucine-rich-repeats, termed variable lymphocyte receptors (VLRs)(3,4), and that the type of VLR expressed is specific to the lymphocyte lineage: T-like lymphocytes express type A VLR (VLRA) genes, and B-like lymphocytes express VLRB genes(5). These clonally diverse anticipatory antigen receptors are assembled from incomplete genomic fragments by gene conversion(6-9), which is thought to be initiated by either of two genes encoding cytosine deaminase(9), cytosine deaminase 1 (CDA1) in T-like cells and CDA2 in B-like cells(5). It is unknown whether jawless fish, like jawed vertebrates, have dedicated primary lymphoid organs, such as the thymus, where the development and selection of lymphocytes takes place(10,11). Here we identify discrete thymus-like lympho-epithelial structures, termed thymoids, in the tips of the gill filaments and the neighbouring secondary lamellae (both within the gill basket) of lamprey larvae. Only in the thymoids was expression of the orthologue of the gene encoding forkhead box N1 (FOXN1)(10), a marker of the thymopoietic microenvironment in jawed vertebrates(12), accompanied by expression of CDA1 and VLRA. This expression pattern was unaffected by immunization of lampreys or by stimulation with a T-cell mitogen. Non-functional VLRA gene assemblies were found frequently in the thymoids but not elsewhere, further implicating the thymoid as the site of development of T-like cells in lampreys. These findings suggest that the similarities underlying the dual nature of the adaptive immune systems in the two sister groups of vertebrates extend to primary lymphoid organs.
C1 [Bajoghli, Baubak; Aghaallaei, Narges; Strohmeier, Christine; Schorpp, Michael; Boehm, Thomas] Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
   [Guo, Peng; Hirano, Masayuki; McCurley, Nathanael; Cooper, Max D.] Emory Vaccine Ctr, Atlanta, GA 30329 USA.
   [Guo, Peng; Hirano, Masayuki; McCurley, Nathanael; Cooper, Max D.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
   [Bockman, Dale E.] Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA.
C3 Max Planck Society; Emory University; Emory University; University System of Georgia; Augusta University
RP Boehm, T (corresponding author), Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, Stuebeweg 51, D-79108 Freiburg, Germany.
EM boehm@immunbio.mpg.de
FU Max Planck Society; Deutsche Forschungsgemeinschaft; National Institutes of Health; Georgia Research Alliance
NR 19
TC 163
Z9 186
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 3
PY 2011
VL 470
IS 7332
BP 90
EP U101
DI 10.1038/nature09655
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400040
PM 21293377
DA 2026-03-09
ER

PT J
AU Burga, A
   Casanueva, MO
   Lehner, B
AF Burga, Alejandro
   Olivia Casanueva, M.
   Lehner, Ben
TI Predicting mutation outcome from early stochastic variation in genetic interaction partners
SO NATURE
LA English
DT Article
ID t-box genes; expression; variability; redundancy; evolution; capacitor; hsp90
AB Many mutations, including those that cause disease, only have a detrimental effect in a subset of individuals. The reasons for this are usually unknown, but may include additional genetic variation and environmental risk factors(1). However, phenotypic discordance remains even in the absence of genetic variation, for example between monozygotic twins(2), and incomplete penetrance of mutations is frequent in isogenic model organisms in homogeneous environments(3,4). Here we propose a model for incomplete penetrance based on genetic interaction networks(5,6). Using Caenorhabditis elegans as a model system, we identify two compensation mechanisms that vary among individuals and influence mutation outcome. First, feedback induction of an ancestral gene duplicate differs across individuals, with high expression masking the effects of a mutation. This supports the hypothesis that redundancy is maintained in genomes to buffer stochastic developmental failure(7). Second, during normal embryonic development we find that there is substantial variation in the induction of molecular chaperones such as Hsp90 (DAF-21). Chaperones act as promiscuous buffers of genetic variation(8,9), and embryos with stronger induction of Hsp90 are less likely to be affected by an inherited mutation. Simultaneously quantifying the variation in these two independent responses allows the phenotypic outcome of a mutation to be more accurately predicted in individuals. Our model and methodology provide a framework for dissecting the causes of incomplete penetrance. Further, the results establish that inter-individual variation in both specific and more general buffering systems combine to determine the outcome inherited mutations in each individual.
C1 [Burga, Alejandro; Olivia Casanueva, M.; Lehner, Ben] Ctr Genom Regulat CRG, EMBL CRG Syst Biol Unit, Barcelona 08003, Spain.
   [Burga, Alejandro; Olivia Casanueva, M.; Lehner, Ben] Univ Pompeu Fabra UPF, Barcelona 08003, Spain.
   [Lehner, Ben] Ctr Genom Regulat CRG, Inst Catalana Recerca & Estudis Avancats, Barcelona 08003, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); ICREA
RP Lehner, B (corresponding author), Ctr Genom Regulat CRG, EMBL CRG Syst Biol Unit, Barcelona 08003, Spain.
EM ben.lehner@crg.eu
FU European Research Council; Institucio Catalana de Recerca i Estudis Avancats; Ministerio de Ciencia e Innovacion Plan Nacional [BFU2008-00365]; Agencia de Gestio d'juts Universitaris i de Recerca; ERASysBio+; European Molecular Biology Organization; EMBL-CRG Systems Biology Program; Formacion de Personal Investigador-Ministerio de Ciencia e Innovacion fellowship; Beatriu de Pinos Fellowship; National Institutes of Health National Center for Research Resources; ICREA Funding Source: Custom
NR 41
TC 142
Z9 170
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 8
PY 2011
VL 480
IS 7376
BP 250
EP U133
DI 10.1038/nature10665
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200053
PM 22158248
DA 2026-03-09
ER

PT J
AU Pall, P
   Aina, T
   Stone, DA
   Stott, PA
   Nozawa, T
   Hilberts, AGJ
   Lohmann, D
   Allen, MR
AF Pall, Pardeep
   Aina, Tolu
   Stone, Daithi A.
   Stott, Peter A.
   Nozawa, Toru
   Hilberts, Arno G. J.
   Lohmann, Dag
   Allen, Myles R.
TI Anthropogenic greenhouse gas contribution to flood risk in England and Wales in autumn 2000
SO NATURE
LA English
DT Article
ID climate-change; extreme rainfall; uk; attribution; emissions; trends
AB Interest in attributing the risk of damaging weather-related events to anthropogenic climate change is increasing(1). Yet climate models used to study the attribution problem typically do not resolve the weather systems associated with damaging events(2) such as the UK floods of October and November 2000. Occurring during the wettest autumn in England and Wales since records began in 1766(3,4), these floods damaged nearly 10,000 properties across that region, disrupted services severely, and caused insured losses estimated at 1.3 pound billion (refs 5, 6). Although the flooding was deemed a 'wakeup call' to the impacts of climate change at the time(7), such claims are typically supported only by general thermodynamic arguments that suggest increased extreme precipitation under global warming, but fail(8,9) to account fully for the complex hydrometeorology(4,10) associated with flooding. Here we present a multi-step, physically based 'probabilistic event attribution' framework showing that it is very likely that global anthropogenic greenhouse gas emissions substantially increased the risk of flood occurrence in England and Wales in autumn 2000. Using publicly volunteered distributed computing(11,12), we generate several thousand seasonal-forecast-resolution climate model simulations of autumn 2000 weather, both under realistic conditions, and under conditions as they might have been had these greenhouse gas emissions and the resulting large-scale warming never occurred. Results are fed into a precipitation-runoff model that is used to simulate severe daily river runoff events in England and Wales (proxy indicators of flood events). The precise magnitude of the anthropogenic contribution remains uncertain, but in nine out of ten cases our model results indicate that twentieth-century anthropogenic greenhouse gas emissions increased the risk of floods occurring in England and Wales in autumn 2000 by more than 20%, and in two out of three cases by more than 90%.
C1 [Pall, Pardeep] Swiss Fed Inst Technol, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Pall, Pardeep; Stone, Daithi A.; Allen, Myles R.] Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
   [Aina, Tolu] Univ Oxford, Oxford E Res Ctr, Oxford OX1 3QG, England.
   [Stone, Daithi A.; Allen, Myles R.] Oxford Univ Ctr Environm, Tyndall Ctr Oxford, Oxford OX1 3QY, England.
   [Stott, Peter A.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Nozawa, Toru] Natl Inst Environm Studies, Tsukuba, Ibaraki 3058506, Japan.
   [Hilberts, Arno G. J.; Lohmann, Dag] Risk Management Solut Ltd, London EC3R 8NB, England.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Oxford; University of Oxford; University of Oxford; Met Office - UK; Hadley Centre; National Institute for Environmental Studies - Japan
RP Pall, P (corresponding author), Swiss Fed Inst Technol, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
EM pardeep.pall@env.ethz.ch
FU NERC; Risk Management Solutions Ltd; WWF International; UK Department for Environment, Food, and Rural Affairs; Joint DECC and Defra Integrated Climate Programme-DECC/Defra [GA01101]; Japanese Ministry of Education, Culture, Sports, Science and Technology; US National Oceanic and Atmospheric Administration's Office; US Department of Energy; European Union [036946]; Smith School of Enterprise and the Environment
NR 37
TC 682
Z9 762
U1 7
U2 417
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 382
EP 385
DI 10.1038/nature09762
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100039
PM 21331040
DA 2026-03-09
ER

PT J
AU Pratt, FL
   Baker, PJ
   Blundell, SJ
   Lancaster, T
   Ohira-Kawamura, S
   Baines, C
   Shimizu, Y
   Kanoda, K
   Watanabe, I
   Saito, G
AF Pratt, F. L.
   Baker, P. J.
   Blundell, S. J.
   Lancaster, T.
   Ohira-Kawamura, S.
   Baines, C.
   Shimizu, Y.
   Kanoda, K.
   Watanabe, I.
   Saito, G.
TI Magnetic and non-magnetic phases of a quantum spin liquid
SO NATURE
LA English
DT Article
ID state; kappa-(bedt-ttf)(2)cu-2(cn)(3)
AB A quantum spin-liquid phase is an intriguing possibility for a system of strongly interacting magnetic units in which the usual magnetically ordered ground state is avoided owing to strong quantum fluctuations. It was first predicted theoretically for a triangular-lattice model with antiferromagnetically coupled S = 1/2 spins(1). Recently, materials have become available showing persuasive experimental evidence for such a state(2). Although many studies show that the ideal triangular lattice of S = 1/2 Heisenberg spins actually orders magnetically into a three-sublattice, non-collinear 1206 arrangement, quantum fluctuations significantly reduce the size of the ordered moment(3). This residual ordering can be completely suppressed when higher-order ring-exchange magnetic interactions are significant, as found in nearly metallic Mott insulators(4). The layered molecular system kappa-(BEDT-TTF)(2)Cu(2)(CN)(3) is a Mott insulator with an almost isotropic, triangular magnetic lattice of spin-1/2 BEDT-TTF dimers(5) that provides a prime example of a spin liquid formed in this way(6-11). Despite a high-temperature exchange coupling, J, of 250 K (ref. 6), no obvious signature of conventional magnetic ordering is seen down to 20 mK (refs 7, 8). Here we show, using muon spin rotation, that applying a small magnetic field to this system produces a quantum phase transition between the spin-liquid phase and an antiferromagnetic phase with a strongly suppressed moment. This can be described as Bose-Einstein condensation of spin excitations with an extremely small spin gap. At higher fields, a second transition is found that suggests a threshold for deconfinement of the spin excitations. Our studies reveal the low-temperature magnetic phase diagram and enable us to measure characteristic critical properties. We compare our results closely with current theoretical models, and this gives some further insight into the nature of the spin-liquid phase.
C1 [Pratt, F. L.; Baker, P. J.] Rutherford Appleton Lab, ISIS Facil, Chilton OX11 0QX, England.
   [Blundell, S. J.; Lancaster, T.] Univ Oxford, Clarendon Lab, Dept Phys, Oxford OX1 3PU, England.
   [Ohira-Kawamura, S.] Japan Atom Energy Agcy, J PARC Ctr, Neutron Sci Sect, Tokai, Ibaraki 3191195, Japan.
   [Shimizu, Y.] Nagoya Univ, Inst Adv Res, Nagoya, Aichi 4648601, Japan.
   [Baines, C.] Paul Scherrer Inst, Lab Muon Spin Spect, CH-5232 Villigen, Switzerland.
   [Kanoda, K.] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1138656, Japan.
   [Watanabe, I.] RIKEN, Meson Sci Lab, Wako, Saitama 3510198, Japan.
   [Saito, G.] Kyoto Univ, Grad Sch Sci, Div Chem, Sakyo Ku, Kyoto 6068502, Japan.
C3 UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of Oxford; Japan Atomic Energy Agency; Nagoya University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Tokyo; RIKEN; Kyoto University
RP Pratt, FL (corresponding author), Rutherford Appleton Lab, ISIS Facil, Chilton OX11 0QX, England.
EM francis.pratt@stfc.ac.uk
FU EPSRC (UK); Grants-in-Aid for Scientific Research [22684018, 22655045, 20110002, 23225005, 20110001] Funding Source: KAKEN; EPSRC [EP/G003092/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G003092/1] Funding Source: researchfish
NR 30
TC 163
Z9 176
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 31
PY 2011
VL 471
IS 7340
BP 612
EP 616
DI 10.1038/nature09910
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200037
PM 21455176
DA 2026-03-09
ER

PT J
AU Martínez-Garcia, A
   Rosell-Melé, A
   Jaccard, SL
   Geibert, W
   Sigman, DM
   Haug, GH
AF Martinez-Garcia, Alfredo
   Rosell-Mele, Antoni
   Jaccard, Samuel L.
   Geibert, Walter
   Sigman, Daniel M.
   Haug, Gerald H.
TI Southern Ocean dust-climate coupling over the past four million years
SO NATURE
LA English
DT Article
ID atmospheric co2; equatorial pacific; polar ocean; iron; stratification; productivity; circulation
AB Dust has the potential to modify global climate by influencing the radiative balance of the atmosphere and by supplying iron and other essential limiting micronutrients to the ocean(1,2). Indeed, dust supply to the Southern Ocean increases during ice ages, and 'iron fertilization' of the subantarctic zone may have contributed up to 40 parts per million by volume (p. p. m. v.) of the decrease (80-100 p. p. m. v.) in atmospheric carbon dioxide observed during late Pleistocene glacial cycles(3-7). So far, however, the magnitude of Southern Ocean dust deposition in earlier times and its role in the development and evolution of Pleistocene glacial cycles have remained unclear. Here we report a high-resolution record of dust and iron supply to the Southern Ocean over the past four million years, derived from the analysis of marine sediments from ODP Site 1090, located in the Atlantic sector of the subantarctic zone. The close correspondence of our dust and iron deposition records with Antarctic ice core reconstructions of dust flux covering the past 800,000 years (refs 8, 9) indicates that both of these archives record large-scale deposition changes that should apply to most of the Southern Ocean, validating previous interpretations of the ice core data. The extension of the record beyond the interval covered by the Antarctic ice cores reveals that, in contrast to the relatively gradual intensification of glacial cycles over the past three million years, Southern Ocean dust and iron flux rose sharply at the Mid-Pleistocene climatic transition around 1.25 million years ago. This finding complements previous observations over late Pleistocene glacial cycles(5,8,9), providing new evidence of a tight connection between high dust input to the Southern Ocean and the emergence of the deep glaciations that characterize the past one million years of Earth history.
C1 [Martinez-Garcia, Alfredo; Jaccard, Samuel L.; Haug, Gerald H.] ETH, Inst Geol, CH-8092 Zurich, Switzerland.
   [Martinez-Garcia, Alfredo; Haug, Gerald H.] Univ Potsdam, Inst Geosci, DFG Leibniz Ctr Surface Proc & Climate Studies, D-14476 Potsdam, Germany.
   [Martinez-Garcia, Alfredo; Rosell-Mele, Antoni] Univ Autonoma Barcelona, ICTA, Bellaterra 08193, Catalonia, Spain.
   [Rosell-Mele, Antoni] ICREA, Barcelona 08010, Catalonia, Spain.
   [Rosell-Mele, Antoni] Oregon State Univ, Coll Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Geibert, Walter] Univ Edinburgh, Sch GeoSci, Edinburgh EH9 3JW, Midlothian, Scotland.
   [Geibert, Walter] Scottish Assoc Marine Sci SAMS, Scottish Marine Lab, Oban PA37 1QA, Argyll, Scotland.
   [Sigman, Daniel M.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Potsdam; Autonomous University of Barcelona; ICREA; Oregon State University; University of Edinburgh; Princeton University
RP Martínez-Garcia, A (corresponding author), ETH, Inst Geol, CH-8092 Zurich, Switzerland.
EM alfredo.martinez-garcia@erdw.ethz.ch
FU Spanish Ministry of Science and Innovation (MICINN); European Commission; Deutsche Forschungsgemeinschaft (DFG); Natural Environment Research Council [dml010007] Funding Source: researchfish; NERC [dml010007] Funding Source: UKRI; ICREA Funding Source: Custom
NR 36
TC 318
Z9 387
U1 6
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 AUG 18
PY 2011
VL 476
IS 7360
BP 312
EP U141
DI 10.1038/nature10310
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500033
PM 21814203
DA 2026-03-09
ER

PT J
AU Baillie, JK
   Barnett, MW
   Upton, KR
   Gerhardt, DJ
   Richmond, TA
   De Sapio, F
   Brennan, P
   Rizzu, P
   Smith, S
   Fell, M
   Talbot, RT
   Gustincich, S
   Freeman, TC
   Mattick, JS
   Hume, DA
   Heutink, P
   Carninci, P
   Jeddeloh, JA
   Faulkner, GJ
AF Baillie, J. Kenneth
   Barnett, Mark W.
   Upton, Kyle R.
   Gerhardt, Daniel J.
   Richmond, Todd A.
   De Sapio, Fioravante
   Brennan, Paul
   Rizzu, Patrizia
   Smith, Sarah
   Fell, Mark
   Talbot, Richard T.
   Gustincich, Stefano
   Freeman, Thomas C.
   Mattick, John S.
   Hume, David A.
   Heutink, Peter
   Carninci, Piero
   Jeddeloh, Jeffrey A.
   Faulkner, Geoffrey J.
TI Somatic retrotransposition alters the genetic landscape of the human brain
SO NATURE
LA English
DT Article
ID l1 retrotransposition; human genome; line-1 retrotransposition; mobile elements; cells; evolution; endonuclease; disruption; mosaicism; insertion
AB Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes(1). At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease(2,3). Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells(4,5), excluding early embryo development and some malignancies(6,7). Recent reports of L1 expression(8,9) and copy number variation(10,11) in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.
C1 [Baillie, J. Kenneth; Barnett, Mark W.; Upton, Kyle R.; De Sapio, Fioravante; Smith, Sarah; Fell, Mark; Talbot, Richard T.; Freeman, Thomas C.; Hume, David A.; Faulkner, Geoffrey J.] Univ Edinburgh, Roslin Inst, Div Genet & Genom, Edinburgh EH25 9RG, Midlothian, Scotland.
   [Baillie, J. Kenneth; Barnett, Mark W.; Upton, Kyle R.; De Sapio, Fioravante; Smith, Sarah; Fell, Mark; Talbot, Richard T.; Freeman, Thomas C.; Hume, David A.; Faulkner, Geoffrey J.] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9RG, Midlothian, Scotland.
   [Gerhardt, Daniel J.; Richmond, Todd A.; Jeddeloh, Jeffrey A.] Roche NimbleGen Inc, Madison, WI 53719 USA.
   [Brennan, Paul] Western Gen Hosp, Edinburgh Canc Res Ctr, Edinburgh EH4 2XR, Midlothian, Scotland.
   [Rizzu, Patrizia; Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Sect Med Genom, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands.
   [Gustincich, Stefano] Int Sch Adv Studies SISSA, Neurobiol Sect, I-34136 Trieste, Italy.
   [Mattick, John S.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
   [Carninci, Piero] RIKEN Yokohama Inst, Om Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
C3 University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; Roche Holding; Roche Holding USA; University of Edinburgh; Vrije Universiteit Amsterdam; Amsterdam University Medical Center; International School for Advanced Studies (SISSA); University of Queensland; RIKEN
RP Faulkner, GJ (corresponding author), Univ Edinburgh, Roslin Inst, Div Genet & Genom, Edinburgh EH25 9RG, Midlothian, Scotland.
EM faulknergj@gmail.com
FU Wellcome Trust [090385/Z/09/Z]; Institute Strategic Programme Grant; British BBSRC [BB/H005935/1]; Australian NHMRC [575585]; Biotechnology and Biological Sciences Research Council [BBS/E/D/05191131, BB/H005935/1, BBS/E/D/05191130] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [575585] Funding Source: National Health and Medical Research Council (NHMRC); Wellcome Trust [090385/Z/09/Z] Funding Source: Wellcome Trust; BBSRC [BB/H005935/1, BBS/E/D/05191130, BBS/E/D/05191131] Funding Source: UKRI
NR 30
TC 544
Z9 653
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 NOV 24
PY 2011
VL 479
IS 7374
BP 534
EP 537
DI 10.1038/nature10531
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600052
PM 22037309
DA 2026-03-09
ER

PT J
AU Kulkarni, S
   Savan, R
   Qi, Y
   Gao, XJ
   Yuki, Y
   Bass, SE
   Martin, MP
   Hunt, P
   Deeks, SG
   Telenti, A
   Pereyra, F
   Goldstein, D
   Wolinsky, S
   Walker, B
   Young, HA
   Carrington, M
AF Kulkarni, Smita
   Savan, Ram
   Qi, Ying
   Gao, Xiaojiang
   Yuki, Yuko
   Bass, Sara E.
   Martin, Maureen P.
   Hunt, Peter
   Deeks, Steven G.
   Telenti, Amalio
   Pereyra, Florencia
   Goldstein, David
   Wolinsky, Steven
   Walker, Bruce
   Young, Howard A.
   Carrington, Mary
TI Differential microRNA regulation of HLA-C expression and its association with HIV control
SO NATURE
LA English
DT Article
ID surface expression; deadenylation; antigens; genome; genes
AB The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism(1), lower expression on the cell surface(2,3), and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors(4). A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV5-7, and with levels of HLA-C messenger RNA transcripts(8) and cell-surface expression(7), but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C-7. Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.
C1 [Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Bass, Sara E.; Martin, Maureen P.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Martin, Maureen P.; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
   [Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Martin, Maureen P.; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Hunt, Peter; Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Aids, San Francisco, CA 94110 USA.
   [Telenti, Amalio] Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland.
   [Goldstein, David] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27708 USA.
   [Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; University of California System; University of California San Francisco; University of Lausanne; Duke University; Northwestern University; Feinberg School of Medicine
RP Carrington, M (corresponding author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E, N02-CP-55504, R01-DA04334, R01-DA12568]; NIH, National Cancer Institute, Center for Cancer Research; Cancer Inflammation Program Project Award; Bill & Melinda Gates Foundation; Mark and Lisa Schwartz Foundation; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung and Blood Institute [UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; Swiss HIV Cohort Study; Swiss National Science Foundation [33CSC0-108787];  [UL1 RR024131];  [P30 AI27763]; National Cancer Institute [ZIABC010791] Funding Source: NIH RePORTER
NR 27
TC 283
Z9 320
U1 0
U2 16
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 495
EP U548
DI 10.1038/nature09914
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600039
PM 21499264
DA 2026-03-09
ER

PT J
AU Xue, T
   Do, MTH
   Riccio, A
   Jiang, Z
   Hsieh, J
   Wang, HC
   Merbs, SL
   Welsbie, DS
   Yoshioka, T
   Weissgerber, P
   Stolz, S
   Flockerzi, V
   Freichel, M
   Simon, MI
   Clapham, DE
   Yau, KW
AF Xue, T.
   Do, M. T. H.
   Riccio, A.
   Jiang, Z.
   Hsieh, J.
   Wang, H. C.
   Merbs, S. L.
   Welsbie, D. S.
   Yoshioka, T.
   Weissgerber, P.
   Stolz, S.
   Flockerzi, V.
   Freichel, M.
   Simon, M. I.
   Clapham, D. E.
   Yau, K. -W.
TI Melanopsin signalling in mammalian iris and retina
SO NATURE
LA English
DT Article
ID ganglion-cells; differential regulation; pupillary constriction; light reflex; phototransduction; expression; mice; photosensitivity; localization; photopigment
AB Non-mammalian vertebrates have an intrinsically photosensitive iris and thus a local pupillary light reflex (PLR). In contrast, it is thought that the PLR in mammals generally requires neuronal circuitry connecting the eye and the brain. Here we report that an intrinsic component of the PLR is in fact widespread in nocturnal and crepuscular mammals. In mouse, this intrinsic PLR requires the visual pigment melanopsin; it also requires PLC beta 4, a vertebrate homologue of the Drosophila NorpA phospholipase C which mediates rhabdomeric phototransduction. The Plcb4(-/-) genotype, in addition to removing the intrinsic PLR, also essentially eliminates the intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1-ipRGCs), which are by far the most photosensitive ipRGC subtype and also have the largest response to light. Ablating in mouse the expression of both TRPC6 and TRPC7, members of the TRP channel superfamily, also essentially eliminated the M1-ipRGC light response but the intrinsic PLR was not affected. Thus, melanopsin signalling exists in both iris and retina, involving a PLC beta 4-mediated pathway that nonetheless diverges in the two locations.
C1 [Xue, T.; Do, M. T. H.; Jiang, Z.; Hsieh, J.; Wang, H. C.; Yoshioka, T.; Yau, K. -W.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Xue, T.; Do, M. T. H.; Jiang, Z.; Yau, K. -W.] Johns Hopkins Univ, Sch Med, Ctr Sensory Biol, Baltimore, MD 21205 USA.
   [Riccio, A.; Clapham, D. E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA.
   [Riccio, A.; Clapham, D. E.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Hsieh, J.] Johns Hopkins Univ, BA MS Concurrent Program Neurosci, Baltimore, MD 21238 USA.
   [Wang, H. C.] Johns Hopkins Univ, Sch Med, Grad Program Neurosci, Baltimore, MD 21205 USA.
   [Merbs, S. L.; Welsbie, D. S.; Yau, K. -W.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Yoshioka, T.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21238 USA.
   [Weissgerber, P.; Stolz, S.; Flockerzi, V.; Freichel, M.] Univ Saarland, Inst Expt & Klin Pharmakol & Toxikol, D-66421 Homburg, Germany.
   [Simon, M. I.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
C3 Johns Hopkins University; Johns Hopkins University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Saarland University; California Institute of Technology
RP Xue, T (corresponding author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
EM txue77@gmail.com; kwyau@mail.jhmi.edu
FU US NIH [EY14596]; Antonio Champalimaud Vision Award (Portugal); National Eye Institute [R01EY014596] Funding Source: NIH RePORTER
NR 50
TC 233
Z9 280
U1 0
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 67
EP 73
DI 10.1038/nature10567
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600033
PM 22051675
DA 2026-03-09
ER

PT J
AU Ladevèze, S
   de Muizon, C
   Beck, RMD
   Germain, D
   Cespedes-Paz, R
AF Ladeveze, Sandrine
   de Muizon, Christian
   Beck, Robin M. D.
   Germain, Damien
   Cespedes-Paz, Ricardo
TI Earliest evidence of mammalian social behaviour in the basal Tertiary of Bolivia
SO NATURE
LA English
DT Article
ID sexual-dimorphism; south-america; marsupials; organization; didelphidae; dasyuridae; paleocene; history; origin
AB The vast majority of Mesozoic and early Cenozoic metatherian mammals (extinct relatives of modern marsupials) are known only from partial jaws or isolated teeth, which give insight into their probable diets and phylogenetic relationships but little else. The few skulls known are generally crushed, incomplete or both(1-4), and associated postcranial material is extremely rare. Here we report the discovery of an exceptionally large number of almost undistorted, nearly complete skulls and skeletons of a stem-metatherian, Pucadelphys andinus, in the early Palaeocene epoch(5) of Tiupampa in Bolivia(6-8). These give an unprecedented glimpse into early metatherian morphology, evolutionary relationships and, especially, ecology. The remains of 35 individuals have been collected, with 22 of these represented by nearly complete skulls and associated postcrania. These individuals were probably buried in a single catastrophic event, and so almost certainly belong to the same population(9). The preservation of multiple adult, sub-adult and juvenile individuals in close proximity (<1 m(2)) is indicative of gregarious social behaviour or at least a high degree of social tolerance and frequent interaction. Such behaviour is unknown in living didelphids, which are highly solitary and have been regarded, perhaps wrongly, as the most generalized living marsupials. The Tiupampan P. andinus population also exhibits strong sexual dimorphism, which, in combination with gregariousness, suggests strong male-male competition and polygyny. Our study shows that social interactions occurred in metatherians as early as the basal Palaeocene and that solitary behaviour may not be plesiomorphic for Metatheria as a whole.
C1 [Ladeveze, Sandrine] Royal Belgian Inst Nat Sci, Dept Palaeontol, B-1000 Brussels, Belgium.
   [de Muizon, Christian; Germain, Damien] UPMC, MNHN, Dept Hist tERRE, CNRS,UMR7207,CR2P, F-75005 Paris, France.
   [Beck, Robin M. D.] Amer Museum Nat Hist, Dept Mammal, New York, NY 10024 USA.
   [Cespedes-Paz, Ricardo] Museo Hist Nat Alcide Orbigny, Cochabamba, Bolivia.
C3 Royal Belgian Institute of Natural Sciences; Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); American Museum of Natural History (AMNH)
RP Ladevèze, S (corresponding author), Royal Belgian Inst Nat Sci, Dept Palaeontol, 29 Rue Vautier, B-1000 Brussels, Belgium.
EM sandrine.ladeveze@naturalsciences.be; muizon@mnhn.fr
FU National Geographic Society [2908-84]; Institut Francais d'Etudes Andines; Belgian Federal Science Policy Office [MO/36/020]; NSF [DEB-0743039]; Direct For Biological Sciences; Division Of Environmental Biology [0946430] Funding Source: National Science Foundation
NR 28
TC 35
Z9 38
U1 2
U2 29
PU 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 2
PY 2011
VL 474
IS 7349
BP 83
EP 86
DI 10.1038/nature09987
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700042
PM 21552278
DA 2026-03-09
ER

PT J
AU Wang, ZC
   Saito, M
   McKenna, KP
   Gu, L
   Tsukimoto, S
   Shluger, AL
   Ikuhara, Y
AF Wang, Zhongchang
   Saito, Mitsuhiro
   McKenna, Keith P.
   Gu, Lin
   Tsukimoto, Susumu
   Shluger, Alexander L.
   Ikuhara, Yuichi
TI Atom-resolved imaging of ordered defect superstructures at individual grain boundaries
SO NATURE
LA English
DT Article
ID mgo; segregation; simulation; microscopy; resolution; alumina
AB The ability to resolve spatially and identify chemically atoms in defects would greatly advance our understanding of the correlation between structure and property in materials(1). This is particularly important in polycrystalline materials, in which the grain boundaries have profound implications for the properties and applications of the final material(2). However, such atomic resolution is still extremely difficult to achieve, partly because grain boundaries are effective sinks for atomic defects and impurities(3-5), which may drive structural transformation of grain boundaries and consequently modify material properties(6,7). Regardless of the origin of these sinks, the interplay between defects and grain boundaries complicates our efforts to pinpoint the exact sites and chemistries of the entities present in the defective regions, thereby limiting our understanding of how specific defects mediate property changes. Here we show that the combination of advanced electron microscopy, spectroscopy and first-principles calculations can provide three-dimensional images of complex, multicomponent grain boundaries with both atomic resolution and chemical sensitivity. The high resolution of these techniques allows us to demonstrate that even for magnesium oxide, which has a simple rock-salt structure, grain boundaries can accommodate complex ordered defect superstructures that induce significant electron trapping in the bandgap of the oxide. These results offer insights into interactions between defects and grain boundaries in ceramics and demonstrate that atomic-scale analysis of complex multicomponent structures in materials is now becoming possible.
C1 [Wang, Zhongchang; Saito, Mitsuhiro; McKenna, Keith P.; Gu, Lin; Tsukimoto, Susumu; Shluger, Alexander L.; Ikuhara, Yuichi] Tohoku Univ, Adv Inst Mat Res, World Premier Int Res Ctr, Aoba Ku, Sendai, Miyagi 9808577, Japan.
   [McKenna, Keith P.; Shluger, Alexander L.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [McKenna, Keith P.; Shluger, Alexander L.] UCL, London Ctr Nanotechnol, London WC1E 6BT, England.
   [Ikuhara, Yuichi] Univ Tokyo, Inst Engn Innovat, Bunkyo Ku, Tokyo 1138656, Japan.
   [Ikuhara, Yuichi] Japan Fine Ceram Ctr, Nanostruct Res Lab, Atsuta Ku, Nagoya, Aichi 4568587, Japan.
C3 Tohoku University; University of London; University College London; University of London; University College London; University of Tokyo; Japan Fine Ceramics Center
RP Wang, ZC (corresponding author), Tohoku Univ, Adv Inst Mat Res, World Premier Int Res Ctr, Aoba Ku, 2-1-1 Katahira, Sendai, Miyagi 9808577, Japan.
EM zcwang@wpi-aimr.tohoku.ac.jp
FU MEXT, Japan [474]; IZUMI Science Foundation; MURATA Science Foundation; Nippon Sheet Glass Foundation;  [22760500];  [23560817];  [22740192]; Grants-in-Aid for Scientific Research [23560817, 19053001, 22760500, 19053003] Funding Source: KAKEN
NR 30
TC 243
Z9 257
U1 4
U2 380
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 17
PY 2011
VL 479
IS 7373
BP 380
EP 383
DI 10.1038/nature10593
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700041
PM 22094698
DA 2026-03-09
ER

PT J
AU Stadler, MB
   Murr, R
   Burger, L
   Ivanek, R
   Lienert, F
   Schöler, A
   Wirbelauer, C
   Oakeley, EJ
   Gaidatzis, D
   Tiwari, VK
   Schübeler, D
AF Stadler, Michael B.
   Murr, Rabih
   Burger, Lukas
   Ivanek, Robert
   Lienert, Florian
   Schoeler, Anne
   Wirbelauer, Christiane
   Oakeley, Edward J.
   Gaidatzis, Dimos
   Tiwari, Vijay K.
   Schuebeler, Dirk
TI DNA-binding factors shape the mouse methylome at distal regulatory regions
SO NATURE
LA English
DT Article
ID embryonic stem-cells; human genome; hypersensitive sites; transcription factor; chromatin-structure; methylation changes; gene-regulation; identification; enhancer; demethylation
AB Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.
C1 [Stadler, Michael B.; Murr, Rabih; Burger, Lukas; Ivanek, Robert; Lienert, Florian; Schoeler, Anne; Wirbelauer, Christiane; Gaidatzis, Dimos; Tiwari, Vijay K.; Schuebeler, Dirk] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Stadler, Michael B.; Burger, Lukas; Schoeler, Anne; Gaidatzis, Dimos] Swiss Inst Bioinformat, CH-4058 Basel, Switzerland.
   [Lienert, Florian; Schoeler, Anne; Schuebeler, Dirk] Univ Basel, Fac Sci, CH-4056 Basel, Switzerland.
   [Oakeley, Edward J.] Novartis Inst BioMed Res, CH-4056 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research; Swiss Institute of Bioinformatics; University of Basel; Novartis
RP Schübeler, D (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM dirk@fmi.ch
FU EMBO; Marie Curie International Incoming fellowship; Novartis Research Foundation; European Union (NoE) [FP7-HEALTH-2010-257082]; European Research Council (ERC EpiGePlas); SNF; Swiss initiative in Systems Biology
NR 50
TC 1073
Z9 1270
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 DEC 22
PY 2011
VL 480
IS 7378
BP 490
EP 495
DI 10.1038/nature10716
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000053
PM 22170606
DA 2026-03-09
ER

PT J
AU Robert, T
   Vanoli, F
   Chiolo, I
   Shubassi, G
   Bernstein, KA
   Rothstein, R
   Botrugno, OA
   Parazzoli, D
   Oldani, A
   Minucci, S
   Foiani, M
AF Robert, Thomas
   Vanoli, Fabio
   Chiolo, Irene
   Shubassi, Ghadeer
   Bernstein, Kara A.
   Rothstein, Rodney
   Botrugno, Oronza A.
   Parazzoli, Dario
   Oldani, Amanda
   Minucci, Saverio
   Foiani, Marco
TI HDACs link the DNA damage response, processing of double-strand breaks and autophagy
SO NATURE
LA English
DT Article
ID valproic acid; end resection; checkpoint; acetylation; activation; yeast; sae2; helicase; sgs1; srs2
AB Protein acetylation is mediated by histone acetyltransferases (HATs) and deacetylases (HDACs), which influence chromatin dynamics, protein turnover and the DNA damage response. ATM and ATR mediate DNA damage checkpoints by sensing double-strand breaks and single-strand-DNA-RFA nucleofilaments, respectively. However, it is unclear how acetylation modulates the DNA damage response. Here we show that HDAC inhibition/ablation specifically counteracts yeast Mec1 (orthologue of human ATR) activation, double-strand-break processing and single-strand-DNA-RFA nucleofilament formation. Moreover, the recombination protein Sae2 (human CtIP) is acetylated and degraded after HDAC inhibition. Two HDACs, Hda1 and Rpd3, and one HAT, Gcn5, have key roles in these processes. We also find that HDAC inhibition triggers Sae2 degradation by promoting autophagy that affects the DNA damage sensitivity of hda1 and rpd3 mutants. Rapamycin, which stimulates autophagy by inhibiting Tor, also causes Sae2 degradation. We propose that Rpd3, Hda1 and Gcn5 control chromosome stability by coordinating the ATR checkpoint and double-strand-break processing with autophagy.
C1 [Robert, Thomas; Vanoli, Fabio; Chiolo, Irene; Shubassi, Ghadeer; Foiani, Marco] Fdn IFOM, I-20139 Milan, Italy.
   [Chiolo, Irene] LBNL, Dept Genome Biol, Berkeley, CA 94710 USA.
   [Bernstein, Kara A.; Rothstein, Rodney] Columbia Univ, Dept Genet & Dev, Med Ctr, New York, NY 10032 USA.
   [Botrugno, Oronza A.; Minucci, Saverio] European Inst Oncol, I-20139 Milan, Italy.
   [Parazzoli, Dario; Oldani, Amanda] Cogentech, I-20139 Milan, Italy.
   [Minucci, Saverio; Foiani, Marco] Univ Milan, DSBB, I-20139 Milan, Italy.
C3 IFOM - FIRC Institute of Molecular Oncology; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Columbia University; IRCCS European Institute of Oncology (IEO); University of Milan
RP Foiani, M (corresponding author), Fdn IFOM, IFOM IEO Campus,Via Adamello 16, I-20139 Milan, Italy.
EM saverio.minucci@ifom-ieo-campus.it; marco.foiani@ifom-ieo-campus.it
FU Italian Association for Cancer Research; Telethon; European Community (GENICA); Italian Ministry of Health; FRM; EMBO; HFSP; FIRC;  [GM50237];  [GM67055];  [GM088413]
NR 47
TC 343
Z9 398
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 MAR 3
PY 2011
VL 471
IS 7336
BP 74
EP 79
DI 10.1038/nature09803
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100036
PM 21368826
DA 2026-03-09
ER

PT J
AU Nandy, D
   Muñoz-Jaramillo, A
   Martens, PCH
AF Nandy, Dibyendu
   Munoz-Jaramillo, Andres
   Martens, Petrus C. H.
TI The unusual minimum of sunspot cycle 23 caused by meridional plasma flow variations
SO NATURE
LA English
DT Article
ID flux-transport; solar dynamo; magnetic-field; model; oscillation; strength
AB Direct observations over the past four centuries(1) show that the number of sunspots observed on the Sun's surface varies periodically, going through successive maxima and minima. Following sunspot cycle 23, the Sun went into a prolonged minimum characterized by a very weak polar magnetic field(2,3) and an unusually large number of days without sunspots(4). Sunspots are strongly magnetized regions(5) generated by a dynamo mechanism(6) that recreates the solar polar field mediated through plasma flows(7). Here we report results from kinematic dynamo simulations which demonstrate that a fast meridional flow in the first half of a cycle, followed by a slower flow in the second half, reproduces both characteristics of the minimum of sunspot cycle 23. Our model predicts that, in general, very deep minima are associated with weak polar fields. Sunspots govern the solar radiative energy(8,9) and radio flux, and, in conjunction with the polar field, modulate the solar wind, the heliospheric open flux and, consequently, the cosmic ray flux at Earth(3,10,11).
C1 [Nandy, Dibyendu] Indian Inst Sci Educ & Res, Dept Phys Sci, Mohanpur 741252, W Bengal, India.
   [Munoz-Jaramillo, Andres; Martens, Petrus C. H.] Montana State Univ, Dept Phys, Bozeman, MT 59717 USA.
   [Munoz-Jaramillo, Andres; Martens, Petrus C. H.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 Indian Institute of Science Education & Research (IISER) - Kolkata; Montana State University System; Montana State University Bozeman; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution
RP Nandy, D (corresponding author), Indian Inst Sci Educ & Res, Dept Phys Sci, Mohanpur 741252, W Bengal, India.
EM dnandi@iiserkol.ac.in
FU Government of India at the Indian Institute of Science Education and Research, Kolkata; NASA; Montana State University
NR 28
TC 115
Z9 124
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 80
EP 82
DI 10.1038/nature09786
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100037
PM 21368827
DA 2026-03-09
ER

PT J
AU Tada, K
   Susumu, H
   Sakuno, T
   Watanabe, Y
AF Tada, Kenji
   Susumu, Hiroaki
   Sakuno, Takeshi
   Watanabe, Yoshinori
TI Condensin association with histone H2A shapes mitotic chromosomes
SO NATURE
LA English
DT Article
ID aurora-b kinase; fission yeast; meiosis-i; budding yeast; schizosaccharomyces-pombe; monopolar attachment; gene-transcription; h3 phosphorylation; mitosis; kinetochores
AB Chromosome structure is dynamically regulated during cell division, and this regulation is dependent, in part, on condensin. The localization of condensin at chromosome arms is crucial for chromosome partitioning during anaphase. Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear. Here we show that fission yeast (Schizosaccharomyces pombe) kinetochore proteins Pcs1 and Mde4-homologues of budding yeast (Saccharomyces cerevisiae) monopolin subunits and known to prevent merotelic kinetochore orientation-act as a condensin 'recruiter' at kinetochores, and that condensin itself may act to clamp microtubule binding sites during metaphase. In addition to the regional recruitment factors, overall condensin association with chromatin is governed by the chromosomal passenger kinase Aurora B. Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin 'receptors' of condensin. Condensin phosphorylation and its deposition onto chromosome arms reach a peak during anaphase, when Aurora B kinase relocates from centromeres to the spindle midzone, where the separating chromosome arms are positioned. Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning.
C1 [Tada, Kenji; Susumu, Hiroaki; Sakuno, Takeshi; Watanabe, Yoshinori] Univ Tokyo, Lab Chromosome Dynam, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
   [Tada, Kenji; Susumu, Hiroaki; Watanabe, Yoshinori] Univ Tokyo, Grad Sch Sci, Grad Program Biophys & Biochem, Tokyo 1130032, Japan.
C3 University of Tokyo; University of Tokyo
RP Watanabe, Y (corresponding author), Univ Tokyo, Lab Chromosome Dynam, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
EM ywatanab@iam.u-tokyo.ac.jp
FU Global COE Program(Integrative Life Science Based on the Study of Biosignaling Mechanisms); Special Coordination Funds for Promoting Science and Technology; MEXT, Japan; Grants-in-Aid for Scientific Research [21000010] Funding Source: KAKEN
NR 58
TC 154
Z9 177
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 23
PY 2011
VL 474
IS 7352
BP 477
EP U105
DI 10.1038/nature10179
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700041
PM 21633354
DA 2026-03-09
ER

PT J
AU Lin, YJ
   Jiménez-García, K
   Spielman, IB
AF Lin, Y. -J.
   Jimenez-Garcia, K.
   Spielman, I. B.
TI Spin-orbit-coupled Bose-Einstein condensates
SO NATURE
LA English
DT Article
ID insulator; state
AB Spin-orbit (SO) coupling-the interaction between a quantum particle's spin and its momentum-is ubiquitous in physical systems. In condensed matter systems, SO coupling is crucial for the spin-Hall effect(1,2) and topological insulators(3-5); it contributes to the electronic properties of materials such as GaAs, and is important for spintronic devices(6). Quantum many-body systems of ultracold atoms can be precisely controlled experimentally, and would therefore seem to provide an ideal platform on which to study SO coupling. Although an atom's intrinsic SO coupling affects its electronic structure, it does not lead to coupling between the spin and the centre-of-mass motion of the atom. Here, we engineer SO coupling (with equal Rashba(7) and Dresselhaus(8) strengths) in a neutral atomic Bose-Einstein condensate by dressing two atomic spin states with a pair of lasers(9). Such coupling has not been realized previously for ultracold atomic gases, or indeed any bosonic system. Furthermore, in the presence of the laser coupling, the interactions between the two dressed atomic spin states are modified, driving a quantum phase transition from a spatially spin-mixed state (lasers off) to a phase-separated state (above a critical laser intensity). We develop a many-body theory that provides quantitative agreement with the observed location of the transition. The engineered SO coupling-equally applicable for bosons and fermions-sets the stage for the realization of topological insulators in fermionic neutral atom systems.
C1 [Lin, Y. -J.; Jimenez-Garcia, K.; Spielman, I. B.] NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
   [Lin, Y. -J.; Jimenez-Garcia, K.; 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 ONR; ARO; DARPA OLE; NSF through the Physics Frontier Center at the Joint Quantum Institute; Division Of Physics; Direct For Mathematical & Physical Scien [0822671] Funding Source: National Science Foundation
NR 30
TC 1928
Z9 2104
U1 8
U2 457
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 83
EP U99
DI 10.1038/nature09887
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100038
PM 21368828
DA 2026-03-09
ER

PT J
AU Bristow, TF
   Bonifacie, M
   Derkowski, A
   Eiler, JM
   Grotzinger, JP
AF Bristow, Thomas F.
   Bonifacie, Magali
   Derkowski, Arkadiusz
   Eiler, John M.
   Grotzinger, John P.
TI A hydrothermal origin for isotopically anomalous cap dolostone cements from south China
SO NATURE
LA English
DT Article
ID gas hydrate; neoproterozoic seawater; doushantuo formation; methane seeps; carbonate; evolution; oxygen; fractionation; temperature; earth
AB The release of methane into the atmosphere through destabilization of clathrates is a positive feedback mechanism capable of amplifying global warming trends that may have operated several times in the geological past(1-3). Such methane release is a hypothesized cause or amplifier for one of the most drastic global warming events in Earth history, the end of the Marinoan 'snowball Earth' ice age, similar to 635 Myr ago(4-7). A key piece of evidence supporting this hypothesis is the occurrence of exceptionally depleted carbon isotope signatures (delta(13)C(PDB) down to -48 parts per thousand; ref. 8) in post-glacial cap dolostones (that is, dolostone overlying glacial deposits) from south China; these signatures have been interpreted as products of methane oxidation at the time of deposition(5,6,8). Here we show, on the basis of carbonate clumped isotope thermometry, (87)Sr/(86)Sr isotope ratios, trace element content and clay mineral evidence, that carbonates bearing the (13)C-depleted signatures crystallized more than 1.6 Myr after deposition of the cap dolostone. Our results indicate that highly (13)C-depleted carbonate cements grew from hydrothermal fluids and suggest that their carbon isotope signatures are a consequence of thermogenic methane oxidation at depth. This finding not only negates carbon isotope evidence for methane release during Marinoan deglaciation in south China, but also eliminates the only known occurrence of a Precambrian sedimentary carbonate with highly (13)C-depleted signatures related to methane oxidation in a seep environment. We propose that the capacity to form highly (13)C-depleted seep carbonates, through biogenic anaeorobic oxidation of methane using sulphate, was limited in the Precambrian period by low sulphate concentrations in sea water(9). As a consequence, although clathrate destabilization may or may not have had a role in the exit from the 'snowball' state, it would not have left extreme carbon isotope signals in cap dolostones.
C1 [Bristow, Thomas F.; Bonifacie, Magali; Eiler, John M.; Grotzinger, John P.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Bonifacie, Magali] Univ Paris Diderot, Equipe Geochim Isotopes Stables, Inst Phys Globe Paris, CNRS,UMR 7154, F-75005 Paris, France.
   [Derkowski, Arkadiusz] Polish Acad Sci, Inst Geol Sci, PL-31002 Krakow, Poland.
C3 California Institute of Technology; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Polish Academy of Sciences; Institute of Geological Sciences of the Polish Academy of Sciences
RP Bristow, TF (corresponding author), NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
EM thomas.f.bristow@nasa.gov
FU O.K. Earl Postdoctoral fellowship; NSF; INSU
NR 37
TC 141
Z9 161
U1 9
U2 138
PU 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 2
PY 2011
VL 474
IS 7349
BP 68
EP U92
DI 10.1038/nature10096
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 771KV
UT WOS:000291156700038
PM 21613997
DA 2026-03-09
ER

PT J
AU Levander, A
   Schmandt, B
   Miller, MS
   Liu, K
   Karlstrom, KE
   Crow, RS
   Lee, CTA
   Humphreys, ED
AF Levander, A.
   Schmandt, B.
   Miller, M. S.
   Liu, K.
   Karlstrom, K. E.
   Crow, R. S.
   Lee, C. -T. A.
   Humphreys, E. D.
TI Continuing Colorado plateau uplift by delamination-style convective lithospheric downwelling
SO NATURE
LA English
DT Article
ID farallon slab; mantle; beneath; preservation; geophysics; magmatism; evolution; crustal; range; waves
AB The Colorado plateau is a large, tectonically intact, physiographic province in the southwestern North American Cordillera that stands at similar to 1,800-2,000 m elevation and has long been thought to be in isostatic equilibrium(1). The origin of these high elevations is unclear because unlike the surrounding provinces, which have undergone significant Cretaceous-Palaeogene compressional deformation followed by Neogene extensional deformation, the Colorado plateau is largely internally undeformed. Here we combine new seismic tomography(2) and receiver function images to resolve a vertical high-seismic-velocity anomaly beneath the west-central plateau that extends more than 200 km in depth. The upper surface of this anomaly is seismically defined by a dipping interface extending from the lower crust to depths of 70-90 km. The base of the continental crust above the anomaly has a similar shape, with an elevated Moho. We interpret these seismic structures as a continuing regional, delamination-style foundering of lower crust and continental lithosphere. This implies that Pliocene (2.6-5.3 Myr ago) uplift of the plateau and the magmatism on its margins are intimately tied to continuing deep lithospheric processes. Petrologic and geochemical observations indicate that late Cretaceous-Palaeogene (similar to 90-40 Myr ago) low-angle subduction hydrated and probably weakened much of the Proterozoic tecto-spheric mantle(3-5) beneath the Colorado plateau. We suggest that mid-Cenozoic (similar to 35-25 Myr ago) to Recent magmatic infiltration subsequently imparted negative compositional buoyancy to the base and sides of the Colorado plateau upper mantle, triggering downwelling. The patterns of magmatic activity suggest that previous such events have progressively removed the Colorado plateau lithosphere inward from its margins(6), and have driven uplift. Using Grand Canyon incision rates(7,8) and Pliocene basaltic volcanism patterns, we suggest that this particular event has been active over the past similar to 6 Myr.
C1 [Levander, A.; Liu, K.; Lee, C. -T. A.] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Schmandt, B.; Humphreys, E. D.] Univ Oregon, Dept Geol Sci, Eugene, OR 97403 USA.
   [Miller, M. S.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
   [Karlstrom, K. E.; Crow, R. S.] Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
C3 Rice University; University of Oregon; University of Southern California; University of New Mexico
RP Levander, A (corresponding author), Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
EM alan@rice.edu
FU NSF [EAR-0844741, EAR-0844760, EAR-0911006]; Alexander von Humboldt Foundation; Division Of Earth Sciences; Directorate For Geosciences [1119629] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0844760, 0844741] Funding Source: National Science Foundation
NR 38
TC 269
Z9 335
U1 2
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 APR 28
PY 2011
VL 472
IS 7344
BP 461
EP U540
DI 10.1038/nature10001
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600032
PM 21525930
DA 2026-03-09
ER

PT J
AU DePaolo, RW
   Abadie, V
   Tang, F
   Fehlner-Peach, H
   Hall, JA
   Wang, W
   Marietta, EV
   Kasarda, DD
   Waldmann, TA
   Murray, JA
   Semrad, C
   Kupfer, SS
   Belkaid, Y
   Guandalini, S
   Jabri, B
AF DePaolo, R. W.
   Abadie, V.
   Tang, F.
   Fehlner-Peach, H.
   Hall, J. A.
   Wang, W.
   Marietta, E. V.
   Kasarda, D. D.
   Waldmann, T. A.
   Murray, J. A.
   Semrad, C.
   Kupfer, S. S.
   Belkaid, Y.
   Guandalini, S.
   Jabri, B.
TI Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens
SO NATURE
LA English
DT Article
ID major histocompatibility complex; regulatory t-cells; gluten sensitivity; transgenic mice; tgf-beta; class-i; differentiation; disease; cytokine; interleukin-15
AB Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens(1,2). A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat(3). The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses(4-6). Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients(3,7), retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.
C1 [DePaolo, R. W.; Abadie, V.; Tang, F.; Fehlner-Peach, H.; Wang, W.; Semrad, C.; Kupfer, S. S.; Jabri, B.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Hall, J. A.; Belkaid, Y.] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Hall, J. A.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
   [Marietta, E. V.] Mayo Clin, Dept Dermatol, Coll Med, Rochester, MN 55905 USA.
   [Marietta, E. V.] Mayo Clin, Dept Immunol, Coll Med, Rochester, MN 55905 USA.
   [Kasarda, D. D.] ARS, USDA, Western Reg Res Ctr, Albany, CA 94710 USA.
   [Waldmann, T. A.] NCI, Metab Branch, Bethesda, MD 20892 USA.
   [Murray, J. A.] Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Coll Med, Rochester, MN 55905 USA.
   [Guandalini, S.; Jabri, B.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   [Jabri, B.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
C3 University of Chicago; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Pennsylvania; Mayo Clinic; Mayo Clinic; United States Department of Agriculture (USDA); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Mayo Clinic; University of Chicago; University of Chicago
RP Jabri, B (corresponding author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM bjabri@bsd.uchicago.edu
FU Digestive Disease Research Core Center at the University of Chicago [DK42086, R01 DK67180, R01DK71003]; Crohn's and Colitis Foundation; University of Chicago Celiac Disease Center; National Cancer Institute [ZIASC004002] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI001132] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK067180, P30DK042086] Funding Source: NIH RePORTER
NR 37
TC 311
Z9 376
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 220
EP U110
DI 10.1038/nature09849
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200038
PM 21307853
DA 2026-03-09
ER

PT J
AU Mueller-Cajar, O
   Stotz, M
   Wendler, P
   Hartl, FU
   Bracher, A
   Hayer-Hartl, M
AF Mueller-Cajar, Oliver
   Stotz, Mathias
   Wendler, Petra
   Hartl, F. Ulrich
   Bracher, Andreas
   Hayer-Hartl, Manajit
TI Structure and function of the AAA+ protein CbbX, a red-type Rubisco activase
SO NATURE
LA English
DT Article
ID ribulose 1,5-bisphosphate carboxylase; high-level expression; form-i; bisphosphate carboxylase; crystal-structure; encoded cbbx; chaperone; visualization; translocation; refinement
AB Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyses the fixation of atmospheric CO2 in photosynthesis, but tends to form inactive complexes with its substrate ribulose 1,5-bisphosphate (RuBP). In plants, Rubisco is reactivated by the AAA(+) (ATPases associated with various cellular activities) protein Rubisco activase (Rca), but no such protein is known for the Rubisco of red algae. Here we identify the protein CbbX as an activase of red-type Rubisco. The 3.0-angstrom crystal structure of unassembled CbbX from Rhodobacter sphaeroides revealed an AAA(+) protein architecture. Electron microscopy and biochemical analysis showed that ATP and RuBP must bind to convert CbbX into functionally active, hexameric rings. The CbbX ATPase is strongly stimulated by RuBP and Rubisco. Mutational analysis suggests that CbbX functions by transiently pulling the carboxy-terminal peptide of the Rubisco large subunit into the hexamer pore, resulting in the release of the inhibitory RuBP. Understanding Rubisco activation may facilitate efforts to improve CO2 uptake and biomass production by photosynthetic organisms.
C1 [Mueller-Cajar, Oliver; Stotz, Mathias; Hartl, F. Ulrich; Bracher, Andreas; Hayer-Hartl, Manajit] Max Planck Inst Biochem, Dept Cellular Biochem, D-82152 Martinsried, Germany.
   [Wendler, Petra] Univ Munich, Dept Biochem, Gene Ctr Munich, D-81377 Munich, Germany.
C3 Max Planck Society; University of Munich
RP Hayer-Hartl, M (corresponding author), Max Planck Inst Biochem, Dept Cellular Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM bracher@biochem.mpg.de; mhartl@biochem.mpg.de
FU Max Planck Institute of Biochemistry (MPIB); European Synchrotron Radiation Facility beamlines; Deutsche Forschungsgemeinschaft (DFG) [SFB 594, WE4628/1]; Korber Foundation
NR 62
TC 140
Z9 166
U1 1
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 194
EP U66
DI 10.1038/nature10568
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800034
PM 22048315
DA 2026-03-09
ER

PT J
AU Nugent, PE
   Sullivan, M
   Cenko, SB
   Thomas, RC
   Kasen, D
   Howell, DA
   Bersier, D
   Bloom, JS
   Kulkarni, SR
   Kandrashoff, MT
   Filippenko, AV
   Silverman, JM
   Marcy, GW
   Howard, AW
   Isaacson, HT
   Maguire, K
   Suzuki, N
   Tarlton, JE
   Pan, YC
   Bildsten, L
   Fulton, BJ
   Parrent, JT
   Sand, D
   Podsiadlowski, P
   Bianco, FB
   Dilday, B
   Graham, ML
   Lyman, J
   James, P
   Kasliwal, MM
   Law, NM
   Quimby, RM
   Hook, IM
   Walker, ES
   Mazzali, P
   Pian, E
   Ofek, EO
   Gal-Yam, A
   Poznanski, D
AF Nugent, Peter E.
   Sullivan, Mark
   Cenko, S. Bradley
   Thomas, Rollin C.
   Kasen, Daniel
   Howell, D. Andrew
   Bersier, David
   Bloom, Joshua S.
   Kulkarni, S. R.
   Kandrashoff, Michael T.
   Filippenko, Alexei V.
   Silverman, Jeffrey M.
   Marcy, Geoffrey W.
   Howard, Andrew W.
   Isaacson, Howard T.
   Maguire, Kate
   Suzuki, Nao
   Tarlton, James E.
   Pan, Yen-Chen
   Bildsten, Lars
   Fulton, Benjamin J.
   Parrent, Jerod T.
   Sand, David
   Podsiadlowski, Philipp
   Bianco, Federica B.
   Dilday, Benjamin
   Graham, Melissa L.
   Lyman, Joe
   James, Phil
   Kasliwal, Mansi M.
   Law, Nicholas M.
   Quimby, Robert M.
   Hook, Isobel M.
   Walker, Emma S.
   Mazzali, Paolo
   Pian, Elena
   Ofek, Eran O.
   Gal-Yam, Avishay
   Poznanski, Dovi
TI Supernova SN 2011fe from an exploding carbon-oxygen white dwarf star
SO NATURE
LA English
DT Article
ID ia supernovae; spectra; 1994d
AB Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe(1-3) even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery(4-6). There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance(7) from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon-oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper(8) uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor.
C1 [Nugent, Peter E.; Thomas, Rollin C.; Kasen, Daniel; Suzuki, Nao; Poznanski, Dovi] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Nugent, Peter E.; Cenko, S. Bradley; Bloom, Joshua S.; Kandrashoff, Michael T.; Filippenko, Alexei V.; Silverman, Jeffrey M.; Marcy, Geoffrey W.; Howard, Andrew W.; Isaacson, Howard T.; Poznanski, Dovi] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Sullivan, Mark; Maguire, Kate; Tarlton, James E.; Pan, Yen-Chen; Podsiadlowski, Philipp; Hook, Isobel M.] Univ Oxford, Dept Phys Astrophys, Oxford OX1 3RH, England.
   [Kasen, Daniel] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Howell, D. Andrew; Fulton, Benjamin J.; Parrent, Jerod T.; Sand, David; Bianco, Federica B.; Dilday, Benjamin; Graham, Melissa L.] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Howell, D. Andrew; Bildsten, Lars; Fulton, Benjamin J.; Sand, David; Bianco, Federica B.; Dilday, Benjamin; Graham, Melissa L.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Bersier, David; Lyman, Joe; James, Phil] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Kulkarni, S. R.; Kasliwal, Mansi M.; Ofek, Eran O.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Bildsten, Lars] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Parrent, Jerod T.] Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA.
   [Law, Nicholas M.] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Quimby, Robert M.] Univ Tokyo, IPMU, Kashiwa, Chiba 2778583, Japan.
   [Hook, Isobel M.] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, RM, Italy.
   [Walker, Emma S.] Scuola Normale Super Pisa, I-56126 Pisa, Italy.
   [Mazzali, Paolo; Pian, Elena] Osserv Astron Padova, INAF, I-35122 Padua, Italy.
   [Mazzali, Paolo; Pian, Elena] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Ofek, Eran O.; Gal-Yam, Avishay] Weizmann Inst Sci, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Poznanski, Dovi] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Oxford; University of California System; University of California Berkeley; University of California System; University of California Santa Barbara; Liverpool John Moores University; California Institute of Technology; University of California System; University of California Santa Barbara; Dartmouth College; University of Toronto; University of Tokyo; Istituto Nazionale Astrofisica (INAF); Scuola Normale Superiore di Pisa; University of Padua; Istituto Nazionale Astrofisica (INAF); Max Planck Society; Weizmann Institute of Science; Tel Aviv University
RP Nugent, PE (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
EM penugent@lbl.gov
FU Office of Science of the US Department of Energy (DOE); US DOE; Royal Society; National Science Foundation (NSF); NSF; TABASGO Foundation; Gary and Cynthia Bengier; Richard and Rhoda Goldman Fund; UK Science and Technology Facilities Council; W. M. Keck Foundation; STFC [ST/G009465/1, PP/E001149/1, ST/I003673/1, ST/H002391/1, PP/E003427/1, ST/I505821/1, ST/G004331/1, ST/H002456/1, ST/H000704/1] Funding Source: UKRI; Direct For Mathematical & Physical Scien [1009991] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109896] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109174, 1009987] Funding Source: National Science Foundation; Division Of Astronomical Sciences [1009991] Funding Source: National Science Foundation; Office of Integrative Activities [0941742] Funding Source: National Science Foundation; Office Of The Director [0941742] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/G009465/1, ST/I003673/1, ST/H002391/1, PP/E001149/1, ST/H000704/1, ST/G004331/1, ST/H002456/1, ST/I505821/1, PP/E003427/1] Funding Source: researchfish
NR 27
TC 417
Z9 481
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 15
PY 2011
VL 480
IS 7377
BP 344
EP 347
DI 10.1038/nature10644
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000045
PM 22170680
DA 2026-03-09
ER

PT J
AU Hara, MR
   Kovacs, JJ
   Whalen, EJ
   Rajagopal, S
   Strachan, RT
   Grant, W
   Towers, AJ
   Williams, B
   Lam, CM
   Xiao, KH
   Shenoy, SK
   Gregory, SG
   Ahn, S
   Duckett, DR
   Lefkowitz, RJ
AF Hara, Makoto R.
   Kovacs, Jeffrey J.
   Whalen, Erin J.
   Rajagopal, Sudarshan
   Strachan, Ryan T.
   Grant, Wayne
   Towers, Aaron J.
   Williams, Barbara
   Lam, Christopher M.
   Xiao, Kunhong
   Shenoy, Sudha K.
   Gregory, Simon G.
   Ahn, Seungkirl
   Duckett, Derek R.
   Lefkowitz, Robert J.
TI A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1
SO NATURE
LA English
DT Article
ID short-interfering rnas; nuclear export signal; beta-arrestins; adenylyl-cyclase; n-domain; receptor; activation; expression; growth; p53
AB The human mind and body respond to stress(1), a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term(2). When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders(3), and epidemiological studies strongly indicate that chronic stress leads to DNA damage(4,5). This stress-induced DNA damage may promote ageing(6), tumorigenesis(4,7), neuropsychiatric conditions(8,9) and miscarriages(10). However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates beta(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos(11). Activated beta(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of beta-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right(12). Here we elucidate a molecular mechanism by which beta-adrenergic catecholamines, acting through both Gs-PKA and beta-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, beta-arrestin-1 (ARRB1), activated via beta(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress(1), and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.
C1 [Hara, Makoto R.; Kovacs, Jeffrey J.; Whalen, Erin J.; Rajagopal, Sudarshan; Strachan, Ryan T.; Towers, Aaron J.; Williams, Barbara; Lam, Christopher M.; Xiao, Kunhong; Shenoy, Sudha K.; Gregory, Simon G.; Ahn, Seungkirl; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Grant, Wayne; Duckett, Derek R.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
   [Towers, Aaron J.; Gregory, Simon G.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA.
   [Lefkowitz, Robert J.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
C3 Duke University; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Duke University; Howard Hughes Medical Institute; Duke University
RP Lefkowitz, RJ (corresponding author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM lefko001@receptor-biol.duke.edu
FU [HL16037];  [HL70631]; National Heart Lung and Blood Institute [R01HL016037] Funding Source: NIH RePORTER
NR 49
TC 360
Z9 396
U1 1
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 349
EP U129
DI 10.1038/nature10368
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400035
PM 21857681
DA 2026-03-09
ER

PT J
AU Villeda, SA
   Luo, J
   Mosher, KI
   Zou, BD
   Britschgi, M
   Bieri, G
   Stan, TM
   Fainberg, N
   Ding, ZQ
   Eggel, A
   Lucin, KM
   Czirr, E
   Park, JS
   Couillard-Després, S
   Aigner, L
   Li, G
   Peskind, ER
   Kaye, JA
   Quinn, JF
   Galasko, DR
   Xie, XMS
   Rando, TA
   Wyss-Coray, T
AF Villeda, Saul A.
   Luo, Jian
   Mosher, Kira I.
   Zou, Bende
   Britschgi, Markus
   Bieri, Gregor
   Stan, Trisha M.
   Fainberg, Nina
   Ding, Zhaoqing
   Eggel, Alexander
   Lucin, Kurt M.
   Czirr, Eva
   Park, Jeong-Soo
   Couillard-Despres, Sebastien
   Aigner, Ludwig
   Li, Ge
   Peskind, Elaine R.
   Kaye, Jeffrey A.
   Quinn, Joseph F.
   Galasko, Douglas R.
   Xie, Xinmin S.
   Rando, Thomas A.
   Wyss-Coray, Tony
TI The ageing systemic milieu negatively regulates neurogenesis and cognitive function
SO NATURE
LA English
DT Article
ID adult hippocampal neurogenesis; neural stem-cells; long-term potentiation; progenitor cells; self-renewal; aged mice; memory; brain; neurons; model
AB In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions(1). Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise(1). Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines-including CCL11 (also known as eotaxin)-the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.
C1 [Villeda, Saul A.; Luo, Jian; Mosher, Kira I.; Britschgi, Markus; Bieri, Gregor; Stan, Trisha M.; Fainberg, Nina; Ding, Zhaoqing; Eggel, Alexander; Lucin, Kurt M.; Czirr, Eva; Park, Jeong-Soo; Rando, Thomas A.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [Villeda, Saul A.; Mosher, Kira I.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Neurosci IDP Program, Stanford, CA 94305 USA.
   [Zou, Bende; Xie, Xinmin S.] AfaSci Res Lab, Redwood City, CA 94063 USA.
   [Bieri, Gregor] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Sch Life Sci, CH-1015 Lausanne, Switzerland.
   [Stan, Trisha M.; Ding, Zhaoqing; Wyss-Coray, Tony] Stanford Univ, Sch Med, Immunol IDP Program, Stanford, CA 94305 USA.
   [Couillard-Despres, Sebastien; Aigner, Ludwig] Paracelsus Med Univ, Inst Mol Regenerat Med, A-5020 Salzburg, Austria.
   [Li, Ge; Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA.
   [Peskind, Elaine R.] Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA 98108 USA.
   [Kaye, Jeffrey A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA.
   [Kaye, Jeffrey A.; Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR 97207 USA.
   [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Rando, Thomas A.; Wyss-Coray, Tony] VA Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA 94304 USA.
   [Rando, Thomas A.] Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Stanford University; Paracelsus Private Medical University; University of Washington; University of Washington Seattle; Oregon Health & Science University; US Department of Veterans Affairs; Veterans Health Administration (VHA); Portland VA Medical Center; University of California System; University of California San Diego; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Stanford University
RP Wyss-Coray, T (corresponding author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
EM twc@stanford.edu
FU Department of Veterans Affairs; National Institutes of Health Institute on Aging [R01 AG027505, P30AG08017]; California Initiative for Regenerative Medicine; National Institutes of Health [R01 MH078194]; Larry L. Hillblom Foundation [2008-A-023-FEL]; Feodor-Lynen postdoctoral fellowship; Swiss National Science Foundation; National Science Foundation; Kirschstein NRSA [AG034045-01, 1 F31 NS066676-01A1]; National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER
NR 32
TC 1429
Z9 1696
U1 8
U2 247
PU 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 1
PY 2011
VL 477
IS 7362
BP 90
EP U157
DI 10.1038/nature10357
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300037
PM 21886162
DA 2026-03-09
ER

PT J
AU Clausen, C
   Usmani, I
   Bussières, F
   Sangouard, N
   Afzelius, M
   de Riedmatten, H
   Gisin, N
AF Clausen, Christoph
   Usmani, Imam
   Bussieres, Felix
   Sangouard, Nicolas
   Afzelius, Mikael
   de Riedmatten, Hugues
   Gisin, Nicolas
TI Quantum storage of photonic entanglement in a crystal
SO NATURE
LA English
DT Article
ID single-photon; atomic ensembles; trapped atom; communication; light; matter
AB Entanglement is the fundamental characteristic of quantum physics-much experimental effort is devoted to harnessing it between various physical systems. In particular, entanglement between light and material systems is interesting owing to their anticipated respective roles as 'flying' and stationary qubits in quantum information technologies (such as quantum repeaters(1-3) and quantum networks(4)). Here we report the demonstration of entanglement between a photon at a telecommunication wavelength (1,338 nm) and a single collective atomic excitation stored in a crystal. One photon from an energy-time entangled pair(5) is mapped onto the crystal and then released into a well-defined spatial mode after a predetermined storage time. The other (telecommunication wavelength) photon is sent directly through a 50-metre fibre link to an analyser. Successful storage of entanglement in the crystal is proved by a violation of the Clauser-Horne-Shimony-Holt inequality(6) by almost three standard deviations (S=2.64 +/- 0.23). These results represent an important step towards quantum communication technologies based on solid-state devices. In particular, our resources pave the way for building multiplexed quantum repeaters(7) for long-distance quantum networks.
C1 [Clausen, Christoph; Usmani, Imam; Bussieres, Felix; Sangouard, Nicolas; Afzelius, Mikael; de Riedmatten, Hugues; Gisin, Nicolas] Univ Geneva, Appl Phys Grp, CH-1211 Geneva 4, Switzerland.
   [de Riedmatten, Hugues] ICFO Inst Ciencies Foton, Barcelona 08860, Spain.
   [de Riedmatten, Hugues] ICREA, Barcelona 08015, Spain.
C3 University of Geneva; Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); ICREA
RP Afzelius, M (corresponding author), Univ Geneva, Appl Phys Grp, CH-1211 Geneva 4, Switzerland.
EM mikael.afzelius@unige.ch
FU Swiss NCCR Quantum Photonics; Science and Technology Cooperation Program Switzerland-Russia; QuRep; ERC-Qore; FQRNT; ICREA Funding Source: Custom
NR 28
TC 420
Z9 462
U1 1
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 JAN 27
PY 2011
VL 469
IS 7331
BP 508
EP U79
DI 10.1038/nature09662
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500027
PM 21228774
DA 2026-03-09
ER

PT J
AU Xu, X
   You, HL
   Du, K
   Han, FL
AF Xu, Xing
   You, Hailu
   Du, Kai
   Han, Fenglu
TI An Archaeopteryx-like theropod from China and the origin of Avialae
SO NATURE
LA English
DT Article
ID early evolution; birds; maniraptoran; dinosaurs; specimen; anatomy; fossil
AB Archaeopteryx is widely accepted as being the most basal bird, and accordingly it is regarded as central to understanding avialan origins; however, recent discoveries of derived maniraptorans have weakened the avialan status of Archaeopteryx. Here we report a new Archaeopteryx-like theropod from China. This find further demonstrates that many features formerly regarded as being diagnostic of Avialae, including long and robust forelimbs, actually characterize the more inclusive group Paraves (composed of the avialans and the deinonychosaurs). Notably, adding the new taxon into a comprehensive phylogenetic analysis shifts Archaeopteryx to the Deinonychosauria. Despite only tentative statistical support, this result challenges the centrality of Archaeopteryx in the transition to birds. If this new phylogenetic hypothesis can be confirmed by further investigation, current assumptions regarding the avialan ancestral condition will need to be re-evaluated.
C1 [Xu, Xing] Linyi Univ, Coll Life Sci, Linyi 276005, Shandong, Peoples R China.
   [Xu, Xing; Han, Fenglu] Chinese Acad Sci, Key Lab Evolutionary Systemat Vertebrates, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [You, Hailu] Chinese Acad Geol Sci, Inst Geol, Beijing 100037, Peoples R China.
   [Du, Kai] Capital Normal Univ, Dept Biol, Beijing 100037, Peoples R China.
C3 Linyi University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; China Geological Survey; Institute of Geology, Chinese Academy of Geological Sciences; Chinese Academy of Geological Sciences; Capital Normal University
RP Xu, X (corresponding author), Linyi Univ, Coll Life Sci, Shuangling Rd, Linyi 276005, Shandong, Peoples R China.
EM xingxu@vip.sina.com
FU National Natural Science Foundation of China; Chinese Academy of Sciences; Special Funds for Major State Basic Research Projects of China
NR 44
TC 201
Z9 250
U1 3
U2 142
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 465
EP 470
DI 10.1038/nature10288
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900033
PM 21796204
DA 2026-03-09
ER

PT J
AU Jex, AR
   Liu, SP
   Li, B
   Young, ND
   Hall, RS
   Li, YR
   Yang, LF
   Zeng, N
   Xu, X
   Xiong, ZJ
   Chen, FY
   Wu, X
   Zhang, GJ
   Fang, XD
   Kang, Y
   Anderson, GA
   Harris, TW
   Campbell, BE
   Vlaminck, J
   Wang, T
   Cantacessi, C
   Schwarz, EM
   Ranganathan, S
   Geldhof, P
   Nejsum, P
   Sternberg, PW
   Yang, HM
   Wang, J
   Wang, J
   Gasser, RB
AF Jex, Aaron R.
   Liu, Shiping
   Li, Bo
   Young, Neil D.
   Hall, Ross S.
   Li, Yingrui
   Yang, Linfeng
   Zeng, Na
   Xu, Xun
   Xiong, Zijun
   Chen, Fangyuan
   Wu, Xuan
   Zhang, Guojie
   Fang, Xiaodong
   Kang, Yi
   Anderson, Garry A.
   Harris, Todd W.
   Campbell, Bronwyn E.
   Vlaminck, Johnny
   Wang, Tao
   Cantacessi, Cinzia
   Schwarz, Erich M.
   Ranganathan, Shoba
   Geldhof, Peter
   Nejsum, Peter
   Sternberg, Paul W.
   Yang, Huanming
   Wang, Jun
   Wang, Jian
   Gasser, Robin B.
TI Ascaris suum draft genome
SO NATURE
LA English
DT Article
ID brugia-malayi; rna-seq; schistosoma-mansoni; parasitic diseases; swiss-prot; gene; database; tool; prediction; nematodes
AB Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America(1). In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years(1). Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death(2). Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality(2). The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 mega-base draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases.
C1 [Jex, Aaron R.; Young, Neil D.; Hall, Ross S.; Anderson, Garry A.; Campbell, Bronwyn E.; Cantacessi, Cinzia; Gasser, Robin B.] Univ Melbourne, Fac Vet Sci, Parkville, Vic 3010, Australia.
   [Liu, Shiping; Li, Bo; Li, Yingrui; Yang, Linfeng; Zeng, Na; Xu, Xun; Xiong, Zijun; Chen, Fangyuan; Wu, Xuan; Zhang, Guojie; Fang, Xiaodong; Kang, Yi; Yang, Huanming; Wang, Jun; Wang, Jian] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Harris, Todd W.] MaRS Ctr, Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Vlaminck, Johnny; Wang, Tao; Geldhof, Peter] Univ Ghent, Lab Parasitol & Parasit Dis, B-9820 Merelbeke, Belgium.
   [Schwarz, Erich M.; Sternberg, Paul W.] CALTECH, Pasadena, CA 91125 USA.
   [Ranganathan, Shoba] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia.
   [Nejsum, Peter] Univ Copenhagen, Fac Life Sci, DK-2200 Copenhagen, Denmark.
C3 University of Melbourne; Beijing Genomics Institute (BGI); University of Toronto; Ontario Institute for Cancer Research; Ghent University; California Institute of Technology; Macquarie University; University of Copenhagen
RP Jex, AR (corresponding author), Univ Melbourne, Fac Vet Sci, Parkville, Vic 3010, Australia.
EM ajex@unimelb.edu.au; wangjun@genomics.org.cn; wangjian@genomics.org.cn; robinbg@unimelb.edu.au
FU Australian Research Council; Victorian Life Sciences Computation Initiative on its Peak Computing Facility at the University of Melbourne [VR0007]
NR 73
TC 221
Z9 240
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 NOV 24
PY 2011
VL 479
IS 7374
BP 529
EP U257
DI 10.1038/nature10553
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600051
PM 22031327
DA 2026-03-09
ER

PT J
AU Tran, JC
   Zamdborg, L
   Ahlf, DR
   Lee, JE
   Catherman, AD
   Durbin, KR
   Tipton, JD
   Vellaichamy, A
   Kellie, JF
   Li, MX
   Wu, C
   Sweet, SMM
   Early, BP
   Siuti, N
   LeDuc, RD
   Compton, PD
   Thomas, PM
   Kelleher, NL
AF Tran, John C.
   Zamdborg, Leonid
   Ahlf, Dorothy R.
   Lee, Ji Eun
   Catherman, Adam D.
   Durbin, Kenneth R.
   Tipton, Jeremiah D.
   Vellaichamy, Adaikkalam
   Kellie, John F.
   Li, Mingxi
   Wu, Cong
   Sweet, Steve M. M.
   Early, Bryan P.
   Siuti, Nertila
   LeDuc, Richard D.
   Compton, Philip D.
   Thomas, Paul M.
   Kelleher, Neil L.
TI Mapping intact protein isoforms in discovery mode using top-down proteomics
SO NATURE
LA English
DT Article
ID chromatography-mass-spectrometry; cellular senescence; quantitative-analysis; large-scale; identification; time; electrophoresis; dissociation; separation; precise
AB A full description of the human proteome relies on the challenging task of detecting mature and changing forms of protein molecules in the body. Large-scale proteome analysis(1) has routinely involved digesting intact proteins followed by inferred protein identification using mass spectrometry(2). This 'bottom-up' process affords a high number of identifications (not always unique to a single gene). However, complications arise from incomplete or ambiguous(2) characterization of alternative splice forms, diverse modifications (for example, acetylation and methylation) and endogenous protein cleavages, especially when combinations of these create complex patterns of intact protein isoforms and species(3). 'Top-down' interrogation of whole proteins can overcome these problems for individual proteins(4,5), but has not been achieved on a proteome scale owing to the lack of intact protein fractionation methods that are well integrated with tandem mass spectrometry. Here we show, using a new four-dimensional separation system, identification of 1,043 gene products from human cells that are dispersed into more than 3,000 protein species created by post-translational modification (PTM), RNA splicing and proteolysis. The overall system produced greater than 20-fold increases in both separation power and proteome coverage, enabling the identification of proteins up to 105 kDa and those with up to 11 transmembrane helices. Many previously undetected isoforms of endogenous human proteins were mapped, including changes in multiply modified species in response to accelerated cellular ageing (senescence) induced by DNA damage. Integrated with the latest version of the Swiss-Prot database(6), the data provide precise correlations to individual genes and proof-of-concept for large-scale interrogation of whole protein molecules. The technology promises to improve the link between proteomics data and complex phenotypes in basic biology and disease research(7).
C1 [Tran, John C.; Zamdborg, Leonid; Ahlf, Dorothy R.; Lee, Ji Eun; Catherman, Adam D.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Kellie, John F.; Li, Mingxi; Wu, Cong; Sweet, Steve M. M.; Early, Bryan P.; Siuti, Nertila; Thomas, Paul M.; Kelleher, Neil L.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Tran, John C.; Zamdborg, Leonid; Ahlf, Dorothy R.; Lee, Ji Eun; Catherman, Adam D.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Kellie, John F.; Li, Mingxi; Wu, Cong; Sweet, Steve M. M.; Early, Bryan P.; Siuti, Nertila; Thomas, Paul M.; Kelleher, Neil L.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
   [Tran, John C.; Zamdborg, Leonid; Ahlf, Dorothy R.; Lee, Ji Eun; Catherman, Adam D.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Kellie, John F.; Li, Mingxi; Wu, Cong; Sweet, Steve M. M.; Early, Bryan P.; Siuti, Nertila; Thomas, Paul M.; Kelleher, Neil L.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Tran, John C.; Ahlf, Dorothy R.; Catherman, Adam D.; Durbin, Kenneth R.; Tipton, Jeremiah D.; Kellie, John F.; Li, Mingxi; Sweet, Steve M. M.; Early, Bryan P.; Compton, Philip D.; Thomas, Paul M.; Kelleher, Neil L.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Tran, John C.; Ahlf, Dorothy R.; Catherman, Adam D.; Durbin, Kenneth R.; Tipton, Jeremiah D.; Kellie, John F.; Li, Mingxi; Sweet, Steve M. M.; Early, Bryan P.; Compton, Philip D.; Thomas, Paul M.; Kelleher, Neil L.] Northwestern Univ, Dept Mol Sci, Evanston, IL 60208 USA.
   [Tran, John C.; Ahlf, Dorothy R.; Catherman, Adam D.; Durbin, Kenneth R.; Tipton, Jeremiah D.; Kellie, John F.; Li, Mingxi; Sweet, Steve M. M.; Early, Bryan P.; Compton, Philip D.; Thomas, Paul M.; Kelleher, Neil L.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
   [Lee, Ji Eun] Korea Inst Sci & Technol, Doping Control Ctr, Seoul, South Korea.
   [Lee, Ji Eun] Korea Inst Sci & Technol, Ctr Theragnosis, Seoul, South Korea.
   [LeDuc, Richard D.] Univ Wisconsin Madison, Dept Great Lakes Bioenergy Res Ctr, Madison, WI 53706 USA.
C3 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; Northwestern University; Northwestern University; Northwestern University; Feinberg School of Medicine; Korea Institute of Science & Technology (KIST); Korea Institute of Science & Technology (KIST); University of Wisconsin System; University of Wisconsin Madison
RP Kelleher, NL (corresponding author), Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
EM n-kelleher@northwestern.edu
FU Chicago Community Trust; Department of Chemistry at the University of Illinois, the Neuroproteomics Center on Cell to Cell Signaling through the National Institute on Drug Abuse [P30DA 018310]; Department of Chemistry at the University of Illinois, the Neuroproteomics Center on Cell to Cell Signaling through the National Institute for General Medical Sciences [GM 067193-08]; Department of Chemistry at the University of Illinois, the Neuroproteomics Center on Cell to Cell Signaling through the National Science Foundation [DMS 0800631]; National Institute on Drug Abuse [P30DA018310] Funding Source: NIH RePORTER
NR 47
TC 542
Z9 687
U1 1
U2 343
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 8
PY 2011
VL 480
IS 7376
BP 254
EP U141
DI 10.1038/nature10575
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200054
PM 22037311
DA 2026-03-09
ER

PT J
AU Quimby, RM
   Kulkarni, SR
   Kasliwal, MM
   Gal-Yam, A
   Arcavi, I
   Sullivan, M
   Nugent, P
   Thomas, R
   Howell, DA
   Nakar, E
   Bildsten, L
   Theissen, C
   Law, NM
   Dekany, R
   Rahmer, G
   Hale, D
   Smith, R
   Ofek, EO
   Zolkower, J
   Velur, V
   Walters, R
   Henning, J
   Bui, K
   McKenna, D
   Poznanski, D
   Cenko, SB
   Levitan, D
AF Quimby, R. M.
   Kulkarni, S. R.
   Kasliwal, M. M.
   Gal-Yam, A.
   Arcavi, I.
   Sullivan, M.
   Nugent, P.
   Thomas, R.
   Howell, D. A.
   Nakar, E.
   Bildsten, L.
   Theissen, C.
   Law, N. M.
   Dekany, R.
   Rahmer, G.
   Hale, D.
   Smith, R.
   Ofek, E. O.
   Zolkower, J.
   Velur, V.
   Walters, R.
   Henning, J.
   Bui, K.
   McKenna, D.
   Poznanski, D.
   Cenko, S. B.
   Levitan, D.
TI Hydrogen-poor superluminous stellar explosions
SO NATURE
LA English
DT Article
ID luminous supernovae; pair-instability; light curves; stars
AB Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more(1). In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements(2) (typically Ni-56), the explosion shock in the envelope of a supergiant star(3), and interaction between the debris and slowly moving, hydrogen-rich circumstellar material(4). Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events(5,6) (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (similar to 10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z>4.
C1 [Quimby, R. M.; Kulkarni, S. R.; Kasliwal, M. M.] CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
   [Gal-Yam, A.; Arcavi, I.] Weizmann Inst Sci, Benoziyo Ctr Astrophys, Fac Phys, IL-76100 Rehovot, Israel.
   [Sullivan, M.] Univ Oxford, Dept Phys Astrophys, Oxford OX1 3RH, England.
   [Nugent, P.; Thomas, R.; Poznanski, D.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Howell, D. A.; Bildsten, L.] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Howell, D. A.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Nakar, E.] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys Astron, IL-69978 Tel Aviv, Israel.
   [Bildsten, L.] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Theissen, C.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Law, N. M.] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Dekany, R.; Rahmer, G.; Hale, D.; Smith, R.; Ofek, E. O.; Zolkower, J.; Velur, V.; Walters, R.; Henning, J.; Bui, K.; McKenna, D.] CALTECH, Caltech Opt Observ, Pasadena, CA 91125 USA.
   [Poznanski, D.; Cenko, S. B.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Levitan, D.] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
C3 California Institute of Technology; Weizmann Institute of Science; University of Oxford; 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 Santa Barbara; Tel Aviv University; University of California System; University of California Santa Barbara; University of California System; University of California San Diego; University of Toronto; California Institute of Technology; University of California System; University of California Berkeley; California Institute of Technology
RP Quimby, RM (corresponding author), CALTECH, Cahill Ctr Astrophys, Pasadena, CA 91125 USA.
EM quimby@astro.caltech.edu
FU Office of Science of the US Department of Energy; Israel Science Foundation; US-Israel Binational Science Foundation; US Department of Energy; Gordon and Betty Moore foundation; Bengier Foundation; Richard and Rhoda Goldman Fund; Royal Society; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009987] Funding Source: National Science Foundation
NR 22
TC 460
Z9 496
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 23
PY 2011
VL 474
IS 7352
BP 487
EP 489
DI 10.1038/nature10095
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700043
PM 21654747
DA 2026-03-09
ER

PT J
AU Ourjoumtsev, A
   Kubanek, A
   Koch, M
   Sames, C
   Pinkse, PWH
   Rempe, G
   Murr, K
AF Ourjoumtsev, A.
   Kubanek, A.
   Koch, M.
   Sames, C.
   Pinkse, P. W. H.
   Rempe, G.
   Murr, K.
TI Observation of squeezed light from one atom excited with two photons
SO NATURE
LA English
DT Article
ID jaynes-cummings model; resonance fluorescence; cavity; states; statistics
AB Single quantum emitters such as atoms are well known as non-classical light sources with reduced noise in the intensity, capable of producing photons one by one at given times(1). However, the light field emitted by a single atom can exhibit much richer dynamics. A prominent example(2,3) is the predicted ability of a single atom to produce quadrature-squeezed light(4), which has fluctuations of amplitude or phase that are below the shot-noise level. However, such squeezing is much more difficult to observe than the emission of single photons(5). Squeezed beams have been generated using macroscopic and mesoscopic media down to a few tens of atoms(6), but despite experimental efforts(7-9), single-atom squeezing has so far escaped observation. Here we generate squeezed light with a single atom in a high-finesse optical resonator. The strong coupling of the atom to the cavity field induces a genuine quantum mechanical nonlinearity(10), which is several orders of magnitude larger than in typical macroscopic media(11-13). This produces observable quadrature squeezing(14-16), with an excitation beam containing on average only two photons per system lifetime. In sharp contrast to the emission of single photons(17), the squeezed light stems from the quantum coherence of photon pairs emitted from the system(18). The ability of a single atom to induce strong coherent interactions between propagating photons opens up new perspectives for photonic quantum logic with single emitters(19-24).
C1 [Ourjoumtsev, A.; Kubanek, A.; Koch, M.; Sames, C.; Pinkse, P. W. H.; Rempe, G.; Murr, K.] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Ourjoumtsev, A.] Univ Paris 11, CNRS UMR 8501, Lab Charles Fabry, Inst Opt, F-91127 Palaiseau, France.
C3 Max Planck Society; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universite Paris Saclay
RP Ourjoumtsev, A (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM alexei.ourjoumtsev@institutoptique.fr; karim.murr@gmail.com
FU Deutsche Forschungsgemeinschaft (Research Unit) [635]; European Union; Bavarian PhD programme of excellence (QCCC)
NR 33
TC 88
Z9 95
U1 3
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 623
EP 626
DI 10.1038/nature10170
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300035
PM 21720367
DA 2026-03-09
ER

PT J
AU Briggman, KL
   Helmstaedter, M
   Denk, W
AF Briggman, Kevin L.
   Helmstaedter, Moritz
   Denk, Winfried
TI Wiring specificity in the direction-selectivity circuit of the retina
SO NATURE
LA English
DT Article
ID starburst amacrine cells; ganglion-cells; rabbit retina; acetylcholine-receptors; dendritic structure; calcium signals; image motion; mechanisms; gaba; connections
AB The proper connectivity between neurons is essential for the implementation of the algorithms used in neural computations, such as the detection of directed motion by the retina. The analysis of neuronal connectivity is possible with electron microscopy, but technological limitations have impeded the acquisition of high-resolution data on a large enough scale. Here we show, using serial block-face electron microscopy and two-photon calcium imaging, that the dendrites of mouse starburst amacrine cells make highly specific synapses with direction-selective ganglion cells depending on the ganglion cell's preferred direction. Our findings indicate that a structural (wiring) asymmetry contributes to the computation of direction selectivity. The nature of this asymmetry supports some models of direction selectivity and rules out others. It also puts constraints on the developmental mechanisms behind the formation of synaptic connections. Our study demonstrates how otherwise intractable neurobiological questions can be addressed by combining functional imaging with the analysis of neuronal connectivity using large-scale electron microscopy.
C1 [Briggman, Kevin L.; Helmstaedter, Moritz; Denk, Winfried] Max Planck Inst Med Res, Dept Biomed Opt, D-69120 Heidelberg, Germany.
C3 Max Planck Society
RP Briggman, KL (corresponding author), Max Planck Inst Med Res, Dept Biomed Opt, D-69120 Heidelberg, Germany.
EM briggman@mpimf-heidelberg.mpg.de
NR 55
TC 633
Z9 773
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 10
PY 2011
VL 471
IS 7337
BP 183
EP U67
DI 10.1038/nature09818
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FK
UT WOS:000288170200030
PM 21390125
DA 2026-03-09
ER

PT J
AU Seibert, MM
   Ekeberg, T
   Maia, FRNC
   Svenda, M
   Andreasson, J
   Jönsson, O
   Odic, D
   Iwan, B
   Rocker, A
   Westphal, D
   Hantke, M
   DePonte, DP
   Barty, A
   Schulz, J
   Gumprecht, L
   Coppola, N
   Aquila, A
   Liang, MN
   White, TA
   Martin, A
   Caleman, C
   Stern, S
   Abergel, C
   Seltzer, V
   Claverie, JM
   Bostedt, C
   Bozek, JD
   Boutet, S
   Miahnahri, AA
   Messerschmidt, M
   Krzywinski, J
   Williams, G
   Hodgson, KO
   Bogan, MJ
   Hampton, CY
   Sierra, RG
   Starodub, D
   Andersson, I
   Bajt, S
   Barthelmess, M
   Spence, JCH
   Fromme, P
   Weierstall, U
   Kirian, R
   Hunter, M
   Doak, RB
   Marchesini, S
   Hau-Riege, SP
   Frank, M
   Shoeman, RL
   Lomb, L
   Epp, SW
   Hartmann, R
   Rolles, D
   Rudenko, A
   Schmidt, C
   Foucar, L
   Kimmel, N
   Holl, P
   Rudek, B
   Erk, B
   Hömke, A
   Reich, C
   Pietschner, D
   Weidenspointner, G
   Strüder, L
   Hauser, G
   Gorke, H
   Ullrich, J
   Schlichting, I
   Herrmann, S
   Schaller, G
   Schopper, F
   Soltau, H
   Kühnel, KU
   Andritschke, R
   Schröter, CD
   Krasniqi, F
   Bott, M
   Schorb, S
   Rupp, D
   Adolph, M
   Gorkhover, T
   Hirsemann, H
   Potdevin, G
   Graafsma, H
   Nilsson, B
   Chapman, HN
   Hajdu, J
AF Seibert, M. Marvin
   Ekeberg, Tomas
   Maia, Filipe R. N. C.
   Svenda, Martin
   Andreasson, Jakob
   Joensson, Olof
   Odic, Dusko
   Iwan, Bianca
   Rocker, Andrea
   Westphal, Daniel
   Hantke, Max
   DePonte, Daniel P.
   Barty, Anton
   Schulz, Joachim
   Gumprecht, Lars
   Coppola, Nicola
   Aquila, Andrew
   Liang, Mengning
   White, Thomas A.
   Martin, Andrew
   Caleman, Carl
   Stern, Stephan
   Abergel, Chantal
   Seltzer, Virginie
   Claverie, Jean-Michel
   Bostedt, Christoph
   Bozek, John D.
   Boutet, Sebastien
   Miahnahri, A. Alan
   Messerschmidt, Marc
   Krzywinski, Jacek
   Williams, Garth
   Hodgson, Keith O.
   Bogan, Michael J.
   Hampton, Christina Y.
   Sierra, Raymond G.
   Starodub, Dmitri
   Andersson, Inger
   Bajt, Sasa
   Barthelmess, Miriam
   Spence, John C. H.
   Fromme, Petra
   Weierstall, Uwe
   Kirian, Richard
   Hunter, Mark
   Doak, R. Bruce
   Marchesini, Stefano
   Hau-Riege, Stefan P.
   Frank, Matthias
   Shoeman, Robert L.
   Lomb, Lukas
   Epp, Sascha W.
   Hartmann, Robert
   Rolles, Daniel
   Rudenko, Artem
   Schmidt, Carlo
   Foucar, Lutz
   Kimmel, Nils
   Holl, Peter
   Rudek, Benedikt
   Erk, Benjamin
   Hoemke, Andre
   Reich, Christian
   Pietschner, Daniel
   Weidenspointner, Georg
   Strueder, Lothar
   Hauser, Guenter
   Gorke, Hubert
   Ullrich, Joachim
   Schlichting, Ilme
   Herrmann, Sven
   Schaller, Gerhard
   Schopper, Florian
   Soltau, Heike
   Kuehnel, Kai-Uwe
   Andritschke, Robert
   Schroeter, Claus-Dieter
   Krasniqi, Faton
   Bott, Mario
   Schorb, Sebastian
   Rupp, Daniela
   Adolph, Marcus
   Gorkhover, Tais
   Hirsemann, Helmut
   Potdevin, Guillaume
   Graafsma, Heinz
   Nilsson, Bjoern
   Chapman, Henry N.
   Hajdu, Janos
TI Single mimivirus particles intercepted and imaged with an X-ray laser
SO NATURE
LA English
DT Article
ID free-electron laser; diffraction microscopy; virophage
AB X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions(1-4). Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma(1). The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval(2). Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a noncrystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source(5). Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
C1 [Seibert, M. Marvin; Ekeberg, Tomas; Maia, Filipe R. N. C.; Svenda, Martin; Andreasson, Jakob; Joensson, Olof; Odic, Dusko; Iwan, Bianca; Rocker, Andrea; Westphal, Daniel; Hantke, Max; Caleman, Carl; Hajdu, Janos] Uppsala Univ, Dept Cell & Mol Biol, Lab Mol Biophys, SE-75124 Uppsala, Sweden.
   [DePonte, Daniel P.; Barty, Anton; Schulz, Joachim; Gumprecht, Lars; Coppola, Nicola; Aquila, Andrew; Liang, Mengning; White, Thomas A.; Martin, Andrew; Caleman, Carl; Stern, Stephan; Chapman, Henry N.] DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Stern, Stephan; Chapman, Henry N.] Univ Hamburg, D-22607 Hamburg, Germany.
   [Abergel, Chantal; Seltzer, Virginie; Claverie, Jean-Michel] Aix Marseille Univ, CNRS, UPR2589, Inst Microbiol & Mediterranee, F-13288 Marseille 9, France.
   [Bostedt, Christoph; Bozek, John D.; Boutet, Sebastien; Miahnahri, A. Alan; Messerschmidt, Marc; Krzywinski, Jacek; Williams, Garth] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Hodgson, Keith O.; Bogan, Michael J.; Hampton, Christina Y.; Sierra, Raymond G.; Starodub, Dmitri] SLAC Natl Accelerator Lab, PULSE Inst, Menlo Pk, CA 94025 USA.
   [Andersson, Inger] Swedish Univ Agr Sci, Uppsala Biomed Ctr, Dept Mol Biol, S-75124 Uppsala, Sweden.
   [Spence, John C. H.; Weierstall, Uwe; Kirian, Richard; Doak, R. Bruce] Arizona State Univ, Dept Phys, PSF470, Tempe, AZ 85287 USA.
   [Fromme, Petra; Hunter, Mark] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Marchesini, Stefano] Lawrence Berkeley Natl Lab, Adv Light Source, Berkeley, CA 94720 USA.
   [Hau-Riege, Stefan P.; Frank, Matthias] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Shoeman, Robert L.; Lomb, Lukas; Rolles, Daniel; Foucar, Lutz; Schlichting, Ilme; Krasniqi, Faton; Bott, Mario] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [Epp, Sascha W.; Rolles, Daniel; Rudenko, Artem; Schmidt, Carlo; Foucar, Lutz; Rudek, Benedikt; Erk, Benjamin; Hoemke, Andre; Strueder, Lothar; Ullrich, Joachim; Schlichting, Ilme; Krasniqi, Faton] Max Planck Adv Study Grp, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Epp, Sascha W.; Rudenko, Artem; Schmidt, Carlo; Rudek, Benedikt; Erk, Benjamin; Hoemke, Andre; Ullrich, Joachim; Kuehnel, Kai-Uwe; Schroeter, Claus-Dieter] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Hartmann, Robert; Holl, Peter; Reich, Christian; Soltau, Heike] PNSensor GmbH, D-80803 Munich, Germany.
   [Kimmel, Nils; Pietschner, Daniel; Weidenspointner, Georg; Strueder, Lothar; Hauser, Guenter; Herrmann, Sven; Schaller, Gerhard; Schopper, Florian; Andritschke, Robert] Max Planck Inst Halbleiterlab, D-81739 Munich, Germany.
   [Kimmel, Nils; Pietschner, Daniel; Weidenspointner, Georg; Strueder, Lothar; Hauser, Guenter; Herrmann, Sven; Schaller, Gerhard; Schopper, Florian; Andritschke, Robert] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Strueder, Lothar] Univ Siegen, D-57068 Siegen, Germany.
   [Gorke, Hubert] Forschungszentrum Julich, Inst ZEL, D-52425 Julich, Germany.
   [Schorb, Sebastian; Rupp, Daniela; Adolph, Marcus; Gorkhover, Tais] Tech Univ Berlin, Inst Opt & Atomare Phys, D-10623 Berlin, Germany.
C3 Uppsala University; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Hamburg; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Swedish University of Agricultural Sciences; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Max Planck Society; Max Planck Society; Max Planck Society; PNSensor GmbH; Max Planck Society; Max Planck Society; Universitat Siegen; Helmholtz Association; Julich Research Centre; Technical University of Berlin
RP Hajdu, J (corresponding author), Uppsala Univ, Dept Cell & Mol Biol, Lab Mol Biophys, Husargatan 3,Box 596, SE-75124 Uppsala, Sweden.
EM chantal.abergel@igs.cnrs-mrs.fr; janos.hajdu@xray.bmc.uu.se
FU Swedish Research Councils; Swedish Foundation for International Cooperation in Research and Higher Education; Stiftelsen Olle Engkvist Byggmastare; Swedish University of Agricultural Sciences; Helmholtz Association [VH-VI-302]; DFG Cluster of Excellence at the Munich Centre for Advanced Photonics; Centre National de la Recherche Scientifique; Agence Nationale de la Recherche [ANR-BLAN08-0089]; Hamburg Ministry of Science and Research; Hamburg School for Structure and Dynamics; Max Planck Society; US National Science Foundation [MCB 0919195, MCB-1021557]; US Department of Energy through the PULSE Institute; Joachim Herz Stiftung, Hamburg Initiative for Excellence in Research (LEXI); Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0919195] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1021557] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM095583] Funding Source: NIH RePORTER
NR 33
TC 736
Z9 826
U1 1
U2 323
PU 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 3
PY 2011
VL 470
IS 7332
BP 78
EP U86
DI 10.1038/nature09748
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400037
PM 21293374
DA 2026-03-09
ER

PT J
AU Yonehara, K
   Balint, K
   Noda, M
   Nagel, G
   Bamberg, E
   Roska, B
AF Yonehara, Keisuke
   Balint, Kamill
   Noda, Masaharu
   Nagel, Georg
   Bamberg, Ernst
   Roska, Botond
TI Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit
SO NATURE
LA English
DT Article
ID selective ganglion-cells; starburst amacrine cells; direction selectivity; rabbit retina; visual experience; mammalian retina; mouse retina; channelrhodopsin-2; architecture; mechanisms
AB Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing(1,2). A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells(3-5). It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell(9,10). We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.
C1 [Yonehara, Keisuke; Balint, Kamill; Roska, Botond] Friedrich Miescher Inst Biomed Res, Neural Circuit Labs, CH-4058 Basel, Switzerland.
   [Noda, Masaharu] Natl Inst Basic Biol, Div Mol Neurobiol, Okazaki, Aichi 4448787, Japan.
   [Noda, Masaharu] Grad Univ Adv Studies, Sch Life Sci, Okazaki, Aichi 4448787, Japan.
   [Nagel, Georg] Univ Wurzburg, D-97082 Wurzburg, Germany.
   [Bamberg, Ernst] Max Planck Inst Biophys, D-60438 Frankfurt, Germany.
   [Bamberg, Ernst] Goethe Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany.
C3 Friedrich Miescher Institute for Biomedical Research; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB); Graduate University for Advanced Studies - Japan; University of Wurzburg; Max Planck Society; Goethe University Frankfurt
RP Roska, B (corresponding author), Friedrich Miescher Inst Biomed Res, Neural Circuit Labs, CH-4058 Basel, Switzerland.
EM botond.roska@fmi.ch
FU Friedrich Miescher Institute for Biomedical Research; US Office of Naval Research; Marie Curie Excellence grant; National Centre of Competence in Research; European Research Council; European Union; EMBO
NR 34
TC 136
Z9 174
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 JAN 20
PY 2011
VL 469
IS 7330
BP 407
EP +
DI 10.1038/nature09711
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600054
PM 21170022
DA 2026-03-09
ER

PT J
AU Trail, D
   Watson, EB
   Tailby, ND
AF Trail, Dustin
   Watson, E. Bruce
   Tailby, Nicholas D.
TI The oxidation state of Hadean magmas and implications for early Earth's atmosphere
SO NATURE
LA English
DT Article
ID detrital zircons; melt inclusions; oxygen fugacity; ti; elements; history; mantle; ma
AB Magmatic outgassing of volatiles from Earth's interior probably played a critical part in determining the composition of the earliest atmosphere, more than 4,000 million years (Myr) ago(1). Given an elemental inventory of hydrogen, carbon, nitrogen, oxygen and sulphur, the identity of molecular species in gaseous volcanic emanations depends critically on the pressure (fugacity) of oxygen. Reduced melts having oxygen fugacities close to that defined by the iron-wustite buffer would yield volatile species such as CH4, H-2, H2S, NH3 and CO, whereas melts close to the fayalite-magnetite-quartz buffer would be similar to present-day conditions and would be dominated by H2O, CO2, SO2 and N-2 (refs 1-4). Direct constraints on the oxidation state of terrestrial magmas before 3,850 Myr before present (that is, the Hadean eon) are tenuous because the rock record is sparse or absent. Samples from this earliest period of Earth's history are limited to igneous detrital zircons that pre-date the known rock record, with ages approaching similar to 4,400 Myr (refs 5-8). Here we report a redox-sensitive calibration to determine the oxidation state of Hadean magmatic melts that is based on the incorporation of cerium into zircon crystals. We find that the melts have average oxygen fugacities that are consistent with an oxidation state defined by the fayalite-magnetite-quartz buffer, similar to present-day conditions. Moreover, selected Hadean zircons (having chemical characteristics consistent with crystallization specifically from mantle-derived melts) suggest oxygen fugacities similar to those of Archaean and present-day mantle-derived lavas(2-4,9,10) as early as similar to 4,350 Myr before present. These results suggest that outgassing of Earth's interior later than similar to 200 Myr into the history of Solar System formation would not have resulted in a reducing atmosphere.
C1 [Trail, Dustin; Watson, E. Bruce; Tailby, Nicholas D.] Rensselaer Polytech Inst, Dept Earth & Environm Sci, Troy, NY 12181 USA.
   [Trail, Dustin; Watson, E. Bruce; Tailby, Nicholas D.] Rensselaer Polytech Inst, New York Ctr Astrobiol, Troy, NY 12180 USA.
C3 Rensselaer Polytechnic Institute; Rensselaer Polytechnic Institute
RP Trail, D (corresponding author), Rensselaer Polytech Inst, Dept Earth & Environm Sci, Troy, NY 12181 USA.
EM traild@rpi.edu
FU NASA Astrobiology Institute [NNA09DA80A]
NR 33
TC 518
Z9 607
U1 5
U2 347
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 1
PY 2011
VL 480
IS 7375
BP 79
EP U238
DI 10.1038/nature10655
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900037
PM 22129728
DA 2026-03-09
ER

PT J
AU Shomura, Y
   Yoon, KS
   Nishihara, H
   Higuchi, Y
AF Shomura, Yasuhito
   Yoon, Ki-Seok
   Nishihara, Hirofumi
   Higuchi, Yoshiki
TI Structural basis for a [4Fe-3S] cluster in the oxygen-tolerant membrane-bound [NiFe]-hydrogenase
SO NATURE
LA English
DT Article
ID ralstonia-eutropha h16; nife hydrogenase; crystal-structure; catalytic cycle; active-site; gas access; refinement; activation; angstrom; centers
AB Membrane-bound respiratory [NiFe]-hydrogenase (MBH), a H-2-uptake enzyme found in the periplasmic space of bacteria, catalyses the oxidation of dihydrogen: H-2 -> 2H(+) + 2e(-) (ref. 1). In contrast to the well-studied O-2-sensitive [NiFe]-hydrogenases (referred to as the standard enzymes), MBH has an O-2-tolerant H-2 oxidation activity(2-4); however, the mechanism of O-2 tolerance is unclear(5). Here we report the crystal structures of Hydrogenovibrio marinus MBH in three different redox conditions at resolutions between 1.18 and 1.32 angstrom. We find that the proximal iron-sulphur (Fe-S) cluster of MBH has a [4Fe-3S] structure coordinated by six cysteine residues-in contrast to the [4Fe-4S] cubane structure coordinated by four cysteine residues found in the proximal Fe-S cluster of the standard enzymes-and that an amide nitrogen of the polypeptide backbone is deprotonated and additionally coordinates the cluster when chemically oxidized, thus stabilizing the superoxidized state of the cluster. The structure of MBH is very similar to that of the O-2-sensitive standard enzymes except for the proximal Fe-S cluster. Our results give a reasonable explanation why the O-2 tolerance of MBH is attributable to the unique proximal Fe-S cluster; we propose that the cluster is not only a component of the electron transfer for the catalytic cycle, but that it also donates two electrons and one proton crucial for the appropriate reduction of O-2 in preventing the formation of an unready, inactive state of the enzyme.
C1 [Shomura, Yasuhito; Higuchi, Yoshiki] Univ Hyogo, Grad Sch Life Sci, Dept Life Sci, Kamigori, Hyogo 6781297, Japan.
   [Shomura, Yasuhito; Higuchi, Yoshiki] RIKEN SPring 8 Ctr, Sayo, Hyogo 6795148, Japan.
   [Yoon, Ki-Seok; Nishihara, Hirofumi] Ibaraki Univ, Coll Agr, Dept Bioresource Sci, Ami, Ibaraki 3000393, Japan.
   [Higuchi, Yoshiki] Japan Sci & Technol Agcy JST, CREST, Kawaguchi, Saitama 3320012, Japan.
C3 University of Hyogo; RIKEN; Ibaraki University; Japan Science & Technology Agency (JST)
RP Higuchi, Y (corresponding author), Univ Hyogo, Grad Sch Life Sci, Dept Life Sci, 3-2-1 Koto, Kamigori, Hyogo 6781297, Japan.
EM hig@sci.u-hyogo.ac.jp
FU Academia Sinica; National Synchrotron Radiation Research Center (Taiwan); MEXT [20051022, 22770111, 18GS0207]; JSPS [20580094, 22370061, 22657031]; University of Hyogo; Hyogo Science and Technology Association; GCOE Program; Japanese Aerospace Exploration Agency Project; JST, Japan; Grants-in-Aid for Scientific Research [22657031, 22121519, 22370061, 20580094, 18GS0207, 22770111] Funding Source: KAKEN
NR 37
TC 236
Z9 261
U1 1
U2 136
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 253
EP U143
DI 10.1038/nature10504
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800048
PM 22002607
DA 2026-03-09
ER

PT J
AU Wang, D
   Garcia-Bassets, I
   Benner, C
   Li, WB
   Su, X
   Zhou, YM
   Qiu, JS
   Liu, W
   Kaikkonen, MU
   Ohgi, KA
   Glass, CK
   Rosenfeld, MG
   Fu, XD
AF Wang, Dong
   Garcia-Bassets, Ivan
   Benner, Chris
   Li, Wenbo
   Su, Xue
   Zhou, Yiming
   Qiu, Jinsong
   Liu, Wen
   Kaikkonen, Minna U.
   Ohgi, Kenneth A.
   Glass, Christopher K.
   Rosenfeld, Michael G.
   Fu, Xiang-Dong
TI Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA
SO NATURE
LA English
DT Article
ID forkhead box a1; prostate-cancer; gene-expression; androgen receptor; histone modifications; nuclear receptors; human genome; in-vivo; chromatin; signatures
AB Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs(1-4), but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA(5)) based on global nuclear run-on sequencing (GRO-seq) analysis(6), with a unique class apparently requiring no nucleosome remodelling to induce specific enhancer-promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.
C1 [Wang, Dong; Benner, Chris; Qiu, Jinsong; Kaikkonen, Minna U.; Glass, Christopher K.; Fu, Xiang-Dong] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Garcia-Bassets, Ivan; Li, Wenbo; Su, Xue; Liu, Wen; Ohgi, Kenneth A.; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA.
   [Garcia-Bassets, Ivan] Univ Calif San Diego, Sch Med, Dept Med, Div Endocrinol & Metab, La Jolla, CA 92093 USA.
   [Su, Xue; Liu, Wen] Univ Calif San Diego, Sch Med, Grad Program Biol, La Jolla, CA 92093 USA.
   [Zhou, Yiming] Digomics LLC, Malden, MA 02148 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Fu, XD (corresponding author), Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM ibassets@ucsd.edu; mrosenfeld@ucsd.edu; xdfu@ucsd.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA097134] Funding Source: Medline; NHGRI NIH HHS [R01 HG004659, HG004659] Funding Source: Medline; NHLBI NIH HHS [R01 HL065445] Funding Source: Medline; NIDDK NIH HHS [DK074868, R01 DK091183, R01 DK039949, P01 DK074868, DK01847, R37 DK039949, DK37949, R01 DK018477] Funding Source: Medline; NIGMS NIH HHS [R01 GM049369, GM049369] Funding Source: Medline; NINDS NIH HHS [NS34934, R01 NS034934] Funding Source: Medline; National Human Genome Research Institute [R01HG004659] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK091183, R01DK039949] Funding Source: NIH RePORTER
NR 40
TC 677
Z9 844
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 JUN 16
PY 2011
VL 474
IS 7351
BP 390
EP +
DI 10.1038/nature10006
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100048
PM 21572438
DA 2026-03-09
ER

PT J
AU Tan, YH
   Luo, ZQ
AF Tan, Yunhao
   Luo, Zhao-Qing
TI Legionella pneumophila SidD is a deAMPylase that modifies Rab1
SO NATURE
LA English
DT Article
ID effector protein drra; ampylation; system; phosphatase; binding; family
AB Legionella pneumophila actively modulates host vesicle trafficking pathways to facilitate its intracellular replication with effectors translocated by the Dot/Icm type IV secretion system (T4SS)(1). The SidM/DrrA protein functions by locking the small GTPase Rab1 into an active form by its guanine nucleotide exchange factor (GEF) and AMPylation activity(2-4). Here we demonstrate that the L. pneumophila protein SidD preferably deAMPylates Rab1. We found that the deAMPylation activity of SidD could suppress the toxicity of SidM to yeast and is required to release Rab1 from bacterial phagosomes efficiently. A molecular mechanism for the temporal control of Rab1 activity in different phases of L. pneumophila infection is thus established. These observations indicate that AMPylation-mediated signal transduction is a reversible process regulated by specific enzymes.
C1 [Tan, Yunhao; Luo, Zhao-Qing] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University
RP Luo, ZQ (corresponding author), Purdue Univ, Dept Biol Sci, 915 W State St, W Lafayette, IN 47907 USA.
EM luoz@purdue.edu
FU NIH-NIAID [R01AI069344, K02AI085403, R21AI092043]
NR 29
TC 190
Z9 239
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 506
EP U102
DI 10.1038/nature10307
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900042
PM 21734656
DA 2026-03-09
ER

PT J
AU Tamsir, A
   Tabor, JJ
   Voigt, CA
AF Tamsir, Alvin
   Tabor, Jeffrey J.
   Voigt, Christopher A.
TI Robust multicellular computing using genetically encoded NOR gates and chemical 'wires'
SO NATURE
LA English
DT Article
ID synthetic gene networks; circuit; quorum; logic; morphogenesis; system; cells; model
AB Computation underlies the organization of cells into higher-order structures, for example during development or the spatial association of bacteria in a biofilm(1-3). Each cell performs a simple computational operation, but when combined with cell-cell communication, intricate patterns emerge. Here we study this process by combining a simple genetic circuit with quorum sensing to produce more complex computations in space. We construct a simple NOR logic gate in Escherichia coli by arranging two tandem promoters that function as inputs to drive the transcription of a repressor. The repressor inactivates a promoter that serves as the output. Individual colonies of E. coli carry the same NOR gate, but the inputs and outputs are wired to different orthogonal quorum-sensing 'sender' and 'receiver' devices(4,5). The quorum molecules form the wires between gates. By arranging the colonies in different spatial configurations, all possible two-input gates are produced, including the difficult XOR and EQUALS functions. The response is strong and robust, with 5- to >300-fold changes between the 'on' and 'off' states. This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between cells.
C1 [Tabor, Jeffrey J.; Voigt, Christopher A.] Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Tamsir, Alvin] Univ Calif San Francisco, Dept Biochem & Biophys, 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 Voigt, CA (corresponding author), Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
EM cavoigt@picasso.ucsf.edu
FU National Science Foundation (NSF) [0943385, CCF-0943385]; Office of Naval Research; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [0943269, 0943385] Funding Source: National Science Foundation
NR 31
TC 599
Z9 781
U1 1
U2 251
PU 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 13
PY 2011
VL 469
IS 7329
BP 212
EP 215
DI 10.1038/nature09565
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400038
PM 21150903
DA 2026-03-09
ER

PT J
AU Reisch, CR
   Stoudemayer, MJ
   Varaljay, VA
   Amster, IJ
   Moran, MA
   Whitman, WB
AF Reisch, Chris R.
   Stoudemayer, Melissa J.
   Varaljay, Vanessa A.
   Amster, I. Jonathan
   Moran, Mary Ann
   Whitman, William B.
TI Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria
SO NATURE
LA English
DT Article
ID acyl-coenzyme-a; dimethyl sulfide; dimethylsulfoniopropionate; sulfur; dmsp; methanethiol; degradation; methionine; abundant; enzyme
AB Dimethylsulphoniopropionate (DMSP) accounts for up to 10% of carbon fixed by marine phytoplankton in ocean surface waters(1,2), producing an estimated 11.7-103 T mol S per year(3), most of which is processed by marine bacteria through the demethylation/demethiolation pathway(4). This pathway releases methanethiol (MeSH) instead of the climatically active gas dimethylsulphide (DMS) and enables marine microorganisms to assimilate the reduced sulphur(5-7). Despite recognition of this critical microbial transformation for over two decades, the biochemical pathway and enzymes responsible have remained unidentified. Here we show that three new enzymes related to fatty acid beta-oxidation constitute the pathway that assimilates methylmercaptopropionate (MMPA), the first product of DMSP demethylation/demethiolation, and that two previously unknown coenzyme A (CoA) derivatives, 3-methylmercaptopropionyl-CoA (MMPA-CoA) and methylthioacryloyl-CoA (MTA-CoA), are formed as novel intermediates. A member of the marine roseobacters, Ruegeria pomeroyi DSS-3, requires the MMPA-CoA pathway for MMPA assimilation and MeSH production. This pathway and the ability to produce MeSH from MMPA are present in diverse bacteria, and the ubiquitous SAR11 clade bacterium Pelagibacter ubique possesses enzymes for at least the first two steps. Analysis of marine metagenomic data indicates that the pathway is widespread among bacterioplankton in the ocean surface waters, making it one of the most important known routes for acquisition of reduced carbon and sulphur by surface ocean heterotrophs.
C1 [Reisch, Chris R.; Varaljay, Vanessa A.; Whitman, William B.] Univ Georgia, Dept Microbiol, Athens, GA 30602 USA.
   [Moran, Mary Ann] Univ Georgia, Dept Marine Sci, Athens, GA 30602 USA.
   [Stoudemayer, Melissa J.; Amster, I. Jonathan] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
C3 University System of Georgia; University of Georgia; University System of Georgia; University of Georgia; University System of Georgia; University of Georgia
RP Whitman, WB (corresponding author), Univ Georgia, Dept Microbiol, Athens, GA 30602 USA.
EM whitman@uga.edu
FU National Science Foundation [MCB-0702125, OCE-0724017]; Gordon and Betty Moore Foundation
NR 38
TC 130
Z9 151
U1 6
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 MAY 12
PY 2011
VL 473
IS 7346
BP 208
EP +
DI 10.1038/nature10078
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200037
PM 21562561
DA 2026-03-09
ER

PT J
AU Roppolo, D
   De Rybel, B
   Tendon, VD
   Pfister, A
   Alassimone, J
   Vermeer, JEM
   Yamazaki, M
   Stierhof, YD
   Beeckman, T
   Geldner, N
AF Roppolo, Daniele
   De Rybel, Bert
   Tendon, Valerie Denervaud
   Pfister, Alexandre
   Alassimone, Julien
   Vermeer, Joop E. M.
   Yamazaki, Misako
   Stierhof, York-Dieter
   Beeckman, Tom
   Geldner, Niko
TI A novel protein family mediates Casparian strip formation in the endodermis
SO NATURE
LA English
DT Article
ID asymmetric cell-division; arabidopsis root; plant; transport; movement; polarity
AB Polarized epithelia are fundamental to multicellular life. In animal epithelia, conserved junctional complexes establish membrane diffusion barriers, cellular adherence and sealing of the extracellular space(1). Plant cellular barriers are of independent evolutionary origin. The root endodermis strongly resembles a polarized epithelium and functions in nutrient uptake and stress resistance(2). Its defining features are the Casparian strips, belts of specialized cell wall material that generate an extracellular diffusion barrier(2). The mechanisms localizing Casparian strips are unknown. Here we identify and characterize a family of transmembrane proteins of previously unknown function. These 'CASPs' (Casparian strip membrane domain proteins) specifically mark a membrane domain that predicts the formation of Casparian strips. CASP1 displays numerous features required for a constituent of a plant junctional complex: it forms complexes with other CASPs; it becomes immobile upon localization; and it sediments like a large polymer. CASP double mutants display disorganized Casparian strips, demonstrating a role for CASPs in structuring and localizing this cell wall modification. To our knowledge, CASPs are the first molecular factors that are shown to establish a plasma membrane and extracellular diffusion barrier in plants, and represent a novel way of epithelial barrier formation in eukaryotes.
C1 [Roppolo, Daniele; Tendon, Valerie Denervaud; Pfister, Alexandre; Alassimone, Julien; Vermeer, Joop E. M.; Yamazaki, Misako; Geldner, Niko] Univ Lausanne, UNIL Sorge, Dept Plant Mol Biol, CH-1015 Lausanne, Switzerland.
   [De Rybel, Bert; Beeckman, Tom] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium.
   [De Rybel, Bert; Beeckman, Tom] VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Stierhof, York-Dieter] Univ Tubingen, ZMBP, D-72076 Tubingen, Germany.
C3 University of Lausanne; Ghent University; Flanders Institute for Biotechnology (VIB); Eberhard Karls University of Tubingen
RP Geldner, N (corresponding author), Univ Lausanne, UNIL Sorge, Dept Plant Mol Biol, CH-1015 Lausanne, Switzerland.
EM niko.geldner@unil.ch
FU Swiss National Science Foundation; European Research Council (ERC); Belgian Interuniversity Attraction Poles program [IUAP VI/33]; Ghent University; Roche Research Foundation; Marie-Curie IEF grant
NR 27
TC 347
Z9 393
U1 10
U2 168
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 380
EP U564
DI 10.1038/nature10070
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400050
PM 21593871
DA 2026-03-09
ER

PT J
AU Hoffmann, AA
   Montgomery, BL
   Popovici, J
   Iturbe-Ormaetxe, I
   Johnson, PH
   Muzzi, F
   Greenfield, M
   Durkan, M
   Leong, YS
   Dong, Y
   Cook, H
   Axford, J
   Callahan, AG
   Kenny, N
   Omodei, C
   McGraw, EA
   Ryan, PA
   Ritchie, SA
   Turelli, M
   O'Neill, SL
AF Hoffmann, A. A.
   Montgomery, B. L.
   Popovici, J.
   Iturbe-Ormaetxe, I.
   Johnson, P. H.
   Muzzi, F.
   Greenfield, M.
   Durkan, M.
   Leong, Y. S.
   Dong, Y.
   Cook, H.
   Axford, J.
   Callahan, A. G.
   Kenny, N.
   Omodei, C.
   McGraw, E. A.
   Ryan, P. A.
   Ritchie, S. A.
   Turelli, M.
   O'Neill, S. L.
TI Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission
SO NATURE
LA English
DT Article
ID life-shortening wolbachia; cytoplasmic incompatibility; genetic-control; aegypti; australia; mosquitos; drosophila; dispersal; infection; replacement
AB Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations(1). Population transformation using the intracellular bacterium Wolbachia is particularly attractive because this maternally-inherited agent provides a powerful mechanism to invade natural populations through cytoplasmic incompatibility(2). When Wolbachia are introduced into mosquitoes, they interfere with pathogen transmission and influence key life history traits such as lifespan(3-6). Here we describe how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster(7), successfully invaded two natural A. aegypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A. aegypti adults. Models with plausible parameter values indicate that Wolbachia-infected mosquitoes suffered relatively small fitness costs, leading to an unstable equilibrium frequency <30% that must be exceeded for invasion. These findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression with potential for area-wide implementation.
C1 [Montgomery, B. L.; Popovici, J.; Iturbe-Ormaetxe, I.; Muzzi, F.; Greenfield, M.; Durkan, M.; Leong, Y. S.; Dong, Y.; Cook, H.; Kenny, N.; McGraw, E. A.; Ryan, P. A.; O'Neill, S. L.] Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
   [Hoffmann, A. A.; Axford, J.; Callahan, A. G.] Univ Melbourne, Dept Genet, Inst Bio21, Melbourne, Vic 3010, Australia.
   [Popovici, J.; Iturbe-Ormaetxe, I.; Dong, Y.; Kenny, N.; McGraw, E. A.; Ryan, P. A.; O'Neill, S. L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [Johnson, P. H.; Omodei, C.; Ritchie, S. A.] James Cook Univ, Sch Publ Hlth & Trop Med & Rehabil Sci, Cairns, Qld 4870, Australia.
   [Ryan, P. A.] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
   [Turelli, M.] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA.
C3 University of Queensland; University of Melbourne; Monash University; James Cook University; Royal Brisbane & Women's Hospital; QIMR Berghofer Medical Research Institute; University of California System; University of California Davis
RP O'Neill, SL (corresponding author), Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
EM scott.oneill@monash.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation; National Health and Medical Research Council, Australia; Queensland Government; NIH; Climate Health Cluster of the CSIRO; National Science Foundation; Australian Research Council
NR 33
TC 1198
Z9 1374
U1 10
U2 475
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 454
EP U107
DI 10.1038/nature10356
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400037
PM 21866160
DA 2026-03-09
ER

PT J
AU Napolitano, M
   Koschorreck, M
   Dubost, B
   Behbood, N
   Sewell, RJ
   Mitchell, MW
AF Napolitano, M.
   Koschorreck, M.
   Dubost, B.
   Behbood, N.
   Sewell, R. J.
   Mitchell, M. W.
TI Interaction-based quantum metrology showing scaling beyond the Heisenberg limit
SO NATURE
LA English
DT Article
AB Quantum metrology aims to use entanglement and other quantum resources to improve precision measurement(1). An interferometer using N independent particles to measure a parameter X can achieve at best the standard quantum limit of sensitivity, delta X proportional to N-1/2. However, using N entangled particles and exotic states(2), such an interferometer(3) can in principle achieve the Heisenberg limit, delta X proportional to N-1. Recent theoretical work(4-6) has argued that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity delta X proportional to N-k with appropriate entangled states and delta X proportional to N-(k-1/2) even without entanglement(7). Here we demonstrate 'super-Heisenberg' scaling of delta X proportional to N-3/2 in a nonlinear, non-destructive(8,9) measurement of the magnetization(10,11) of an atomic ensemble(12). We use fast optical nonlinearities to generate a pairwise photon-photon interaction(13) (corresponding to k = 2) while preserving quantum-noise-limited performance(7,14). We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large numbers by higher order nonlinear effects, in good agreement with theory(13). For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other situations, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship between scaling and sensitivity in nonlinear systems. Our work shows that interparticle interactions can improve sensitivity in a quantum-limited measurement, and experimentally demonstrates a new resource for quantum metrology.
C1 [Napolitano, M.; Koschorreck, M.; Dubost, B.; Behbood, N.; Sewell, R. J.; Mitchell, M. W.] ICFO Inst Ciencies Foton, Castelldefels 08860, Barcelona, Spain.
   [Dubost, B.] Univ Paris Diderot, Lab Mat & Phenomenes Quant, F-75205 Paris 13, France.
   [Dubost, B.] CNRS, UMR 7162, F-75205 Paris 13, France.
C3 Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); Universite Paris Cite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP)
RP Napolitano, M (corresponding author), ICFO Inst Ciencies Foton, Mediterranean Technol Pk, Castelldefels 08860, Barcelona, Spain.
EM mario.napolitano@icfo.es
FU Spanish Ministry of Science and Innovation [FIS2009-07676-E/FIS, FIS2008-01051]; Marie-Curie RTN EMALI; Fundacio CELLEX Barcelona
NR 23
TC 203
Z9 222
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 24
PY 2011
VL 471
IS 7339
BP 486
EP 489
DI 10.1038/nature09778
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200056
PM 21430776
DA 2026-03-09
ER

PT J
AU Luo, ZX
   Yuan, CX
   Meng, QJ
   Ji, Q
AF Luo, Zhe-Xi
   Yuan, Chong-Xi
   Meng, Qing-Jin
   Ji, Qiang
TI A Jurassic eutherian mammal and divergence of marsupials and placentals
SO NATURE
LA English
DT Article
ID tribosphenic mammals; dual origin; evolution; mongolia; biota; age
AB Placentals are the most abundant mammals that have diversified into every niche for vertebrates and dominated the world's terrestrial biotas in the Cenozoic. A critical event in mammalian history is the divergence of eutherians, the clade inclusive of all living placentals, from the metatherian-marsupial clade(1-8). Here we report the discovery of a new eutherian of 160 Myr from the Jurassic of China, which extends the first appearance of the eutherian-placental clade by about 35 Myr from the previous record, reducing and resolving a discrepancy between the previous fossil record and the molecular estimate for the placental-marsupial divergence(9-13). This mammal has scansorial forelimb features, and provides the ancestral condition for dental and other anatomical features of eutherians.
C1 [Luo, Zhe-Xi] CarnegieMuseum Nat Hist, Pittsburgh, PA 15213 USA.
   [Yuan, Chong-Xi; Ji, Qiang] Chinese Acad Geol Sci, Beijing 100037, Peoples R China.
   [Meng, Qing-Jin] Beijing Museum Nat Hist, Beijing 100050, Peoples R China.
C3 China Geological Survey; Chinese Academy of Geological Sciences
RP Luo, ZX (corresponding author), CarnegieMuseum Nat Hist, Pittsburgh, PA 15213 USA.
EM luoz@carnegiemnh.org
FU National Science Foundation (USA); National Natural Science Foundation-China; Chinese Academy of Geological Sciences; Ministry of Science and Technology of China
NR 30
TC 416
Z9 487
U1 0
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 442
EP 445
DI 10.1038/nature10291
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400034
PM 21866158
DA 2026-03-09
ER

PT J
AU Pruszynski, JA
   Kurtzer, I
   Nashed, JY
   Omrani, M
   Brouwer, B
   Scott, SH
AF Pruszynski, J. Andrew
   Kurtzer, Isaac
   Nashed, Joseph Y.
   Omrani, Mohsen
   Brouwer, Brenda
   Scott, Stephen H.
TI Primary motor cortex underlies multi-joint integration for fast feedback control
SO NATURE
LA English
DT Article
ID latency stretch reflexes; corticomotoneuronal cells; human arm; responses; motion; monkey; movements; neurons; perturbations
AB A basic difficulty for the nervous system is integrating locally ambiguous sensory information to form accurate perceptions about the outside world(1-4). This local-to-global problem is also fundamental to motor control of the arm, because complex mechanical interactions between shoulder and elbow allow a particular amount of motion at one joint to arise from an infinite combination of shoulder and elbow torques(5). Here we show, in humans and rhesus monkeys, that a transcortical pathway through primary motor cortex (M1) resolves this ambiguity during fast feedback control. We demonstrate that single M1 neurons of behaving monkeys can integrate shoulder and elbow motion information into motor commands that appropriately counter the underlying torque within about 50 milliseconds of a mechanical perturbation. Moreover, we reveal a causal link between M1 processing and multi-joint integration in humans by showing that shoulder muscle responses occurring 50 milliseconds after pure elbow displacement can be potentiated by transcranial magnetic stimulation. Taken together, our results show that transcortical processing through M1 permits feedback responses to express a level of sophistication that rivals voluntary control; this provides neurophysiological support for influential theories positing that voluntary movement is generated by the intelligent manipulation of sensory feedback(6,7).
C1 [Pruszynski, J. Andrew; Kurtzer, Isaac; Nashed, Joseph Y.; Omrani, Mohsen; Brouwer, Brenda; Scott, Stephen H.] Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6, Canada.
   [Pruszynski, J. Andrew] Umea Univ, Dept Integrat Med Biol, Physiol Sect, SE-90187 Umea, Sweden.
   [Kurtzer, Isaac] New York Coll Osteopath Med, Dept Neurosci & Histol, Old Westbury, NY 11568 USA.
   [Brouwer, Brenda] Queens Univ, Sch Rehabil Therapy, Kingston, ON K7L 3N6, Canada.
   [Scott, Stephen H.] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada.
   [Scott, Stephen H.] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada.
C3 Queens University - Canada; Umea University; New York Institute Technology; Queens University - Canada; Queens University - Canada; Queens University - Canada
RP Scott, SH (corresponding author), Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6, Canada.
EM steve.scott@queensu.ca
FU Canadian Institutes of Health Research (CIHR); National Sciences and Engineering Research Council of Canada (NSERC)
NR 30
TC 242
Z9 300
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 20
PY 2011
VL 478
IS 7369
BP 387
EP +
DI 10.1038/nature10436
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100046
PM 21964335
DA 2026-03-09
ER

PT J
AU Reuter, M
   Berninger, P
   Chuma, S
   Shah, H
   Hosokawa, M
   Funaya, C
   Antony, C
   Sachidanandam, R
   Pillai, RS
AF Reuter, Michael
   Berninger, Philipp
   Chuma, Shinichiro
   Shah, Hardik
   Hosokawa, Mihoko
   Funaya, Charlotta
   Antony, Claude
   Sachidanandam, Ravi
   Pillai, Ramesh S.
TI Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing
SO NATURE
LA English
DT Article
ID piwi-interacting rnas; male germ-cells; dna methylation; chromatoid body; family-members; pathway; protein; mice; gene; spermatogenesis
AB Repetitive-element-derived Piwi-interacting RNAs (piRNAs)(1,2) act together with Piwi proteins Mili (also known as Piwil2) and Miwi2 (also known as Piwil4) in a genome defence mechanism that initiates transposon silencing via DNA methylation in the mouse male embryonic germ line. This silencing depends on the participation of the Piwi proteins in a slicer-dependent piRNA amplification pathway and is essential for male fertility(3,4). A third Piwi family member, Miwi (also known as Piwil1), is expressed in specific postnatal germ cells and associates with a unique set of piRNAs of unknown function(5-7). Here we show that Miwi is a small RNA-guided RNase (slicer) that requires extensive complementarity for target cleavage in vitro. Disruption of its catalytic activity in mice by a single point mutation causes male infertility, and mutant germ cells show increased accumulation of LINE1 retrotransposon transcripts. We provide evidence for Miwi slicer activity directly cleaving transposon messenger RNAs, offering an explanation for the continued maintenance of repeat-derived piRNAs long after transposon silencing is established in germline stem cells. Furthermore, our study supports a slicer-dependent silencing mechanism that functions without piRNA amplification. Thus, Piwi proteins seem to act in a two-pronged mammalian transposon silencing strategy: one promotes transcriptional repression in the embryo, the other reinforces silencing at the post-transcriptional level after birth.
C1 [Reuter, Michael; Berninger, Philipp; Pillai, Ramesh S.] European Mol Biol Lab, F-38042 Grenoble, France.
   [Reuter, Michael; Berninger, Philipp; Pillai, Ramesh S.] CNRS, UJF, EMBL Int Unit, UMI Virus Host Cell Interact UVHCI 3265, F-38042 Grenoble, France.
   [Chuma, Shinichiro; Hosokawa, Mihoko] Kyoto Univ, Inst Frontier Med Sci, Kyoto 6068507, Japan.
   [Chuma, Shinichiro; Hosokawa, Mihoko] Kyoto Univ, Inst Integrated Cell Mat Sci iCeMS, Kyoto 6068501, Japan.
   [Shah, Hardik; Sachidanandam, Ravi] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Antony, Claude] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL); Centre National de la Recherche Scientifique (CNRS); European Molecular Biology Laboratory (EMBL); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Kyoto University; Kyoto University; Icahn School of Medicine at Mount Sinai; European Molecular Biology Laboratory (EMBL)
RP Pillai, RS (corresponding author), European Mol Biol Lab, 6 Rue Jules Horowitz,BP 181, F-38042 Grenoble, France.
EM pillai@embl.fr
FU Deutsche Forschungsgemeinschaft (DFG); Agence National de la Recherche (ANR) (piRmachines); European Union (European Research Council, ERC); EMBL; Grants-in-Aid for Scientific Research [22019018, 22770210, 20062004] Funding Source: KAKEN
NR 47
TC 344
Z9 391
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 DEC 8
PY 2011
VL 480
IS 7376
BP 264
EP U154
DI 10.1038/nature10672
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200056
PM 22121019
DA 2026-03-09
ER

PT J
AU Lee, MSY
   Jago, JB
   García-Bellido, DC
   Edgecombe, GD
   Gehling, JG
   Paterson, JR
AF Lee, Michael S. Y.
   Jago, James B.
   Garcia-Bellido, Diego C.
   Edgecombe, Gregory D.
   Gehling, James G.
   Paterson, John R.
TI Modern optics in exceptionally preserved eyes of Early Cambrian arthropods from Australia
SO NATURE
LA English
DT Article
ID emu bay shale; south-australia; kangaroo island; visual-system; lagerstatte; trilobites; evolution; tuzoia
AB Despite the status of the eye as an "organ of extreme perfection"(1), theory suggests that complex eyes can evolve very rapidly(2). The fossil record has, until now, been inadequate in providing insight into the early evolution of eyes during the initial radiation of many animal groups known as the Cambrian explosion. This is surprising because Cambrian Burgess-Shale-type deposits are replete with exquisitely preserved animals, especially arthropods, that possess eyes(3-5). However, with the exception of biomineralized trilobite eyes, virtually nothing is known about the details of their optical design. Here we report exceptionally preserved fossil eyes from the Early Cambrian (similar to 515 million years ago) Emu Bay Shale of South Australia, revealing that some of the earliest arthropods possessed highly advanced compound eyes, each with over 3,000 large ommatidial lenses and a specialized 'bright zone'. These are the oldest non-biomineralized eyes known in such detail, with preservation quality exceeding that found in the Burgess Shale and Chengjiang deposits. Non-biomineralized eyes of similar complexity are otherwise unknown until about 85 million years later(6,7). The arrangement and size of the lenses indicate that these eyes belonged to an active predator that was capable of seeing in low light. The eyes are more complex than those known from contemporaneous trilobites and are as advanced as those of many living forms. They provide further evidence that the Cambrian explosion involved rapid innovation in fine-scale anatomy as well as gross morphology, and are consistent with the concept that the development of advanced vision helped to drive this great evolutionary event(8).
C1 [Lee, Michael S. Y.; Jago, James B.; Gehling, James G.] S Australian Museum, Adelaide, SA 5000, Australia.
   [Lee, Michael S. Y.] Univ Adelaide, Sch Earth & Environm Sci, Adelaide, SA 5005, Australia.
   [Jago, James B.] Univ S Australia, Sch Nat & Built Environm, Mawson Lakes, SA 5095, Australia.
   [Garcia-Bellido, Diego C.] Inst Geociencias CSIC UCM, Inst Geol Econ, Dept Paleontol, Madrid 28040, Spain.
   [Edgecombe, Gregory D.] Nat Hist Museum, Dept Paleontol, London SW7 5BD, England.
   [Paterson, John R.] Univ New England, Sch Environm & Rural Sci, Div Earth Sci, Armidale, NSW 2351, Australia.
C3 Adelaide University; University of Adelaide; Adelaide University; University of South Australia; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UCM - Instituto de Geologia Economica (IGE); Complutense University of Madrid; CSIC-UCM - Instituto de Geociencias (IGEO); Natural History Museum London; University of New England
RP Lee, MSY (corresponding author), S Australian Museum, Adelaide, SA 5000, Australia.
EM mike.lee@samuseum.sa.gov.au; jpater20@une.edu.au
FU Australian Research Council [LP0774959]; South Australian Museum; Spanish Ministry of Science [RYC2007-00090, CGL2009-07073]; Beach Energy and Sealink Pty Ltd; Australian Research Council [LP0774959] Funding Source: Australian Research Council
NR 30
TC 66
Z9 73
U1 1
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 631
EP 634
DI 10.1038/nature10097
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300037
PM 21720369
DA 2026-03-09
ER

PT J
AU Gore, A
   Li, Z
   Fung, HL
   Young, JE
   Agarwal, S
   Antosiewicz-Bourget, J
   Canto, I
   Giorgetti, A
   Israel, MA
   Kiskinis, E
   Lee, JH
   Loh, YH
   Manos, PD
   Montserrat, N
   Panopoulos, AD
   Ruiz, S
   Wilbert, ML
   Yu, JY
   Kirkness, EF
   Belmonte, JCI
   Rossi, DJ
   Thomson, JA
   Eggan, K
   Daley, GQ
   Goldstein, LSB
   Zhang, K
AF Gore, Athurva
   Li, Zhe
   Fung, Ho-Lim
   Young, Jessica E.
   Agarwal, Suneet
   Antosiewicz-Bourget, Jessica
   Canto, Isabel
   Giorgetti, Alessandra
   Israel, Mason A.
   Kiskinis, Evangelos
   Lee, Je-Hyuk
   Loh, Yuin-Han
   Manos, Philip D.
   Montserrat, Nuria
   Panopoulos, Athanasia D.
   Ruiz, Sergio
   Wilbert, Melissa L.
   Yu, Junying
   Kirkness, Ewen F.
   Izpisua Belmonte, Juan Carlos
   Rossi, Derrick J.
   Thomson, James A.
   Eggan, Kevin
   Daley, George Q.
   Goldstein, Lawrence S. B.
   Zhang, Kun
TI Somatic coding mutations in human induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID fibroblasts; generation; efficient; variants
AB Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.
C1 [Young, Jessica E.; Canto, Isabel; Israel, Mason A.; Wilbert, Melissa L.; Goldstein, Lawrence S. B.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Young, Jessica E.; Canto, Isabel; Israel, Mason A.; Wilbert, Melissa L.; Goldstein, Lawrence S. B.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Gore, Athurva; Li, Zhe; Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Inst Genom Med, Dept Bioengn, La Jolla, CA 92093 USA.
   [Gore, Athurva; Li, Zhe; Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; Manos, Philip D.; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; Manos, Philip D.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Antosiewicz-Bourget, Jessica; Yu, Junying; Thomson, James A.] Univ Wisconsin, Dept Anat, Madison, WI 53705 USA.
   [Giorgetti, Alessandra; Montserrat, Nuria; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med, Barcelona 08003, Spain.
   [Kiskinis, Evangelos; Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Lee, Je-Hyuk] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02135 USA.
   [Panopoulos, Athanasia D.; Ruiz, Sergio; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Kirkness, Ewen F.] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Rossi, Derrick J.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Wisconsin System; University of Wisconsin Madison; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; Harvard University; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Salk Institute; J. Craig Venter Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM)
RP Goldstein, LSB (corresponding author), Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM lgoldstein@ucsd.edu; kzhang@bioeng.ucsd.edu
FU NIH [R01 HL094963]; UCSD; California Institute for Regenerative Medicine [TG2-01154]; CIRM [RC1-00116]; Focht-Powell Fellowship; National Institute of General Medical Sciences [T32 GM008666]; A*Star Institute of Medical Biology; Singapore Stem Cell Consortium; MICINN; Sanofi-Aventis; G. Harold and Leila Y. Mathers Foundation; Cellex Foundation; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008666] Funding Source: NIH RePORTER
NR 41
TC 984
Z9 1142
U1 0
U2 216
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 63
EP U76
DI 10.1038/nature09805
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100034
PM 21368825
DA 2026-03-09
ER

PT J
AU Luther, S
   Fenton, FH
   Kornreich, BG
   Squires, A
   Bittihn, P
   Hornung, D
   Zabel, M
   Flanders, J
   Gladuli, A
   Campoy, L
   Cherry, EM
   Luther, G
   Hasenfuss, G
   Krinsky, VI
   Pumir, A
   Gilmour, RF
   Bodenschatz, E
AF Luther, Stefan
   Fenton, Flavio H.
   Kornreich, Bruce G.
   Squires, Amgad
   Bittihn, Philip
   Hornung, Daniel
   Zabel, Markus
   Flanders, James
   Gladuli, Andrea
   Campoy, Luis
   Cherry, Elizabeth M.
   Luther, Gisa
   Hasenfuss, Gerd
   Krinsky, Valentin I.
   Pumir, Alain
   Gilmour, Robert F., Jr.
   Bodenschatz, Eberhard
TI Low-energy control of electrical turbulence in the heart
SO NATURE
LA English
DT Article
ID cardiac tissue; spiral waves; defibrillation; fibrillation; termination; field; propagation; activation; mechanisms; shocks
AB Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate(1-4). In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation(5-7). Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density rho(E) and a characteristic time, tau, for tissue depolarization that obeys the power law tau proportional to E-alpha. These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. Weshow in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.
C1 [Luther, Stefan; Fenton, Flavio H.; Squires, Amgad; Bittihn, Philip; Hornung, Daniel; Cherry, Elizabeth M.; Luther, Gisa; Krinsky, Valentin I.; Bodenschatz, Eberhard] Max Planck Inst Dynam & Self Org, D-37077 Gottingen, Germany.
   [Luther, Stefan; Fenton, Flavio H.; Cherry, Elizabeth M.; Gilmour, Robert F., Jr.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
   [Luther, Stefan; Bittihn, Philip; Hornung, Daniel; Luther, Gisa; Bodenschatz, Eberhard] Georg August Univ, Inst Nonlinear Dynam, D-37077 Gottingen, Germany.
   [Luther, Stefan; Zabel, Markus; Hasenfuss, Gerd; Bodenschatz, Eberhard] Heart Res Ctr Gottingen HRCG, D-37075 Gottingen, Germany.
   [Kornreich, Bruce G.; Flanders, James; Gladuli, Andrea; Campoy, Luis] Cornell Univ, Dept Clin Sci, Ithaca, NY 14853 USA.
   [Squires, Amgad; Bodenschatz, Eberhard] Cornell Univ, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
   [Zabel, Markus; Hasenfuss, Gerd] Univ Med Ctr UMG, Dept Cardiol & Pneumol, D-37075 Gottingen, Germany.
   [Cherry, Elizabeth M.] Rochester Inst Technol, Sch Math Sci, Rochester, NY 14623 USA.
   [Krinsky, Valentin I.] Inst Nonlineaire Nice, F-06560 Valbonne, France.
   [Pumir, Alain] Univ Lyon 1, Lab Phys, Ecole Normale Super Lyon, F-69007 Lyon, France.
   [Pumir, Alain] CNRS, F-69007 Lyon, France.
   [Bodenschatz, Eberhard] Cornell Univ, Dept Mech & Aerosp Engn, Ithaca, NY 14853 USA.
C3 Max Planck Society; Cornell University; University of Gottingen; Cornell University; Cornell University; Rochester Institute of Technology; Universite Cote d'Azur; Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Cornell University
RP Luther, S (corresponding author), Max Planck Inst Dynam & Self Org, Fassberg 17, D-37077 Gottingen, Germany.
EM stefan.luther@ds.mpg.de; flavio.h.fenton@cornell.edu
FU National Science Foundation (NSF) [0800793, 0926190]; National Institutes of Health (NIH) [HL075515-S04, HL075515, HL073644]; IFCPAR Project [3404-4]; German Ministry for Education and Research [FKZ 01EZ0905/6]; Kavli Institute for Theoretical Physics [NSFPHY05-51164]; Pittsburgh Supercomputing Center (NSF TeraGrid); Pittsburgh NMR Center for Biomedical Research [NIH P41-EB001977]; European Community [HEALTH-F2-2009-241526]; Max Planck Society; Direct For Computer & Info Scie & Enginr; Division Of Computer and Network Systems [0926190] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0800793] Funding Source: National Science Foundation
NR 30
TC 263
Z9 291
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 JUL 14
PY 2011
VL 475
IS 7355
BP 235
EP U152
DI 10.1038/nature10216
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500052
PM 21753855
DA 2026-03-09
ER

PT J
AU Ehret, GB
   Munroe, PB
   Rice, KM
   Bochud, M
   Johnson, AD
   Chasman, DI
   Smith, AV
   Tobin, MD
   Verwoert, GC
   Hwang, SJ
   Pihur, V
   Vollenweider, P
   O'Reilly, PF
   Amin, N
   Bragg-Gresham, JL
   Teumer, A
   Glazer, NL
   Launer, L
   Zhao, JH
   Aulchenko, Y
   Heath, S
   Sober, S
   Parsa, A
   Luan, JA
   Arora, P
   Dehghan, A
   Zhang, F
   Lucas, G
   Hicks, AA
   Jackson, AU
   Peden, JF
   Tanaka, T
   Wild, SH
   Rudan, I
   Igl, W
   Milaneschi, Y
   Parker, AN
   Fava, C
   Chambers, JC
   Fox, ER
   Kumari, M
   Go, MJ
   van der Harst, P
   Kao, WHL
   Sjögren, M
   Vinay, DG
   Alexander, M
   Tabara, Y
   Shaw-Hawkins, S
   Whincup, PH
   Liu, YM
   Shi, G
   Kuusisto, J
   Tayo, B
   Seielstad, M
   Sim, X
   Nguyen, KDH
   Lehtimäki, T
   Matullo, G
   Wu, Y
   Gaunt, TR
   Onland-Moret, NC
   Cooper, MN
   Platou, CGP
   Org, E
   Hardy, R
   Dahgam, S
   Palmen, J
   Vitart, V
   Braund, PS
   Kuznetsova, T
   Uiterwaal, CSPM
   Adeyemo, A
   Palmas, W
   Campbell, H
   Ludwig, B
   Tomaszewski, M
   Tzoulaki, I
   Palmer, ND
   Aspelund, T
   Garcia, M
   Chang, YPC
   O'Connell, JR
   Steinle, NI
   Grobbee, DE
   Arking, DE
   Kardia, SL
   Morrison, AC
   Hernandez, D
   Najjar, S
   McArdle, WL
   Hadley, D
   Brown, MJ
   Connell, JM
   Hingorani, AD
   Day, INM
   Lawlor, DA
   Beilby, JP
   Lawrence, RW
   Clarke, R
   Hopewell, JC
   Ongen, H
   Dreisbach, AW
   Li, YL
   Young, JH
   Bis, JC
   Kähönen, M
   Viikari, J
   Adair, LS
   Lee, NR
   Chen, MH
   Olden, M
   Pattaro, C
   Bolton, JAH
   Köttgen, A
   Bergmann, S
   Mooser, V
   Chaturvedi, N
   Frayling, TM
   Islam, M
   Jafar, TH
   Erdmann, J
   Kulkarni, SR
   Bornstein, SR
   Grässler, J
   Groop, L
   Voight, BF
   Kettunen, J
   Howard, P
   Taylor, A
   Guarrera, S
   Ricceri, F
   Emilsson, V
   Plump, A
   Barroso, IS
   Khaw, KT
   Weder, AB
   Hunt, SC
   Sun, YV
   Bergman, RN
   Collins, FS
   Bonnycastle, LL
   Scott, LJ
   Stringham, HM
   Peltonen, L
   Perola, M
   Vartiainen, E
   Brand, SM
   Staessen, JA
   Wang, TJ
   Burton, PR
   Artigas, MS
   Dong, YB
   Snieder, H
   Wang, XL
   Zhu, HD
   Lohman, KK
   Rudock, ME
   Heckbert, SR
   Smith, NL
   Wiggins, KL
   Doumatey, A
   Shriner, D
   Veldre, G
   Viigimaa, M
   Kinra, S
   Prabhakaran, D
   Tripathy, V
   Langefeld, CD
   Rosengren, A
   Thelle, DS
   Corsi, AM
   Singleton, A
   Forrester, T
   Hilton, G
   McKenzie, CA
   Salako, T
   Iwai, N
   Kita, Y
   Ogihara, T
   Ohkubo, T
   Okamura, T
   Ueshima, H
   Umemura, S
   Eyheramendy, S
   Meitinger, T
   Wichmann, HE
   Cho, YS
   Kim, HL
   Lee, JY
   Scott, J
   Sehmi, JS
   Zhang, WH
   Hedblad, B
   Nilsson, P
   Smith, GD
   Wong, A
   Narisu, N
   Stancáková, A
   Raffel, LJ
   Yao, J
   Kathiresan, S
   O'Donnell, CJ
   Schwartz, SM
   Ikram, MA
   Longstreth, WT
   Mosley, TH
   Seshadri, S
   Shrine, NRG
   Wain, LV
   Morken, MA
   Swift, AJ
   Laitinen, J
   Prokopenko, I
   Zitting, P
   Cooper, JA
   Humphries, SE
   Danesh, J
   Rasheed, A
   Goel, A
   Hamsten, A
   Watkins, H
   Bakker, SJL
   van Gilst, WH
   Janipalli, CS
   Mani, KR
   Yajnik, CS
   Hofman, A
   Mattace-Raso, FUS
   Oostra, BA
   Demirkan, A
   Isaacs, A
   Rivadeneira, F
   Lakatta, EG
   Orru, M
   Scuteri, A
   Ala-Korpela, M
   Kangas, AJ
   Lyytikäinen, LP
   Soininen, P
   Tukiainen, T
   Würtz, P
   Ong, RTH
   Dörr, M
   Kroemer, HK
   Völker, U
   Völzke, H
   Galan, P
   Hercberg, S
   Lathrop, M
   Zelenika, D
   Deloukas, P
   Mangino, M
   Spector, TD
   Zhai, GJ
   Meschia, JF
   Nalls, MA
   Sharma, P
   Terzic, J
   Kumar, MVK
   Denniff, M
   Zukowska-Szczechowska, E
   Wagenknecht, LE
   Fowkes, FGR
   Charchar, FJ
   Schwarz, PEH
   Hayward, C
   Guo, XQ
   Rotimi, C
   Bots, ML
   Brand, E
   Samani, NJ
   Polasek, O
   Talmud, PJ
   Nyberg, F
   Kuh, D
   Laan, M
   Hveem, K
   Palmer, LJ
   van der Schouw, YT
   Casas, JP
   Mohlke, KL
   Vineis, P
   Raitakari, O
   Ganesh, SK
   Wong, TY
   Tai, ES
   Cooper, RS
   Laakso, M
   Rao, DC
   Harris, TB
   Morris, RW
   Dominiczak, AF
   Kivimaki, M
   Marmot, MG
   Miki, T
   Saleheen, D
   Chandak, GR
   Coresh, J
   Navis, G
   Salomaa, V
   Han, BG
   Zhu, XF
   Kooner, JS
   Melander, O
   Ridker, PM
   Bandinelli, S
   Gyllensten, UB
   Wright, AF
   Wilson, JF
   Ferrucci, L
   Farrall, M
   Tuomilehto, J
   Pramstaller, PP
   Elosua, R
   Soranzo, N
   Sijbrands, EJG
   Altshuler, D
   Loos, RJF
   Shuldiner, AR
   Gieger, C
   Meneton, P
   Uitterlinden, AG
   Wareham, NJ
   Gudnason, V
   Rotter, JI
   Rettig, R
   Uda, M
   Strachan, DP
   Witteman, JCM
   Hartikainen, AL
   Beckmann, JS
   Boerwinkle, E
   Vasan, RS
   Boehnke, M
   Larson, MG
   Järvelin, MR
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   Abecasis, Goncalo R.
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   Caulfield, Mark J.
   Johnson, Toby
TI Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
SO NATURE
LA English
DT Article
ID genome-wide association; common variants; hypertension; loci; metaanalysis; population; cloning; health
AB Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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   [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England.
   [Li, Yali; Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
   [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Tampere 33521, Finland.
   [Viikari, Jorma] Univ Turku, Dept Med, Turku 20521, Finland.
   [Viikari, Jorma] Turku Univ Hosp, Turku 20521, Finland.
   [Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
   [Lee, Nanette R.] Univ San Carlos, Off Populat Studies Fdn, Cebu 6000, Philippines.
   [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Chen, Ming-Huei] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA.
   [Olden, Matthias] Univ Med Ctr Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany.
   [Olden, Matthias] Univ Med Ctr Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
   [Koettgen, Anna] Univ Hosp Freiburg, Div Renal, D-79095 Freiburg, Germany.
   [Bergmann, Sven; Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland.
   [Bergmann, Sven] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Mooser, Vincent] GlaxoSmithKline, Div Genet, Philadelphia, PA 19101 USA.
   [Chaturvedi, Nish] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, London SW7 2AZ, England.
   [Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England.
   [Islam, Muhammad; Jafar, Tazeen H.] Aga Khan Univ, Dept Community Hlth Sci, Karachi 74800, Pakistan.
   [Islam, Muhammad; Jafar, Tazeen H.] Aga Khan Univ, Dept Med, Karachi 74800, Pakistan.
   [Erdmann, Jeanette] Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
   [Kulkarni, Smita R.; Yajnik, Chittaranjan S.] KEM Hosp & Res Ctr, Diabet Unit, Pune 411011, Maharashtra, India.
   [Groop, Leif] Univ Hosp, Diabet & Endocrinol Res Unit, Dept Clin Sci, S-20502 Malmo, Sweden.
   [Groop, Leif] Lund Univ, S-20502 Malmo, Sweden.
   [Voight, Benjamin F.; Altshuler, David; Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02139 USA.
   [Kettunen, Johannes] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00251, Finland.
   [Kettunen, Johannes; Peltonen, Leena] Biomedicum, Inst Mol Med, FIMM, Helsinki 00251, Finland.
   [Howard, Philip] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.
   [Emilsson, Valur; Plump, Andrew] Merck Res Lab, Rahway, NJ 07065 USA.
   [Barroso, Ine S.; Peltonen, Leena; Deloukas, Panos; Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, S Cambs, England.
   [Barroso, Ine S.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 OQQ, England.
   [Weder, Alan B.] Univ Michigan, Sch Med, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
   [Hunt, Steven C.] Univ Utah, Sch Med, Salt Lake City, UT 84132 USA.
   [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Phys & Biophys, Los Angeles, CA 90033 USA.
   [Collins, Francis S.; Bonnycastle, Lori L.; Narisu, Narisu; Morken, Mario A.; Swift, Amy J.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki 00271, Finland.
   [Peltonen, Leena] Broad Inst, Cambridge, MA 02142 USA.
   [Brand, Stefan-Martin] Univ Munster, Dept Mol Genet Cardiovasc Dis, Leibniz Inst Arteriosclerosis Res, D-48149 Munster, Germany.
   [Brand, Stefan-Martin] Univ Munster, Fac Med, Dept Mol Genet Cardiovasc Dis, D-48149 Munster, Germany.
   [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   [Dong, Yanbin; Snieder, Harold; Wang, Xiaoling; Zhu, Haidong] Med Coll Georgia, Dept Pediat, Georgia Prevent Inst, Augusta, GA 30912 USA.
   [Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, NL-9713 GZ Groningen, Netherlands.
   [Lohman, Kurt K.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
   [Heckbert, Susan R.; Smith, Nicholas L.; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98124 USA.
   [Smith, Nicholas L.] Vet Hlth Adm Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA.
   [Wiggins, Kerri L.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Veldre, Gudrun] Univ Tartu, Dept Cardiol, EE-51014 Tartu, Estonia.
   [Viigimaa, Margus] Tallinn Univ Technol, Inst Biomed Engn, EE-19086 Tallinn, Estonia.
   [Viigimaa, Margus] N Estonia Med Ctr, Ctr Cardiol, EE-13419 Tallinn, Estonia.
   [Kinra, Sanjay] Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England.
   [Prabhakaran, Dorairaj; Tripathy, Vikal] Publ Hlth Fdn India, S Asia Network Chron Dis, New Delhi 100016, India.
   [Rosengren, Annika] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Emergency & Cardiovasc Med, S-41685 Gothenburg, Sweden.
   [Thelle, Dag S.] Univ Oslo, Inst Basic Med Sci, Dept Biostat, N-0317 Oslo, Norway.
   [Corsi, Anna Maria] Tuscany Reg Hlth Agcy, I-50129 Florence, Italy.
   [Forrester, Terrence; McKenzie, Colin A.] Univ W Indies, Res Inst Trop Med, Kingston 7, Jamaica.
   [Salako, Tunde] Univ Ibadan, Ibadan, Nigeria.
   [Iwai, Naoharu; Okamura, Tomonori] Natl Cerebral & Cardiovasc Res Ctr, Dept Genom Med, Suita, Osaka 5658565, Japan.
   [Iwai, Naoharu; Okamura, Tomonori] Natl Cerebral & Cardiovasc Res Ctr, Dept Prevent Cardiol, Suita, Osaka 5658565, Japan.
   [Kita, Yoshikuni; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 5202192, Japan.
   [Ogihara, Toshio] Osaka Univ, Grad Sch Med, Dept Geriatr Med, Suita, Osaka 5650871, Japan.
   [Ohkubo, Takayoshi] Tohoku Univ, Grad Sch Pharmaceut Sci & Med, Sendai, Miyagi 9808578, Japan.
   [Ueshima, Hirotsugu] Shiga Univ Med Sci, Lifestyle Related Dis Prevent Ctr, Otsu, Shiga 5202192, Japan.
   [Umemura, Satoshi] Yokohama City Univ, Sch Med, Dept Med Sci & Cardiorenal Med, Yokohama, Kanagawa 2360004, Japan.
   [Eyheramendy, Susana] Pontificia Univ Catolica Chile, Dept Stat, Santiago, Chile.
   [Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
   [Wichmann, H. -Erich; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Epidemiol, D-85764 Neuherberg, Germany.
   [Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany.
   [Wichmann, H. -Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
   [Scott, James; Sehmi, Joban S.; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W12 0HS, England.
   [Raffel, Leslie J.; Yao, Jie; Guo, Xiuqing; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge Ctr 5, Cambridge, MA 02142 USA.
   [O'Donnell, Christopher J.] NHLBI, Framingham, MA 01702 USA.
   [O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
   [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol & Med, Seattle, WA 98195 USA.
   [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA.
   [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu 90220, Finland.
   [Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Zitting, Paavo] Lapland Cent Hosp, Dept Physiatr, Rovaniemi 96101, Finland.
   [Rasheed, Asif; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi 74800, Pakistan.
   [Hamsten, Anders] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, S-17177 Stockholm, Sweden.
   [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
   [Lakatta, Edward G.; Scuteri, Angelo] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
   [Orru, Marco; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy.
   [Orru, Marco] Presidio Osped Santa Barbara, Div Med, Unita Operat Semplice Cardiol, I-09016 Iglesias, Italy.
   [Ala-Korpela, Mika; Kangas, Antti J.; Soininen, Pasi; Tukiainen, Taru; Wurtz, Peter] Univ Oulu, Inst Clin Med, Computat Med Res Grp, Oulu, Finland.
   [Ala-Korpela, Mika] 90014 Univ Oulu, Bioctr Oulu, Clin Res Ctr, Oulu, Finland.
   [Ala-Korpela, Mika; Soininen, Pasi] Univ Eastern Finland, Dept Biosci, NMR Metabon Lab, Kuopio 70211, Finland.
   [Ala-Korpela, Mika] 90014 Univ Oulu, Dept Internal Med, Oulu, Finland.
   [Tukiainen, Taru; Wurtz, Peter] 00014 Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
   [Tukiainen, Taru] Aalto Univ, Dept Biomed Engn & Computat Sci, Sch Sci & Technol, Espoo 00076, Finland.
   [Ong, Rick Twee-Hee] NUS Grad Sch Integrat Sci & Engn NGS, Ctr Life Sci CeLS, Singapore 117456, Singapore.
   [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, D-17487 Greifswald, Germany.
   [Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmacol, D-17487 Greifswald, Germany.
   [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17487 Greifswald, Germany.
   [Galan, Pilar; Hercberg, Serge] Univ Paris 13, Inst Natl Rech Agron U1125, Inst Natl Sante & Rech Med U557, F-93017 Bobigny, France.
   [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
   [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Imperial Coll Cerebrovasc Unit ICCRU, London W6 8RF, England.
   [Terzic, Janos] Univ Split, Fac Med, Split 21000, Croatia.
   [Zukowska-Szczechowska, Ewa] Med Univ Silesia, Dept Internal Med Diabetol & Nephrol, PL-41800 Zabrze, Poland.
   [Fowkes, F. Gerald R.] Univ Edinburgh, Sch Med, Div Community Hlth Sci, Publ Hlth Sci Sect, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Charchar, Fadi J.] Univ Ballarat, Sch Sci & Engn, Ballarat, Vic 3353, Australia.
   [Schwarz, Peter E. H.] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, D-01307 Dresden, Germany.
   [Brand, Eva] Univ Hosp Munster, Munster, Germany.
   [Polasek, Ozren] Univ Zagreb, Andrija Stampar Sch Publ Hlth, Dept Med Stat Epidemiol & Med Informat, Zagreb 10000, Croatia.
   [Nyberg, Fredrik] AstraZeneca R&D, S-43183 Molndal, Sweden.
   [Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada.
   [Palmer, Lyle J.] Univ Toronto, Samuel Lunenfeld Inst Med Res, Toronto, ON M5S 1A1, Canada.
   [Casas, Juan P.] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Population Hlth, London WC1E 7HT, England.
   [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
   [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20521, Finland.
   [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, Turku 20521, Finland.
   [Ganesh, Santhi K.] Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
   [Wong, Tien Y.] Singapore Eye Res Inst, Singapore 168751, Singapore.
   [Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 119074, Singapore.
   [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119074, Singapore.
   [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore.
   [Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
   [Morris, Richard W.] UCL, Dept Primary Care & Populat Hlth, London NW3 2PF, England.
   [Dominiczak, Anna F.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
   [Coresh, Josef] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
   [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9713 GZ Groningen, Netherlands.
   [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02215 USA.
   [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, I-50100 Florence, Italy.
   [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki 00271, Finland.
   [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki 00014, Finland.
   [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland.
   [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid 28046, Spain.
   [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy.
   [Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona 08003, Spain.
   [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
   [Meneton, Pierre] Ctr Rech Cordeliers, Inst Natl Sante & Rech Med U872, F-75006 Paris, France.
   [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, D-17487 Greifswald, Germany.
   [Hartikainen, Anna-Liisa] Univ Oulu, Inst Clin Med Obstet & Gynecol, Oulu 90014, Finland.
   [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Boerwinkle, Eric] Ctr Human Genet, Houston, TX 77030 USA.
   [Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Epidemiol & Prevent, Boston, MA 02215 USA.
   [Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland.
   [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu 90101, Finland.
   [Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
   [van Duijn, Cornelia M.] NGI Erasmus Med Ctr, Ctr Med Syst Biol CMSB 1 2, Rotterdam, Netherlands.
C3 Johns Hopkins University; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Geneva; University of London; Queen Mary University London; University of Washington; University of Washington Seattle; Framingham Heart Study; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Iceland; Icelandic Heart Association; University of Leicester; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Imperial College London; University of Michigan System; University of Michigan; Universitat Greifswald; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Cambridge; CEA; Universite Paris Saclay; University of Tartu; University System of Maryland; University of Maryland Baltimore; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of London; King's College London; European Academy of Bozen-Bolzano; University of Lubeck; University of Michigan System; University of Michigan; University of Oxford; Wellcome Centre for Human Genetics; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Edinburgh; University of Edinburgh; University of Split; Uppsala University; Amgen; Lund University; University of Verona; Imperial College London; University of Mississippi; University of Mississippi Medical Center; University of London; University College London; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Genome Science; University of Groningen; Johns Hopkins University; Johns Hopkins University; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); University of Cambridge; Ehime University; Ehime University; City St Georges, University of London; Wake Forest University; Wake Forest Baptist Medical Center; Washington University (WUSTL); Washington University (WUSTL); University of Eastern Finland; University of Eastern Finland; University of Eastern Finland Hospital; Kuopio University Hospital; Loyola University Chicago; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); National University of Singapore; Tampere University; Tampere University; Tampere University Hospital; University of Turin; University of North Carolina; University of North Carolina Chapel Hill; University of Bristol; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; University of Western Australia; Norwegian University of Science & Technology (NTNU); University of Gothenburg; University of London; University College London; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; KU Leuven; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Columbia University; Technische Universitat Dresden; Carl Gustav Carus University Hospital; Imperial College London; University of Ioannina; Wake Forest University; Wake Forest University School of Medicine; University of Michigan System; University of Michigan; University of Texas System; University of Texas Health Science Center Houston; University of Texas School Public Health; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); MedStar Washington Hospital Center; University of Bristol; State University System of Florida; University of South Florida; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Dundee; University of London; University College London; University of Oxford; University of Oxford; University System of Ohio; Case Western Reserve University; Tampere University; University of Turku; University of Turku; University of North Carolina; University of North Carolina Chapel Hill; University of San Carlos; Boston University; Framingham Heart Study; Boston University; University of Regensburg; University of Regensburg; University of Freiburg; University of Lausanne; Swiss Institute of Bioinformatics; GlaxoSmithKline; Glaxosmithkline USA; Imperial College London; University of Exeter; Aga Khan University; Aga Khan University; University of Lubeck; Lund University; Skane University Hospital; Lund University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Finland National Institute for Health & Welfare; University of Helsinki; University of London; Queen Mary University London; Merck & Company; Wellcome Trust Sanger Institute; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Michigan System; University of Michigan; Utah System of Higher Education; University of Utah; University of Southern California; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Finland National Institute for Health & Welfare; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Munster; University of Munster; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University System of Georgia; Augusta University; University of Groningen; Wake Forest University; Wake Forest Baptist Medical Center; University of Washington; University of Washington Seattle; Group Health Cooperative; US Department of Veterans Affairs; Veterans Health Administration (VHA); University of Washington; University of Washington Seattle; University of Tartu; Tallinn University of Technology; University of London; London School of Hygiene & Tropical Medicine; Public Health Foundation of India; University of Gothenburg; University of Oslo; University West Indies Mona Jamaica; University of Ibadan; Shiga University of Medical Science; University of Osaka; Tohoku University; Shiga University of Medical Science; Yokohama City University; Pontificia Universidad Catolica de Chile; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; University of Munich; Imperial College London; Cedars Sinai Medical Center; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Framingham Heart Study; University of Washington; University of Washington Seattle; University of Mississippi Medical Center; University of Mississippi; Boston University; Finnish Institute of Occupational Health; University of Oxford; Wellcome Centre for Human Genetics; Karolinska Institutet; Erasmus University Rotterdam; Erasmus MC; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Consiglio Nazionale delle Ricerche (CNR); University of Oulu; University of Oulu; University of Eastern Finland; University of Oulu; University of Helsinki; Aalto University; National University of Singapore; Center Life Science - NUS; Universitat Greifswald; Universitat Greifswald; Universitat Greifswald; Universite Paris 13; Institut National de la Sante et de la Recherche Medicale (Inserm); INRAE; Mayo Clinic; Imperial College London; University of Split; Medical University of Silesia; University of Edinburgh; Federation University Australia; Technische Universitat Dresden; Carl Gustav Carus University Hospital; University of Munster; University of Zagreb; AstraZeneca; University of Toronto; Ontario Institute for Cancer Research; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of London; London School of Hygiene & Tropical Medicine; Imperial College London; University of Turku; University of Turku; University of Michigan System; University of Michigan; National University of Singapore; Singapore National Eye Center; National University of Singapore; National University of Singapore; National University of Singapore; Washington University (WUSTL); University of London; University College London; University of Glasgow; Johns Hopkins University; University of Groningen; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Finland National Institute for Health & Welfare; University of Helsinki; Hospital Universitario La Paz; Krankenhaus Bozen; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; US Department of Veterans Affairs; Veterans Health Administration (VHA); Geriatric Research Education & Clinical Center; Universite Paris Cite; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universitat Greifswald; University of Oulu; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Boston University; Boston University; University of Oulu; Finland National Institute for Health & Welfare; Imperial College London
RP Chakravarti, A (corresponding author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA.
EM p.b.munroe@qmul.ac.uk; aravinda@jhmi.edu; cnewtoncheh@chgr.mgh.harvard.edu; levyd@nhlbi.nih.gov; m.j.caulfield@qmul.ac.uk
FU NIH/NHLBI; National Heart Lung and Blood Institute [ZIAHL006001, R01HL105756, R01HL059367, R01HL086694] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK062370, U01DK062370, R01DK072193, P30DK056350, R01DK075787, P30DK063491] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [P30ES007033, P30ES010126] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG001050, ZIAAG007480, R01AG017644] Funding Source: NIH RePORTER; Austrian Science Fund (FWF) [P 20545] Funding Source: researchfish; British Heart Foundation [RG/07/008/23674, RG/08/014/24067, RG/08/008/25291, RG/08/013/25942] Funding Source: researchfish; Chief Scientist Office [CZB/4/710] Funding Source: researchfish; Kidney Research UK [RP24/2/2006] Funding Source: researchfish; Medical Research Council [G9521010, MC_UP_A100_1003, MC_U106179471, G0902313, G19/35, MC_PC_U127561128, MC_U123092720, MC_U127561128, G1000143, MC_PC_U127527180, MC_U137686857, G0902037, G0400874, G0801056, G0100222, G0401527, G0601966, G0600705, G0600331, G0801056B, G0000934, MC_U106188470, G0700931, G0701863, G0501942, MC_U123092723, G8802774] Funding Source: researchfish; National Institute for Health Research [NF-SI-0507-10315] Funding Source: researchfish; MRC [MC_U106188470, G0601966, MC_U127561128, G0501942, G0801056, MC_U123092720, G0000934, G0600705, G0600331, G0700931, MC_U137686857, G0400874, MC_U123092723, MC_UP_A100_1003, MC_PC_U127527180, MC_PC_U127561128, G0701863, G9521010, G0902313, G0902037] Funding Source: UKRI; Grants-in-Aid for Scientific Research [20390185, 21390099] Funding Source: KAKEN
NR 28
TC 1638
Z9 1832
U1 4
U2 427
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 103
EP 109
DI 10.1038/nature10405
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400043
PM 21909115
DA 2026-03-09
ER

PT J
AU Guo, CG
   Yoon, HS
   Franklin, A
   Jain, S
   Ebert, A
   Cheng, HL
   Hansen, E
   Despo, O
   Bossen, C
   Vettermann, C
   Bates, JG
   Richards, N
   Myers, D
   Patel, H
   Gallagher, M
   Schlissel, MS
   Murre, C
   Busslinger, M
   Giallourakis, CC
   Alt, FW
AF Guo, Chunguang
   Yoon, Hye Suk
   Franklin, Andrew
   Jain, Suvi
   Ebert, Anja
   Cheng, Hwei-Ling
   Hansen, Erica
   Despo, Orion
   Bossen, Claudia
   Vettermann, Christian
   Bates, Jamie G.
   Richards, Nicholas
   Myers, Darienne
   Patel, Harin
   Gallagher, Michael
   Schlissel, Mark S.
   Murre, Cornelis
   Busslinger, Meinrad
   Giallourakis, Cosmas C.
   Alt, Frederick W.
TI CTCF-binding elements mediate control of V(D)J recombination
SO NATURE
LA English
DT Article
ID b-cell development; heavy-chain locus; vh gene segments; igh locus; regulatory elements; intronic enhancer; antisense transcription; lymphocyte development; nuclear-organization; region
AB Immunoglobulin heavy chain (IgH) variable region exons are assembled from V-H, D and J(H) gene segments in developing B lymphocytes. Within the 2.7-megabase mouse Igh locus, V(D)J recombination is regulated to ensure specific and diverse antibody repertoires. Here we report in mice a key Igh V(D)J recombination regulatory region, termed intergenic control region 1 (IGCR1), which lies between the V-H and D clusters. Functionally, IGCR1 uses CTCF looping/insulator factor-binding elements and, correspondingly, mediates Igh loops containing distant enhancers. IGCR1 promotes normal B-cell development and balances antibody repertoires by inhibiting transcription and rearrangement of D-H-proximal V-H gene segments and promoting rearrangement of distal V-H segments. IGCR1 maintains ordered and lineage-specific V-H(D)J(H) recombination by suppressing V-H joining to D segments not joined to J(H) segments, and V-H to DJ(H) joins in thymocytes, respectively. IGCR1 is also required for feedback regulation and allelic exclusion of proximal V-H-to-DJ(H) recombination. Our studies elucidate a long-sought Igh V(D) J recombination control region and indicate a new role for the generally expressed CTCF protein.
C1 [Guo, Chunguang; Yoon, Hye Suk; Franklin, Andrew; Jain, Suvi; Cheng, Hwei-Ling; Hansen, Erica; Despo, Orion; Richards, Nicholas; Myers, Darienne; Patel, Harin; Gallagher, Michael; Giallourakis, Cosmas C.; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA.
   [Guo, Chunguang; Yoon, Hye Suk; Franklin, Andrew; Jain, Suvi; Cheng, Hwei-Ling; Hansen, Erica; Despo, Orion; Richards, Nicholas; Myers, Darienne; Patel, Harin; Gallagher, Michael; Giallourakis, Cosmas C.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Ebert, Anja; Busslinger, Meinrad] Res Inst Mol Pathol, A-1030 Vienna, Austria.
   [Bossen, Claudia; Murre, Cornelis] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Vettermann, Christian; Bates, Jamie G.; Schlissel, Mark S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Giallourakis, Cosmas C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); University of California System; University of California San Diego; University of California System; University of California Berkeley; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Alt, FW (corresponding author), Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM cgiallourakis@partners.org; alt@enders.tch.harvard.edu
FU NIH [RO1 AI20047, RO1 HL48702, RO1 AI40227, CA054198-20, K08 AI070839]; Austrian GEN-AU initiative; Boehringer Ingelheim; Cancer Research Institute; Marie Curie Fellowship; EMBO; National Institute of Allergy and Infectious Diseases [R01AI020047] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 53
TC 218
Z9 281
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 424
EP U182
DI 10.1038/nature10495
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500032
PM 21909113
DA 2026-03-09
ER

PT J
AU Treister, E
   Schawinski, K
   Volonteri, M
   Natarajan, P
   Gawiser, E
AF Treister, Ezequiel
   Schawinski, Kevin
   Volonteri, Marta
   Natarajan, Priyamvada
   Gawiser, Eric
TI Black hole growth in the early Universe is self-regulated and largely hidden from view
SO NATURE
LA English
DT Article
ID active galactic nuclei; ultra deep field; luminosity function; redshift quasars; galaxy; discovery; density; models; origin; agn
AB The formation of the first massive objects in the infant Universe remains impossible to observe directly and yet it sets the stage for the subsequent evolution of galaxies(1-3). Although some black holes with masses more than 10(9) times that of the Sun have been detected in luminous quasars less than one billion years after the Big Bang(4,5), these individual extreme objects have limited utility in constraining the channels of formation of the earliest black holes; this is because the initial conditions of black hole seed properties are quickly erased during the growth process(6). Here we report a measurement of the amount of black hole growth in galaxies at redshift z = 6-8 (0.95-0.7 billion years after the Big Bang), based on optimally stacked, archival X-ray observations. Our results imply that black holes grow in tandem with their host galaxies throughout cosmic history, starting from the earliest times. We find that most copiously accreting black holes at these epochs are buried in significant amounts of gas and dust that absorb most radiation except for the highest-energy X-rays. This suggests that black holes grew significantly more during these early bursts than was previously thought, but because of the obscuration of their ultraviolet emission they did not contribute to the re-ionization of the Universe.
C1 [Treister, Ezequiel] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Treister, Ezequiel] Univ Concepcion, Dept Astron, Concepcion, Chile.
   [Schawinski, Kevin; Natarajan, Priyamvada] Yale Ctr Astron & Astrophys, New Haven, CT 06520 USA.
   [Schawinski, Kevin; Natarajan, Priyamvada] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Volonteri, Marta] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Natarajan, Priyamvada] Yale Univ, Dept Astron, New Haven, CT 06520 USA.
   [Natarajan, Priyamvada] Harvard Univ, Inst Theory & Computat, Cambridge, MA 02138 USA.
   [Gawiser, Eric] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
C3 University of Hawaii System; Universidad de Concepcion; Yale University; Yale University; University of Michigan System; University of Michigan; Yale University; Harvard University; Rutgers University System; Rutgers University New Brunswick
RP Treister, E (corresponding author), Univ Hawaii, Inst Astron, 2680 Woodlawn Dr, Honolulu, HI 96822 USA.
EM treister@ifa.hawaii.edu
FU Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0807570] Funding Source: National Science Foundation
NR 30
TC 62
Z9 68
U1 0
U2 3
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 356
EP 358
DI 10.1038/nature10103
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100040
PM 21677753
DA 2026-03-09
ER

PT J
AU Brandt, P
   Funk, A
   Hormann, V
   Dengler, M
   Greatbatch, RJ
   Toole, JM
AF Brandt, Peter
   Funk, Andreas
   Hormann, Verena
   Dengler, Marcus
   Greatbatch, Richard J.
   Toole, John M.
TI Interannual atmospheric variability forced by the deep equatorial Atlantic Ocean
SO NATURE
LA English
DT Article
ID tropical atlantic; climate variability; jets; pacific; fluctuations; currents; sector; waves; nino
AB Climate variability in the tropical Atlantic Ocean is determined by large-scale ocean-atmosphere interactions, which particularly affect deep atmospheric convection over the ocean and surrounding continents(1). Apart from influences from the Pacific El Nino/Southern Oscillation(2) and the North Atlantic Oscillation(3), the tropical Atlantic variability is thought to be dominated by two distinct ocean-atmosphere coupled modes of variability that are characterized by meridional(4,5) and zonal(6,7) sea-surface-temperature gradients and are mainly active on decadal and interannual timescales, respectively(8,9). Here we report evidence that the intrinsic ocean dynamics of the deep equatorial Atlantic can also affect sea surface temperature, wind and rainfall in the tropical Atlantic region and constitutes a 4.5-yr climate cycle. Specifically, vertically alternating deep zonal jets of short vertical wavelength with a period of about 4.5 yr and amplitudes of more than 10 cm s(-1) are observed, in the deep Atlantic, to propagate their energy upwards, towards the surface(10,11). They are linked, at the sea surface, to equatorial zonal current anomalies and eastern Atlantic temperature anomalies that have amplitudes of about 6 cm s(-1) and 0.4 degrees C, respectively, and are associated with distinct wind and rainfall patterns. Although deep jets are also observed in the Pacific(12) and Indian(13) oceans, only the Atlantic deep jets seem to oscillate on interannual timescales. Our knowledge of the persistence and regularity of these jets is limited by the availability of high-quality data. Despite this caveat, the oscillatory behaviour can still be used to improve predictions of sea surface temperature in the tropical Atlantic. Deep-jet generation and upward energy transmission through the Equatorial Undercurrent warrant further theoretical study.
C1 [Brandt, Peter; Funk, Andreas; Hormann, Verena; Dengler, Marcus; Greatbatch, Richard J.] Univ Kiel, Leibniz Inst Meereswissensch, IFM GEOMAR, D-24105 Kiel, Germany.
   [Toole, John M.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
C3 Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; University of Kiel; Woods Hole Oceanographic Institution
RP Brandt, P (corresponding author), Univ Kiel, Leibniz Inst Meereswissensch, IFM GEOMAR, Dusternbrooker Weg 20, D-24105 Kiel, Germany.
EM pbrandt@ifm-geomar.de
FU German Federal Ministry of Education and Research; German Science Foundation [Sonderforschungsbereich 754]; Woods Hole Oceanographic Institution's Columbus O'Donnell Iselin Chair for Excellence in Oceanography; Directorate For Geosciences; Division Of Ocean Sciences [0850175] Funding Source: National Science Foundation
NR 30
TC 68
Z9 74
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 MAY 26
PY 2011
VL 473
IS 7348
BP 497
EP U237
DI 10.1038/nature10013
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300037
PM 21593764
DA 2026-03-09
ER

PT J
AU Weber, BN
   Chi, AWS
   Chavez, A
   Yashiro-Ohtani, Y
   Yang, Q
   Shestova, O
   Bhandoola, A
AF Weber, Brittany Nicole
   Chi, Anthony Wei-Shine
   Chavez, Alejandro
   Yashiro-Ohtani, Yumi
   Yang, Qi
   Shestova, Olga
   Bhandoola, Avinash
TI A critical role for TCF-1 in T-lineage specification and differentiation
SO NATURE
LA English
DT Article
ID beta-catenin; transcription factor; notch1; cells; hematopoiesis; inactivation; checkpoint; expression; receptor; fate
AB The vertebrate thymus provides an inductive environment for T-cell development. Within the mouse thymus, Notch signals are indispensable for imposing the T-cell fate on multipotential haematopoietic progenitors, but the downstream effectors that impart T-lineage specification and commitment are not well understood. Here we show that a transcription factor, T-cell factor 1 (TCF-1; also known as transcription factor 7, T-cell specific, TCF7), is a critical regulator in T-cell specification. TCF-1 is highly expressed in the earliest thymic progenitors, and its expression is upregulated by Notch signals. Most importantly, when TCF-1 is forcibly expressed in bone marrow (BM) progenitors, it drives the development of T-lineage cells in the absence of T-inductive Notch1 signals. Further characterization of these TCF-1-induced cells revealed expression of many T-lineage genes, including T-cell-specific transcription factors Gata3 and Bcl11b, and components of the T-cell receptor. Our data suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating expression of T-cell essential genes.
C1 [Weber, Brittany Nicole; Chi, Anthony Wei-Shine; Chavez, Alejandro; Yashiro-Ohtani, Yumi; Yang, Qi; Shestova, Olga; Bhandoola, Avinash] Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania
RP Bhandoola, A (corresponding author), Univ Penn, Dept Pathol & Lab Med, Sch Med, 3620 Hamilton Walk, Philadelphia, PA 19104 USA.
EM bhandooa@mail.med.upenn.edu
FU NIH [AI059621]; Leukemia and Lymphoma Society;  [T32AI055428];  [T32CA09140]; National Cancer Institute [T32CA009140] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI055428] Funding Source: NIH RePORTER
NR 35
TC 337
Z9 418
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 4
PY 2011
VL 476
IS 7358
BP 63
EP +
DI 10.1038/nature10279
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300029
PM 21814277
DA 2026-03-09
ER

PT J
AU Weismann, D
   Hartvigsen, K
   Lauer, N
   Bennett, KL
   Scholl, HPN
   Issa, PC
   Cano, M
   Brandstätter, H
   Tsimikas, S
   Skerka, C
   Superti-Furga, G
   Handa, JT
   Zipfel, PF
   Witztum, JL
   Binder, CJ
AF Weismann, David
   Hartvigsen, Karsten
   Lauer, Nadine
   Bennett, Keiryn L.
   Scholl, Hendrik P. N.
   Issa, Peter Charbel
   Cano, Marisol
   Brandstaetter, Hubert
   Tsimikas, Sotirios
   Skerka, Christine
   Superti-Furga, Giulio
   Handa, James T.
   Zipfel, Peter F.
   Witztum, Joseph L.
   Binder, Christoph J.
TI Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
SO NATURE
LA English
DT Article
ID retinal-pigment epithelium; macular degeneration; apoptotic cells; innate immunity; end-products; age; phagocytosis; proteins; risk; phospholipids
AB Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.
C1 [Weismann, David; Hartvigsen, Karsten; Bennett, Keiryn L.; Superti-Furga, Giulio; Binder, Christoph J.] Austrian Acad Sci, CeMM, A-1090 Vienna, Austria.
   [Weismann, David; Hartvigsen, Karsten; Brandstaetter, Hubert; Binder, Christoph J.] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria.
   [Hartvigsen, Karsten; Tsimikas, Sotirios; Witztum, Joseph L.; Binder, Christoph J.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Lauer, Nadine; Skerka, Christine; Zipfel, Peter F.] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany.
   [Lauer, Nadine; Skerka, Christine; Zipfel, Peter F.] Univ Jena, D-07745 Jena, Germany.
   [Scholl, Hendrik P. N.; Cano, Marisol; Handa, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Issa, Peter Charbel] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
   [Brandstaetter, Hubert] Octapharma PPGmbH, Res & Dev, A-1100 Vienna, Austria.
C3 Austrian Academy of Sciences; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; Medical University of Vienna; University of California System; University of California San Diego; Leibniz Association; Hans Knoll Institute (HKI); Friedrich Schiller University of Jena; Johns Hopkins University; Johns Hopkins Medicine; University of Oxford; Octapharma
RP Binder, CJ (corresponding author), Austrian Acad Sci, CeMM, A-1090 Vienna, Austria.
EM christoph.binder@meduniwien.ac.at
FU Austrian Academy of Sciences; Austrian Research Promotion Agency; SFB Lipotox F30 of the Austrian Science Fund; NIH [HL088093, RO1 HL086599, EY14005, EY019044]; Edward N. & Della L. Thome Memorial Foundation; Research to Prevent Blindness (Wilmer Eye institute); Deutsche Forschungsgemeinschaft; ProRetina Foundation; Fondation Leducq; Wynn-Gund Translational Research Acceleration Program Enhanced Research and Clinical Training Award; National Neurovision Research Institute - Foundation Fighting Blindness; Macular Degeneration Research Award; American Health Assistance Foundation; European Commission; European Community; American Heart Association [0630228N]; American Heart Association (AHA) [0630228N] Funding Source: American Heart Association (AHA)
NR 42
TC 475
Z9 527
U1 0
U2 116
PU 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 6
PY 2011
VL 478
IS 7367
BP 76
EP 81
DI 10.1038/nature10449
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400037
PM 21979047
DA 2026-03-09
ER

PT J
AU Mackereth, CD
   Madl, T
   Bonnal, S
   Simon, B
   Zanier, K
   Gasch, A
   Rybin, V
   Valcárcel, J
   Sattler, M
AF Mackereth, Cameron D.
   Madl, Tobias
   Bonnal, Sophie
   Simon, Bernd
   Zanier, Katia
   Gasch, Alexander
   Rybin, Vladimir
   Valcarcel, Juan
   Sattler, Michael
TI Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF
SO NATURE
LA English
DT Article
ID auxiliary factor u2af(65); polypyrimidine tract; recognition; dynamics; binding; relaxation; domain; restraints; sequences; mechanism
AB Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65)(1-3) as a key early step in pre-mRNA splicing(4). We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly(1,5-8). Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins(9,10).
C1 [Mackereth, Cameron D.; Madl, Tobias; Sattler, Michael] Helmholtz Zentrum Munchen, Inst Struct Biol, D-85764 Neuherberg, Germany.
   [Mackereth, Cameron D.] Univ Bordeaux, F-33607 Pessac, France.
   [Mackereth, Cameron D.] Inst Europe Chim & Biol, F-33607 Pessac, France.
   [Mackereth, Cameron D.; Simon, Bernd; Zanier, Katia; Gasch, Alexander; Rybin, Vladimir; Sattler, Michael] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Madl, Tobias; Sattler, Michael] Tech Univ Munich, Dept Chem, Munich Ctr Integrated Prot Sci, D-85747 Garching, Germany.
   [Bonnal, Sophie; Valcarcel, Juan] Univ Pompeu Fabra, Ctr Regulacio Genom, Barcelona 08003, Spain.
   [Valcarcel, Juan] Inst Catalana Recerca & Estudis Avancats, Barcelona 08003, Spain.
   [Madl, Tobias; Sattler, Michael] Tech Univ Munich, Chair Biomol NMR, Dept Chem, D-85747 Garching, Germany.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Universite de Bordeaux; European Molecular Biology Laboratory (EMBL); Technical University of Munich; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); ICREA; Technical University of Munich
RP Sattler, M (corresponding author), Helmholtz Zentrum Munchen, Inst Struct Biol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM sattler@helmholtz-muenchen.de
FU EMBO Long Term Fellowship; ICSN; Aquitaine regional government; Austrian Science Fund (FWF); EMBO; European Commission [226507]; EURASNET; AICR; Fundacion Marcelino Botin; ICREA Funding Source: Custom
NR 36
TC 184
Z9 206
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 408
EP U174
DI 10.1038/nature10171
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200049
PM 21753750
DA 2026-03-09
ER

PT J
AU Huismans, R
   Beaumont, C
AF Huismans, Ritske
   Beaumont, Christopher
TI Depth-dependent extension, two-stage breakup and cratonic underplating at rifted margins
SO NATURE
LA English
DT Article
ID continental-crust; upper-mantle; lithospheric mantle; deep-structure; evolution; wave; architecture; constraints; models; origin
AB Uniform lithospheric extension(1) predicts basic properties of nonvolcanic rifted margins but fails to explain other important characteristics(2,3). Significant discrepancies are observed at 'type I' margins (such as the Iberia-Newfoundland conjugates), where large tracts of continental mantle lithosphere are exposed at the sea floor(4), and 'type II' margins (such as some ultrawide central South Atlantic margins), where thin continental crust spans wide regions below which continental lower crust and mantle lithosphere have apparently been removed(5,6). Neither corresponds to uniform extension. Instead, either crust or mantle lithosphere has been preferentially removed. Using dynamical models, we demonstrate that these margins are opposite end members: in type I, depth-dependent extension results in crustal-necking breakup before mantle-lithosphere breakup and in type II, the converse is true. These two-layer, two-stage breakup behaviours explain the discrepancies and have implications for the styles of the associated sedimentary basins. Laterally flowing lower-mantle cratonic lithosphere may underplate some type II margins, thereby contributing to their anomalous characteristics.
C1 [Huismans, Ritske] Univ Bergen, Dept Earth Sci, N-5007 Bergen, Norway.
   [Beaumont, Christopher] Dalhousie Univ, Dept Oceanog, Halifax, NS B3H 4J1, Canada.
C3 University of Bergen; Dalhousie University
RP Huismans, R (corresponding author), Univ Bergen, Dept Earth Sci, N-5007 Bergen, Norway.
EM ritske.huismans@geo.uib.no
FU Department of Earth Science, University of Bergen, Norway; Canada Research Chair in Geodynamics
NR 36
TC 467
Z9 527
U1 1
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 74
EP U85
DI 10.1038/nature09988
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300033
PM 21544144
DA 2026-03-09
ER

PT J
AU Burns, DM
   D'Ambrogio, A
   Nottrott, S
   Richter, JD
AF Burns, David M.
   D'Ambrogio, Andrea
   Nottrott, Stephanie
   Richter, Joel D.
TI CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation
SO NATURE
LA English
DT Article
ID mediated cytoplasmic polyadenylation; ribosomal-protein l26; cellular senescence; synaptic plasticity; micrornas; gld-2; stabilization; mouse; cells; mice
AB Cytoplasmic polyadenylation-induced translation controls germ cell development(1,2), neuronal synaptic plasticity(3-5) and cellular senescence(6,7), a tumour-suppressor mechanism that limits the replicative lifespan of cells(8,9). The cytoplasmic polyadenylation element binding protein (CPEB) promotes polyadenylation by nucleating a group of factors including defective in germline development 2 (Gld2), a non-canonical poly(A) polymerase(10-12), on specific messenger RNA (mRNA) 3' untranslated regions (UTRs). Because CPEB regulation of p53 mRNA polyadenylation/translation is necessary for cellular senescence in primary human diploid fibroblasts(6), we surmised that Gld2 would be the enzyme responsible for poly(A) addition. Here we show that depletion of Gld2 surprisingly promotes rather than inhibits p53 mRNA polyadenylation/translation, induces premature senescence and enhances the stability of CPEB mRNA. The CPEB 3' UTR contains two miR-122 binding sites, which when deleted, elevate mRNA translation, as does an antagomir of miR-122. Although miR-122 is thought to be liver specific, it is present in primary fibroblasts and destabilized by Gld2 depletion. Gld4, a second non-canonical poly(A) polymerase, was found to regulate p53 mRNA polyadenylation/translation in a CPEB-dependent manner. Thus, translational regulation of p53 mRNA and cellular senescence is coordinated by Gld2/miR-122/CPEB/Gld4.
C1 [Burns, David M.; D'Ambrogio, Andrea; Nottrott, Stephanie; Richter, Joel D.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP Richter, JD (corresponding author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
EM joel.richter@umassmed.edu
FU Max Planck Society; European Molecular Biology Organization [ALTF 995-2004]; National Institutes of Health [AG30323]; National Institute of General Medical Sciences [R01GM046779] Funding Source: NIH RePORTER
NR 27
TC 169
Z9 202
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 MAY 5
PY 2011
VL 473
IS 7345
BP 105
EP U125
DI 10.1038/nature09908
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300040
PM 21478871
DA 2026-03-09
ER

PT J
AU Sánchez-Lavega, A
   del Río-Gaztelurrutia, T
   Hueso, R
   Gómez-Forrellad, JM
   Sanz-Requena, JF
   Legarreta, J
   García-Melendo, E
   Colas, F
   Lecacheux, J
   Fletcher, LN
   Barrado-Navascués, D
   Parker, D
AF Sanchez-Lavega, A.
   del Rio-Gaztelurrutia, T.
   Hueso, R.
   Gomez-Forrellad, J. M.
   Sanz-Requena, J. F.
   Legarreta, J.
   Garcia-Melendo, E.
   Colas, F.
   Lecacheux, J.
   Fletcher, L. N.
   Barrado-Navascues, D.
   Parker, D.
TI Deep winds beneath Saturn's upper clouds from a seasonal long-lived planetary-scale storm
SO NATURE
LA English
DT Article
ID 1990 equatorial disturbance; zonal winds; atmosphere; model; jet
AB Convective storms occur regularly in Saturn's atmosphere(1-4). Huge storms known as Great White Spots, which are ten times larger than the regular storms, are rarer and occur about once per Saturnian year (29.5 Earth years). Current models propose that the outbreak of a Great White Spot is due to moist convection induced by water(5,6). However, the generation of the global disturbance and its effect on Saturn's permanent winds(1,7) have hitherto been unconstrained(8) by data, because there was insufficient spatial resolution and temporal sampling(9-11) to infer the dynamics of Saturn's weather layer (the layer in the troposphere where the cloud forms). Theoretically, it has been suggested that this phenomenon is seasonally controlled(5,9,10). Here we report observations of a storm at northern latitudes in the peak of a weak westward jet during the beginning of northern springtime, in accord with the seasonal cycle but earlier than expected. The storm head moved faster than the jet, was active during the two-month observation period, and triggered a planetary-scale disturbance that circled Saturn but did not significantly alter the ambient zonal winds. Numerical simulations of the phenomenon show that, as on Jupiter(12), Saturn's winds extend without decay deep down into the weather layer, at least to the water-cloud base at pressures of 10-12 bar, which is much deeper than solar radiation penetrates.
C1 [Sanchez-Lavega, A.; del Rio-Gaztelurrutia, T.; Hueso, R.] Univ Basque Country, Escuela Tecn Super Ingn, Dept Fis Aplicada 1, Bilbao 48013, Spain.
   [Gomez-Forrellad, J. M.; Garcia-Melendo, E.] Esteve Duran Observ Fdn, Seva 08553, Spain.
   [Sanz-Requena, J. F.] Univ Europea Miguel de Cervantes, Valladolid 47012, Spain.
   [Legarreta, J.] Univ Basque Country, EUITI, Dept Ingn Sistemas & Automat, Bilbao 48012, Spain.
   [Garcia-Melendo, E.] Fac Ciencies, Inst Ciencies Espai CSIC IEEC, E-08193 Bellaterra, Spain.
   [Colas, F.] CNRS, UMR 8028, Observ Paris, Inst Mecan Celeste & Calculdes Ephemerides, F-75014 Paris, France.
   [Lecacheux, J.] LESIA, Observ Paris, F-92195 Meudon, France.
   [Fletcher, L. N.] Univ Oxford, Clarendon Lab, Dept Phys, Oxford OX1 3PU, England.
   [Barrado-Navascues, D.] MPIA CSIC, Ctr Astron Hispano Aleman, Observ Calar Alto, Almeria 04004, Spain.
   [Parker, D.] ALPO, Coral Gables, FL 33156 USA.
C3 University of Basque Country; Miguel de Cervantes European University (UEMC); University of Basque Country; University of Barcelona; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris; Sorbonne Universite; Universite Paris Cite; Universite PSL; Observatoire de Paris; University of Oxford; Consejo Superior de Investigaciones Cientificas (CSIC)
RP Sánchez-Lavega, A (corresponding author), Univ Basque Country, Escuela Tecn Super Ingn, Dept Fis Aplicada 1, Alameda Urquijo S-N, Bilbao 48013, Spain.
EM agustin.sanchez@ehu.es
FU Spanish MICIIN; FEDER; Gobierno Vasco; University of Oxford
NR 29
TC 94
Z9 101
U1 1
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 71
EP 74
DI 10.1038/nature10203
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300046
PM 21734704
DA 2026-03-09
ER

PT J
AU Jirawatnotai, S
   Hu, YD
   Michowski, W
   Elias, JE
   Becks, L
   Bienvenu, F
   Zagozdzon, A
   Goswami, T
   Wang, YYE
   Clark, AB
   Kunkel, TA
   van Harn, T
   Xia, B
   Correll, M
   Quackenbush, J
   Livingston, DM
   Gygi, SP
   Sicinski, P
AF Jirawatnotai, Siwanon
   Hu, Yiduo
   Michowski, Wojciech
   Elias, Joshua E.
   Becks, Lisa
   Bienvenu, Frederic
   Zagozdzon, Agnieszka
   Goswami, Tapasree
   Wang, Yaoyu E.
   Clark, Alan B.
   Kunkel, Thomas A.
   van Harn, Tanja
   Xia, Bing
   Correll, Mick
   Quackenbush, John
   Livingston, David M.
   Gygi, Steven P.
   Sicinski, Piotr
TI A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers
SO NATURE
LA English
DT Article
ID human rad51 protein; double-strand break; phosphorylation; damage; overexpression; absence; cells
AB Cyclin D1 is a component of the core cell cycle machinery(1). Abnormally high levels of cyclin D1 are detected in many human cancer types(2). To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process(3). We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation(4,5). These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.
C1 [Jirawatnotai, Siwanon; Hu, Yiduo; Michowski, Wojciech; Becks, Lisa; Bienvenu, Frederic; Zagozdzon, Agnieszka; van Harn, Tanja; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Jirawatnotai, Siwanon; Hu, Yiduo; Michowski, Wojciech; Becks, Lisa; Bienvenu, Frederic; Zagozdzon, Agnieszka; van Harn, Tanja; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA.
   [Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya 73170, Nakhon Prathom, Thailand.
   [Elias, Joshua E.; Goswami, Tapasree; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Becks, Lisa] Massachusetts Coll Pharm & Hlth Sci, Dept Pharmacol, Boston, MA 02115 USA.
   [Wang, Yaoyu E.; Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
   [Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Xia, Bing] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ 08903 USA.
   [Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Mahidol University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rutgers Cancer Institute of New Jersey; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health
RP Sicinski, P (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM peter_sicinski@dfci.harvard.edu
FU NIH [R01 CA083688, P01 CA080111, P01 CA109901]; Thailand Research Fund [MRG5280248]; Foundation for Polish Science; CCCB; Dana-Farber Strategic Plan Initiative; Division of Intramural Research of the NIH, NIEHS [Z01 ES065089]; National Cancer Institute [R01CA138804] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [ZIAES065089] Funding Source: NIH RePORTER; National Institute on Aging; National Heart Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institute of Nursing Research; National Institute on Minority Health and Health Disparities; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Dental and Craniofacial Research; National Cancer Institute [P30AI060354] Funding Source: NIH RePORTER
NR 29
TC 272
Z9 308
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 230
EP 234
DI 10.1038/nature10155
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800054
PM 21654808
DA 2026-03-09
ER

PT J
AU Gubbins, D
   Sreenivasan, B
   Mound, J
   Rost, S
AF Gubbins, David
   Sreenivasan, Binod
   Mound, Jon
   Rost, Sebastian
TI Melting of the Earth's inner core
SO NATURE
LA English
DT Article
ID boundary heat-flow; lateral variations; magnetic-field; geomagnetic reversals; numerical dynamos; secular variation; outer-core; mantle; convection; layer
AB The Earth's magnetic field is generated by a dynamo in the liquid iron core, which convects in response to cooling of the overlying rocky mantle. The core freezes from the innermost surface outward, growing the solid inner core and releasing light elements that drive compositional convection(1-3). Mantle convection extracts heat from the core at a rate that has enormous lateral variations(4). Here we use geodynamo simulations to show that these variations are transferred to the inner-core boundary and can be large enough to cause heat to flow into the inner core. If this were to occur in the Earth, it would cause localized melting. Melting releases heavy liquid that could form the variable-composition layer suggested by an anomaly in seismic velocity in the 150 kilometres immediately above the inner-core boundary(5-7). This provides a very simple explanation of the existence of this layer, which otherwise requires additional assumptions such as locking of the inner core to the mantle, translation from its geopotential centre(7,8) or convection with temperature equal to the solidus but with composition varying from the outer to the inner core(9). The predominantly narrow downwellings associated with freezing and broad upwellings associated with melting mean that the area of melting could be quite large despite the average dominance of freezing necessary to keep the dynamo going. Localized melting and freezing also provides a strong mechanism for creating seismic anomalies in the inner core itself, much stronger than the effects of variations in heat flow so far considered(10).
C1 [Sreenivasan, Binod] Indian Inst Technol, Dept Mech Engn, Kanpur 208016, Uttar Pradesh, India.
   [Gubbins, David] SIO, IGPP, La Jolla, CA 92093 USA.
   [Gubbins, David; Mound, Jon; Rost, Sebastian] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
C3 Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Kanpur; University of Leeds
RP Sreenivasan, B (corresponding author), Indian Inst Technol, Dept Mech Engn, Kanpur 208016, Uttar Pradesh, India.
EM bsreeni@iitk.ac.in
NR 31
TC 126
Z9 134
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 MAY 19
PY 2011
VL 473
IS 7347
BP 361
EP U53
DI 10.1038/nature10068
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400045
PM 21593868
DA 2026-03-09
ER

PT J
AU Che, H
   Drake, JF
   Swisdak, M
AF Che, H.
   Drake, J. F.
   Swisdak, M.
TI A current filamentation mechanism for breaking magnetic field lines during reconnection
SO NATURE
LA English
DT Article
ID electrostatic solitary waves; particle simulations; turbulence; holes
AB During magnetic reconnection, the field lines must break and reconnect to release the energy that drives solar and stellar flares(1,2) and other explosive events in space(3) and in the laboratory(4). Exactly how this happens has been unclear, because dissipation is needed to break magnetic field lines and classical collisions are typically weak. Ion-electron drag arising from turbulence(5), dubbed 'anomalous resistivity', and thermal momentum transport(6) are two mechanisms that have been widely invoked. Measurements of enhanced turbulence near reconnection sites in space(7,8) and in the laboratory(9,10) support the anomalous resistivity idea but there has been no demonstration from measurements that this turbulence produces the necessary enhanced drag(11). Here we report computer simulations that show that neither of the two previously favoured mechanisms controls how magnetic field lines reconnect in the plasmas of greatest interest, those in which the magnetic field dominates the energy budget. Rather, we find that when the current layers that form during magnetic reconnection become too intense, they disintegrate and spread into a complex web of filaments that causes the rate of reconnection to increase abruptly. This filamentary web can be explored in the laboratory or in space with satellites that can measure the resulting electromagnetic turbulence.
C1 [Che, H.] Univ Colorado, Dept Phys, Ctr Integrated Plasma Studies, Boulder, CO 80309 USA.
   [Drake, J. F.; Swisdak, M.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Drake, J. F.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
C3 University of Colorado System; University of Colorado Boulder; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park
RP Che, H (corresponding author), Univ Colorado, Dept Phys, Ctr Integrated Plasma Studies, Boulder, CO 80309 USA.
EM haihong.che@colorado.edu
FU NSF/DOE; NASA; NASA through Magnetospheric Multiscale Mission Science Team
NR 28
TC 153
Z9 162
U1 1
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 184
EP 187
DI 10.1038/nature10091
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800043
PM 21633355
DA 2026-03-09
ER

PT J
AU Nikolova, EN
   Kim, E
   Wise, AA
   O'Brien, PJ
   Andricioaei, I
   Al-Hashimi, HM
AF Nikolova, Evgenia N.
   Kim, Eunae
   Wise, Abigail A.
   O'Brien, Patrick J.
   Andricioaei, Ioan
   Al-Hashimi, Hashim M.
TI Transient Hoogsteen base pairs in canonical duplex DNA
SO NATURE
LA English
DT Article
ID double-helical dna; nucleic-acids; tata box; molecular-structure; generalized born; spin relaxation; protein; nmr; dynamics; proton
AB Sequence-directed variations in the canonical DNA double helix structure that retain Watson-Crick base-pairing have important roles in DNA recognition, topology and nucleosome positioning. By using nuclear magnetic resonance relaxation dispersion spectroscopy in concert with steered molecular dynamics simulations, we have observed transient sequence-specific excursions away from Watson-Crick base-pairing at CA and TA steps inside canonical duplex DNA towards low-populated and short-lived A.T and G.C Hoogsteen base pairs. The observation of Hoogsteen base pairs in DNA duplexes specifically bound to transcription factors and in damaged DNA sites implies that the DNA double helix intrinsically codes for excited state Hoogsteen base pairs as a means of expanding its structural complexity beyond that which can be achieved based on Watson-Crick base-pairing. The methods presented here provide a new route for characterizing transient low-populated nucleic acid structures, which we predict will be abundant in the genome and constitute a second transient layer of the genetic code.
C1 [Nikolova, Evgenia N.; Wise, Abigail A.; Al-Hashimi, Hashim M.] Univ Michigan, Dept Chem & Biophys, Ann Arbor, MI 48109 USA.
   [Kim, Eunae; Andricioaei, Ioan] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA.
   [O'Brien, Patrick J.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of California System; University of California Irvine; University of Michigan System; University of Michigan
RP Al-Hashimi, HM (corresponding author), Univ Michigan, Dept Chem & Biophys, 930 N Univ Ave, Ann Arbor, MI 48109 USA.
EM andricio@uci.edu; hashimi@umich.edu
FU NSF [MCB 0644278, CHE-0918817]; NIH [R01GM089846]; Rackham International; University of Michigan; National Institute of General Medical Sciences [R01GM089846] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Chemistry [0918817] Funding Source: National Science Foundation
NR 58
TC 281
Z9 360
U1 1
U2 117
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 498
EP U84
DI 10.1038/nature09775
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900034
PM 21270796
DA 2026-03-09
ER

PT J
AU Le Breton, JC
   Sharma, S
   Saito, H
   Yuasa, S
   Jansen, R
AF Le Breton, Jean-Christophe
   Sharma, Sandeep
   Saito, Hidekazu
   Yuasa, Shinji
   Jansen, Ron
TI Thermal spin current from a ferromagnet to silicon by Seebeck spin tunnelling
SO NATURE
LA English
DT Article
ID metal
AB Heat generation by electric current, which is ubiquitous in electronic devices and circuits, raises energy consumption and will become increasingly problematic in future generations of high-density electronics. The control and re-use of heat are therefore important topics for existing and emerging technologies, including spintronics. Recently it was reported that heat flow within a ferromagnet can produce a flow of spin angular momentum-a spin current-and an associated voltage(1). This spin Seebeck effect has been observed in metallic(1,2), insulating(3) and semiconductor ferromagnets(4) with temperature gradients across them. Here we describe and report the demonstration of Seebeck spin tunnelling-a distinctly different thermal spin flow, of purely interfacial nature-generated in a tunnel contact between electrodes of different temperatures when at least one of the electrodes is a ferromagnet. The Seebeck spin current is governed by the energy derivative of the tunnel spin polarization. By exploiting this in ferromagnet-oxide-silicon tunnel junctions, we observe thermal transfer of spins from the ferromagnet to the silicon without a net tunnel charge current. The induced spin accumulation scales linearly with heating power and changes sign when the temperature differential is reversed. This thermal spin current can be used by itself, or in combination with electrical spin injection, to increase device efficiency. The results highlight the engineering of heat transport in spintronic devices and facilitate the functional use of heat.
C1 [Sharma, Sandeep; Saito, Hidekazu; Yuasa, Shinji; Jansen, Ron] Natl Inst Adv Ind Sci & Technol, Spintron Res Ctr, Tsukuba, Ibaraki 3058568, Japan.
   [Le Breton, Jean-Christophe; Sharma, Sandeep] Netherlands Fdn Fundamental Res Matter FOM, NL-3502 GA Utrecht, Netherlands.
   [Sharma, Sandeep] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
C3 National Institute of Advanced Industrial Science & Technology (AIST); University of Groningen
RP Jansen, R (corresponding author), Natl Inst Adv Ind Sci & Technol, Spintron Res Ctr, Tsukuba, Ibaraki 3058568, Japan.
EM ron.jansen@aist.go.jp
FU Netherlands Foundation for Fundamental Research on Matter (FOM)
NR 25
TC 220
Z9 233
U1 2
U2 171
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 82
EP 85
DI 10.1038/nature10224
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300049
PM 21716285
DA 2026-03-09
ER

PT J
AU Noudoost, B
   Moore, T
AF Noudoost, Behrad
   Moore, Tirin
TI Control of visual cortical signals by prefrontal dopamine
SO NATURE
LA English
DT Article
ID frontal eye field; attentional modulation; receptor actions; messenger-rnas; neurons; cortex; selection; expression
AB The prefrontal cortex is thought to modulate sensory signals in posterior cortices during top-down attention(1,2), but little is known about the underlying neural circuitry. Experimental and clinical evidence indicate that prefrontal dopamine has an important role in cognitive functions(3), acting predominantly through D1 receptors. Here we show that dopamine D1 receptors mediate prefrontal control of signals in the visual cortex of macaques (Macaca mulatta). We pharmacologically altered D1-receptor-mediated activity in the frontal eye field of the prefrontal cortex and measured the effect on the responses of neurons in area V4 of the visual cortex. This manipulation was sufficient to enhance the magnitude, the orientation selectivity and the reliability of V4 visual responses to an extent comparable with the known effects of top-down attention. The enhancement of V4 signals was restricted to neurons with response fields overlapping the part of visual space affected by the D1 receptor manipulation. Altering either D1- or D2-receptor-mediated frontal eye field activity increased saccadic target selection but the D2 receptor manipulation did not enhance V4 signals. Our results identify a role for D1 receptors in mediating the control of visual cortical signals by the prefrontal cortex and suggest how processing in sensory areas could be altered in mental disorders involving prefrontal dopamine.
C1 [Noudoost, Behrad; Moore, Tirin] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Noudoost, Behrad; Moore, Tirin] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University
RP Noudoost, B (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Fairchild Bldg,299 Campus Dr W, Stanford, CA 94305 USA.
EM behrad@stanford.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NEI NIH HHS [R56 EY014924, R01 EY014924, EY014924] Funding Source: Medline; National Eye Institute [R01EY014924] Funding Source: NIH RePORTER
NR 30
TC 268
Z9 304
U1 1
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 372
EP 375
DI 10.1038/nature09995
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100044
PM 21572439
DA 2026-03-09
ER

PT J
AU Fu, SN
   Yang, L
   Li, P
   Hofmann, O
   Dicker, L
   Hide, W
   Lin, XH
   Watkins, SM
   Ivanov, AR
   Hotamisligil, GS
AF Fu, Suneng
   Yang, Ling
   Li, Ping
   Hofmann, Oliver
   Dicker, Lee
   Hide, Winston
   Lin, Xihong
   Watkins, Steven M.
   Ivanov, Alexander R.
   Hotamisligil, Goekhan S.
TI Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity
SO NATURE
LA English
DT Article
ID glucose-homeostasis; mass-spectrometry; adipose-tissue; er stress; mice; ca2+-atpase; insulin; phosphatidylethanolamine; cholesterol; activation
AB The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response(1). Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity(2). However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity.
C1 [Fu, Suneng; Yang, Ling; Li, Ping; Ivanov, Alexander R.; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
   [Fu, Suneng; Yang, Ling; Li, Ping; Ivanov, Alexander R.; Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Hofmann, Oliver; Dicker, Lee; Hide, Winston; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Watkins, Steven M.] Lip Technol Inc, W Sacramento, CA 95691 USA.
   [Hotamisligil, Goekhan S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Hotamisligil, GS (corresponding author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM ghotamis@hsph.harvard.edu
FU National Institutes of Health [DK52539, 1RC4-DK090942]; Syndexa Pharmaceuticals; NIH/NIEHS [T32ES007155]
NR 24
TC 866
Z9 1000
U1 4
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 MAY 26
PY 2011
VL 473
IS 7348
BP 528
EP 531
DI 10.1038/nature09968
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300044
PM 21532591
DA 2026-03-09
ER

PT J
AU Mutreja, A
   Kim, DW
   Thomson, NR
   Connor, TR
   Lee, JH
   Kariuki, S
   Croucher, NJ
   Choi, SY
   Harris, SR
   Lebens, M
   Niyogi, SK
   Kim, EJ
   Ramamurthy, T
   Chun, J
   Wood, JLN
   Clemens, JD
   Czerkinsky, C
   Nair, GB
   Holmgren, J
   Parkhill, J
   Dougan, G
AF Mutreja, Ankur
   Kim, Dong Wook
   Thomson, Nicholas R.
   Connor, Thomas R.
   Lee, Je Hee
   Kariuki, Samuel
   Croucher, Nicholas J.
   Choi, Seon Young
   Harris, Simon R.
   Lebens, Michael
   Niyogi, Swapan Kumar
   Kim, Eun Jin
   Ramamurthy, T.
   Chun, Jongsik
   Wood, James L. N.
   Clemens, John D.
   Czerkinsky, Cecil
   Nair, G. Balakrish
   Holmgren, Jan
   Parkhill, Julian
   Dougan, Gordon
TI Evidence for several waves of global transmission in the seventh cholera pandemic
SO NATURE
LA English
DT Article
ID vibrio-cholerae; el-tor; evolution; populations; sequences; vietnam; strains; element; o139
AB Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic(1). Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 (refs 2, 3) can cause epidemic cholera(2). It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic(1). Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.
C1 [Mutreja, Ankur; Thomson, Nicholas R.; Connor, Thomas R.; Croucher, Nicholas J.; Harris, Simon R.; Parkhill, Julian; Dougan, Gordon] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Kim, Dong Wook; Lee, Je Hee; Choi, Seon Young; Kim, Eun Jin; Clemens, John D.; Czerkinsky, Cecil] SNU Res Pk, Int Vaccine Inst, Seoul 151919, South Korea.
   [Kim, Dong Wook] Hanyang Univ, Coll Pharm, Dept Pharm, Kyeonggi Do 426791, South Korea.
   [Lee, Je Hee; Choi, Seon Young; Chun, Jongsik] Seoul Natl Univ, Seoul 151742, South Korea.
   [Kariuki, Samuel] KEMRI Kenyatta Hosp Compound, Ctr Microbiol Res, Nairobi, Kenya.
   [Lebens, Michael; Holmgren, Jan] Univ Gothenburg, Sahlgrenska Acad, Dept Microbiol & Immunol, S-40530 Gothenburg, Sweden.
   [Lebens, Michael; Holmgren, Jan] Univ Gothenburg, Sahlgrenska Acad, Vaccine Res Inst, S-40530 Gothenburg, Sweden.
   [Niyogi, Swapan Kumar; Ramamurthy, T.; Nair, G. Balakrish] Natl Inst Cholera & Enter Dis, Kolkata 700010, India.
   [Wood, James L. N.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England.
C3 Wellcome Trust Sanger Institute; International Vaccine Institute; Seoul National University (SNU); Hanyang University; Seoul National University (SNU); University of Gothenburg; University of Gothenburg; University of Gothenburg Institute for Vaccine Research; Indian Council of Medical Research (ICMR); ICMR - National Institute of Cholera & Enteric Diseases (NICED); University of Cambridge
RP Parkhill, J (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM parkhill@sanger.ac.uk
FU Wellcome Trust [076964]; Government of Korea; Government of Sweden; Government of Kuwait; Ministry of Knowledge and Economy (MKE), Korea [RTI05-01-01]; Korea Science and Engineering Foundation [R01-2006-000-10255-0]; Alborada Trust; Science & Technology Directorate, Department of Homeland Security
NR 29
TC 547
Z9 633
U1 4
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 SEP 22
PY 2011
VL 477
IS 7365
BP 462
EP U111
DI 10.1038/nature10392
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500040
PM 21866102
DA 2026-03-09
ER

PT J
AU Wang, ZN
   Klipfell, E
   Bennett, BJ
   Koeth, R
   Levison, BS
   Dugar, B
   Feldstein, AE
   Britt, EB
   Fu, XM
   Chung, YM
   Wu, YP
   Schauer, P
   Smith, JD
   Allayee, H
   Tang, WHW
   DiDonato, JA
   Lusis, AJ
   Hazen, SL
AF Wang, Zeneng
   Klipfell, Elizabeth
   Bennett, Brian J.
   Koeth, Robert
   Levison, Bruce S.
   Dugar, Brandon
   Feldstein, Ariel E.
   Britt, Earl B.
   Fu, Xiaoming
   Chung, Yoon-Mi
   Wu, Yuping
   Schauer, Phil
   Smith, Jonathan D.
   Allayee, Hooman
   Tang, W. H. Wilson
   DiDonato, Joseph A.
   Lusis, Aldons J.
   Hazen, Stanley L.
TI Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
SO NATURE
LA English
DT Article
ID trimethylamine-n-oxide; coronary-heart-disease; gene-expression; chlamydia-pneumoniae; murine macrophages; mass-spectrometry; dna methylation; atherosclerosis; mouse; mice
AB Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine-choline, trimethylamine N-oxide (TMAO) and betaine-were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
C1 [Wang, Zeneng; Klipfell, Elizabeth; Koeth, Robert; Levison, Bruce S.; Dugar, Brandon; Feldstein, Ariel E.; Britt, Earl B.; Fu, Xiaoming; Chung, Yoon-Mi; Smith, Jonathan D.; Tang, W. H. Wilson; DiDonato, Joseph A.; Hazen, Stanley L.] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44195 USA.
   [Wang, Zeneng; Klipfell, Elizabeth; Levison, Bruce S.; Feldstein, Ariel E.; Britt, Earl B.; Fu, Xiaoming; Chung, Yoon-Mi; Tang, W. H. Wilson; DiDonato, Joseph A.; Hazen, Stanley L.] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA.
   [Bennett, Brian J.; Lusis, Aldons J.] Univ Calif Los Angeles, Ctr Hlth Sci BH 307, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA.
   [Wu, Yuping] Cleveland State Univ, Dept Math, Cleveland, OH 44115 USA.
   [Schauer, Phil] Cleveland Clin, Bariatr & Metab Inst, Cleveland, OH 44195 USA.
   [Smith, Jonathan D.; Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA.
   [Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
   [Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA.
C3 Cleveland Clinic Foundation; Cleveland Clinic Foundation; University of California System; University of California Los Angeles; University System of Ohio; Cleveland State University; Cleveland Clinic Foundation; Cleveland Clinic Foundation; University of Southern California; University of Southern California
RP Hazen, SL (corresponding author), Cleveland Clin, Dept Cell Biol, Cleveland, OH 44195 USA.
EM hazens@ccf.org
FU National Institutes of Health [R01 HL103866, P01 HL098055, P01HL087018-020001, P01 HL28481, P01 HL30568, T32-DK07789]; Cleveland Clinic Foundation General Clinical Research Center of the Cleveland Clinic/Case Western Reserve University CTSA [1UL1RR024989]; Abbott Diagnostics;  [P01 HL076491-055328];  [R01 HL103931];  [R01 DK080732]; National Heart Lung and Blood Institute; NIH Office of the Director [R01HL103866] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007250] Funding Source: NIH RePORTER
NR 68
TC 4417
Z9 5140
U1 27
U2 1589
PU 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 7
PY 2011
VL 472
IS 7341
BP 57
EP U82
DI 10.1038/nature09922
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400036
PM 21475195
DA 2026-03-09
ER

PT J
AU Ozawa, S
   Nishimura, T
   Suito, H
   Kobayashi, T
   Tobita, M
   Imakiire, T
AF Ozawa, Shinzaburo
   Nishimura, Takuya
   Suito, Hisashi
   Kobayashi, Tomokazu
   Tobita, Mikio
   Imakiire, Tetsuro
TI Coseismic and postseismic slip of the 2011 magnitude-9 Tohoku-Oki earthquake
SO NATURE
LA English
DT Article
ID northeastern japan; subduction zone; continuous gps; spatial-distribution; crustal deformation; plate boundary; data inversion; fault slip; interplate; model
AB Most large earthquakes occur along an oceanic trench, where an oceanic plate subducts beneath a continental plate. Massive earthquakes with a moment magnitude, M-w, of nine have been known to occur in only a few areas, including Chile, Alaska, Kamchatka and Sumatra. No historical records exist of a M-w = 9 earthquake along the Japan trench, where the Pacific plate subducts beneath the Okhotsk plate, with the possible exception of the AD 869 Jogan earthquake(1), the magnitude of which has not been well constrained. However, the strain accumulation rate estimated there from recent geodetic observations is much higher than the average strain rate released in previous interplate earthquakes(2-6). This finding raises the question of how such areas release the accumulated strain. A megathrust earthquake with M-w = 9.0 (hereafter referred to as the Tohoku-Oki earthquake) occurred on 11 March 2011, rupturing the plate boundary off the Pacific coast of northeastern Japan. Here we report the distributions of the coseismic slip and postseismic slip as determined from ground displacement detected using a network based on the Global Positioning System. The coseismic slip area extends approximately 400 km along the Japan trench, matching the area of the pre-seismic locked zone(4). The afterslip has begun to overlap the coseismic slip area and extends into the surrounding region. In particular, the afterslip area reached a depth of approximately 100 km, with M-w = 8.3, on 25 March 2011. Because the Tohoku-Oki earthquake released the strain accumulated for several hundred years, the paradox of the strain budget imbalance may be partly resolved. This earthquake reminds us of the potential for M-w approximate to 9 earthquakes to occur along other trench systems, even if no past evidence of such events exists. Therefore, it is imperative that strain accumulation be monitored using a space geodetic technique to assess earthquake potential.
C1 [Ozawa, Shinzaburo; Nishimura, Takuya; Suito, Hisashi; Kobayashi, Tomokazu; Tobita, Mikio; Imakiire, Tetsuro] Geospatial Informat Author Japan, Tsukuba, Ibaraki 3050811, Japan.
RP Ozawa, S (corresponding author), Geospatial Informat Author Japan, Tsukuba, Ibaraki 3050811, Japan.
EM ozawa@gsi.go.jp
NR 37
TC 633
Z9 722
U1 8
U2 234
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 373
EP U123
DI 10.1038/nature10227
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200041
PM 21677648
DA 2026-03-09
ER

PT J
AU Kudernac, T
   Ruangsupapichat, N
   Parschau, M
   Maciá, B
   Katsonis, N
   Harutyunyan, SR
   Ernst, KH
   Feringa, BL
AF Kudernac, Tibor
   Ruangsupapichat, Nopporn
   Parschau, Manfred
   Macia, Beatriz
   Katsonis, Nathalie
   Harutyunyan, Syuzanna R.
   Ernst, Karl-Heinz
   Feringa, Ben L.
TI Electrically driven directional motion of a four-wheeled molecule on a metal surface
SO NATURE
LA English
DT Article
ID single-molecule; scale; adsorption; machines; dynamics; cu(111); motors; work
AB Propelling single molecules in a controlled manner along an unmodified surface remains extremely challenging because it requires molecules that can use light, chemical or electrical energy to modulate their interaction with the surface in a way that generates motion. Nature's motor proteins(1,2) have mastered the art of converting conformational changes into directed motion, and have inspired the design of artificial systems(3) such as DNA walkers(4,5) and light-and redox-driven molecular motors(6-11). But although controlled movement of single molecules along a surface has been reported(12-16), the molecules in these examples act as passive elements that either diffuse along a preferential direction with equal probability for forward and backward movement or are dragged by an STM tip. Here we present a molecule with four functional units-our previously reported rotary motors(6,8,17)-that undergo continuous and defined conformational changes upon sequential electronic and vibrational excitation. Scanning tunnelling microscopy confirms that activation of the conformational changes of the rotors through inelastic electron tunnelling propels the molecule unidirectionally across a Cu(111) surface. The system can be adapted to follow either linear or random surface trajectories or to remain stationary, by tuning the chirality of the individual motor units. Our design provides a starting point for the exploration of more sophisticated molecular mechanical systems with directionally controlled motion.
C1 [Kudernac, Tibor; Macia, Beatriz; Katsonis, Nathalie; Harutyunyan, Syuzanna R.; Feringa, Ben L.] Univ Groningen, Stratingh Inst Chem, Ctr Syst Chem, NL-9747 AG Groningen, Netherlands.
   [Kudernac, Tibor; Ruangsupapichat, Nopporn; Katsonis, Nathalie; Feringa, Ben L.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Parschau, Manfred; Ernst, Karl-Heinz] Empa, Swiss Fed Labs Mat Sci & Technol, Nanoscale Mat Sci, CH-8600 Dubendorf, Switzerland.
   [Ernst, Karl-Heinz] Univ Zurich, Dept Chem, CH-8057 Zurich, Switzerland.
C3 University of Groningen; University of Groningen; Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); University of Zurich
RP Harutyunyan, SR (corresponding author), Univ Groningen, Stratingh Inst Chem, Ctr Syst Chem, Nijenborgh 4, NL-9747 AG Groningen, Netherlands.
EM s.harutyunyan@rug.nl; karl-heinz.ernst@empa.ch; b.l.feringa@rug.nl
FU Netherlands Organization for Scientific Research (NWO-CW); Swiss Secretary for Education and Research; Swiss National Science Foundation; European Research Council (ERC) [227897]
NR 29
TC 641
Z9 729
U1 11
U2 691
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 208
EP 211
DI 10.1038/nature10587
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800037
PM 22071765
DA 2026-03-09
ER

PT J
AU Nury, H
   Van Renterghem, C
   Weng, Y
   Tran, A
   Baaden, M
   Dufresne, V
   Changeux, JP
   Sonner, JM
   Delarue, M
   Corringer, PJ
AF Nury, Hugues
   Van Renterghem, Catherine
   Weng, Yun
   Tran, Alphonso
   Baaden, Marc
   Dufresne, Virginie
   Changeux, Jean-Pierre
   Sonner, James M.
   Delarue, Marc
   Corringer, Pierre-Jean
TI X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel
SO NATURE
LA English
DT Article
ID nicotinic acetylcholine-receptor; molecular-dynamics; binding-site; allosteric transitions; crystal-structures; glycine receptors; gaba(a) receptors; high-resolution; identification; modulation
AB General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels(1,2) (pLGICs) such as inhibitory GABA(A) (gamma-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus(3) (GLIC), whose X-ray structure was recently solved(4,5), is also sensitive to clinical concentrations of general anaesthetics(6). Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC. These reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer. Both molecules establish van der Waals interactions with the protein; propofol binds at the entrance of the cavity whereas the smaller, more flexible, desflurane binds deeper inside. Mutations of some amino acids lining the binding site profoundly alter the ionic response of GLIC to protons, and affect its general-anaesthetic pharmacology. Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects. These data provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs.
C1 [Nury, Hugues; Van Renterghem, Catherine; Dufresne, Virginie; Corringer, Pierre-Jean] Inst Pasteur, Grp Recepteurs Canaux, F-75015 Paris, France.
   [Nury, Hugues; Van Renterghem, Catherine; Dufresne, Virginie; Changeux, Jean-Pierre; Corringer, Pierre-Jean] CNRS, URA2182, F-75015 Paris, France.
   [Nury, Hugues; Delarue, Marc] Inst Pasteur, Unite Dynam Struct Macromol, F-75015 Paris, France.
   [Nury, Hugues; Delarue, Marc] CNRS, URA2185, F-75015 Paris, France.
   [Weng, Yun; Tran, Alphonso; Sonner, James M.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
   [Baaden, Marc] CNRS, UPR 9080, Inst Biol Physicochim, F-75005 Paris, France.
   [Changeux, Jean-Pierre] Coll France, F-75005 Paris, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California San Francisco; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; College de France
RP Corringer, PJ (corresponding author), Inst Pasteur, Grp Recepteurs Canaux, F-75015 Paris, France.
EM delarue@pasteur.fr; pjcorrin@pasteur.fr
FU Commission of the European Communities; Louis D. Foundation of the Institut de France; Network of European Neuroscience Institutes (ENI-NET); National Institutes of Health [NIGMS R01 GM069379]; Grand Equipement National de Calcul Intensif, Institut du Developpement et des Ressources en Informatique Scientifique (GENCI-IDRIS) [2009-072292]
NR 47
TC 363
Z9 404
U1 0
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 20
PY 2011
VL 469
IS 7330
BP 428
EP +
DI 10.1038/nature09647
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600059
PM 21248852
DA 2026-03-09
ER

PT J
AU Stewart, MP
   Helenius, J
   Toyoda, Y
   Ramanathan, SP
   Muller, DJ
   Hyman, AA
AF Stewart, Martin P.
   Helenius, Jonne
   Toyoda, Yusuke
   Ramanathan, Subramanian P.
   Muller, Daniel J.
   Hyman, Anthony A.
TI Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding
SO NATURE
LA English
DT Article
ID atomic-force microscope; shape; flow; morphogenesis; oscillations; retraction; membrane; rigidity; division; moesin
AB During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round(1-3). Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division(4-7). However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment(2). Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.
C1 [Toyoda, Yusuke; Hyman, Anthony A.] Max Planck Inst Mol Cell Biol & Genet, D-1307 Dresden, Germany.
   [Stewart, Martin P.; Helenius, Jonne; Ramanathan, Subramanian P.; Muller, Daniel J.] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
   [Stewart, Martin P.] Tech Univ Dresden, Ctr Biotechnol, D-01307 Dresden, Germany.
C3 Max Planck Society; Swiss Federal Institutes of Technology Domain; ETH Zurich; Technische Universitat Dresden
RP Hyman, AA (corresponding author), Max Planck Inst Mol Cell Biol & Genet, D-1307 Dresden, Germany.
EM daniel.muller@bsse.ethz.ch
FU DFG; BMBF; SNF; JSPS; Max Planck Society
NR 35
TC 520
Z9 611
U1 4
U2 168
PU 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 13
PY 2011
VL 469
IS 7329
BP 226
EP 230
DI 10.1038/nature09642
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400041
PM 21196934
DA 2026-03-09
ER

PT J
AU Lindblad-Toh, K
   Garber, M
   Zuk, O
   Lin, MF
   Parker, BJ
   Washietl, S
   Kheradpour, P
   Ernst, J
   Jordan, G
   Mauceli, E
   Ward, LD
   Lowe, CB
   Holloway, AK
   Clamp, M
   Gnerre, S
   Alföldi, J
   Beal, K
   Chang, J
   Clawson, H
   Cuff, J
   Di Palma, F
   Fitzgerald, S
   Flicek, P
   Guttman, M
   Hubisz, MJ
   Jaffe, DB
   Jungreis, I
   Kent, WJ
   Kostka, D
   Lara, M
   Martins, AL
   Massingham, T
   Moltke, I
   Raney, BJ
   Rasmussen, MD
   Robinson, J
   Stark, A
   Vilella, AJ
   Wen, JY
   Xie, XH
   Zody, MC
   Worley, KC
   Kovar, CL
   Muzny, DM
   Gibbs, RA
   Warren, WC
   Mardis, ER
   Weinstock, GM
   Wilson, RK
   Birney, E
   Margulies, EH
   Herrero, J
   Green, ED
   Haussler, D
   Siepel, A
   Goldman, N
   Pollard, KS
   Pedersen, JS
   Lander, ES
   Kellis, M
AF Lindblad-Toh, Kerstin
   Garber, Manuel
   Zuk, Or
   Lin, Michael F.
   Parker, Brian J.
   Washietl, Stefan
   Kheradpour, Pouya
   Ernst, Jason
   Jordan, Gregory
   Mauceli, Evan
   Ward, Lucas D.
   Lowe, Craig B.
   Holloway, Alisha K.
   Clamp, Michele
   Gnerre, Sante
   Alfoeldi, Jessica
   Beal, Kathryn
   Chang, Jean
   Clawson, Hiram
   Cuff, James
   Di Palma, Federica
   Fitzgerald, Stephen
   Flicek, Paul
   Guttman, Mitchell
   Hubisz, Melissa J.
   Jaffe, David B.
   Jungreis, Irwin
   Kent, W. James
   Kostka, Dennis
   Lara, Marcia
   Martins, Andre L.
   Massingham, Tim
   Moltke, Ida
   Raney, Brian J.
   Rasmussen, Matthew D.
   Robinson, Jim
   Stark, Alexander
   Vilella, Albert J.
   Wen, Jiayu
   Xie, Xiaohui
   Zody, Michael C.
   Worley, Kim C.
   Kovar, Christie L.
   Muzny, Donna M.
   Gibbs, Richard A.
   Warren, Wesley C.
   Mardis, Elaine R.
   Weinstock, George M.
   Wilson, Richard K.
   Birney, Ewan
   Margulies, Elliott H.
   Herrero, Javier
   Green, Eric D.
   Haussler, David
   Siepel, Adam
   Goldman, Nick
   Pollard, Katherine S.
   Pedersen, Jakob S.
   Lander, Eric S.
   Kellis, Manolis
TI A high-resolution map of human evolutionary constraint using 29 mammals
SO NATURE
LA English
DT Article
ID reliable prediction; genome sequence; coding sequence; discovery; elements; reveals; gene; expression; selection; dynamics
AB The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
C1 [Lindblad-Toh, Kerstin; Garber, Manuel; Zuk, Or; Lin, Michael F.; Kheradpour, Pouya; Ernst, Jason; Mauceli, Evan; Ward, Lucas D.; Clamp, Michele; Gnerre, Sante; Alfoeldi, Jessica; Chang, Jean; Di Palma, Federica; Guttman, Mitchell; Jaffe, David B.; Lara, Marcia; Robinson, Jim; Xie, Xiaohui; Zody, Michael C.; Lander, Eric S.; Kellis, Manolis] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, SE-75123 Uppsala, Sweden.
   [Lin, Michael F.; Washietl, Stefan; Kheradpour, Pouya; Ernst, Jason; Ward, Lucas D.; Jungreis, Irwin; Rasmussen, Matthew D.; Kellis, Manolis] MIT Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Parker, Brian J.; Moltke, Ida; Wen, Jiayu; Pedersen, Jakob S.] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
   [Jordan, Gregory; Beal, Kathryn; Fitzgerald, Stephen; Flicek, Paul; Massingham, Tim; Vilella, Albert J.; Birney, Ewan; Herrero, Javier; Goldman, Nick] EMBL EBI, Hinxton CB10 1SD, England.
   [Lowe, Craig B.; Clawson, Hiram; Raney, Brian J.; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Lowe, Craig B.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Lowe, Craig B.; Haussler, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Holloway, Alisha K.; Kent, W. James; Kostka, Dennis; Pollard, Katherine S.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA.
   [Clamp, Michele] BioTeam Inc, Middleton, MA 01949 USA.
   [Cuff, James] Harvard Univ, Fac Arts & Sci, Div Sci, Cambridge, MA 02138 USA.
   [Hubisz, Melissa J.; Martins, Andre L.; Siepel, Adam] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [Stark, Alexander] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
   [Worley, Kim C.; Kovar, Christie L.; Muzny, Donna M.; Gibbs, Richard A.; Weinstock, George M.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Warren, Wesley C.; Mardis, Elaine R.; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Margulies, Elliott H.] NHGRI, Genome Informat Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Green, Eric D.] NHGRI, NISC Comparat Sequencing Program, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Green, Eric D.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94158 USA.
   [Pedersen, Jakob S.] Aarhus Univ Hosp, Dept Mol Med MOMA, DK-8200 Aarhus N, Denmark.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Uppsala University; Massachusetts Institute of Technology (MIT); University of Copenhagen; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of California System; University of California Santa Cruz; Stanford University; Howard Hughes Medical Institute; University of California System; University of California San Francisco; The J David Gladstone Institutes; Harvard University; Cornell University; Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); Baylor College of Medicine; Washington University (WUSTL); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of California System; University of California San Francisco; University of California System; University of California San Francisco; Aarhus University
RP Lindblad-Toh, K (corresponding author), Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM kersli@broadinstitute.org; lander@broadinstitute.org; manoli@mit.edu
FU National Human Genome Research Institute (NHGRI) [U54 HG003273]; National Institute for General Medicine (NIGMS) [GM82901]; European Science Foundation; NSF National Science Foundation (NSF) [0905968, 0644282]; NIH [R01 HG004037]; Sloan Foundation; Austrian Fonds zur Forderung der Wissenschaftlichen Forschung; Gates Cambridge Trust; Novo Nordisk Foundation; Department of Mathematical Sciences, University of Copenhagen; David and Lucile Packard Foundation; Danish Council for Independent Research Medical Sciences; Lundbeck Foundation; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF); Direct For Biological Sciences; Div Of Biological Infrastructure [0905968] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0846218, 0644282] Funding Source: National Science Foundation; Lundbeck Foundation [R5-2006-123] Funding Source: researchfish
NR 50
TC 833
Z9 1130
U1 1
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 476
EP 482
DI 10.1038/nature10530
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200035
PM 21993624
DA 2026-03-09
ER

PT J
AU Taoka, K
   Ohki, I
   Tsuji, H
   Furuita, K
   Hayashi, K
   Yanase, T
   Yamaguchi, M
   Nakashima, C
   Purwestri, YA
   Tamaki, S
   Ogaki, Y
   Shimada, C
   Nakagawa, A
   Kojima, C
   Shimamoto, K
AF Taoka, Ken-ichiro
   Ohki, Izuru
   Tsuji, Hiroyuki
   Furuita, Kyoko
   Hayashi, Kokoro
   Yanase, Tomoko
   Yamaguchi, Midori
   Nakashima, Chika
   Purwestri, Yekti Asih
   Tamaki, Shojiro
   Ogaki, Yuka
   Shimada, Chihiro
   Nakagawa, Atsushi
   Kojima, Chojiro
   Shimamoto, Ko
TI 14-3-3 proteins act as intracellular receptors for rice Hd3a florigen
SO NATURE
LA English
DT Article
ID structural basis; signals; system; growth; ft; crystallography; agrobacterium; regulator; reveals; vectors
AB 'Florigen' was proposed 75 years ago(1) to be synthesized in the leaf and transported to the shoot apex, where it induces flowering. Only recently have genetic and biochemical studies established that florigen is encoded by FLOWERING LOCUS T (FT), a gene that is universally conserved in higher plants(2-4). Nonetheless, the exact function of florigen during floral induction remains poorly understood and receptors for florigen have not been identified. Here we show that the rice FT homologue Hd3a(5) interacts with 14-3-3 proteins in the apical cells of shoots, yielding a complex that translocates to the nucleus and binds to the Oryza sativa (Os)FD1 transcription factor, a rice homologue of Arabidopsis thaliana FD. The resultant ternary 'florigen activation complex' (FAC) induces transcription of OsMADS15, a homologue of A. thaliana APETALA1 (AP1), which leads to flowering. We have determined the 2.4 angstrom crystal structure of rice FAC, which provides a mechanistic basis for florigen function in flowering. Our results indicate that 14-3-3 proteins act as intracellular receptors for florigen in shoot apical cells, and offer new approaches to manipulate flowering in various crops and trees.
C1 [Ohki, Izuru; Furuita, Kyoko; Hayashi, Kokoro; Kojima, Chojiro] Nara Inst Sci & Technol, Lab Biophys, Grad Sch Biol Sci, Nara 6300192, Japan.
   [Taoka, Ken-ichiro; Tsuji, Hiroyuki; Yanase, Tomoko; Yamaguchi, Midori; Nakashima, Chika; Purwestri, Yekti Asih; Tamaki, Shojiro; Ogaki, Yuka; Shimada, Chihiro; Shimamoto, Ko] Nara Inst Sci & Technol, Lab Plant Mol Genet, Grad Sch Biol Sci, Nara 6300192, Japan.
   [Nakagawa, Atsushi] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan.
C3 Nara Institute of Science & Technology; Nara Institute of Science & Technology; University of Osaka
RP Kojima, C (corresponding author), Nara Inst Sci & Technol, Lab Biophys, Grad Sch Biol Sci, 8916-5 Takayama, Nara 6300192, Japan.
EM kojima@protein.osaka-u.ac.jp; simamoto@bs.naist.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); Global COE Program at NAIST; Bio-oriented Research Advancement Institution (BRAIN)
NR 46
TC 619
Z9 724
U1 11
U2 324
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 332
EP U97
DI 10.1038/nature10272
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500038
PM 21804566
DA 2026-03-09
ER

PT J
AU Bivona, TG
   Hieronymus, H
   Parker, J
   Chang, K
   Taron, M
   Rosell, R
   Moonsamy, P
   Dahlman, K
   Miller, VA
   Costa, C
   Hannon, G
   Sawyers, CL
AF Bivona, Trever G.
   Hieronymus, Haley
   Parker, Joel
   Chang, Kenneth
   Taron, Miquel
   Rosell, Rafael
   Moonsamy, Philicia
   Dahlman, Kimberly
   Miller, Vincent A.
   Costa, Carlota
   Hannon, Gregory
   Sawyers, Charles L.
TI FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR
SO NATURE
LA English
DT Article
ID acquired-resistance; met amplification; erlotinib; mutations; kinase; cells; adenocarcinoma; inhibition; gefitinib; apoptosis
AB Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient(1,2). This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-kappa B pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-kappa B through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of I kappa B (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-kappa B enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-kappa B inhibitor I kappa B predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-kappa B as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.
C1 [Bivona, Trever G.; Hieronymus, Haley; Moonsamy, Philicia; Dahlman, Kimberly; Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Parker, Joel] Express Anal Inc, Durham, NC 27713 USA.
   [Chang, Kenneth; Hannon, Gregory] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Taron, Miquel; Rosell, Rafael; Costa, Carlota] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Barcelona 08916, Spain.
   [Taron, Miquel; Rosell, Rafael; Costa, Carlota] USP Dexeus Univ Inst, Barcelona 08028, Spain.
   [Hannon, Gregory; Sawyers, Charles L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Memorial Sloan Kettering Cancer Center; Cold Spring Harbor Laboratory; Hospital Germans Trias i Pujol; Institut Catala d'Oncologia; Howard Hughes Medical Institute
RP Sawyers, CL (corresponding author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA.
EM sawyersc@mskcc.org
FU Charles A. Dana Foundation; ASCO YIA; Caine Halter Lung Cancer Research Fund/Uniting Against Lung Cancer; National Cancer Institute [P01CA013106] Funding Source: NIH RePORTER
NR 23
TC 346
Z9 396
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 523
EP 526
DI 10.1038/nature09870
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200064
PM 21430781
DA 2026-03-09
ER

PT J
AU Tachiwana, H
   Kagawa, W
   Shiga, T
   Osakabe, A
   Miya, Y
   Saito, K
   Hayashi-Takanaka, Y
   Oda, T
   Sato, M
   Park, SY
   Kimura, H
   Kurumizaka, H
AF Tachiwana, Hiroaki
   Kagawa, Wataru
   Shiga, Tatsuya
   Osakabe, Akihisa
   Miya, Yuta
   Saito, Kengo
   Hayashi-Takanaka, Yoko
   Oda, Takashi
   Sato, Mamoru
   Park, Sam-Yong
   Kimura, Hiroshi
   Kurumizaka, Hitoshi
TI Crystal structure of the human centromeric nucleosome containing CENP-A
SO NATURE
LA English
DT Article
ID histone h3; protein; dna; features; variant; cse4
AB In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment(1,2). Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A(3-12). Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate alpha-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the alpha N helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome(13). A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.
C1 [Tachiwana, Hiroaki; Kagawa, Wataru; Shiga, Tatsuya; Osakabe, Akihisa; Miya, Yuta; Saito, Kengo; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, Tokyo 1628480, Japan.
   [Hayashi-Takanaka, Yoko; Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Oda, Takashi; Sato, Mamoru] Yokohama City Univ, Grad Sch Nanobiosci, Dept Supramol Biol, Div Macromol Crystallog, Yokohama, Kanagawa 2300045, Japan.
   [Park, Sam-Yong] Yokohama City Univ, Grad Sch Nanobiosci, Dept Supramol Biol, Prot Design Lab, Yokohama, Kanagawa 2300045, Japan.
C3 Waseda University; University of Osaka; Yokohama City University; Yokohama City University
RP Kurumizaka, H (corresponding author), Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM kurumizaka@waseda.jp
FU Japanese Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; Waseda Research Institute for Science and Engineering; Grants-in-Aid for Scientific Research [21370048, 23770008, 09J40035, 21113002, 09J04280, 20114001, 21570196] Funding Source: KAKEN
NR 40
TC 322
Z9 387
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 AUG 11
PY 2011
VL 476
IS 7359
BP 232
EP U135
DI 10.1038/nature10258
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900042
PM 21743476
DA 2026-03-09
ER

PT J
AU Konhauser, KO
   Lalonde, SV
   Planavsky, NJ
   Pecoits, E
   Lyons, TW
   Mojzsis, SJ
   Rouxel, OJ
   Barley, ME
   Rosìere, C
   Fralick, PW
   Kump, LR
   Bekker, A
AF Konhauser, Kurt O.
   Lalonde, Stefan V.
   Planavsky, Noah J.
   Pecoits, Ernesto
   Lyons, Timothy W.
   Mojzsis, Stephen J.
   Rouxel, Olivier J.
   Barley, Mark E.
   Rosiere, Carlos
   Fralick, Phillip W.
   Kump, Lee R.
   Bekker, Andrey
TI Aerobic bacterial pyrite oxidation and acid rock drainage during the Great Oxidation Event
SO NATURE
LA English
DT Article
ID banded iron-formations; atmospheric oxygen; hexavalent chromium; dissolved-oxygen; sulfur isotopes; geochemistry; rise; evolution; sediments; genesis
AB The enrichment of redox-sensitive trace metals in ancient marine sedimentary rocks has been used to determine the timing of the oxidation of the Earth's land surface(1,2). Chromium (Cr) is among the emerging proxies for tracking the effects of atmospheric oxygenation on continental weathering; this is because its supply to the oceans is dominated by terrestrial processes that can be recorded in the Cr isotope composition of Precambrian iron formations(3). However, the factors controlling past and present seawater Cr isotope composition are poorly understood. Here we provide an independent and complementary record of marine Cr supply, in the form of Cr concentrations and authigenic enrichment in iron-rich sedimentary rocks. Our data suggest that Cr was largely immobile on land until around 2.48 Gyr ago, but within the 160 Myr that followed-and synchronous with independent evidence for oxygenation associated with the Great Oxidation Event (see, for example, refs 4-6)-marked excursions in Cr content and Cr/Ti ratios indicate that Cr was solubilized at a scale unrivalled in history. As Cr isotope fractionations at that time were muted, Cr must have been mobilized predominantly in reduced, Cr(III), form. We demonstrate that only the oxidation of an abundant and previously stable crustal pyrite reservoir by aerobic-respiring, chemolithoautotrophic bacteria could have generated the degree of acidity required to solubilize Cr(III) from ultramafic source rocks and residual soils(7). This profound shift in weathering regimes beginning at 2.48 Gyr ago constitutes the earliest known geochemical evidence for acidophilic aerobes and the resulting acid rock drainage, and accounts for independent evidence of an increased supply of dissolved sulphate(8) and sulphide-hosted trace elements to the oceans around that time(1,9). Our model adds to amassing evidence that the Archaean-Palaeoproterozoic boundary was marked by a substantial shift in terrestrial geochemistry and biology.
C1 [Konhauser, Kurt O.; Lalonde, Stefan V.; Pecoits, Ernesto] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Lalonde, Stefan V.; Rouxel, Olivier J.] Univ Europeene Bretagne, Inst Univ Europeen Mer, F-29280 Plouzane, France.
   [Planavsky, Noah J.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Mojzsis, Stephen J.] Univ Colorado, Dept Geol Sci, Boulder, CO 80309 USA.
   [Rouxel, Olivier J.] IFREMER, Ctr Brest, F-29280 Plouzane, France.
   [Barley, Mark E.] Univ Western Australia, Sch Earth & Environm, Crawley, WA 6009, Australia.
   [Rosiere, Carlos] Univ Fed Minas Gerais, Inst Geociencias, BR-3127091 Belo Horizonte, MG, Brazil.
   [Fralick, Phillip W.] Lakehead Univ, Dept Geol, Thunder Bay, ON P7B 5E1, Canada.
   [Kump, Lee R.] Penn State Univ, Dept Geosci, University Pk, PA 16827 USA.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
C3 University of Alberta; Universite de Bretagne Occidentale; Institut Universitaire Europeen de la Mer (IUEM); University of California System; University of California Riverside; University of Colorado System; University of Colorado Boulder; Ifremer; University of Western Australia; Universidade Federal de Minas Gerais; Lakehead University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Manitoba
RP Konhauser, KO (corresponding author), Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
EM kurtk@ualberta.ca
FU Natural Sciences and Engineering Research Council of Canada; National Science Foundation Division of Earth Sciences; National Science Foundation; Agouron Institute; NASA; NASA's Astrobiology Institute; Australian Research Council; Conselho Nacional de Desenvolvimento Cientifico e Technologico; Directorate For Geosciences [0951998] Funding Source: National Science Foundation; Division Of Earth Sciences [0951998] Funding Source: National Science Foundation
NR 37
TC 285
Z9 321
U1 5
U2 299
PU 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 20
PY 2011
VL 478
IS 7369
BP 369
EP +
DI 10.1038/nature10511
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100042
PM 22012395
DA 2026-03-09
ER

PT J
AU Nakar, E
   Piran, T
AF Nakar, Ehud
   Piran, Tsvi
TI Detectable radio flares following gravitational waves from mergers of binary neutron stars
SO NATURE
LA English
DT Article
ID gamma-ray bursts; compact object mergers; nucleosynthesis; calorimetry; transients; supernovae; signatures; radiation; models
AB Mergers of neutron-star/neutron-star binaries are strong sources of gravitational waves(1-3). They can also launch subrelativistic and mildly relativistic outflows(4-8) and are often assumed to be the sources of short gamma-ray bursts(9). An electromagnetic signature that persisted for weeks to months after the event would strengthen any future claim of a detection of gravitational waves(10). Here we present results of calculations showing that the interaction of mildly relativistic outflows with the surrounding medium produces radio flares with peak emission at 1.4 gigahertz that persist at detectable (submillijansky) levels for weeks, out to a redshift of 0.1. Slower subrelativistic outflows produce flares detectable for years at 150 megahertz, as well as at 1.4 gigahertz, from slightly shorter distances. The radio transient RT 19870422 (ref. 11) has the properties predicted by our model, and its most probable origin is the merger of a compact neutron-star/neutron-star binary. The lack of radio detections usually associated with short gamma-ray bursts does not constrain the radio transients that we discuss here (from mildly relativistic and subrelativistic outflows) because short gamma-ray burst redshifts are typically >0.1 and the appropriate timescales (longer than weeks) have not been sampled.
C1 [Piran, Tsvi] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Nakar, Ehud] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
C3 Hebrew University of Jerusalem; Tel Aviv University
RP Piran, T (corresponding author), Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
EM udini@wise.tau.ac.il; tsvi@phys.huji.ac.il
FU ERC; Israeli Center for Excellence for High Energy Astrophysics; ISF [174/08]; IRG grant
NR 30
TC 335
Z9 378
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 82
EP 84
DI 10.1038/nature10365
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400038
PM 21964342
DA 2026-03-09
ER

PT J
AU Ressler, KJ
   Mercer, KB
   Bradley, B
   Jovanovic, T
   Mahan, A
   Kerley, K
   Norrholm, SD
   Kilaru, V
   Smith, AK
   Myers, AJ
   Ramirez, M
   Engel, A
   Hammack, SE
   Toufexis, D
   Braas, KM
   Binder, EB
   May, V
AF Ressler, Kerry J.
   Mercer, Kristina B.
   Bradley, Bekh
   Jovanovic, Tanja
   Mahan, Amy
   Kerley, Kimberly
   Norrholm, Seth D.
   Kilaru, Varun
   Smith, Alicia K.
   Myers, Amanda J.
   Ramirez, Manuel
   Engel, Anzhelika
   Hammack, Sayamwong E.
   Toufexis, Donna
   Braas, Karen M.
   Binder, Elisabeth B.
   May, Victor
TI Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor
SO NATURE
LA English
DT Article
ID cyclase-activating polypeptide; adenylate-cyclase; signal-transduction; brain-development; stria terminalis; gene-expression; fear inhibition; bed nucleus; amygdala; ptsd
AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.
C1 [Ressler, Kerry J.; Mercer, Kristina B.; Kerley, Kimberly] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Ressler, Kerry J.; Bradley, Bekh; Jovanovic, Tanja; Norrholm, Seth D.; Kilaru, Varun; Smith, Alicia K.; Binder, Elisabeth B.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
   [Bradley, Bekh; Norrholm, Seth D.] Atlanta VA Med Ctr, Atlanta, GA 30033 USA.
   [Ressler, Kerry J.; Mahan, Amy; Toufexis, Donna] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Myers, Amanda J.; Ramirez, Manuel; Engel, Anzhelika] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
   [Hammack, Sayamwong E.; Toufexis, Donna] Univ Vermont, Dept Psychol, Burlington, VT 05401 USA.
   [Braas, Karen M.; May, Victor] Univ Vermont, Coll Med, Dept Anat & Neurobiol, Burlington, VT 05401 USA.
   [Braas, Karen M.; May, Victor] Univ Vermont, Coll Med, Dept Pharmacol, Burlington, VT 05401 USA.
   [Binder, Elisabeth B.] Max Planck Inst Psychiat, D-80804 Munich, Germany.
C3 Howard Hughes Medical Institute; Emory University; US Department of Veterans Affairs; Veterans Health Administration (VHA); Atlanta VA Health Care System; Atlanta VA Medical Center; University of Miami; University of Vermont; University of Vermont; University of Vermont; Max Planck Society
RP Ressler, KJ (corresponding author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM kressle@emory.edu
FU NIH [MH071537, DA019624, HD27468]; Emory and Grady Memorial Hospital General Clinical Research Center; NIH National Centers for Research Resources [M01RR00039, P20RR16435]; American Foundation for Suicide Prevention; Burroughs Wellcome Fund; National Institute on Aging [AG034504]
NR 41
TC 625
Z9 744
U1 0
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 492
EP 497
DI 10.1038/nature09856
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900033
PM 21350482
DA 2026-03-09
ER

PT J
AU Cerling, TE
   Wynn, JG
   Andanje, SA
   Bird, MI
   Korir, DK
   Levin, NE
   Mace, W
   Macharia, AN
   Quade, J
   Remien, CH
AF Cerling, Thure E.
   Wynn, Jonathan G.
   Andanje, Samuel A.
   Bird, Michael I.
   Korir, David Kimutai
   Levin, Naomi E.
   Mace, William
   Macharia, Anthony N.
   Quade, Jay
   Remien, Christopher H.
TI Woody cover and hominin environments in the past 6 million years
SO NATURE
LA English
DT Article
ID human-evolution; ardipithecus-ramidus; climate-change; stable carbon; isotopic composition; turkana basin; east-africa; c-4 plants; vegetation; delta-c-13
AB The role of African savannahs in the evolution of early hominins has been debated for nearly a century. Resolution of this issue has been hindered by difficulty in quantifying the fraction of woody cover in the fossil record. Here we show that the fraction of woody cover in tropical ecosystems can be quantified using stable carbon isotopes in soils. Furthermore, we use fossil soils from hominin sites in the Awash and Omo-Turkana basins in eastern Africa to reconstruct the fraction of woody cover since the Late Miocene epoch (about 7 million years ago). C-13/C-12 ratio data from 1,300 palaeosols at or adjacent to hominin sites dating to at least 6 million years ago show that woody cover was predominantly less than similar to 40% at most sites. These data point to the prevalence of open environments at the majority of hominin fossil sites in eastern Africa over the past 6 million years.
C1 [Cerling, Thure E.; Mace, William; Macharia, Anthony N.; Remien, Christopher H.] Univ Utah, Salt Lake City, UT 84112 USA.
   [Wynn, Jonathan G.] Univ S Florida, Tampa, FL 33620 USA.
   [Andanje, Samuel A.; Korir, David Kimutai] Kenya Wildlife Serv, Nairobi, Kenya.
   [Bird, Michael I.] James Cook Univ, Cairns, Qld 4870, Australia.
   [Levin, Naomi E.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
   [Quade, Jay] Univ Arizona, Tucson, AZ 85721 USA.
C3 Utah System of Higher Education; University of Utah; State University System of Florida; University of South Florida; James Cook University; Johns Hopkins University; University of Arizona
RP Cerling, TE (corresponding author), Univ Utah, Salt Lake City, UT 84112 USA.
EM thure.cerling@utah.edu
FU LSB Leakey Foundation; NSF [BCS 0621542, EAR-0617010, EAR-0937819, BCS-0321893]
NR 50
TC 411
Z9 493
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 AUG 4
PY 2011
VL 476
IS 7358
BP 51
EP 56
DI 10.1038/nature10306
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300027
PM 21814275
DA 2026-03-09
ER

PT J
AU Autry, AE
   Adachi, M
   Nosyreva, E
   Na, ES
   Los, MF
   Cheng, PF
   Kavalali, ET
   Monteggia, LM
AF Autry, Anita E.
   Adachi, Megunai
   Nosyreva, Elena
   Na, Elisa S.
   Los, Maarten F.
   Cheng, Peng-fei
   Kavalali, Ege T.
   Monteggia, Lisa M.
TI NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
SO NATURE
LA English
DT Article
ID neurotrophic factor; protein-synthesis; presynaptic function; depression; ketamine; bdnf; neurotransmission; models; pharmacokinetics; antagonist
AB Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear(1-3). Depressed patients report the alleviation of major depressive disorder symptoms within two hours of a single, low-dose intravenous infusion of ketamine, with effects lasting up to two weeks(1-3), unlike traditional antidepressants (serotonin re-uptake inhibitors), which take weeks to reach efficacy. This delay is a major drawback to current therapies for major depressive disorder and faster-acting antidepressants are needed, particularly for suicide-risk patients'. The ability of ketamine to produce rapidly acting, long-lasting antidepressant responses in depressed patients provides a unique opportunity to investigate underlying cellular mechanisms. Here we show that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor. We find that the ketamine-mediated blockade of NMDAR at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase (also called CaMKIII), resulting in reduced eEF2 phosphorylation and de-suppression of translation of brain-derived neurotrophic factor. Furthermore, we find that inhibitors of eEF2 kinase induce fast-acting behavioural antidepressant-like effects. Our findings indicate that the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast-acting antidepressants.
C1 [Autry, Anita E.; Adachi, Megunai; Na, Elisa S.; Los, Maarten F.; Cheng, Peng-fei; Monteggia, Lisa M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
   [Nosyreva, Elena; Kavalali, Ege T.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Kavalali, ET (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM ege.kavalali@utsouthwestern.edu
FU UT Southwestern Medical Center;  [MH070727];  [MH066198];  [T32 MH 76690-02]; National Institute of Mental Health [R01MH066198, R01MH070727] Funding Source: NIH RePORTER
NR 33
TC 1562
Z9 1804
U1 4
U2 359
PU 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 7
PY 2011
VL 475
IS 7354
BP 91
EP U109
DI 10.1038/nature10130
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300051
PM 21677641
DA 2026-03-09
ER

PT J
AU Amblard, A
   Cooray, A
   Serra, P
   Altieri, B
   Arumugam, V
   Aussel, H
   Blain, A
   Bock, J
   Boselli, A
   Buat, V
   Castro-Rodríguez, N
   Cava, A
   Chanial, P
   Chapin, E
   Clements, DL
   Conley, A
   Conversi, L
   Dowell, CD
   Dwek, E
   Eales, S
   Elbaz, D
   Farrah, D
   Franceschini, A
   Gear, W
   Glenn, J
   Griffin, M
   Halpern, M
   Hatziminaoglou, E
   Ibar, E
   Isaak, K
   Ivison, RJ
   Khostovan, AA
   Lagache, G
   Levenson, L
   Lu, N
   Madden, S
   Maffei, B
   Mainetti, G
   Marchetti, L
   Marsden, G
   Mitchell-Wynne, K
   Nguyen, HT
   O'Halloran, B
   Oliver, SJ
   Omont, A
   Page, MJ
   Panuzzo, P
   Papageorgiou, A
   Pearson, CP
   Pérez-Fournon, I
   Pohlen, M
   Rangwala, N
   Roseboom, IG
   Rowan-Robinson, M
   Portal, MS
   Schulz, B
   Scott, D
   Seymour, N
   Shupe, DL
   Smith, AJ
   Stevens, JA
   Symeonidis, M
   Trichas, M
   Tugwell, K
   Vaccari, M
   Valiante, E
   Valtchanov, I
   Vieira, JD
   Vigroux, L
   Wang, L
   Ward, R
   Wright, G
   Xu, CK
   Zemcov, M
AF Amblard, Alexandre
   Cooray, Asantha
   Serra, Paolo
   Altieri, B.
   Arumugam, V.
   Aussel, H.
   Blain, A.
   Bock, J.
   Boselli, A.
   Buat, V.
   Castro-Rodriguez, N.
   Cava, A.
   Chanial, P.
   Chapin, E.
   Clements, D. L.
   Conley, A.
   Conversi, L.
   Dowell, C. D.
   Dwek, E.
   Eales, S.
   Elbaz, D.
   Farrah, D.
   Franceschini, A.
   Gear, W.
   Glenn, J.
   Griffin, M.
   Halpern, M.
   Hatziminaoglou, E.
   Ibar, E.
   Isaak, K.
   Ivison, R. J.
   Khostovan, A. A.
   Lagache, G.
   Levenson, L.
   Lu, N.
   Madden, S.
   Maffei, B.
   Mainetti, G.
   Marchetti, L.
   Marsden, G.
   Mitchell-Wynne, K.
   Nguyen, H. T.
   O'Halloran, B.
   Oliver, S. J.
   Omont, A.
   Page, M. J.
   Panuzzo, P.
   Papageorgiou, A.
   Pearson, C. P.
   Perez-Fournon, I.
   Pohlen, M.
   Rangwala, N.
   Roseboom, I. G.
   Rowan-Robinson, M.
   Sanchez Portal, M.
   Schulz, B.
   Scott, Douglas
   Seymour, N.
   Shupe, D. L.
   Smith, A. J.
   Stevens, J. A.
   Symeonidis, M.
   Trichas, M.
   Tugwell, K.
   Vaccari, M.
   Valiante, E.
   Valtchanov, I.
   Vieira, J. D.
   Vigroux, L.
   Wang, L.
   Ward, R.
   Wright, G.
   Xu, C. K.
   Zemcov, M.
TI Submillimetre galaxies reside in dark matter haloes with masses greater than 3 x 1011 solar masses
SO NATURE
LA English
DT Article
ID herschel-spire instrument; star-formation; number counts; hermes; redshift; spitzer; atlas; bias
AB The extragalactic background light at far-infrared wavelengths(1-3) comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year(4). These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes(5,6). Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations(7-10). A previous attempt(11) at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model(12). Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500 mu m. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M-min, such that log(10)[M-min/M-circle dot] = 11.5(-0.2)(+0.7) at 350 mu m, where M-circle dot is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe(13), and is lower than that predicted by semi-analytical models for galaxy formation(14).
C1 [Amblard, Alexandre; Cooray, Asantha; Serra, Paolo; Khostovan, A. A.; Mitchell-Wynne, K.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Altieri, B.; Conversi, L.; Sanchez Portal, M.; Valtchanov, I.] European Space Astron Ctr, Herschel Sci Ctr, Madrid 28691, Spain.
   [Arumugam, V.; Ivison, R. J.] Univ Edinburgh, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Aussel, H.; Elbaz, D.; Madden, S.; Panuzzo, P.] Univ Paris Diderot, CNRS, Lab AIM Paris Saclay, CEA DSM Irfu,CE Saclay, F-91191 Gif Sur Yvette, France.
   [Bock, J.; Dowell, C. D.; Levenson, L.; Nguyen, H. T.; Zemcov, M.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Boselli, A.; Buat, V.] Univ Aix Marseille, CNRS, OAMP, Lab Astrophys Marseille, F-13388 Marseille 13, France.
   [Castro-Rodriguez, N.; Cava, A.; Perez-Fournon, I.] Inst Astrofis Canarias, E-38200 San Cristobal la Laguna, Tenerife, Spain.
   [Castro-Rodriguez, N.; Cava, A.; Perez-Fournon, I.] Univ La Laguna, Dept Astrofis, E-38205 Tenerife, Spain.
   [Chanial, P.; Clements, D. L.; O'Halloran, B.; Rowan-Robinson, M.; Trichas, M.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, London SW7 2AZ, England.
   [Chapin, E.; Halpern, M.; Marsden, G.; Scott, Douglas; Valiante, E.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Conley, A.; Glenn, J.; Rangwala, N.] Univ Colorado, Dept Astrophys & Planetary Sci, CASA UCB 389, Boulder, CO 80309 USA.
   [Dwek, E.] NASA, Goddard Space Flight Ctr, Observat Cosmol Lab, Greenbelt, MD 20771 USA.
   [Eales, S.; Gear, W.; Griffin, M.; Isaak, K.; Papageorgiou, A.; Pohlen, M.] Cardiff Univ, Cardiff Sch Phys & Astron, Cardiff CF24 3AA, S Glam, Wales.
   [Farrah, D.; Oliver, S. J.; Roseboom, I. G.; Smith, A. J.; Wang, L.; Ward, R.] Univ Sussex, Dept Phys & Astron, Ctr Astron, Brighton BN1 9QH, E Sussex, England.
   [Franceschini, A.; Mainetti, G.; Marchetti, L.; Vaccari, M.] Univ Padua, Dipartimento Astron, I-35122 Padua, Italy.
   [Hatziminaoglou, E.] ESO, D-85748 Garching, Germany.
   [Ibar, E.; Ivison, R. J.; Wright, G.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Lagache, G.] Univ Paris 11, Inst Astrophys Spatiale, F-91405 Orsay, France.
   [Lagache, G.] CNRS, UMR 8617, F-91405 Orsay, France.
   [Lu, N.; Schulz, B.; Shupe, D. L.; Xu, C. K.] CALTECH, Jet Prop Lab, Infrared Proc & Anal Ctr, Pasadena, CA 91125 USA.
   [Maffei, B.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Omont, A.; Vigroux, L.] Univ Paris 06, CNRS, UMR7095, Inst Astrophys Paris, F-75014 Paris, France.
   [Page, M. J.; Pearson, C. P.; Seymour, N.; Symeonidis, M.] Rutherford Appleton Lab, Space Sci & Technol Dept, Didcot OX11 0QX, Oxon, England.
   [Tugwell, K.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Pearson, C. P.] Univ Lethbridge, Inst Space Imaging Sci, Lethbridge, AB T1K 3M4, Canada.
   [Stevens, J. A.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
C3 University of California System; University of California Irvine; European Space Agency; European Space Astronomy Center; University of Edinburgh; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite Paris Saclay; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Instituto de Astrofisica de Canarias; Universidad de la Laguna; Imperial College London; University of British Columbia; University of Colorado System; University of Colorado Boulder; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Cardiff University; University of Sussex; University of Padua; University of Edinburgh; Universite Paris Saclay; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of Manchester; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of London; University College London; University of Lethbridge; University of Hertfordshire
RP Cooray, A (corresponding author), Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
EM 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 [PP/E005306/1, ST/H00260X/1, ST/H001530/1, ST/F002858/1, ST/F007019/1, ST/I005765/1, ST/G002630/1] Funding Source: researchfish; UK Space Agency [ST/F012373/1, ST/G003874/1] Funding Source: researchfish; STFC [ST/H001530/1, ST/H00260X/1, PP/E005306/1, ST/F007019/1, ST/F002858/1, ST/I005765/1, ST/G002630/1] Funding Source: UKRI
NR 30
TC 100
Z9 109
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 510
EP 512
DI 10.1038/nature09771
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900036
PM 21326201
DA 2026-03-09
ER

PT J
AU Frankel, N
   Erezyilmaz, DF
   McGregor, AP
   Wang, S
   Payre, F
   Stern, DL
AF Frankel, Nicolas
   Erezyilmaz, Deniz F.
   McGregor, Alistair P.
   Wang, Shu
   Payre, Francois
   Stern, David L.
TI Morphological evolution caused by many subtle-effect substitutions in regulatory DNA
SO NATURE
LA English
DT Article
ID drosophila-sechellia; adaptive evolution; natural-selection; gene; perspective; divergence; underly; epistasis; sequence; origin
AB Morphology evolves often through changes in developmental genes, but the causal mutations, and their effects, remain largely unknown. The evolution of naked cuticle on larvae of Drosophila sechellia resulted from changes in five transcriptional enhancers of shavenbaby (svb), a transcript of the ovo locus that encodes a transcription factor that governs morphogenesis of microtrichiae, hereafter called 'trichomes'. Here we show that the function of one of these enhancers evolved through multiple single-nucleotide substitutions that altered both the timing and level of svb expression. The consequences of these nucleotide substitutions on larval morphology were quantified with a novel functional assay. We found that each substitution had a relatively small phenotypic effect, and that many nucleotide changes account for this large morphological difference. In addition, we observed that the substitutions had non-additive effects. These data provide unprecedented resolution of the phenotypic effects of substitutions and show how individual nucleotide changes in a transcriptional enhancer have caused morphological evolution.
C1 [Frankel, Nicolas; Erezyilmaz, Deniz F.; Wang, Shu; Stern, David L.] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
   [Frankel, Nicolas; Erezyilmaz, Deniz F.; Wang, Shu; Stern, David L.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [McGregor, Alistair P.] Vet Med Univ Wien, Inst Populat Genet, A-1210 Vienna, Austria.
   [Payre, Francois] Univ Toulouse, F-31062 Toulouse, France.
   [Payre, Francois] Ctr Dev Biol, Ctr Natl Rech Sci, UMR5547, F-31062 Toulouse, France.
C3 Princeton University; Howard Hughes Medical Institute; Princeton University; University of Veterinary Medicine Vienna; Universite de Toulouse; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Toulouse; Universite Toulouse III - Paul Sabatier
RP Stern, DL (corresponding author), Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
EM dstern@princeton.edu
FU Pew Charitable Trusts; Ruth L. Kirschstein National Research Service Award [F32 GM 83546-02]; Agence Nationale de la Recherche; NIH [GM063622-06A1]; NSF [IOS-0640339]
NR 44
TC 163
Z9 203
U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 598
EP 603
DI 10.1038/nature10200
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300030
PM 21720363
DA 2026-03-09
ER

PT J
AU Schreiner, PR
   Chernish, LV
   Gunchenko, PA
   Tikhonchuk, EY
   Hausmann, H
   Serafin, M
   Schlecht, S
   Dahl, JEP
   Carlson, RMK
   Fokin, AA
AF Schreiner, Peter R.
   Chernish, Lesya V.
   Gunchenko, Pavel A.
   Tikhonchuk, Evgeniya Yu.
   Hausmann, Heike
   Serafin, Michael
   Schlecht, Sabine
   Dahl, Jeremy E. P.
   Carlson, Robert M. K.
   Fokin, Andrey A.
TI Overcoming lability of extremely long alkane carbon-carbon bonds through dispersion forces
SO NATURE
LA English
DT Article
ID density-functional thermochemistry; van-der-waals; thermolabile hydrocarbons; hexaphenylethane; energy; chemistry; lengths; strain
AB Steric effects in chemistry are a consequence of the space required to accommodate the atoms and groups within a molecule, and are often thought to be dominated by repulsive forces arising from overlapping electron densities (Pauli repulsion). An appreciation of attractive interactions such as van der Waals forces (which include London dispersion forces) is necessary to understand chemical bonding and reactivity fully. This is evident from, for example, the strongly debated origin of the higher stability of branched alkanes relative to linear alkanes(1,2) and the possibility of constructing hydrocarbons with extraordinarily long C-C single bonds through steric crowding(3). Although empirical bond distance/bond strength relationships have been established for C-C bonds(4) (longer C-C bonds have smaller bond dissociation energies), these have no present theoretical basis(5). Nevertheless, these empirical considerations are fundamental to structural and energetic evaluations in chemistry(6,7), as summarized by Pauling(8) as early as 1960 and confirmed more recently(4). Here we report the preparation of hydrocarbons with extremely long C-C bonds (up to 1.704 angstrom), the longest such bonds observed so far in alkanes. The prepared compounds are unexpectedly stable-noticeable decomposition occurs only above 200 degrees C. We prepared the alkanes by coupling nanometre-sized, diamond-like, highly rigid structures known as diamondoids(9). The extraordinary stability of the coupling products is due to overall attractive dispersion interactions between the intramolecular H center dot center dot center dot H contact surfaces, as is evident from density functional theory computations with(10) and without inclusion of dispersion corrections.
C1 [Schreiner, Peter R.; Hausmann, Heike; Fokin, Andrey A.] Univ Giessen, Inst Organ Chem, D-35392 Giessen, Germany.
   [Chernish, Lesya V.; Gunchenko, Pavel A.; Tikhonchuk, Evgeniya Yu.; Fokin, Andrey A.] Kiev Polytech Inst, Dept Organ Chem, UA-03056 Kiev, Ukraine.
   [Serafin, Michael; Schlecht, Sabine] Univ Giessen, Inst Anorgan Chem, D-35392 Giessen, Germany.
   [Dahl, Jeremy E. P.; Carlson, Robert M. K.] Stanford Univ, Stanford Inst Mat & Energy Sci, Stanford, CA 94305 USA.
C3 Justus Liebig University Giessen; Ministry of Education & Science of Ukraine; Igor Sikorsky Kyiv Polytechnic Institute; Justus Liebig University Giessen; Stanford University
RP Schreiner, PR (corresponding author), Univ Giessen, Inst Organ Chem, Heinrich Buff Ring 58, D-35392 Giessen, Germany.
EM prs@org.chemie.uni-giessen.de; aaf@xtf.ntu-kpi.kiev.ua
FU Deutsche Forschungsgemeinschaft; National Science Foundation of the USA; Department of Energy, Office of Basic Energy Sciences, Division of Materials Science and Engineering [DE-AC02-76SF00515]; Ministry of Science and Education of Ukraine; Ukrainian State Basic Research Fund
NR 38
TC 366
Z9 409
U1 0
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 308
EP U73
DI 10.1038/nature10367
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400026
PM 21921913
DA 2026-03-09
ER

PT J
AU Harismendy, O
   Notani, D
   Song, XY
   Rahim, NG
   Tanasa, B
   Heintzman, N
   Ren, B
   Fu, XD
   Topol, EJ
   Rosenfeld, MG
   Frazer, KA
AF Harismendy, Olivier
   Notani, Dimple
   Song, Xiaoyuan
   Rahim, Nazli G.
   Tanasa, Bogdan
   Heintzman, Nathaniel
   Ren, Bing
   Fu, Xiang-Dong
   Topol, Eric J.
   Rosenfeld, Michael G.
   Frazer, Kelly A.
TI 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response
SO NATURE
LA English
DT Article
ID genome-wide association; negative regulator; rapid evolution; noncoding rna; protein ctcf; locus; susceptibility; sequence; project; anril
AB Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the 9p21 gene desert associated with coronary artery disease (CAD)(1-4) and type 2 diabetes(5-7). Despite evidence for a role of the associated interval in neighbouring gene regulation(8-10), the biological underpinnings of these genetic associations with CAD or type 2 diabetes have not yet been explained. Here we identify 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and six times denser than the whole genome (P < 6.55 x 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1. Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD non-risk haplotype, binding of STAT1 inhibits CDKN2BAS (also known as CDKN2B-AS1) expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, we find that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus, the MTAP gene and an interval downstream of IFNA21. In human vascular endothelial cells, interferon-c activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1-binding, long-range enhancer interactions and altered expression of neighbouring genes. Our findings establish a link between CAD genetic susceptibility and the response to inflammatory signalling in a vascular cell type and thus demonstrate the utility of genome-wide association study findings in directing studies to novel genomic loci and biological processes important for disease aetiology.
C1 [Rahim, Nazli G.; Topol, Eric J.] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA.
   [Harismendy, Olivier; Frazer, Kelly A.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA.
   [Harismendy, Olivier; Frazer, Kelly A.] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA.
   [Harismendy, Olivier; Frazer, Kelly A.] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA.
   [Notani, Dimple; Song, Xiaoyuan; Tanasa, Bogdan; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA.
   [Tanasa, Bogdan] Scripps Res Inst, Kellogg Sch Sci & Technol, La Jolla, CA 92037 USA.
   [Heintzman, Nathaniel; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Fu, Xiang-Dong] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Frazer, Kelly A.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
C3 Scripps Research Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; Scripps Research Institute; University of California System; University of California San Diego; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Topol, EJ (corresponding author), Scripps Res Inst, Scripps Translat Sci Inst, 3344 N Torrey Pines Court, La Jolla, CA 92037 USA.
EM etopol@scripps.edu; mrosenfeld@ucsd.edu; kafrazer@ucsd.edu
FU National Center for Research Resources [1U54RR025204, 1UL1RR025774, 1UL1RR031980-01]; National Institutes of Health [HL065445, DK39949, DK018477, DK074868, L65445, CA97134, DK74686, NS34934, 1R21CA152613-01]; Department of Defence [BC075019]; Prostate Cancer Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK039949] Funding Source: NIH RePORTER; National Institute on Aging [P01AG025204] Funding Source: NIH RePORTER
NR 45
TC 504
Z9 609
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 FEB 10
PY 2011
VL 470
IS 7333
BP 264
EP +
DI 10.1038/nature09753
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200045
PM 21307941
DA 2026-03-09
ER

PT J
AU Paterson, JR
   García-Bellido, DC
   Lee, MSY
   Brock, GA
   Jago, JB
   Edgecombe, GD
AF Paterson, John R.
   Garcia-Bellido, Diego C.
   Lee, Michael S. Y.
   Brock, Glenn A.
   Jago, James B.
   Edgecombe, Gregory D.
TI Acute vision in the giant Cambrian predator Anomalocaris and the origin of compound eyes
SO NATURE
LA English
DT Article
ID bay shale lagerstatte; burgess shale; south-australia; arthropod; evolution; animals; china; biota
AB Until recently(1), intricate details of the optical design of non-biomineralized arthropod eyes remained elusive in Cambrian Burgess-Shale-type deposits, despite exceptional preservation of soft-part anatomy in such Konservat-Lagerstatten(2,3). The structure and development of ommatidia in arthropod compound eyes support a single origin some time before the latest common ancestor of crown-group arthropods(4), but the appearance of compound eyes in the arthropod stem group has been poorly constrained in the absence of adequate fossils. Here we report 2-3-cm paired eyes from the early Cambrian (approximately 515 million years old) Emu Bay Shale of South Australia, assigned to the Cambrian apex predator Anomalocaris. Their preserved visual surfaces are composed of at least 16,000 hexagonally packed ommatidial lenses (in a single eye), rivalling the most acute compound eyes in modern arthropods. The specimens show two distinct taphonomic modes, preserved as iron oxide (after pyrite) and calcium phosphate, demonstrating that disparate styles of early diagenetic mineralization can replicate the same type of extracellular tissue (that is, cuticle) within a single Burgess-Shale-type deposit. These fossils also provide compelling evidence for the arthropod affinities of anomalocaridids, push the origin of compound eyes deeper down the arthropod stem lineage, and indicate that the compound eye evolved before such features as a hardened exoskeleton. The inferred acuity of the anomalocaridid eye is consistent with other evidence that these animals were highly mobile visual predators in the water column(5,6). The existence of large, macrophagous nektonic predators possessing sharp vision-such as Anomalocaris-within the early Cambrian ecosystem probably helped to accelerate the escalatory 'arms race' that began over half a billion years ago(7,8).
C1 [Paterson, John R.] Univ New England, Sch Environm & Rural Sci, Div Earth Sci, Armidale, NSW 2351, Australia.
   [Garcia-Bellido, Diego C.] Inst Geociencias CSIC UCM, Dept Geol Sedimentaria & Cambio Ambiental, Madrid 28040, Spain.
   [Lee, Michael S. Y.; Jago, James B.] S Australian Museum, Adelaide, SA 5000, Australia.
   [Lee, Michael S. Y.] Univ Adelaide, Sch Earth & Environm Sci, Adelaide, SA 5005, Australia.
   [Brock, Glenn A.] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
   [Jago, James B.] Univ S Australia, Sch Nat & Built Environm, Mawson Lakes, SA 5095, Australia.
   [Edgecombe, Gregory D.] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England.
C3 University of New England; Complutense University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UCM - Instituto de Geociencias (IGEO); Adelaide University; University of Adelaide; Macquarie University; Adelaide University; University of South Australia; Natural History Museum London
RP Paterson, JR (corresponding author), Univ New England, Sch Environm & Rural Sci, Div Earth Sci, Armidale, NSW 2351, Australia.
EM jpater20@une.edu.au
FU Australian Research Council [LP0774959]; South Australian Museum; University of Adelaide; MICINN-Spanish Ministry of Science [RYC2007-00090, CGL2009-07073]; Beach Energy; Sealink Pty Ltd
NR 30
TC 148
Z9 162
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 DEC 8
PY 2011
VL 480
IS 7376
BP 237
EP 240
DI 10.1038/nature10689
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200050
PM 22158247
DA 2026-03-09
ER

PT J
AU O'Doherty, JE
   Lebedev, MA
   Ifft, PJ
   Zhuang, KZ
   Shokur, S
   Bleuler, H
   Nicolelis, MAL
AF O'Doherty, Joseph E.
   Lebedev, Mikhail A.
   Ifft, Peter J.
   Zhuang, Katie Z.
   Shokur, Solaiman
   Bleuler, Hannes
   Nicolelis, Miguel A. L.
TI Active tactile exploration using a brain-machine-brain interface
SO NATURE
LA English
DT Article
ID cortical control; cortex; arm; neurons; stimulation; grip; skin
AB Brain-machine interfaces(1,2) use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses.
C1 [O'Doherty, Joseph E.; Ifft, Peter J.; Zhuang, Katie Z.; Nicolelis, Miguel A. L.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
   [O'Doherty, Joseph E.; Lebedev, Mikhail A.; Ifft, Peter J.; Zhuang, Katie Z.; Nicolelis, Miguel A. L.] Duke Univ, Ctr Neuroengn, Durham, NC 27710 USA.
   [Lebedev, Mikhail A.; Nicolelis, Miguel A. L.] Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
   [Shokur, Solaiman; Bleuler, Hannes] Ecole Polytech Fed Lausanne, STIIMT, CH-1015 Lausanne, Switzerland.
   [Nicolelis, Miguel A. L.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA.
   [Nicolelis, Miguel A. L.] Edmond & Lily Safra Int Inst Neurosci Natal, BR-59066060 Natal, RN, Brazil.
C3 Duke University; Duke University; Duke University; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Duke University
RP Nicolelis, MAL (corresponding author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
EM nicoleli@neuro.duke.edu
FU DARPA [N66001-06-C-2019]; TATRC [W81XWH-08-2-0119]; NIH [NS073125, DP1OD006798]; NICHD/OD [RC1HD063390]
NR 30
TC 451
Z9 562
U1 8
U2 328
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 228
EP U106
DI 10.1038/nature10489
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800042
PM 21976021
DA 2026-03-09
ER

PT J
AU Willbold, M
   Elliott, T
   Moorbath, S
AF Willbold, Matthias
   Elliott, Tim
   Moorbath, Stephen
TI The tungsten isotopic composition of the Earth's mantle before the terminal bombardment
SO NATURE
LA English
DT Article
ID ionization mass-spectrometry; core formation; siderophile elements; chromium isotopes; differentiation; terrestrial; rocks; accretion; fractionation; constraints
AB Many precious, 'iron-loving' metals, such as gold, are surprisingly abundant in the accessible parts of the Earth, given the efficiency with which core formation should have removed them to the planet's deep interior(1). One explanation of their over-abundance is a 'late veneer'-a flux of meteorites added to the Earth after core formation as a 'terminal' bombardment that culminated in the cratering of the Moon(2). Some 3.8 billion-year-old rocks from Isua, Greenland, are derived from sources that retain an isotopic memory of events pre-dating this cataclysmic meteorite shower(3,4). These Isua samples thus provide a window on the composition of the Earth before such a late veneer and allow a direct test of its importance in modifying the composition of the planet. Using high-precision (less than 6 parts per million, 2 standard deviations) tungsten isotope analyses of these rocks, here we show that they have a isotopic tungsten ratio W-182/W-184 that is significantly higher (about 13 parts per million) than modern terrestrial samples. This finding is in good agreement with the expected influence of a late veneer. We also show that alternative interpretations, such as partial remixing of a deep-mantle reservoir formed in the Hadean eon(5,6) (more than four billion years ago) or core-mantle interaction(7), do not explain the W isotope data well. The decrease in mantle W-182/W-184 occurs during the Archean eon (about four to three billion years ago), potentially on the same timescale as a notable decrease in Nd-142/Nd-144 (refs 3 and 6). We speculate that both observations can be explained if late meteorite bombardment triggered the onset of the current style of mantle convection.
C1 [Willbold, Matthias; Elliott, Tim] Univ Bristol, Sch Earth Sci, Bristol Isotope Grp, Bristol BS8 1RJ, Avon, England.
   [Moorbath, Stephen] Univ Oxford, Dept Earth Sci, Oxford OX1 3AN, England.
C3 University of Bristol; University of Oxford
RP Willbold, M (corresponding author), Univ Bristol, Sch Earth Sci, Bristol Isotope Grp, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM m.willbold@bristol.ac.uk
FU NERC [NE/DO12805/1, NE/H011927/1]; STFC [ST/F002734/1]; DFG [WI 3579/1-1]; Natural Environment Research Council [NE/D012805/1, NE/H011927/1] Funding Source: researchfish; Science and Technology Facilities Council [ST/F002734/1] Funding Source: researchfish; NERC [NE/H011927/1, NE/D012805/1] Funding Source: UKRI; STFC [ST/F002734/1] Funding Source: UKRI
NR 35
TC 241
Z9 261
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 195
EP U91
DI 10.1038/nature10399
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900032
PM 21901010
DA 2026-03-09
ER

PT J
AU Blumhagen, F
   Zhu, PX
   Shum, J
   Schärer, YPZ
   Yaksi, E
   Deisseroth, K
   Friedrich, RW
AF Blumhagen, Francisca
   Zhu, Peixin
   Shum, Jennifer
   Schaerer, Yan-Ping Zhang
   Yaksi, Emre
   Deisseroth, Karl
   Friedrich, Rainer W.
TI Neuronal filtering of multiplexed odour representations
SO NATURE
LA English
DT Article
ID olfactory-bulb; coincidence detection; transient dynamics; zebrafish; oscillations; circuits; cortex; information; inhibition; synchrony
AB Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons ( mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes.
C1 [Blumhagen, Francisca; Zhu, Peixin; Shum, Jennifer; Schaerer, Yan-Ping Zhang; Friedrich, Rainer W.] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Yaksi, Emre] Neuroelect Res Flanders, B-3001 Louvain, Belgium.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Friedrich, Rainer W.] Univ Basel, CH-4003 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research; Stanford University; University of Basel
RP Friedrich, RW (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM Rainer.Friedrich@fmi.ch
FU Novartis Research Foundation; Max-Planck-Society; Swiss National Fonds (SNF); Deutsche Forschungsgemeinschaft (DFG); Human Frontier Science Program (HFSP); Whitaker Foundation
NR 53
TC 79
Z9 85
U1 0
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 493
EP U215
DI 10.1038/nature10633
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600042
PM 22080956
DA 2026-03-09
ER

PT J
AU Yu, M
   Wang, CB
   Kyle, AF
   Jakubec, P
   Dixon, DJ
   Schrock, RR
   Hoveyda, AH
AF Yu, Miao
   Wang, Chenbo
   Kyle, Andrew F.
   Jakubec, Pavol
   Dixon, Darren J.
   Schrock, Richard R.
   Hoveyda, Amir H.
TI Synthesis of macrocyclic natural products by catalyst-controlled stereoselective ring-closing metathesis
SO NATURE
LA English
DT Article
ID microtubule-stabilizing agents; alkyne metathesis; epothilone-a; molybdenum; efficient; nakadomarin; complexes; analogs
AB Many natural products contain a C=C double bond through which various other derivatives can be prepared; the stereochemical identity of the alkene can be critical to the biological activities of such molecules. Catalytic ring-closing metathesis (RCM) is a widely used method for the synthesis of large unsaturated rings(1,2); however, cyclizations often proceed without control of alkene stereochemistry(2). This shortcoming is particularly costly when the cyclization reaction is performed after a long sequence of other chemical transformations(2). Here we outline a reliable, practical and general approach for the efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% of the Z isomer owing to control induced by a tungsten-based alkylidene. Utility is demonstrated through the stereoselective preparation of epothilone C (refs 3-5) and nakadomarin A (ref. 6), the previously reported syntheses of which have been marred by late-stage, non-selective RCM(7-12). The tungsten alkylidene can be manipulated in air, delivering the products in useful yields with high stereoselectivity. As a result of efficient RCM and re-incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways, even under relatively high substrate concentration.
C1 [Yu, Miao; Wang, Chenbo; Hoveyda, Amir H.] Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
   [Kyle, Andrew F.; Jakubec, Pavol; Dixon, Darren J.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
   [Schrock, Richard R.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Boston College; University of Oxford; Massachusetts Institute of Technology (MIT)
RP Hoveyda, AH (corresponding author), Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU United States National Institutes of Health, Institute of General Medical Sciences [GM-59426]; EPSRC-GlaxoSmithKline; EPSRC; EPSRC [EP/G007802/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G007802/1] Funding Source: researchfish
NR 30
TC 175
Z9 224
U1 3
U2 137
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 88
EP 93
DI 10.1038/nature10563
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600037
PM 22051677
DA 2026-03-09
ER

PT J
AU Fabbiano, G
   Wang, JF
   Elvis, M
   Risaliti, G
AF Fabbiano, G.
   Wang, Junfeng
   Elvis, M.
   Risaliti, G.
TI A close nuclear black-hole pair in the spiral galaxy NGC 3393
SO NATURE
LA English
DT Article
ID active galactic nuclei; x-ray source; system; reflection; discovery; binary; ngc-3393; suzaku
AB The current picture of galaxy evolution(1) advocates co-evolution of galaxies and their nuclear massive black holes, through accretion and galactic merging. Pairs of quasars, each with a massive black hole at the centre of its galaxy, have separations of 6,000 to 300,000 light years (refs 2 and 3; 1 parsec = 3.26 light years) and exemplify the first stages of this gravitational interaction. The final stages of the black-hole merging process, through binary black holes and final collapse into a single black hole with gravitational wave emission, are consistent with the sub-light-year separation inferred from the optical spectra(4) and light-variability(5) of two such quasars. The double active nuclei of a few nearby galaxies with disrupted morphology and intense star formation (such as NGC 6240 with a separation(6) of about 2,600 light years and Mrk 463 with a separation(7) of about 13,000 light years between the nuclei) demonstrate the importance of major mergers of equal-mass spiral galaxies in this evolution; such mergers lead to an elliptical galaxy(8), as in the case of the double-radio-nucleus elliptical galaxy 0402+379 (with a separation of about 24 light years between the nuclei)(9). Minor mergers of a spiral galaxy with a smaller companion should be a more common occurrence, evolving into spiral galaxies with active massive black-hole pairs(10), but have hitherto not been seen. Here we report the presence of two active massive black holes, separated by about 490 light years, in the Seyfert(11) galaxy NGC 3393 (50 Mpc, about 160 million light years). The regular spiral morphology and predominantly old circum-nuclear stellar population(12) of this galaxy, and the closeness of the black holes embedded in the bulge, provide a hitherto missing observational point to the study of galaxy/black hole evolution. Comparison of our observations with current theoretical models of mergers suggests that they are the result of minor merger evolution(10).
C1 [Fabbiano, G.; Wang, Junfeng; Elvis, M.; Risaliti, G.] Harvard Smithsonian Ctr Astrophys CfA, Cambridge, MA 02138 USA.
   [Risaliti, G.] INAF Arcetri, I-50125 Florence, Italy.
C3 Harvard University; Smithsonian Institution; Istituto Nazionale Astrofisica (INAF)
RP Fabbiano, G (corresponding author), Harvard Smithsonian Ctr Astrophys CfA, 60 Garden St, Cambridge, MA 02138 USA.
EM gfabbiano@cfa.harvard.edu
FU NASA
NR 30
TC 89
Z9 100
U1 0
U2 4
PU 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 22
PY 2011
VL 477
IS 7365
BP 431
EP 434
DI 10.1038/nature10364
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500033
PM 21881560
DA 2026-03-09
ER

PT J
AU Ko, H
   Hofer, SB
   Pichler, B
   Buchanan, KA
   Sjöström, PJ
   Mrsic-Flogel, TD
AF Ko, Ho
   Hofer, Sonja B.
   Pichler, Bruno
   Buchanan, Katherine A.
   Sjoestroem, P. Jesper
   Mrsic-Flogel, Thomas D.
TI Functional specificity of local synaptic connections in neocortical networks
SO NATURE
LA English
DT Article
ID primary visual-cortex; in-vivo; horizontal connections; intracortical circuits; neuronal networks; cortical networks; striate cortex; simple cells; cat; inhibition
AB Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli(1-4). But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.
C1 [Ko, Ho; Hofer, Sonja B.; Pichler, Bruno; Buchanan, Katherine A.; Sjoestroem, P. Jesper; Mrsic-Flogel, Thomas D.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England.
C3 University of London; University College London
RP Mrsic-Flogel, TD (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, 21 Univ St, London WC1E 6DE, England.
EM t.mrsic-flogel@ucl.ac.uk
FU Wellcome Trust; European Research Council; European Molecular Biology Organisation; Medical Research Council [243914]; Overseas Research Students Award; UCL; Medical Research Council [G0700188] Funding Source: researchfish; MRC [G0700188] Funding Source: UKRI
NR 38
TC 619
Z9 753
U1 3
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 87
EP U100
DI 10.1038/nature09880
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300036
PM 21478872
DA 2026-03-09
ER

PT J
AU Geballe, TR
   Najarro, F
   Figer, DF
   Schlegelmilch, BW
   de la Fuente, D
AF Geballe, T. R.
   Najarro, F.
   Figer, D. F.
   Schlegelmilch, B. W.
   de la Fuente, D.
TI Infrared diffuse interstellar bands in the Galactic Centre region
SO NATURE
LA English
DT Article
ID field stars; clouds; spectroscopy; quintuplet; features; h-3(+); dust
AB The spectrum of any star viewed through a sufficient quantity of diffuse interstellar material reveals a number of absorption features collectively called 'diffuse interstellar bands' (DIBs). The first DIBs were reported about 90 years ago(1), and currently well over 500 are known(2). None of them has been convincingly identified with any specific element or molecule, although recent studies suggest that the DIB carriers are polyatomic molecules containing carbon(3-5). Most of the DIBs currently known are at visible and very near-infrared wavelengths, with only two previously known at wavelengths beyond one micrometre (10,000 angstroms), the longer of which is at 1.318 micrometres (ref. 6). Here we report 13 diffuse interstellar bands in the 1.5-1.8 micrometre interval on high-extinction sightlines towards stars in the Galactic Centre. We argue that they originate almost entirely in the Galactic Centre region, a considerably warmer and harsher environment than where DIBs have been observed previously. The relative strengths of these DIBs towards the Galactic Centre and the Cygnus OB2 diffuse cloud are consistent with their strengths scaling mainly with the extinction by diffuse material.
C1 [Geballe, T. R.] Gemini Observ, Hilo, HI 96720 USA.
   [Najarro, F.; de la Fuente, D.] Ctr Astrobiol CSIC INTA, Torrejon De Ardoz 28850, Spain.
   [Figer, D. F.] Rochester Inst Technol, Ctr Detectors, Rochester, NY 14623 USA.
   [Schlegelmilch, B. W.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Rochester Institute of Technology; University of California System; University of California Los Angeles
RP Geballe, TR (corresponding author), Gemini Observ, 670 N Aohoku Pl, Hilo, HI 96720 USA.
EM tgeballe@gemini.edu
FU Spanish Ministerio de Ciencia e Innovacion
NR 20
TC 77
Z9 79
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 NOV 10
PY 2011
VL 479
IS 7372
BP 200
EP 202
DI 10.1038/nature10527
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800035
PM 22048316
DA 2026-03-09
ER

PT J
AU Kim, EB
   Fang, XD
   Fushan, AA
   Huang, ZY
   Lobanov, AV
   Han, LJ
   Marino, SM
   Sun, XQ
   Turanov, AA
   Yang, PC
   Yim, SH
   Zhao, X
   Kasaikina, MV
   Stoletzki, N
   Peng, CF
   Polak, P
   Xiong, ZQ
   Kiezun, A
   Zhu, YB
   Chen, YX
   Kryukov, GV
   Zhang, Q
   Peshkin, L
   Yang, L
   Bronson, RT
   Buffenstein, R
   Wang, B
   Han, CL
   Li, QY
   Chen, L
   Zhao, W
   Sunyaev, SR
   Park, TJ
   Zhang, GJ
   Wang, J
   Gladyshev, VN
AF Kim, Eun Bae
   Fang, Xiaodong
   Fushan, Alexey A.
   Huang, Zhiyong
   Lobanov, Alexei V.
   Han, Lijuan
   Marino, Stefano M.
   Sun, Xiaoqing
   Turanov, Anton A.
   Yang, Pengcheng
   Yim, Sun Hee
   Zhao, Xiang
   Kasaikina, Marina V.
   Stoletzki, Nina
   Peng, Chunfang
   Polak, Paz
   Xiong, Zhiqiang
   Kiezun, Adam
   Zhu, Yabing
   Chen, Yuanxin
   Kryukov, Gregory V.
   Zhang, Qiang
   Peshkin, Leonid
   Yang, Lan
   Bronson, Roderick T.
   Buffenstein, Rochelle
   Wang, Bo
   Han, Changlei
   Li, Qiye
   Chen, Li
   Zhao, Wei
   Sunyaev, Shamil R.
   Park, Thomas J.
   Zhang, Guojie
   Wang, Jun
   Gladyshev, Vadim N.
TI Genome sequencing reveals insights into physiology and longevity of the naked mole rat
SO NATURE
LA English
DT Article
ID longest-living rodent; heterocephalus-glaber; resistance; fossorial; protein-1; cells
AB The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal(1). Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death(2). In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis(3,4). Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress(5), the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination(6). Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates(7). They also live in full darkness, at low oxygen and high carbon dioxide concentrations(8), and are unable to sustain thermogenesis(9) nor feel certain types of pain(10,11). Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
C1 [Fang, Xiaodong; Huang, Zhiyong; Han, Lijuan; Sun, Xiaoqing; Yang, Pengcheng; Zhao, Xiang; Peng, Chunfang; Xiong, Zhiqiang; Zhu, Yabing; Chen, Yuanxin; Zhang, Qiang; Yang, Lan; Wang, Bo; Han, Changlei; Li, Qiye; Chen, Li; Zhao, Wei; Zhang, Guojie; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Kim, Eun Bae; Fushan, Alexey A.; Gladyshev, Vadim N.] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea.
   [Lobanov, Alexei V.; Marino, Stefano M.; Turanov, Anton A.; Yim, Sun Hee; Kasaikina, Marina V.; Stoletzki, Nina; Polak, Paz; Kiezun, Adam; Kryukov, Gregory V.; Sunyaev, Shamil R.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA.
   [Kryukov, Gregory V.; Sunyaev, Shamil R.; Gladyshev, Vadim N.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Peshkin, Leonid] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Bronson, Roderick T.] Harvard Univ, Sch Med, Rodent Histopathol Lab, Boston, MA 02115 USA.
   [Buffenstein, Rochelle] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA.
   [Buffenstein, Rochelle] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
   [Park, Thomas J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA.
   [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen N, Denmark.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen N, Denmark.
C3 Beijing Genomics Institute (BGI); Ewha Womans University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Novo Nordisk Foundation; University of Copenhagen; University of Copenhagen
RP Zhang, GJ (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM zhanggj@genomics.org.cn; wangj@genomics.org.cn; vgladyshev@rics.bwh.harvard.edu
FU WCU [R31-2008-000-10010-0]; NIH [AG038004, AG021518, CA080946]; Shenzhen Municipal Government [ZYC200903240077A]; National Natural Science Foundation of China [30725008]; National Science Foundation [0744979]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0744979] Funding Source: National Science Foundation
NR 29
TC 452
Z9 537
U1 5
U2 416
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 223
EP 227
DI 10.1038/nature10533
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800041
PM 21993625
DA 2026-03-09
ER

PT J
AU Wertz, IE
   Kusam, S
   Lam, C
   Okamoto, T
   Sandoval, W
   Anderson, DJ
   Helgason, E
   Ernst, JA
   Eby, M
   Liu, JF
   Belmont, LD
   Kaminker, JS
   O'Rourke, KM
   Pujara, K
   Kohli, PB
   Johnson, AR
   Chiu, ML
   Lill, JR
   Jackson, PK
   Fairbrother, WJ
   Seshagiri, S
   Ludlam, MJC
   Leong, KG
   Dueber, EC
   Maecker, H
   Huang, DCS
   Dixit, VM
AF Wertz, Ingrid E.
   Kusam, Saritha
   Lam, Cynthia
   Okamoto, Toru
   Sandoval, Wendy
   Anderson, Daniel J.
   Helgason, Elizabeth
   Ernst, James A.
   Eby, Mike
   Liu, Jinfeng
   Belmont, Lisa D.
   Kaminker, Josh S.
   O'Rourke, Karen M.
   Pujara, Kanan
   Kohli, Pawan Bir
   Johnson, Adam R.
   Chiu, Mark L.
   Lill, Jennie R.
   Jackson, Peter K.
   Fairbrother, Wayne J.
   Seshagiri, Somasekar
   Ludlam, Mary J. C.
   Leong, Kevin G.
   Dueber, Erin C.
   Maecker, Heather
   Huang, David C. S.
   Dixit, Vishva M.
TI Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
SO NATURE
LA English
DT Article
ID ubiquitin ligase; mitotic exit; cancer; cells; apoptosis; resistance; catalyzes; proteins; division
AB Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics(1). Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas(1). These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms(2). The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear(2). Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.
C1 [Wertz, Ingrid E.; Kusam, Saritha; Lam, Cynthia; Helgason, Elizabeth; Ernst, James A.; Fairbrother, Wayne J.; Dueber, Erin C.] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA.
   [Okamoto, Toru; Huang, David C. S.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Sandoval, Wendy; Ernst, James A.; Lill, Jennie R.] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Anderson, Daniel J.; Eby, Mike; Belmont, Lisa D.; Jackson, Peter K.; Ludlam, Mary J. C.; Leong, Kevin G.; Maecker, Heather] Genentech Inc, Dept Res Oncol, San Francisco, CA 94080 USA.
   [Liu, Jinfeng; Kaminker, Josh S.] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
   [O'Rourke, Karen M.; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
   [Pujara, Kanan; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Kohli, Pawan Bir; Johnson, Adam R.] Genentech Inc, Dept Biochem Pharmacol, San Francisco, CA 94080 USA.
   [Chiu, Mark L.] Abbott Labs, Dept Biol Struct, Abbott Pk, IL 60064 USA.
   [Huang, David C. S.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
C3 Roche Holding; Roche Holding USA; Genentech; Walter & Eliza Hall Institute; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Abbott Laboratories; University of Melbourne
RP Wertz, IE (corresponding author), Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA.
EM ingrid@gene.com
FU National Health and Medical Research Council [461221, 361646]; Leukemia and Lymphoma Society [SCOR 7413]; National Institutes of Health [CA043540, CA80188]; Australian Cancer Research Foundation; Australian Research Council
NR 20
TC 663
Z9 785
U1 1
U2 104
PU 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 3
PY 2011
VL 471
IS 7336
BP 110
EP 114
DI 10.1038/nature09779
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100044
PM 21368834
DA 2026-03-09
ER

PT J
AU Snyder, JS
   Soumier, A
   Brewer, M
   Pickel, J
   Cameron, HA
AF Snyder, Jason S.
   Soumier, Amelie
   Brewer, Michelle
   Pickel, James
   Cameron, Heather A.
TI Adult hippocampal neurogenesis buffers stress responses and depressive behaviour
SO NATURE
LA English
DT Article
ID glucocorticoid-receptor; transgenic mice; animal-model; astrocytes; neurons; antidepressants; forebrain; lesions; brain; rats
AB Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness(1,2). In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis(3). Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking(4,5). Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis(6,7). Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.
C1 [Snyder, Jason S.; Soumier, Amelie; Brewer, Michelle; Pickel, James; Cameron, Heather A.] NIMH, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
RP Cameron, HA (corresponding author), NIMH, NIH, Bethesda, MD 20892 USA.
EM heathercameron@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health, USA [ZIA MH002784]; National Institute of Mental Health [ZICMH002901, ZIAMH002784] Funding Source: NIH RePORTER
NR 30
TC 1170
Z9 1380
U1 4
U2 365
PU 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 25
PY 2011
VL 476
IS 7361
BP 458
EP U112
DI 10.1038/nature10287
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400038
PM 21814201
DA 2026-03-09
ER

PT J
AU Sousa-Nunes, R
   Yee, LL
   Gould, AP
AF Sousa-Nunes, Rita
   Yee, Lih Ling
   Gould, Alex P.
TI Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila
SO NATURE
LA English
DT Article
ID neural stem-cells; phosphoinositide 3-kinase; transcription factors; molecular-mechanisms; temporal identity; nervous-system; growth; proliferation; receptor; size
AB Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated(1-5). The signals triggering entry into and exit from this reversible dormant state are not well understood. In the developing Drosophila central nervous system, multipotent self-renewing progenitors called neuroblasts(6-9) undergo quiescence in a stereotypical spatiotemporal pattern(10). Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer(11-13). Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids(14). Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body(14). Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling(15) activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size(16-18) but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body-glia-neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour.
C1 [Sousa-Nunes, Rita; Yee, Lih Ling; Gould, Alex P.] Natl Inst Med Res, MRC, Div Dev Neurobiol, London NW7 1AA, England.
C3 MRC National Institute for Medical Research
RP Gould, AP (corresponding author), Natl Inst Med Res, MRC, Div Dev Neurobiol, London NW7 1AA, England.
EM agould@nimr.mrc.ac.uk
FU Medical Research Council [U117584237]; MRC [MC_U117584237] Funding Source: UKRI; Medical Research Council [MC_U117584237] Funding Source: researchfish
NR 54
TC 309
Z9 348
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 508
EP +
DI 10.1038/nature09867
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200061
PM 21346761
DA 2026-03-09
ER

PT J
AU Gu, TP
   Guo, F
   Yang, H
   Wu, HP
   Xu, GF
   Liu, W
   Xie, ZG
   Shi, LY
   He, XY
   Jin, SG
   Iqbal, K
   Shi, YJG
   Deng, ZX
   Szabó, PE
   Pfeifer, GP
   Li, JS
   Xu, GL
AF Gu, Tian-Peng
   Guo, Fan
   Yang, Hui
   Wu, Hai-Ping
   Xu, Gui-Fang
   Liu, Wei
   Xie, Zhi-Guo
   Shi, Linyu
   He, Xinyi
   Jin, Seung-gi
   Iqbal, Khursheed
   Shi, Yujiang Geno
   Deng, Zixin
   Szabo, Piroska E.
   Pfeifer, Gerd P.
   Li, Jinsong
   Xu, Guo-Liang
TI The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
SO NATURE
LA English
DT Article
ID primordial germ-cells; embryonic stem-cells; paternal genome; cre recombinase; mouse zygotes; 5-hydroxymethylcytosine; demethylation; genes; 5-methylcytosine; methylation
AB Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization(1). The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis(2,3). The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear(4). Here we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation process of the paternal Oct4 and Nanog genes and delays the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning.
C1 [Yang, Hui; Shi, Linyu; Li, Jinsong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.
   [Gu, Tian-Peng; Guo, Fan; Wu, Hai-Ping; Xu, Gui-Fang; Liu, Wei; Xie, Zhi-Guo; Xu, Guo-Liang] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Grp DNA Metab,State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
   [He, Xinyi; Deng, Zixin] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Microbial Metab, Shanghai 200030, Peoples R China.
   [Jin, Seung-gi; Pfeifer, Gerd P.] Beckman Res Inst City Hope, Dept Canc Biol, Duarte, CA 91010 USA.
   [Iqbal, Khursheed; Szabo, Piroska E.] Beckman Res Inst City Hope, Dept Mol & Cellular Biol, Duarte, CA 91010 USA.
   [Shi, Yujiang Geno] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA.
   [Shi, Yujiang Geno] Brigham & Womens Hosp, BCMP, Boston, MA 02115 USA.
   [Shi, Yujiang Geno] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Shanghai Jiao Tong University; City of Hope; Beckman Research Institute of City of Hope; City of Hope; Beckman Research Institute of City of Hope; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Li, JS (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.
EM jsli@sibs.ac.cn; glxu@sibs.ac.cn
FU Ministry of Science and Technology China [2007CB947503, 2007CB947101, 2009CB941101]; National Science Foundation of China [30730059, 30871430]; Chinese Academy of Sciences [XDA01010301, XDA01010403, KSCX2-YW-R-110]; NIH [GM078458]
NR 38
TC 924
Z9 1128
U1 2
U2 285
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 29
PY 2011
VL 477
IS 7366
BP 606
EP U136
DI 10.1038/nature10443
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900043
PM 21892189
DA 2026-03-09
ER

PT J
AU Chen, SK
   Badea, TC
   Hattar, S
AF Chen, S. -K.
   Badea, T. C.
   Hattar, S.
TI Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; melanopsin; morphology; responses; projections; diversity
AB Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and regulate a wide array of light-dependent physiological processes(1-11). Genetic ablation of ipRGCs eliminates circadian photoentrainment and severely disrupts the pupillary light reflex (PLR)(12,13). Here we show that ipRGCs consist of distinct subpopulations that differentially express the Brn3b transcription factor, and can be functionally distinguished. Brn3b-negative M1 ipRGCs innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas Brn3b-positive ipRGCs innervate all other known brain targets, including the olivary pre-tectal nucleus. Consistent with these innervation patterns, selective ablation of Brn3b-positive ipRGCs severely disrupts the PLR, but does not impair circadian photoentrainment. Thus, we find that molecularly distinct subpopulations of M1 ipRGCs, which are morphologically and electrophysiologically similar, innervate different brain regions to execute specific light-induced functions.
C1 [Chen, S. -K.; Hattar, S.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
   [Badea, T. C.] NEI, Retinal Circuit Dev & Genet Unit, N NRL, NIH, Bethesda, MD 20892 USA.
   [Hattar, S.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA.
C3 Johns Hopkins University; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI); Johns Hopkins University
RP Hattar, S (corresponding author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM tudor.badea@nih.gov; shattar@jhu.edu
FU Johns Hopkins University Mouse Tri-Lab; National Institutes of Health [GM076430]; David and Lucile Packard Foundation; Alfred P. Sloan Foundation; National Eye Institute [ZIAEY000504] Funding Source: NIH RePORTER
NR 28
TC 347
Z9 436
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 AUG 4
PY 2011
VL 476
IS 7358
BP 92
EP +
DI 10.1038/nature10206
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300036
PM 21765429
DA 2026-03-09
ER

PT J
AU Wang, T
   Sha, RJ
   Dreyfus, R
   Leunissen, ME
   Maass, C
   Pine, DJ
   Chaikin, PM
   Seeman, NC
AF Wang, Tong
   Sha, Ruojie
   Dreyfus, Remi
   Leunissen, Mirjam E.
   Maass, Corinna
   Pine, David J.
   Chaikin, Paul M.
   Seeman, Nadrian C.
TI Self-replication of information-bearing nanoscale patterns
SO NATURE
LA English
DT Article
ID dna; crystallization; colloids; enzyme; design; acid
AB DNA molecules provide what is probably the most iconic example of self-replication-the ability of a system to replicate, or make copies of, itself. In living cells the process is mediated by enzymes and occurs autonomously, with the number of replicas increasing exponentially over time without the need for external manipulation. Self-replication has also been implemented with synthetic systems, including RNA enzymes designed to undergo self-sustained exponential amplification(1-5). An exciting next step would be to use self-replication in materials fabrication, which requires robust and general systems capable of copying and amplifying functional materials or structures. Here we report a first development in this direction, using DNA tile motifs that can recognize and bind complementary tiles in a pre-programmed fashion. We first design tile motifs so they form a seven-tile seed sequence; then use the seeds to instruct the formation of a first generation of complementary seven-tile daughter sequences; and finally use the daughters to instruct the formation of seven-tile granddaughter sequences that are identical to the initial seed sequences. Considering that DNA is a functional material that can organize itself and other molecules into useful structures(6-13), our findings raise the tantalizing prospect that we may one day be able to realize self-replicating materials with various patterns or useful functions.
C1 [Dreyfus, Remi; Leunissen, Mirjam E.; Maass, Corinna; Pine, David J.; Chaikin, Paul M.] NYU, Ctr Soft Matter Res, New York, NY 10003 USA.
   [Wang, Tong; Sha, Ruojie; Seeman, Nadrian C.] NYU, Dept Chem, New York, NY 10003 USA.
C3 New York University; New York University
RP Chaikin, PM (corresponding author), NYU, Ctr Soft Matter Res, 550 1St Ave, New York, NY 10003 USA.
EM chaikin@nyu.edu; ned.seeman@nyu.edu
FU W.M. Keck Foundation; National Science Foundation [DMR-0820341, CTS-0608889, CCF-0726378]; NASA [NNX08AK04G]; National Institute of General Medical Sciences [GM-29554]; Army Research Office [48681-EL, W911NF-07-1-0439]; Office of Naval Research [N000140910181, N000140911118]; Netherlands Organization for Scientific Research; DAAD
NR 24
TC 99
Z9 119
U1 0
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 OCT 13
PY 2011
VL 478
IS 7368
BP 225
EP U107
DI 10.1038/nature10500
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800046
PM 21993758
DA 2026-03-09
ER

PT J
AU Pastor, WA
   Pape, UJ
   Huang, Y
   Henderson, HR
   Lister, R
   Ko, M
   McLoughlin, EM
   Brudno, Y
   Mahapatra, S
   Kapranov, P
   Tahiliani, M
   Daley, GQ
   Liu, XS
   Ecker, JR
   Milos, PM
   Agarwal, S
   Rao, A
AF Pastor, William A.
   Pape, Utz J.
   Huang, Yun
   Henderson, Hope R.
   Lister, Ryan
   Ko, Myunggon
   McLoughlin, Erin M.
   Brudno, Yevgeny
   Mahapatra, Sahasransu
   Kapranov, Philipp
   Tahiliani, Mamta
   Daley, George Q.
   Liu, X. Shirley
   Ecker, Joseph R.
   Milos, Patrice M.
   Agarwal, Suneet
   Rao, Anjana
TI Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
SO NATURE
LA English
DT Article
ID developmental regulators; myeloid cancers; dna methylation; 5-methylcytosine; hydroxylation; tet1; quantification; specification; pluripotent; conversion
AB 5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals(1-5). 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC)(1,2,4-7). 5hmC and TET proteins have been implicated in stem cell biology and cancer(1,4,5,8,9), but information on the genome-wide distribution of 5hmC is limited. Here we describe two novel and specific approaches to profile the genomic localization of 5hmC. The first approach, termed GLIB (glucosylation, periodate oxidation, biotinylation) uses a combination of enzymatic and chemical steps to isolate DNA fragments containing as few as a single 5hmC. The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation of CMS-containing DNA with a specific antiserum to CMS5. High-throughput sequencing of 5hmC-containing DNA from mouse embryonic stem (ES) cells showed strong enrichment within exons and near transcriptional start sites. 5hmC was especially enriched at the start sites of genes whose promoters bear dual histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 4 trimethylation (H3K4me3) marks. Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the 'poised' chromatin signature found at developmentally-regulated genes in ES cells.
C1 [McLoughlin, Erin M.; Daley, George Q.; Agarwal, Suneet] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   [Pape, Utz J.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [McLoughlin, Erin M.; Daley, George Q.; Agarwal, Suneet] Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Pastor, William A.; Pape, Utz J.; Henderson, Hope R.; Tahiliani, Mamta; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
   [Pastor, William A.; Pape, Utz J.; Henderson, Hope R.; Tahiliani, Mamta; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Pastor, William A.; Huang, Yun; Henderson, Hope R.; Ko, Myunggon; Mahapatra, Sahasransu; Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
   [Pape, Utz J.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Lister, Ryan; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA.
   [Brudno, Yevgeny] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Kapranov, Philipp; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); La Jolla Institute for Immunology; Harvard University; Harvard T.H. Chan School of Public Health; Salk Institute; Harvard University
RP Agarwal, S (corresponding author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
EM Suneet.Agarwal@childrens.harvard.edu; arao@idi.harvard.edu
FU National Science Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine; National Institute of Health [RC1 DA028422, R01 AI44432, 1 R01 HD065812-01A1, NIH K08 HL089150]; Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [1 UL1 RR 025758-02]; Mary. K. Chapman Foundation
NR 28
TC 675
Z9 833
U1 1
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 394
EP 397
DI 10.1038/nature10102
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400053
PM 21552279
DA 2026-03-09
ER

PT J
AU Wang, KC
   Yang, YW
   Liu, B
   Sanyal, A
   Corces-Zimmerman, R
   Chen, Y
   Lajoie, BR
   Protacio, A
   Flynn, RA
   Gupta, RA
   Wysocka, J
   Lei, M
   Dekker, J
   Helms, JA
   Chang, HY
AF Wang, Kevin C.
   Yang, Yul W.
   Liu, Bo
   Sanyal, Amartya
   Corces-Zimmerman, Ryan
   Chen, Yong
   Lajoie, Bryan R.
   Protacio, Angeline
   Flynn, Ryan A.
   Gupta, Rajnish A.
   Wysocka, Joanna
   Lei, Ming
   Dekker, Job
   Helms, Jill A.
   Chang, Howard Y.
TI A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
SO NATURE
LA English
DT Article
ID anatomic demarcation; histone h3; transcription; elements; methylation; diversity; genome; 5c
AB The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing(1,2). Potential roles of lincRNAs in gene activation are much less understood(3-5). Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control(6). Some locus control elements and enhancers transcribe lincRNAs(7-10), hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5' of the cluster(11). Here we identify HOTTIP, a lincRNA transcribed from the 5' tip of the HOXA locus that coordinates the activation of several 5' HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.
C1 [Wang, Kevin C.; Yang, Yul W.; Corces-Zimmerman, Ryan; Protacio, Angeline; Flynn, Ryan A.; Gupta, Rajnish A.; Chang, Howard Y.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Wang, Kevin C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA.
   [Liu, Bo; Helms, Jill A.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA.
   [Sanyal, Amartya; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Chen, Yong; Lei, Ming] Univ Michigan, Sch Med, Howard Hughes Med Inst, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Wysocka, Joanna] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University; University of California System; University of California San Francisco; Stanford University; University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; Stanford University
RP Chang, HY (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Program Epithelial Biol, Stanford, CA 94305 USA.
EM howchang@stanford.edu
FU California Institute for Regenerative Medicine; National Institutes of Health [HG003143]; Scleroderma Research Foundation; Dermatology Foundation; W. M. Keck Foundation; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER
NR 45
TC 1675
Z9 1993
U1 0
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 APR 7
PY 2011
VL 472
IS 7341
BP 120
EP U158
DI 10.1038/nature09819
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400049
PM 21423168
DA 2026-03-09
ER

PT J
AU Gaillard, F
   Scaillet, B
   Arndt, NT
AF Gaillard, Fabrice
   Scaillet, Bruno
   Arndt, Nicholas T.
TI Atmospheric oxygenation caused by a change in volcanic degassing pressure
SO NATURE
LA English
DT Article
ID redox evolution; silicate melts; mantle redox; sulfur; rise; tectonics; fluxes; earth
AB The Precambrian history of our planet is marked by two major events: a pulse of continental crust formation at the end of the Archaean eon and a weak oxygenation of the atmosphere (the Great Oxidation Event) that followed, at 2.45 billion years ago. This oxygenation has been linked to the emergence of oxygenic cyanobacteria(1,2) and to changes in the compositions of volcanic gases(3,4), but not to the composition of erupting lavas-geochemical constraints indicate that the oxidation state of basalts and their mantle sources has remained constant since 3.5 billion years ago(5,6). Here we propose that a decrease in the average pressure of volcanic degassing changed the oxidation state of sulphur in volcanic gases, initiating the modern biogeochemical sulphur cycle and triggering atmospheric oxygenation. Using thermodynamic calculations simulating gas-melt equilibria in erupting magmas, we suggest that mostly submarine Archaean volcanoes produced gases with SO2/H2S < 1 and low sulphur content. Emergence of the continents due to a global decrease in sea level and growth of the continental crust in the late Archaean then led to widespread subaerial volcanism, which in turn yielded gases much richer in sulphur and dominated by SO2. Dissolution of sulphur in sea water and the onset of sulphate reduction processes could then oxidize the atmosphere.
C1 [Gaillard, Fabrice; Scaillet, Bruno] Univ Tours, Univ Orleans, CNRS INSU, Inst Sci Terre Orleans, F-45071 Orleans 2, France.
   [Arndt, Nicholas T.] Univ Grenoble 1, CNRS, ISTerre, F-38400 St Martin Dheres, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Tours; Universite de Orleans; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite Gustave-Eiffel; Universite Savoie Mont Blanc
RP Gaillard, F (corresponding author), Univ Tours, Univ Orleans, CNRS INSU, Inst Sci Terre Orleans, 1A Rue Ferollerie, F-45071 Orleans 2, France.
EM gaillard@cnrs-orleans.fr
FU INSU-PNP; ANR [ANR-10-BLAN-60301, ANR-10-BLAN-62101]
NR 37
TC 247
Z9 279
U1 2
U2 162
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 13
PY 2011
VL 478
IS 7368
BP 229
EP U112
DI 10.1038/nature10460
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800047
PM 21993759
DA 2026-03-09
ER

PT J
AU Li, H
   Durbin, R
AF Li, Heng
   Durbin, Richard
TI Inference of human population history from individual whole-genome sequences
SO NATURE
LA English
DT Article
ID allele frequency-spectrum; genetic drift; nucleotide; coalescent; dispersal; reveals; model; east
AB The history of human population size is important for understanding human evolution. Various studies(1-5) have found evidence for a founder event (bottleneck) in East Asian and European populations, associated with the human dispersal out-of-Africa event around 60 thousand years (kyr) ago. However, these studies have had to assume simplified demographic models with few parameters, and they do not provide a precise date for the start and stop times of the bottleneck. Here, with fewer assumptions on population size changes, we present a more detailed history of human population sizes between approximately ten thousand and a million years ago, using the pairwise sequentially Markovian coalescent model applied to the complete diploid genome sequences of a Chinese male (YH)(6), a Korean male (SJK)(7), three European individuals (J. C. Venter(8), NA12891 and NA12878 (ref. 9)) and two Yoruba males (NA18507 (ref. 10) and NA19239). We infer that European and Chinese populations had very similar population-size histories before 10-20 kyr ago. Both populations experienced a severe bottleneck 10-60 kyr ago, whereas African populations experienced a milder bottleneck from which they recovered earlier. All three populations have an elevated effective population size between 60 and 250 kyr ago, possibly due to population substructure(11). We also infer that the differentiation of genetically modern humans may have started as early as 100-120 kyr ago(12), but considerable genetic exchanges may still have occurred until 20-40 kyr ago.
C1 [Li, Heng; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Li, Heng] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
C3 Wellcome Trust Sanger Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Durbin, R (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM lh3@sanger.ac.uk; rd@sanger.ac.uk
FU Wellcome Trust [WT077192]
NR 29
TC 1894
Z9 2174
U1 9
U2 529
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 493
EP U84
DI 10.1038/nature10231
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900039
PM 21753753
DA 2026-03-09
ER

PT J
AU Singarayer, JS
   Valdes, PJ
   Friedlingstein, P
   Nelson, S
   Beerling, DJ
AF Singarayer, Joy S.
   Valdes, Paul J.
   Friedlingstein, Pierre
   Nelson, Sarah
   Beerling, David J.
TI Late Holocene methane rise caused by orbitally controlled increase in tropical sources
SO NATURE
LA English
DT Article
ID last glacial maximum; atmospheric co2 concentrations; pmip2 coupled simulations; isoprene emissions; ice core; climate; model; midholocene; feedbacks; responses
AB Considerable debate surrounds the source of the apparently 'anomalous'(1) increase of atmospheric methane concentrations since the mid-Holocene (5,000 years ago) compared to previous interglacial periods as recorded in polar ice core records(2). Proposed mechanisms for the rise in methane concentrations relate either to methane emissions from anthropogenic early rice cultivation(1,3) or an increase in natural wetland emissions from tropical(4) or boreal sources(5,6). Here we show that our climate and wetland simulations of the global methane cycle over the last glacial cycle (the past 130,000 years) recreate the ice core record and capture the late Holocene increase in methane concentrations. Our analyses indicate that the late Holocene increase results from natural changes in the Earth's orbital configuration, with enhanced emissions in the Southern Hemisphere tropics linked to precession-induced modification of seasonal precipitation. Critically, our simulations capture the declining trend in methane concentrations at the end of the last interglacial period (115,000-130,000 years ago) that was used to diagnose the Holocene methane rise as unique. The difference between the two time periods results from differences in the size and rate of regional insolation changes and the lack of glacial inception in the Holocene. Our findings also suggest that no early agricultural sources are required to account for the increase in methane concentrations in the 5,000 years before the industrial era.
C1 [Singarayer, Joy S.; Valdes, Paul J.; Friedlingstein, Pierre; Nelson, Sarah] Univ Bristol, Sch Geog Sci, Bristol Res Initiat Dynam Global Environm, Bristol BS8 1SS, Avon, England.
   [Friedlingstein, Pierre] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
   [Beerling, David J.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
C3 University of Bristol; University of Exeter; University of Sheffield
RP Singarayer, JS (corresponding author), Univ Bristol, Sch Geog Sci, Bristol Res Initiat Dynam Global Environm, Univ Rd, Bristol BS8 1SS, Avon, England.
EM joy.singarayer@bristol.ac.uk
FU Royal Society; Leverhulme Trust; NERC [NE/D001846/1, NE/E007600/1] Funding Source: UKRI; Natural Environment Research Council [NE/E007600/1, NE/D001846/1] Funding Source: researchfish
NR 45
TC 120
Z9 130
U1 3
U2 121
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 82
EP U91
DI 10.1038/nature09739
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400038
PM 21293375
DA 2026-03-09
ER

PT J
AU Chen, Q
   Bae, SC
   Granick, S
AF Chen, Qian
   Bae, Sung Chul
   Granick, Steve
TI Directed self-assembly of a colloidal kagome lattice
SO NATURE
LA English
DT Article
ID crystallization; nanoparticles; complex; growth
AB A challenging goal in materials chemistry and physics is spontaneously to form intended superstructures from designed building blocks. In fields such as crystal engineering(1) and the design of porous materials(2-4), this typically involves building blocks of organic molecules, sometimes operating together with metallic ions or clusters. The translation of such ideas to nanoparticles and colloidal-sized building blocks would potentially open doors to new materials and new properties(5-7), but the pathways to achieve this goal are still undetermined. Here we show how colloidal spheres can be induced to self-assemble into a complex predetermined colloidal crystal-in this case a colloidal kagome lattice(8-12)-through decoration of their surfaces with a simple pattern of hydrophobic domains. The building blocks are simple micrometre-sized spheres with interactions (electrostatic repulsion in the middle, hydrophobic attraction at the poles, which we call 'triblock Janus') that are also simple, but the self-assembly of the spheres into an open kagome structure contrasts with previously known close-packed periodic arrangements of spheres(13-15). This open network is of interest for several theoretical reasons(8-10). With a view to possible enhanced functionality, the resulting lattice structure possesses two families of pores, one that is hydrophobic on the rims of the pores and another that is hydrophilic. This strategy of 'convergent' self-assembly from easily fabricated(16) colloidal building blocks encodes the target supracolloidal architecture, not in localized attractive spots but instead in large redundantly attractive regions, and can be extended to form other supracolloidal networks.
C1 [Chen, Qian; Bae, Sung Chul; Granick, Steve] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [Granick, Steve] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Granick, Steve] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
C3 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 Granick, S (corresponding author), Univ Illinois, Dept Mat Sci & Engn, 1304 W Green St, Urbana, IL 61801 USA.
EM sgranick@illinois.edu
FU US Department of Energy, Division of Materials Science through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign [DE-FG02-07ER46471]; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [0853737] Funding Source: National Science Foundation
NR 28
TC 1107
Z9 1278
U1 8
U2 903
PU 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 20
PY 2011
VL 469
IS 7330
BP 381
EP 384
DI 10.1038/nature09713
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600048
PM 21248847
DA 2026-03-09
ER

PT J
AU Alilain, WJ
   Horn, KP
   Hu, HM
   Dick, TE
   Silver, J
AF Alilain, Warren J.
   Horn, Kevin P.
   Hu, Hongmei
   Dick, Thomas E.
   Silver, Jerry
TI Functional regeneration of respiratory pathways after spinal cord injury
SO NATURE
LA English
DT Article
ID crossed phrenic phenomenon; intermittent hypoxia; axonal regeneration; plasticity; recovery; abnormality; motoneurons; agonists; bridges; grafts
AB Spinal cord injuries often occur at the cervical level above the phrenic motor pools, which innervate the diaphragm. The effects of impaired breathing are a leading cause of death from spinal cord injuries, underscoring the importance of developing strategies to restore respiratory activity. Here we show that, after cervical spinal cord injury, the expression of chondroitin sulphate proteoglycans (CSPGs) associated with the perineuronal net (PNN) is upregulated around the phrenic motor neurons. Digestion of these potently inhibitory extracellular matrix molecules with chondroitinase ABC (denoted ChABC) could, by itself, promote the plasticity of tracts that were spared and restore limited activity to the paralysed diaphragm. However, when combined with a peripheral nerve autograft, ChABC treatment resulted in lengthy regeneration of serotonin-containing axons and other bulbospinal fibres and remarkable recovery of diaphragmatic function. After recovery and initial transection of the graft bridge, there was an unusual, overall increase in tonic electromyographic activity of the diaphragm, suggesting that considerable remodelling of the spinal cord circuitry occurs after regeneration. This increase was followed by complete elimination of the restored activity, proving that regeneration is crucial for the return of function. Overall, these experiments present a way to markedly restore the function of a single muscle after debilitating trauma to the central nervous system, through both promoting the plasticity of spared tracts and regenerating essential pathways.
C1 [Alilain, Warren J.; Horn, Kevin P.; Hu, Hongmei; Dick, Thomas E.; Silver, Jerry] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA.
   [Dick, Thomas E.] Case Western Reserve Univ, Sch Med, Div Pulm Crit Care & Sleep Med, Dept Med, Cleveland, OH 44106 USA.
C3 University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University
RP Silver, J (corresponding author), Case Western Reserve Univ, Sch Med, Dept Neurosci, 2109 Adelbert Rd, Cleveland, OH 44106 USA.
EM wja4@case.edu; jxs10@case.edu
FU Christopher and Dana Reeve Foundation; International Spinal Research Trust; National Institute of Neurological Disorders and Stroke [NS25713, NS060767]; National Heart, Lung and Blood Institute [HL080318]; Brumagin Memorial Fund; Ellen Becker Neuroscience Regenerative Medicine Research Fund
NR 33
TC 328
Z9 381
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 196
EP U95
DI 10.1038/nature10199
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500043
PM 21753849
DA 2026-03-09
ER

PT J
AU Gross, C
   Strobel, H
   Nicklas, E
   Zibold, T
   Bar-Gill, N
   Kurizki, G
   Oberthaler, MK
AF Gross, C.
   Strobel, H.
   Nicklas, E.
   Zibold, T.
   Bar-Gill, N.
   Kurizki, G.
   Oberthaler, M. K.
TI Atomic homodyne detection of continuous-variable entangled twin-atom states
SO NATURE
LA English
DT Article
ID podolsky-rosen paradox; quantum; teleportation; beams; limit
AB Historically, the completeness of quantum theory has been questioned using the concept of bipartite continuous-variable entanglement(1). The non-classical correlations (entanglement) between the two subsystems imply that the observables of one subsystem are determined by the measurement choice on the other, regardless of the distance between the subsystems. Nowadays, continuous-variable entanglement is regarded as an essential resource, allowing for quantum enhanced measurement resolution(2), the realization of quantum teleportation(3-5) and quantum memories(3,6), or the demonstration of the Einstein-Podolsky-Rosen paradox(1,7-9). These applications rely on techniques to manipulate and detect coherences of quantum fields, the quadratures. Whereas in optics coherent homodyne detection(10) of quadratures is a standard technique, for massive particles a corresponding method was missing. Here we report the realization of an atomic analogue to homodyne detection for the measurement of matter-wave quadratures. The application of this technique to a quantum state produced by spin-changing collisions in a Bose-Einstein condensate(11,12) reveals continuous-variable entanglement, as well as the twin-atom character of the state(13). Our results provide a rare example of continuous-variable entanglement of massive particles(6,14). The direct detection of atomic quadratures has applications not only in experimental quantum atom optics, but also for the measurement of fields in many-body systems of massive particles(15).
C1 [Gross, C.; Strobel, H.; Nicklas, E.; Zibold, T.; Oberthaler, M. K.] Univ Heidelberg, Kirchhoff Inst Phys, D-69120 Heidelberg, Germany.
   [Bar-Gill, N.; Kurizki, G.] Weizmann Inst Sci, IL-76100 Rehovot, Israel.
C3 Ruprecht Karls University Heidelberg; Weizmann Institute of Science
RP Oberthaler, MK (corresponding author), Univ Heidelberg, Kirchhoff Inst Phys, Neuenheimer Feld 227, D-69120 Heidelberg, Germany.
EM homodyning@matterwave.de
FU Deutsche Forschungsgemeinschaft; German-Israeli Foundation; Heidelberg Center for Quantum Dynamics; Landesstiftung Baden-Wurttemberg; ExtreMe Matter Institute; European Commission; Humboldt-Meitner Award; Deutsche-Israelische Projektgruppe (DIP);  [Forschergruppe FOR760]
NR 30
TC 191
Z9 201
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 DEC 8
PY 2011
VL 480
IS 7376
BP 219
EP 223
DI 10.1038/nature10654
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 857TR
UT WOS:000297744200046
PM 22139418
DA 2026-03-09
ER

PT J
AU Volz, J
   Gehr, R
   Dubois, G
   Estève, J
   Reichel, J
AF Volz, Juergen
   Gehr, Roger
   Dubois, Guilhem
   Esteve, Jerome
   Reichel, Jakob
TI Measurement of the internal state of a single atom without energy exchange
SO NATURE
LA English
DT Article
ID quantum; cavity
AB A measurement necessarily changes the quantum state being measured, a phenomenon known as back-action. Real measurements, however, almost always cause a much stronger back-action than is required by the laws of quantum mechanics. Quantum non-demolition measurements have been devised(1-6) that keep the additional back-action entirely within observables other than the one being measured. However, this back-action on other observables often imposes its own constraints. In particular, free-space optical detection methods for single atoms and ions (such as the shelving technique(7), a sensitive and well-developed method) inevitably require spontaneous scattering, even in the dispersive regime(8). This causes irreversible energy exchange (heating), which is a limitation in atom-based quantum information processing, where it obviates straightforward reuse of the qubit. No such energy exchange is required by quantum mechanics(9). Here we experimentally demonstrate optical detection of an atomic qubit with significantly less than one spontaneous scattering event. We measure the transmission and reflection of an optical cavity(10-13) containing the atom. In addition to the qubit detection itself, we quantitatively measure how much spontaneous scattering has occurred. This allows us to relate the information gained to the amount of spontaneous emission, and we obtain a detection error below 10 per cent while scattering less than 0.2 photons on average. Furthermore, we performa quantum Zeno-type experiment to quantify the measurement back-action, and find that every incident photon leads to an almost complete state collapse. Together, these results constitute a full experimental characterization of a quantum measurement in the 'energy exchange-free' regime below a single spontaneous emission event. Besides its fundamental interest, this approach could significantly simplify proposed neutral-atom quantum computation schemes(14), and may enable sensitive detection of molecules and atoms lacking closed transitions.
C1 [Volz, Juergen; Gehr, Roger; Dubois, Guilhem; Esteve, Jerome; Reichel, Jakob] Univ Paris 06, CNRS, ENS, Lab Kastler Brossel, F-75005 Paris, France.
C3 Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite
RP Reichel, J (corresponding author), Univ Paris 06, CNRS, ENS, Lab Kastler Brossel, 24 Rue Lhomond, F-75005 Paris, France.
EM jakob.reichel@ens.fr
FU EU [247687]; Institut Francilien pour la Recherche sur les Atomes Froids (IFRAF); EURYI grant 'Integrated Quantum Devices'
NR 26
TC 101
Z9 109
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 210
EP U117
DI 10.1038/nature10225
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500046
PM 21753851
DA 2026-03-09
ER

PT J
AU Walker, T
   Johnson, PH
   Moreira, LA
   Iturbe-Ormaetxe, I
   Frentiu, FD
   McMeniman, CJ
   Leong, YS
   Dong, Y
   Axford, J
   Kriesner, P
   Lloyd, AL
   Ritchie, SA
   O'Neill, SL
   Hoffmann, AA
AF Walker, T.
   Johnson, P. H.
   Moreira, L. A.
   Iturbe-Ormaetxe, I.
   Frentiu, F. D.
   McMeniman, C. J.
   Leong, Y. S.
   Dong, Y.
   Axford, J.
   Kriesner, P.
   Lloyd, A. L.
   Ritchie, S. A.
   O'Neill, S. L.
   Hoffmann, A. A.
TI The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations
SO NATURE
LA English
DT Article
ID virus; infection; culicidae; diptera; models; spread
AB Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries(1,2). Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing(2-4). Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti(5,6). These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control(7-9). For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines(8). This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens(9-11) has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression(12).
C1 [Walker, T.; Moreira, L. A.; Iturbe-Ormaetxe, I.; Frentiu, F. D.; McMeniman, C. J.; Leong, Y. S.; Dong, Y.; O'Neill, S. L.] Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
   [Axford, J.; Kriesner, P.; Hoffmann, A. A.] Univ Melbourne, Dept Genet, Inst Bio21, Melbourne, Vic 3010, Australia.
   [Johnson, P. H.; Ritchie, S. A.] James Cook Univ, Sch Publ Hlth & Trop Med & Rehabil Sci, Cairns, Qld 4870, Australia.
   [Lloyd, A. L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA.
   [Lloyd, A. L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA.
   [Lloyd, A. L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [O'Neill, S. L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
C3 University of Queensland; University of Melbourne; James Cook University; North Carolina State University; North Carolina State University; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC); Monash University
RP O'Neill, SL (corresponding author), Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
EM scott.oneill@monash.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation; National Health and Medical Research Council, Australia; NIH; Climate and Health Cluster of the CSIRO; Australian Research Council
NR 36
TC 1041
Z9 1213
U1 7
U2 327
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 450
EP U101
DI 10.1038/nature10355
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400036
PM 21866159
DA 2026-03-09
ER

PT J
AU Rougier, GW
   Apesteguía, S
   Gaetano, LC
AF Rougier, Guillermo W.
   Apesteguia, Sebastian
   Gaetano, Leandro C.
TI Highly specialized mammalian skulls from the Late Cretaceous of South America
SO NATURE
LA English
DT Article
ID argentina; patagonia; symmetrodonta; phylogeny
AB Dryolestoids are an extinct mammalian group belonging to the lineage leading to modern marsupials and placentals(1,2). Dryolestoids are known by teeth and jaws from the Jurassic period of North America and Europe(2,3), but they thrived in South America up to the end of the Mesozoic era and survived to the beginnings of the Cenozoic(2,4-7). Isolated teeth and jaws from the latest Cretaceous of South America provide mounting evidence that, at least in western Gondwana, dryolestoids developed into strongly endemic groups by the Late Cretaceous(4-9). However, the lack of pre-Late Cretaceous dryolestoid remains made study of their origin and early diversification intractable. Here we describe the first mammalian remains from the early Late Cretaceous of South America, including two partial skulls and jaws of a derived dryolestoid showing dental and cranial features unknown among any other group of Mesozoic mammals, such as single-rooted molars preceded by double-rooted premolars, combined with a very long muzzle, exceedingly long canines and evidence of highly specialized masticatory musculature. On one hand, the new mammal shares derived features of dryolestoids(1-3) with forms from the Jurassic of Laurasia, whereas on the other hand, it is very specialized and highlights the endemic, diverse dryolestoid fauna from the Cretaceous of South America. Our specimens include only the second mammalian skull known for the Cretaceous of Gondwana, bridging a previous 60-million-year gap in the fossil record, and document the whole cranial morphology of a dryolestoid, revealing an unsuspected morphological and ecological diversity for non-tribosphenic mammals.
C1 [Rougier, Guillermo W.] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA.
   [Apesteguia, Sebastian] Univ Maimonides, CEBBAD Fdn Hist Nat Felix de Azara, RA-1405 Buenos Aires, DF, Argentina.
   [Apesteguia, Sebastian; Gaetano, Leandro C.] Consejo Nacl Invest Cient & Tecn, CONICET, Buenos Aires, DF, Argentina.
   [Gaetano, Leandro C.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Cs Geol, Buenos Aires, DF, Argentina.
C3 University of Louisville; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires
RP Rougier, GW (corresponding author), Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA.
EM grougier@louisville.edu
FU Antorchas Foundation; American Museum of Natural History; NSF [DEB 0946430, DEB 1068089, ATOL 0629959]; Jurassic Foundation; NASA; Field Museum Womens' Board; Division Of Environmental Biology; Direct For Biological Sciences [0946430] Funding Source: National Science Foundation
NR 30
TC 95
Z9 109
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 98
EP 102
DI 10.1038/nature10591
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600039
PM 22051679
DA 2026-03-09
ER

PT J
AU Green, ED
   Guyer, MS
AF Green, Eric D.
   Guyer, Mark S.
TI Charting a course for genomic medicine from base pairs to bedside
SO NATURE
LA English
DT Article
ID abl tyrosine kinase; american society; myeloid-leukemia; wide association; gene-mutations; disease; information; autophagy; care; risk
AB There has been much progress in genomics in the ten years since a draft sequence of the human genome was published. Opportunities for understanding health and disease are now unprecedented, as advances in genomics are harnessed to obtain robust foundational knowledge about the structure and function of the human genome and about the genetic contributions to human health and disease. Here we articulate a 2011 vision for the future of genomics research and describe the path towards an era of genomic medicine.
C1 [Green, Eric D.; Guyer, Mark S.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Green, ED (corresponding author), NHGRI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM egreen@nhgri.nih.gov
NR 103
TC 650
Z9 767
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 FEB 10
PY 2011
VL 470
IS 7333
BP 204
EP 213
DI 10.1038/nature09764
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200034
PM 21307933
DA 2026-03-09
ER

PT J
AU Petersen, JM
   Zielinski, FU
   Pape, T
   Seifert, R
   Moraru, C
   Amann, R
   Hourdez, S
   Girguis, PR
   Wankel, SD
   Barbe, V
   Pelletier, E
   Fink, D
   Borowski, C
   Bach, W
   Dubilier, N
AF Petersen, Jillian M.
   Zielinski, Frank U.
   Pape, Thomas
   Seifert, Richard
   Moraru, Cristina
   Amann, Rudolf
   Hourdez, Stephane
   Girguis, Peter R.
   Wankel, Scott D.
   Barbe, Valerie
   Pelletier, Eric
   Fink, Dennis
   Borowski, Christian
   Bach, Wolfgang
   Dubilier, Nicole
TI Hydrogen is an energy source for hydrothermal vent symbioses
SO NATURE
LA English
DT Article
ID mid-atlantic ridge; membrane-bound hydrogenase; riftia-pachyptila jones; molecular-hydrogen; dual symbiosis; tube worm; h-2; fluids; 15-degrees-n; community
AB The discovery of deep-sea hydrothermal vents in 1977 revolutionized our understanding of the energy sources that fuel primary productivity on Earth. Hydrothermal vent ecosystems are dominated by animals that live in symbiosis with chemosynthetic bacteria. So far, only two energy sources have been shown to power chemosynthetic symbioses: reduced sulphur compounds and methane. Using metagenome sequencing, single-gene fluorescence in situ hybridization, immunohistochemistry, shipboard incubations and in situ mass spectrometry, we show here that the symbionts of the hydrothermal vent mussel Bathymodiolus from the Mid-Atlantic Ridge use hydrogen to power primary production. In addition, we show that the symbionts of Bathymodiolus mussels from Pacific vents have hupL, the key gene for hydrogen oxidation. Furthermore, the symbionts of other vent animals such as the tubeworm Riftia pachyptila and the shrimp Rimicaris exoculata also have hupL. We propose that the ability to use hydrogen as an energy source is widespread in hydrothermal vent symbioses, particularly at sites where hydrogen is abundant.
C1 [Petersen, Jillian M.; Zielinski, Frank U.; Moraru, Cristina; Amann, Rudolf; Fink, Dennis; Borowski, Christian; Dubilier, Nicole] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
   [Zielinski, Frank U.] UFZ Helmholtz Ctr Environm Res, D-04318 Leipzig, Germany.
   [Pape, Thomas] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28334 Bremen, Germany.
   [Pape, Thomas; Bach, Wolfgang] Univ Bremen, Dept Geosci, D-28334 Bremen, Germany.
   [Seifert, Richard] Univ Hamburg, Inst Biogeochem & Marine Chem, D-20146 Hamburg, Germany.
   [Hourdez, Stephane] CNRS UPMC UMR 7144, Biol Stn, Equipe Genet Adaptat Milieux Extremes, F-29682 Roscoff, France.
   [Girguis, Peter R.; Wankel, Scott D.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Barbe, Valerie; Pelletier, Eric] Commissariat Energie Atom Genoscope, F-91000 Evry, France.
   [Barbe, Valerie; Pelletier, Eric] CNRS, UMR8030, F-91000 Evry, France.
   [Barbe, Valerie; Pelletier, Eric] Univ Evry Val dEssone, F-91000 Evry, France.
C3 Max Planck Society; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); University of Bremen; University of Bremen; University of Hamburg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Harvard University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CEA; Universite Paris Saclay; Universite Paris Saclay
RP Dubilier, N (corresponding author), Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany.
EM ndubilie@mpi-bremen.de
FU German Science Foundation (DFG) [1144, 60]; DFG Cluster of Excellence "The Ocean in the Earth System" at MARUM (Center for Marine Environmental Sciences); Max Planck Society
NR 48
TC 222
Z9 263
U1 4
U2 326
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 176
EP 180
DI 10.1038/nature10325
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900029
PM 21833083
DA 2026-03-09
ER

PT J
AU Flagel, SB
   Clark, JJ
   Robinson, TE
   Mayo, L
   Czuj, A
   Willuhn, I
   Akers, CA
   Clinton, SM
   Phillips, PEM
   Akil, H
AF Flagel, Shelly B.
   Clark, Jeremy J.
   Robinson, Terry E.
   Mayo, Leah
   Czuj, Alayna
   Willuhn, Ingo
   Akers, Christina A.
   Clinton, Sarah M.
   Phillips, Paul E. M.
   Akil, Huda
TI A selective role for dopamine in stimulus-reward learning
SO NATURE
LA English
DT Article
ID pavlovian approach behavior; nucleus-accumbens core; incentive salience; novelty-seeking; acquisition; sensitization; performance; receptors; systems; nmda
AB Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.
C1 [Clark, Jeremy J.; Willuhn, Ingo; Akers, Christina A.; Phillips, Paul E. M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Clark, Jeremy J.; Willuhn, Ingo; Akers, Christina A.; Phillips, Paul E. M.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Flagel, Shelly B.; Mayo, Leah; Clinton, Sarah M.; Akil, Huda] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
   [Robinson, Terry E.; Czuj, Alayna] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Phillips, PEM (corresponding author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
EM pemp@uw.edu; akil@umich.edu
FU National Institutes of Health [R01-MH079292, R01-DA027858, T32-DA07278, F32-DA24540, R37-DA04294, 5P01-DA021633-02]; Office of Naval Research [N00014-02-1-0879]; National Institute on Drug Abuse [T32DA007278] Funding Source: NIH RePORTER
NR 35
TC 748
Z9 933
U1 0
U2 167
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 6
PY 2011
VL 469
IS 7328
BP 53
EP U63
DI 10.1038/nature09588
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600029
PM 21150898
DA 2026-03-09
ER

PT J
AU Liu, CL
   Yang, XV
   Wu, JJ
   Kuei, C
   Mani, NS
   Zhang, L
   Yu, JX
   Sutton, SW
   Qin, N
   Banie, H
   Karlsson, L
   Sun, SQ
   Lovenberg, TW
AF Liu, Changlu
   Yang, Xia V.
   Wu, Jiejun
   Kuei, Chester
   Mani, Neelakandha S.
   Zhang, Li
   Yu, Jingxue
   Sutton, Steven W.
   Qin, Ning
   Banie, Homayon
   Karlsson, Lars
   Sun, Siquan
   Lovenberg, Timothy W.
TI Oxysterols direct B-cell migration through EBI2
SO NATURE
LA English
DT Article
ID cholesterol-metabolism; nuclear receptor; identification; activation; catalyzes; responses; mouse
AB EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein-Barr-virus infection(1). Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production(2-6). Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism(7-9). The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors(10,11). Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7 alpha,25-dihydroxycholesterol (OHC), with a dissociation constant of 450 pM for EBI2. In vitro, 7 alpha,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7 alpha,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7 alpha,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7 alpha,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.
C1 [Liu, Changlu; Yang, Xia V.; Wu, Jiejun; Kuei, Chester; Mani, Neelakandha S.; Zhang, Li; Yu, Jingxue; Sutton, Steven W.; Qin, Ning; Banie, Homayon; Karlsson, Lars; Sun, Siquan; Lovenberg, Timothy W.] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA.
C3 Johnson & Johnson; Johnson & Johnson USA
RP Liu, CL (corresponding author), Johnson & Johnson Pharmaceut Res & Dev LLC, 3210 Merryfield Row, San Diego, CA 92121 USA.
EM cliu9@its.jnj.com
NR 29
TC 320
Z9 357
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 519
EP U121
DI 10.1038/nature10226
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900045
PM 21796211
DA 2026-03-09
ER

PT J
AU Pryor, WR
   Rymer, AM
   Mitchell, DG
   Hill, TW
   Young, DT
   Saur, J
   Jones, GH
   Jacobsen, S
   Cowley, SWH
   Mauk, BH
   Coates, AJ
   Gustin, J
   Grodent, D
   Gérard, JC
   Lamy, L
   Nichols, JD
   Krimigis, SM
   Esposito, LW
   Dougherty, MK
   Jouchoux, AJ
   Stewart, AIF
   McClintock, WE
   Holsclaw, GM
   Ajello, JM
   Colwell, JE
   Hendrix, AR
   Crary, FJ
   Clarke, JT
   Zhou, XY
AF Pryor, Wayne R.
   Rymer, Abigail M.
   Mitchell, Donald G.
   Hill, Thomas W.
   Young, David T.
   Saur, Joachim
   Jones, Geraint H.
   Jacobsen, Sven
   Cowley, Stan W. H.
   Mauk, Barry H.
   Coates, Andrew J.
   Gustin, Jacques
   Grodent, Denis
   Gerard, Jean-Claude
   Lamy, Laurent
   Nichols, Jonathan D.
   Krimigis, Stamatios M.
   Esposito, Larry W.
   Dougherty, Michele K.
   Jouchoux, Alain J.
   Stewart, A. Ian F.
   McClintock, William E.
   Holsclaw, Gregory M.
   Ajello, Joseph M.
   Colwell, Joshua E.
   Hendrix, Amanda R.
   Crary, Frank J.
   Clarke, John T.
   Zhou, Xiaoyan
TI The auroral footprint of Enceladus on Saturn
SO NATURE
LA English
DT Article
ID io flux tube; cassini; atmosphere; magnetosphere; spectrometer; jupiter; origin; plasma; plume
AB Although there are substantial differences between the magnetospheres of Jupiter and Saturn, it has been suggested that cryovolcanic activity at Enceladus(1-9) could lead to electrodynamic coupling between Enceladus and Saturn like that which links Jupiter with Io, Europa and Ganymede. Powerful field-aligned electron beams associated with the Io-Jupiter coupling, for example, create an auroral footprint in Jupiter's ionosphere(10,11). Auroral ultraviolet emission associated with Enceladus-Saturn coupling is anticipated to be just a few tenths of a kilorayleigh (ref. 12), about an order of magnitude dimmer than Io's footprint and below the observable threshold, consistent with its non-detection(13). Here we report the detection of magnetic-field-aligned ion and electron beams (offset several moon radii downstream from Enceladus) with sufficient power to stimulate detectable aurora, and the subsequent discovery of Enceladus-associated aurora in a few per cent of the scans of the moon's footprint. The footprint varies in emission magnitude more than can plausibly be explained by changes in magnetospheric parameters-and as such is probably indicative of variable plume activity.
C1 [Rymer, Abigail M.; Mitchell, Donald G.; Mauk, Barry H.; Krimigis, Stamatios M.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Pryor, Wayne R.] Cent Arizona Coll, Dept Sci, Coolidge, AZ 85128 USA.
   [Pryor, Wayne R.] Space Environm Technol, Pacific Palisades, CA 90272 USA.
   [Hill, Thomas W.] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
   [Young, David T.; Crary, Frank J.] SW Res Inst, Space Sci & Engn Div, San Antonio, TX 78238 USA.
   [Saur, Joachim; Jacobsen, Sven] Univ Cologne, Inst Geophys & Meteorol, D-50923 Cologne, Germany.
   [Jones, Geraint H.; Coates, Andrew J.] Univ Coll London, Mullard Space Sci Lab, Dept Space & Climate Phys, Dorking RH5 6NT, Surrey, England.
   [Jones, Geraint H.] Univ London Birkbeck Coll, Ctr Planetary Sci, London WC1E 6BT, England.
   [Cowley, Stan W. H.; Nichols, Jonathan D.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Gustin, Jacques; Grodent, Denis; Gerard, Jean-Claude] Univ Liege, Lab Phys Atmospher & Planetaire, Dept Astrophys Geophys & Oceanog, B-4000 Liege, Belgium.
   [Lamy, Laurent] Univ Paris Diderot, Univ Pierre & Marie Curie, Lab Etud Spatiales & Instrumentat Astrophys, Observ Paris,Ctr Natl Rech Sci, F-92195 Meudon, France.
   [Krimigis, Stamatios M.] Acad Athens, Athens 11527, Greece.
   [Esposito, Larry W.; Jouchoux, Alain J.; Stewart, A. Ian F.; McClintock, William E.; Holsclaw, Gregory M.] Univ Colorado, Lab Atmospher & Space Phys, Boulder, CO 80303 USA.
   [Dougherty, Michele K.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, London SW7 2AZ, England.
   [Ajello, Joseph M.; Hendrix, Amanda R.; Zhou, Xiaoyan] Jet Prop Lab, Pasadena, CA 91109 USA.
   [Colwell, Joshua E.] Univ Cent Florida, Dept Phys, Orlando, FL 32816 USA.
   [Clarke, John T.] Boston Univ, Dept Astron, Boston, MA 02215 USA.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; Central Arizona College; Rice University; Southwest Research Institute; University of Cologne; University of London; University College London; University of London; Birkbeck University London; University of Leicester; University of Liege; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Academy of Athens; University of Colorado System; University of Colorado Boulder; Imperial College London; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); State University System of Florida; University of Central Florida; Boston University
RP Rymer, AM (corresponding author), Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
EM abigail.rymer@jhuapl.edu
FU NASA/ESA; NASA; STFC [PP/D005213/1, ST/H00260X/1, ST/H002480/1, ST/I00212X/1, PP/E001076/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/D005213/1, ST/H002480/1, ST/I00212X/1, ST/H00260X/1, PP/E001076/1] Funding Source: researchfish; UK Space Agency [ST/J00460X/1, PP/D00084X/1, ST/I002642/1] Funding Source: researchfish
NR 30
TC 89
Z9 96
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 APR 21
PY 2011
VL 472
IS 7343
BP 331
EP 333
DI 10.1038/nature09928
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600035
PM 21512570
DA 2026-03-09
ER

PT J
AU Zhao, TB
   Zhang, ZN
   Rong, ZL
   Xu, Y
AF Zhao, Tongbiao
   Zhang, Zhen-Ning
   Rong, Zhili
   Xu, Yang
TI Immunogenicity of induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID generation; fibroblasts; expression
AB Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells(1-5). Whereas it has been generally assumed that these autologous cells should be immune-tolerated by the recipient from whom the iPSCs are derived, their immunogenicity has not been vigorously examined. We show here that, whereas embryonic stem cells (ESCs) derived from inbred C57BL/6 (B6) mice can efficiently form teratomas in B6 mice without any evident immune rejection, the allogeneic ESCs from 129/SvJ mice fail to form teratomas in B6 mice due to rapid rejection by recipients. B6 mouse embryonic fibroblasts (MEFs) were reprogrammed into iPSCs by either retroviral approach (ViPSCs) or a novel episomal approach (EiPSCs) that causes no genomic integration. In contrast to B6 ESCs, teratomas formed by B6 ViPSCs were mostly immune-rejected by B6 recipients. In addition, the majority of teratomas formed by B6 EiPSCs were immunogenic in B6 mice with T cell infiltration, and apparent tissue damage and regression were observed in a small fraction of teratomas. Global gene expression analysis of teratomas formed by B6 ESCs and EiPSCs revealed a number of genes frequently over-expressed in teratomas derived from EiPSCs, and several such gene products were shown to contribute directly to the immunogenicity of the B6 EiPSC-derived cells in B6 mice. These findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients. Therefore, the immunogenicity of therapeutically valuable cells derived from patient-specific iPSCs should be evaluated before any clinical application of these autologous cells into the patients.
C1 [Zhao, Tongbiao; Zhang, Zhen-Ning; Rong, Zhili; Xu, Yang] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego
RP Xu, Y (corresponding author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM yangxu@ucsd.edu
FU NIH; California Institute for Regenerative Medicine [ET-01277]
NR 23
TC 1104
Z9 1281
U1 6
U2 268
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 212
EP U251
DI 10.1038/nature10135
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800050
PM 21572395
DA 2026-03-09
ER

PT J
AU Yoo, AS
   Sun, AX
   Li, L
   Shcheglovitov, A
   Portmann, T
   Li, YL
   Lee-Messer, C
   Dolmetsch, RE
   Tsien, RW
   Crabtree, GR
AF Yoo, Andrew S.
   Sun, Alfred X.
   Li, Li
   Shcheglovitov, Aleksandr
   Portmann, Thomas
   Li, Yulong
   Lee-Messer, Chris
   Dolmetsch, Ricardo E.
   Tsien, Richard W.
   Crabtree, Gerald R.
TI MicroRNA-mediated conversion of human fibroblasts to neurons
SO NATURE
LA English
DT Article
ID chromatin-remodeling complexes; subventricular zone; neural development; gene-expression; mir-124; rest; differentiation; neurogenesis; neocortex; network
AB Neurogenic transcription factors and evolutionarily conserved signalling pathways have been found to be instrumental in the formation of neurons(1,2). However, the instructive role of microRNAs (miRNAs) in neurogenesis remains unexplored. We recently discovered that miR-9* and miR-124 instruct compositional changes of SWI/SNF-like BAF chromatin-remodelling complexes, a process important for neuronal differentiation and function(3-6). Nearing mitotic exit of neural progenitors, miR-9* and miR-124 repress the BAF53a subunit of the neural-progenitor (np)BAF chromatin-remodelling complex. After mitotic exit, BAF53a is replaced by BAF53b, and BAF45a by BAF45b and BAF45c, which are then incorporated into neuron-specific (n)BAF complexes essential for post-mitotic functions(4). Because miR-9/9* and miR-124 also control multiple genes regulating neuronal differentiation and function(5,7-13), we proposed that these miRNAs might contribute to neuronal fates. Here we show that expression of miR-9/9* and miR-124 (miR-9/9*-124) in human fibroblasts induces their conversion into neurons, a process facilitated by NEUROD2. Further addition of neurogenic transcription factors ASCL1 and MYT1L enhances the rate of conversion and the maturation of the converted neurons, whereas expression of these transcription factors alone without miR-9/9*-124 was ineffective. These studies indicate that the genetic circuitry involving miR-9/9*-124 can have an instructive role in neural fate determination.
C1 [Yoo, Andrew S.; Crabtree, Gerald R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Yoo, Andrew S.; Crabtree, Gerald R.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Yoo, Andrew S.; Crabtree, Gerald R.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
   [Sun, Alfred X.] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA.
   [Li, Li; Li, Yulong; Tsien, Richard W.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Li, Li] Stanford Univ, Med Scientist Training Program, Stanford, CA 94305 USA.
   [Li, Li] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Shcheglovitov, Aleksandr; Portmann, Thomas; Dolmetsch, Ricardo E.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   [Lee-Messer, Chris] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
RP Crabtree, GR (corresponding author), Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM yooa@wustl.edu; crabtree@stanford.edu
FU Agency of Science, Technology and Research of Singapore (A*STAR); Stanford Medical Scientist Training Program; National Institutes of Mental Health (NIMH) [F30MH093125]; Frances B. Nelson predoctoral fellowship; CIRM; Swiss National Science Foundation SNSF [PA00P3_134196]; NIH [HD55391, AI060037, NS046789, NS24067, GM58234, MH064070]; Simon's Foundation; Simons Family Foundation; Mathers Family Foundation; Burnett Family Foundation; Howard Hughes Medical Institute; Swiss National Science Foundation (SNF) [PA00P3_134196] Funding Source: Swiss National Science Foundation (SNF)
NR 27
TC 794
Z9 981
U1 0
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 228
EP U123
DI 10.1038/nature10323
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900041
PM 21753754
DA 2026-03-09
ER

PT J
AU Cho, J
   Jeon, S
   Wilson, SA
   Liu, LV
   Kang, EA
   Braymer, JJ
   Lim, MH
   Hedman, B
   Hodgson, KO
   Valentine, JS
   Solomon, EI
   Nam, W
AF Cho, Jaeheung
   Jeon, Sujin
   Wilson, Samuel A.
   Liu, Lei V.
   Kang, Eun A.
   Braymer, Joseph J.
   Lim, Mi Hee
   Hedman, Britt
   Hodgson, Keith O.
   Valentine, Joan Selverstone
   Solomon, Edward I.
   Nam, Wonwoo
TI Structure and reactivity of a mononuclear non-haem iron(III)-peroxo complex
SO NATURE
LA English
DT Article
ID electronic-structure; spectroscopic characterization; crystal-structure; peroxo complex; iron; bond; deformylation; biosynthesis; intermediate; dioxygenase
AB Oxygen-containing mononuclear iron species-iron(III)-peroxo, iron(III)-hydroperoxo and iron(IV)-oxo-are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes(1-7). It has been difficult to generate synthetic analogues of these three active iron-oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(III)-peroxo complex, [Fe(III)(TMC)(OO)](+). We also report a series of chemical reactions in which this iron(III)-peroxo complex is cleanly converted to the iron(III)-hydroperoxo complex, [Fe(III)(TMC)(OOH)](2+), via a short-lived intermediate on protonation. This iron(III)-hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)](2+), via homolytic O-O bond cleavage of the iron(III)-hydroperoxo species. All three of these iron species-the three most biologically relevant iron-oxygen intermediates-have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)-hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)-oxo complex in C-H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)-hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes.
C1 [Cho, Jaeheung; Jeon, Sujin; Kang, Eun A.; Valentine, Joan Selverstone; Nam, Wonwoo] Ewha Womans Univ, Dept Chem & Nano Sci, Ctr Biomimet Syst, Dept Bioinspired Sci, Seoul 120750, South Korea.
   [Wilson, Samuel A.; Liu, Lei V.; Hodgson, Keith O.; Solomon, Edward I.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Braymer, Joseph J.; Lim, Mi Hee] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Braymer, Joseph J.; Lim, Mi Hee] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
   [Hedman, Britt; Hodgson, Keith O.; Solomon, Edward I.] Stanford Univ, SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
   [Valentine, Joan Selverstone] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
C3 Ewha Womans University; Stanford University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; University of California System; University of California Los Angeles
RP Valentine, JS (corresponding author), Ewha Womans Univ, Dept Chem & Nano Sci, Ctr Biomimet Syst, Dept Bioinspired Sci, Seoul 120750, South Korea.
EM jsv@chem.ucla.edu; edward.solomon@stanford.edu; wwnam@ewha.ac.kr
FU NRF/MEST of Korea through the CRI; NRF/MEST of Korea through the GRL [2010-00353]; NRF/MEST of Korea through the WCU [R31-2008-000-10010-0]; NIH [GM 40392, RR-001209]; NSF [MCB 0919027]; NSF EAPSI [OISE-1014685]; University of Michigan; Department of Energy (DOE) Office of Science; DOE, Office of Biological and Environmental Research; NIH, National Center for Research Resources [5P41RR001209]; National Institute of General Medical Sciences [R01GM040392] Funding Source: NIH RePORTER
NR 30
TC 286
Z9 323
U1 7
U2 279
PU 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 27
PY 2011
VL 478
IS 7370
BP 502
EP 505
DI 10.1038/nature10535
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200040
PM 22031443
DA 2026-03-09
ER

PT J
AU Ford, MGJ
   Jenni, S
   Nunnari, J
AF Ford, Marijn G. J.
   Jenni, Simon
   Nunnari, Jodi
TI The crystal structure of dynamin
SO NATURE
LA English
DT Article
ID pleckstrin homology domain; clathrin-mediated endocytosis; gtpase activity; in-vivo; conformational-changes; binding proteins; mechanism; fission; mitochondrial; constriction
AB Dynamin-related proteins (DRPs) are multi-domain GTPases that function via oligomerization and GTP-dependent conformational changes to play central roles in regulating membrane structure across phylogenetic kingdoms. How DRPs harness self-assembly and GTP-dependent conformational changes to remodel membranes is not understood. Here we present the crystal structure of an assembly-deficient mammalian endocytic DRP, dynamin 1, lacking the proline-rich domain, in its nucleotide-free state. The dynamin 1 monomer is an extended structure with the GTPase domain and bundle signalling element positioned on top of a long helical stalk with the pleckstrin homology domain flexibly attached on its opposing end. Dynamin 1 dimer and higher order dimer multimers form via interfaces located in the stalk. Analysis of these interfaces provides insight into DRP family member specificity and regulation and provides a framework for understanding the biogenesis of higher order DRP structures and the mechanism of DRP-mediated membrane scission events.
C1 [Ford, Marijn G. J.; Nunnari, Jodi] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Jenni, Simon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 University of California System; University of California Davis; Harvard University; Harvard Medical School
RP Nunnari, J (corresponding author), Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
EM jmnunnari@ucdavis.edu
FU Howard Hughes Medical Institute [DRG-2004-09]; American Heart Innovator Award; NIH [R01GM062942S1, R01GM097432]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]
NR 42
TC 214
Z9 254
U1 1
U2 39
PU 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 29
PY 2011
VL 477
IS 7366
BP 561
EP 566
DI 10.1038/nature10441
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900033
PM 21927001
DA 2026-03-09
ER

PT J
AU Simon, J
   Bakr, WS
   Ma, RC
   Tai, ME
   Preiss, PM
   Greiner, M
AF Simon, Jonathan
   Bakr, Waseem S.
   Ma, Ruichao
   Tai, M. Eric
   Preiss, Philipp M.
   Greiner, Markus
TI Quantum simulation of antiferromagnetic spin chains in an optical lattice
SO NATURE
LA English
DT Article
ID atomic mott insulator; ultracold atoms; trapped ions; gas; transition; superfluid; criticality; symmetry; physics; state
AB Understanding exotic forms of magnetism in quantum mechanical systems is a central goal of modern condensed matter physics, with implications for systems ranging from high-temperature superconductors to spintronic devices. Simulating magnetic materials in the vicinity of a quantum phase transition is computationally intractable on classical computers, owing to the extreme complexity arising from quantum entanglement between the constituent magnetic spins. Here we use a degenerate Bose gas of rubidium atoms confined in an optical lattice to simulate a chain of interacting quantum Ising spins as they undergo a phase transition. Strong spin interactions are achieved through a site-occupation to pseudo-spin mapping. As we vary a magnetic field, quantum fluctuations drive a phase transition from a paramagnetic phase into an antiferromagnetic phase. In the paramagnetic phase, the interaction between the spins is overwhelmed by the applied field, which aligns the spins. In the antiferromagnetic phase, the interaction dominates and produces staggered magnetic ordering. Magnetic domain formation is observed through both in situ site-resolved imaging and noise correlation measurements. By demonstrating a route to quantum magnetism in an optical lattice, this work should facilitate further investigations of magnetic models using ultracold atoms, thereby improving our understanding of real magnetic materials.
C1 [Simon, Jonathan; Bakr, Waseem S.; Ma, Ruichao; Tai, M. Eric; Preiss, Philipp M.; Greiner, Markus] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 Harvard University
RP Greiner, M (corresponding author), Harvard Univ, Dept Phys, 17 Oxford St, Cambridge, MA 02138 USA.
EM greiner@physics.harvard.edu
FU Army Research Office DARPA OLE; AFOSR MURI; NSF
NR 49
TC 779
Z9 894
U1 1
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 21
PY 2011
VL 472
IS 7343
BP 307
EP U200
DI 10.1038/nature09994
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600031
PM 21490600
DA 2026-03-09
ER

PT J
AU Rappuoli, R
   Aderem, A
AF Rappuoli, Rino
   Aderem, Alan
TI A 2020 vision for vaccines against HIV, tuberculosis and malaria
SO NATURE
LA English
DT Article
ID cell-mediated-immunity; yellow-fever vaccine; double-blind; systems biology; efficacy; design; antibody; trial; immunogenicity; immunization
AB Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.
C1 [Rappuoli, Rino] Novartis Vaccines & Diagnost, I-53100 Siena, Italy.
   [Aderem, Alan] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
C3 Novartis; Novartis Italy; Center for Infectious Disease Research
RP Rappuoli, R (corresponding author), Novartis Vaccines & Diagnost, I-53100 Siena, Italy.
EM rino.rappuoli@novartis.com
NR 58
TC 219
Z9 246
U1 1
U2 58
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 26
PY 2011
VL 473
IS 7348
BP 463
EP 469
DI 10.1038/nature10124
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300031
PM 21614073
DA 2026-03-09
ER

PT J
AU Purcell, CW
   Bullock, JS
   Tollerud, EJ
   Rocha, M
   Chakrabarti, S
AF Purcell, Chris W.
   Bullock, James S.
   Tollerud, Erik J.
   Rocha, Miguel
   Chakrabarti, Sukanya
TI The Sagittarius impact as an architect of spirality and outer rings in the Milky Way
SO NATURE
LA English
DT Article
ID sky survey view; dwarf galaxy; substructure; stars
AB Like many galaxies of its size, the Milky Way is a disk with prominent spiral arms rooted in a central bar(1), although our knowledge of its structure and origin is incomplete. Traditional attempts to understand our Galaxy's morphology assume that it has been unperturbed by major external forces. Here we report simulations of the response of the Milky Way to the infall of the Sagittarius(2) dwarf galaxy (Sgr), which results in the formation of spiral arms, influences the central bar and produces a flared outer disk. Two ring-like wrappings emerge towards the Galactic anti-Centre in our model that are reminiscent of the low-latitude arcs observed in the same area of the Milky Way. Previous models have focused on Sgr itself(3,4) to reproduce the dwarf's orbital history and place associated constraints on the shape of the Milky Way gravitational potential, treating the Sgr impact event as a trivial influence on the Galactic disk. Our results show that the Milky Way's morphology is not purely secular in origin and that low-mass minor mergers predicted to be common throughout the Universe(5) probably have a similarly important role in shaping galactic structure.
C1 [Purcell, Chris W.] Univ Pittsburgh, Dept Phys & Astron, Pittsburgh, PA 15260 USA.
   [Purcell, Chris W.; Bullock, James S.; Tollerud, Erik J.; Rocha, Miguel] Univ Calif Irvine, Dept Phys & Astron, Ctr Cosmol, Irvine, CA 92697 USA.
   [Chakrabarti, Sukanya] Florida Atlantic Univ, Dept Phys, Boca Raton, FL 33431 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of California System; University of California Irvine; State University System of Florida; Florida Atlantic University
RP Purcell, CW (corresponding author), Univ Pittsburgh, Dept Phys & Astron, Pittsburgh, PA 15260 USA.
EM cpurcell@pitt.edu
FU Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009973] Funding Source: National Science Foundation
NR 30
TC 219
Z9 236
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 301
EP 303
DI 10.1038/nature10417
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400024
PM 21921911
DA 2026-03-09
ER

PT J
AU Shultz, S
   Opie, C
   Atkinson, QD
AF Shultz, Susanne
   Opie, Christopher
   Atkinson, Quentin D.
TI Stepwise evolution of stable sociality in primates
SO NATURE
LA English
DT Article
ID correlated evolution; organization; dispersal; selection; brain; birds
AB Although much attention has been focused on explaining and describing the diversity of social grouping patterns among primates(1-3), less effort has been devoted to understanding the evolutionary history of social living(4). This is partly because social behaviours do not fossilize, making it difficult to infer changes over evolutionary time. However, primate social behaviour shows strong evidence for phylogenetic inertia, permitting the use of Bayesian comparative methods to infer changes in social behaviour through time, thereby allowing us to evaluate alternative models of social evolution. Here we present a model of primate social evolution, whereby sociality progresses from solitary foraging individuals directly to large multi-male/multi-female aggregations (approximately 52 million years (Myr) ago), with pair-living (approximately 16 Myr ago) or single-male harem systems (approximately 16 Myr ago) derivative from this second stage. This model fits the data significantly better than the two widely accepted alternatives (an unstructured model implied by the socioecological hypothesis or a model that allows linear stepwise changes in social complexity through time). We also find strong support for the co-evolution of social living with a change from nocturnal to diurnal activity patterns, but not with sex-biased dispersal. This supports suggestions that social living may arise because of increased predation risk associated with diurnal activity. Sociality based on loose aggregation is followed by a second shift to stable or bonded groups. This structuring facilitates the evolution of cooperative behaviours(5) and may provide the scaffold for other distinctive anthropoid traits including coalition formation, cooperative resource defence and large brains.
C1 [Shultz, Susanne; Opie, Christopher; Atkinson, Quentin D.] Univ Oxford, Inst Cognit & Evolutionary Anthropol, Oxford OX2 6PN, England.
   [Atkinson, Quentin D.] Univ Auckland, Dept Psychol, Auckland, New Zealand.
C3 University of Oxford; University of Auckland
RP Shultz, S (corresponding author), Univ Oxford, Inst Cognit & Evolutionary Anthropol, 64 Banbury Rd, Oxford OX2 6PN, England.
EM susanne.shultz@anthro.ox.ac.uk
FU Royal Society
NR 41
TC 260
Z9 304
U1 0
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 10
PY 2011
VL 479
IS 7372
BP 219
EP U96
DI 10.1038/nature10601
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800040
PM 22071768
DA 2026-03-09
ER

PT J
AU Mukherjee, S
   Liu, XY
   Arasaki, K
   McDonough, J
   Galán, JE
   Roy, CR
AF Mukherjee, Shaeri
   Liu, Xiaoyun
   Arasaki, Kohei
   McDonough, Justin
   Galan, Jorge E.
   Roy, Craig R.
TI Modulation of Rab GTPase function by a protein phosphocholine transferase
SO NATURE
LA English
DT Article
ID legionella-pneumophila; identification; ampylation; domain; drra; displacement
AB The intracellular pathogen Legionella pneumophila modulates the activity of host GTPases to direct the transport and assembly of the membrane-bound compartment in which it resides(1-6). In vitro studies have indicated that the Legionella protein DrrA post-translationally modifies the GTPase Rab1 by a process called AMPylation(7). Here we used mass spectrometry to investigate post-translational modifications to Rab1 that occur during infection of host cells by Legionella. Consistent with in vitro studies, DrrA-mediated AMPylation of a conserved tyrosine residue in the switch II region of Rab1 was detected during infection. In addition, a modification to an adjacent serine residue in Rab1 was discovered, which was independent of DrrA. The Legionella effector protein AnkX was required for this modification. Biochemical studies determined that AnkX directly mediates the covalent attachment of a phosphocholine moiety to Rab1. This phosphocholine transferase activity used CDP-choline as a substrate and required a conserved histidine residue located in the FIC domain of the AnkX protein. During infection, AnkX modified both Rab1 and Rab35, which explains how this protein modulates membrane transport through both the endocytic and exocytic pathways of the host cell. Thus, phosphocholination of Rab GTPases represents a mechanism by which bacterial FIC-domain-containing proteins can alter host-cell functions.
C1 [Mukherjee, Shaeri; Liu, Xiaoyun; Arasaki, Kohei; McDonough, Justin; Galan, Jorge E.; Roy, Craig R.] Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA.
C3 Yale University
RP Roy, CR (corresponding author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, 295 Congress Ave, New Haven, CT 06536 USA.
EM craig.roy@yale.edu
FU Anna Fuller Fellowship; National Institutes of Health (NIH) [F32 AI082927, R01-AI064559, R01-AI048770]; Northeast Biodefense Center [U54-AI057158-Lipkin]
CR Allaire PD, 2010, MOL CELL, V37, P370, DOI 10.1016/j.molcel.2009.12.037
   Arasaki K, 2010, TRAFFIC, V11, P587, DOI 10.1111/j.1600-0854.2010.01050.x
   BERGER KH, 1994, MOL MICROBIOL, V14, P809, DOI 10.1111/j.1365-2958.1994.tb01317.x
   Brombacher E, 2009, J BIOL CHEM, V284, P4846, DOI 10.1074/jbc.M807505200
   Chen C, 2010, P NATL ACAD SCI USA, V107, P21755, DOI 10.1073/pnas.1010485107
   Grabitzki J, 2008, MOL BIOCHEM PARASIT, V161, P101, DOI 10.1016/j.molbiopara.2008.06.014
   GROSS ML, 1994, J AM SOC MASS SPECTR, V5, P57, DOI 10.1016/1044-0305(94)85036-4
   Ingmundson A, 2007, NATURE, V450, P365, DOI 10.1038/nature06336
   Kagan JC, 2004, J EXP MED, V199, P1201, DOI 10.1084/jem.20031706
   Kinch LN, 2009, PLOS ONE, V4, P0, DOI 10.1371/journal.pone.0005818
   Li ZY, 2008, J LIPID RES, V49, P1187, DOI 10.1194/jlr.R700019-JLR200
   Lovell TM, 2007, J MOL ENDOCRINOL, V39, P189, DOI 10.1677/JME-07-0007
   Machner MP, 2007, SCIENCE, V318, P974, DOI 10.1126/science.1149121
   Machner MP, 2006, DEV CELL, V11, P47, DOI 10.1016/j.devcel.2006.05.013
   Müller MP, 2010, SCIENCE, V329, P946, DOI 10.1126/science.1192276
   Murata T, 2006, NAT CELL BIOL, V8, P971, DOI 10.1038/ncb1463
   Nagai H, 2002, SCIENCE, V295, P679, DOI 10.1126/science.1067025
   Ninio S, 2007, TRENDS MICROBIOL, V15, P372, DOI 10.1016/j.tim.2007.06.006
   Pan XX, 2008, SCIENCE, V320, P1651, DOI 10.1126/science.1158160
   Roy CR, 2009, SCI SIGNAL, V2, P0, DOI 10.1126/scisignal.262pe14
   Schoebel S, 2009, MOL CELL, V36, P1060, DOI 10.1016/j.molcel.2009.11.014
   Suh HY, 2010, EMBO J, V29, P496, DOI 10.1038/emboj.2009.347
   Worby CA, 2009, MOL CELL, V34, P93, DOI 10.1016/j.molcel.2009.03.008
   Yarbrough ML, 2009, NAT CHEM BIOL, V5, P378, DOI 10.1038/nchembio0609-378
   Yarbrough ML, 2009, SCIENCE, V323, P269, DOI 10.1126/science.1166382
   Zhu YQ, 2010, P NATL ACAD SCI USA, V107, P4699, DOI 10.1073/pnas.0914231107
   Zuckman DM, 1999, MOL MICROBIOL, V32, P990, DOI 10.1046/j.1365-2958.1999.01410.x
NR 27
TC 258
Z9 330
U1 0
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 103
EP U122
DI 10.1038/nature10335
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300040
PM 21822290
DA 2026-03-09
ER

PT J
AU Radu, I
   Vahaplar, K
   Stamm, C
   Kachel, T
   Pontius, N
   Dürr, HA
   Ostler, TA
   Barker, J
   Evans, RFL
   Chantrell, RW
   Tsukamoto, A
   Itoh, A
   Kirilyuk, A
   Rasing, T
   Kimel, AV
AF Radu, I.
   Vahaplar, K.
   Stamm, C.
   Kachel, T.
   Pontius, N.
   Duerr, H. A.
   Ostler, T. A.
   Barker, J.
   Evans, R. F. L.
   Chantrell, R. W.
   Tsukamoto, A.
   Itoh, A.
   Kirilyuk, A.
   Rasing, Th.
   Kimel, A. V.
TI Transient ferromagnetic-like state mediating ultrafast reversal of antiferromagnetically coupled spins
SO NATURE
LA English
DT Article
ID nickel
AB Ferromagnetic or antiferromagnetic spin ordering is governed by the exchange interaction, the strongest force in magnetism(1-4). Understanding spin dynamics in magnetic materials is an issue of crucial importance for progress in information processing and recording technology. Usually the dynamics are studied by observing the collective response of exchange-coupled spins, that is, spin resonances, after an external perturbation by a pulse of magnetic field, current or light. The periods of the corresponding resonances range from one nanosecond for ferromagnets down to one picosecond for antiferromagnets. However, virtually nothing is known about the behaviour of spins in a magnetic material after being excited on a timescale faster than that corresponding to the exchange interaction (10-100 fs), that is, in a non-adiabatic way. Here we use the element-specific technique X-ray magnetic circular dichroism to study spin reversal in GdFeCo that is optically excited on a timescale pertinent to the characteristic time of the exchange interaction between Gd and Fe spins. We unexpectedly find that the ultrafast spin reversal in this material, where spins are coupled antiferromagnetically, occurs by way of a transient ferromagnetic-like state. Following the optical excitation, the net magnetizations of the Gd and Fe sublattices rapidly collapse, switch their direction and rebuild their net magnetic moments at substantially different timescales; the net magnetic moment of the Gd sublattice is found to reverse within 1.5 picoseconds, which is substantially slower than the Fe reversal time of 300 femtoseconds. Consequently, a transient state characterized by a temporary parallel alignment of the net Gd and Fe moments emerges, despite their ground-state antiferromagnetic coupling. These surprising observations, supported by atomistic simulations, provide a concept for the possibility of manipulating magnetic order on the timescale of the exchange interaction.
C1 [Radu, I.; Vahaplar, K.; Kirilyuk, A.; Rasing, Th.; Kimel, A. V.] Radboud Univ Nijmegen, Inst Mol & Mat, NL-6525 AJ Nijmegen, Netherlands.
   [Radu, I.; Stamm, C.; Kachel, T.; Pontius, N.; Duerr, H. A.] BESSY II, Helmholtz Zentrum Berlin Mat & Energie, D-12489 Berlin, Germany.
   [Duerr, H. A.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Ostler, T. A.; Barker, J.; Evans, R. F. L.; Chantrell, R. W.] Univ York, Dept Phys, York YO10 5DD, N Yorkshire, England.
   [Tsukamoto, A.; Itoh, A.] Nihon Univ, Coll Sci & Technol, Chiba, Japan.
   [Tsukamoto, A.] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan.
C3 Radboud University Nijmegen; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; University of York - UK; Nihon University; Japan Science & Technology Agency (JST)
RP Radu, I (corresponding author), Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.
EM i.radu@science.ru.nl; a.kimel@science.ru.nl
FU European Community [NMP3-SL-2008-214469, 214810, 226716]; Foundation for Fundamental Research on Matter (FOM); Netherlands Organization for Scientific Research (NWO); Nihon University; US Department of Energy [DE-AC02-76SF00515]
NR 18
TC 907
Z9 988
U1 7
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 APR 14
PY 2011
VL 472
IS 7342
BP 205
EP 208
DI 10.1038/nature09901
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100039
PM 21451521
DA 2026-03-09
ER

PT J
AU Lister, R
   Pelizzola, M
   Kida, YS
   Hawkins, RD
   Nery, JR
   Hon, G
   Antosiewicz-Bourget, J
   O'Malley, R
   Castanon, R
   Klugman, S
   Downes, M
   Yu, R
   Stewart, R
   Ren, B
   Thomson, JA
   Evans, RM
   Ecker, JR
AF Lister, Ryan
   Pelizzola, Mattia
   Kida, Yasuyuki S.
   Hawkins, R. David
   Nery, Joseph R.
   Hon, Gary
   Antosiewicz-Bourget, Jessica
   O'Malley, Ronan
   Castanon, Rosa
   Klugman, Sarit
   Downes, Michael
   Yu, Ruth
   Stewart, Ron
   Ren, Bing
   Thomson, James A.
   Evans, Ronald M.
   Ecker, Joseph R.
TI Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID dna methylation; differentiation; genes; mice
AB Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.
C1 [Lister, Ryan; Pelizzola, Mattia; Nery, Joseph R.; O'Malley, Ronan; Castanon, Rosa; Ecker, Joseph R.] Salk Inst Biol Studies, Genome Anal Lab, La Jolla, CA 92037 USA.
   [Kida, Yasuyuki S.; Downes, Michael; Yu, Ruth; Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA.
   [Hawkins, R. David; Hon, Gary; Klugman, Sarit; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Antosiewicz-Bourget, Jessica; Stewart, Ron; Thomson, James A.] Morgridge Inst Res, Madison, WI 53707 USA.
   [Antosiewicz-Bourget, Jessica; Stewart, Ron; Thomson, James A.] Genome Ctr Wisconsin, Madison, WI 53706 USA.
   [Ren, Bing] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Thomson, James A.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
   [Thomson, James A.] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA.
C3 Salk Institute; Salk Institute; Howard Hughes Medical Institute; Ludwig Institute for Cancer Research; University of Wisconsin System; University of Wisconsin Madison; The Morgridge Institute for Research, Inc.; University of California System; University of California San Diego; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Ecker, JR (corresponding author), Salk Inst Biol Studies, Genome Anal Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ecker@salk.edu
FU California Institute; Catharina Foundation; American Cancer Society; Japan Society for the Promotion of Science; Mary K. Chapman Foundation; National Science Foundation (NSF) [NSF 0726408]; National Institutes of Health (NIH) [U01 ES017166, U01 1U01ES017166-01, DK062434]; California Institute for Regenerative Medicine [RB2-01530]; Morgridge Institute for Research; Howard Hughes Medical Institute; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER
NR 37
TC 1196
Z9 1431
U1 1
U2 334
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 3
PY 2011
VL 471
IS 7336
BP 68
EP U84
DI 10.1038/nature09798
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100035
PM 21289626
DA 2026-03-09
ER

PT J
AU Li, HJ
   Haurigot, V
   Doyon, Y
   Li, TJ
   Wong, SNY
   Bhagwat, AS
   Malani, N
   Anguela, XM
   Sharma, R
   Ivanciu, L
   Murphy, SL
   Finn, JD
   Khazi, FR
   Zhou, SZ
   Paschon, DE
   Rebar, EJ
   Bushman, FD
   Gregory, PD
   Holmes, MC
   High, KA
AF Li, Hojun
   Haurigot, Virginia
   Doyon, Yannick
   Li, Tianjian
   Wong, Sunnie Y.
   Bhagwat, Anand S.
   Malani, Nirav
   Anguela, Xavier M.
   Sharma, Rajiv
   Ivanciu, Lacramiora
   Murphy, Samuel L.
   Finn, Jonathan D.
   Khazi, Fayaz R.
   Zhou, Shangzhen
   Paschon, David E.
   Rebar, Edward J.
   Bushman, Frederic D.
   Gregory, Philip D.
   Holmes, Michael C.
   High, Katherine A.
TI In vivo genome editing restores haemostasis in a mouse model of haemophilia
SO NATURE
LA English
DT Article
ID zinc-finger nucleases; lebers congenital amaurosis; gene-therapy; factor-ix; chimeric nucleases; cells; transduction; vector; disruption; deficiency
AB Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation(1). In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus(2-4), but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.
C1 [Li, Hojun; Haurigot, Virginia; Bhagwat, Anand S.; Anguela, Xavier M.; Sharma, Rajiv; Ivanciu, Lacramiora; Murphy, Samuel L.; Finn, Jonathan D.; Khazi, Fayaz R.; Zhou, Shangzhen; High, Katherine A.] Childrens Hosp Philadelphia, CTRB 5000, Div Hematol, Philadelphia, PA 19104 USA.
   [Doyon, Yannick; Li, Tianjian; Wong, Sunnie Y.; Paschon, David E.; Rebar, Edward J.; Gregory, Philip D.; Holmes, Michael C.] Sangamo BioSci, Point Richmond Tech Ctr, Richmond, CA 94804 USA.
   [Malani, Nirav; Bushman, Frederic D.] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [High, Katherine A.] Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Sangamo Therapeutics, Inc.; University of Pennsylvania; Howard Hughes Medical Institute
RP High, KA (corresponding author), Childrens Hosp Philadelphia, CTRB 5000, Div Hematol, 3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM mholmes@sangamo.com; high@email.chop.edu
FU National Institutes of Health; Howard Hughes Medical Institute; National Heart Lung and Blood Institute [T32HL007150] Funding Source: NIH RePORTER
NR 30
TC 429
Z9 625
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 JUL 14
PY 2011
VL 475
IS 7355
BP 217
EP U128
DI 10.1038/nature10177
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500048
PM 21706032
DA 2026-03-09
ER

PT J
AU Navarrete, A
   van Schaik, CP
   Isler, K
AF Navarrete, Ana
   van Schaik, Carel P.
   Isler, Karin
TI Energetics and the evolution of human brain size
SO NATURE
LA English
DT Article
ID expensive-tissue hypothesis; hominins; mammals; birds; intelligence; vertebrates; metabolism; primates; system; costs
AB The human brain stands out among mammals by being unusually large. The expensive-tissue hypothesis(1) explains its evolution by proposing a trade-off between the size of the brain and that of the digestive tract, which is smaller than expected for a primate of our body size. Although this hypothesis is widely accepted, empirical support so far has been equivocal. Here we test it in a sample of 100 mammalian species, including 23 primates, by analysing brain size and organ mass data. We found that, controlling for fat-free body mass, brain size is not negatively correlated with the mass of the digestive tract or any other expensive organ, thus refuting the expensive-tissue hypothesis. Nonetheless, consistent with the existence of energy trade-offs with brain size, we find that the size of brains and adipose depots are negatively correlated in mammals, indicating that encephalization and fat storage are compensatory strategies to buffer against starvation. However, these two strategies can be combined if fat storage does not unduly hamper locomotor efficiency. We propose that human encephalization was made possible by a combination of stabilization of energy inputs and a redirection of energy from locomotion, growth and reproduction.
C1 [Navarrete, Ana; van Schaik, Carel P.; Isler, Karin] Univ Zurich, Anthropol Inst & Museum, CH-8057 Zurich, Switzerland.
C3 University of Zurich
RP Navarrete, A (corresponding author), Univ Zurich, Anthropol Inst & Museum, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM a.navarrete@aim.uzh.ch; kisler@aim.uzh.ch
FU Swiss National Science Foundation [3100A0-117789]; A.H. Schultz-Stiftung; European Integrated Activities grant SYNTHESYS [HU-TAF-4916]
NR 35
TC 348
Z9 402
U1 1
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 DEC 1
PY 2011
VL 480
IS 7375
BP 91
EP U252
DI 10.1038/nature10629
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PO
UT WOS:000298031900040
PM 22080949
DA 2026-03-09
ER

PT J
AU Attwood, BK
   Bourgognon, JM
   Patel, S
   Mucha, M
   Schiavon, E
   Skrzypiec, AE
   Young, KW
   Shiosaka, S
   Korostynski, M
   Piechota, M
   Przewlocki, R
   Pawlak, R
AF Attwood, Benjamin K.
   Bourgognon, Julie-Myrtille
   Patel, Satyam
   Mucha, Mariusz
   Schiavon, Emanuele
   Skrzypiec, Anna E.
   Young, Kenneth W.
   Shiosaka, Sadao
   Korostynski, Michal
   Piechota, Marcin
   Przewlocki, Ryszard
   Pawlak, Robert
TI Neuropsin cleaves EphB2 in the amygdala to control anxiety
SO NATURE
LA English
DT Article
ID tissue-plasminogen activator; nmda receptors; stress; brain; gene; polymorphisms; hippocampal; modulation; expression; behavior
AB A minority of individuals experiencing traumatic events develop anxiety disorders. The reason for the lack of correspondence between the prevalence of exposure to psychological trauma and the development of anxiety is unknown. Extracellular proteolysis contributes to fear-associated responses by facilitating neuronal plasticity at the neuron-matrix interface(1-4). Here we show in mice that the serine protease neuropsin is critical for stress-related plasticity in the amygdala by regulating the dynamics of the EphB2-NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour. Stress results in neuropsin-dependent cleavage of EphB2 in the amygdala causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2-NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression and enhances behavioural signatures of anxiety. On stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2-NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety. The behavioural response to stress can be restored by intra-amygdala injection of neuropsin into neuropsin-deficient mice and disrupted by the injection of either anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of wild-type mice. Our findings establish a novel neuronal pathway linking stress-induced proteolysis of EphB2 in the amygdala to anxiety.
C1 [Attwood, Benjamin K.; Bourgognon, Julie-Myrtille; Patel, Satyam; Mucha, Mariusz; Schiavon, Emanuele; Skrzypiec, Anna E.; Pawlak, Robert] Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
   [Young, Kenneth W.] MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England.
   [Shiosaka, Sadao] Nara Inst Sci & Technol, Div Struct Cell Biol, Nara 6300192, Japan.
   [Korostynski, Michal; Piechota, Marcin; Przewlocki, Ryszard] Polish Acad Sci, Inst Pharmacol, Dept Mol Neuropharmacol, PL-31343 Krakow, Poland.
C3 University of Leicester; University of Leicester; Nara Institute of Science & Technology; Polish Academy of Sciences
RP Pawlak, R (corresponding author), Univ Leicester, Dept Cell Physiol & Pharmacol, Univ Rd, Leicester LE1 9HN, Leics, England.
EM rp135@le.ac.uk
FU Medical Research Council [G0500231/73852]; European Commission [MEXT-CT-2006-042265, LSHM-CT-2004-005166]; Medisearch Fellowship; Ministry of Education, Culture, Sports, Science and Technology of Japan [20300128]; Japan Science and Technology Agency; Ministry of Science and Higher Education of Poland [NN405 274137]; MRC [G0500231] Funding Source: UKRI; Grants-in-Aid for Scientific Research [20300128] Funding Source: KAKEN; Medical Research Council [G0500231] Funding Source: researchfish
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   Pawlak R, 2003, NAT NEUROSCI, V6, P168, DOI 10.1038/nn998
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NR 30
TC 169
Z9 191
U1 0
U2 27
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 19
PY 2011
VL 473
IS 7347
BP 372
EP U553
DI 10.1038/nature09938
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 765QA
UT WOS:000290722400048
PM 21508957
DA 2026-03-09
ER

PT J
AU Haldane, AG
   May, RM
AF Haldane, Andrew G.
   May, Robert M.
TI Systemic risk in banking ecosystems
SO NATURE
LA English
DT Article
ID network structure; complex-systems; ecology; model
AB In the run-up to the recent financial crisis, an increasingly elaborate set of financial instruments emerged, intended to optimize returns to individual institutions with seemingly minimal risk. Essentially no attention was given to their possible effects on the stability of the system as a whole. Drawing analogies with the dynamics of ecological food webs and with networks within which infectious diseases spread, we explore the interplay between complexity and stability in deliberately simplified models of financial networks. We suggest some policy lessons that can be drawn from such models, with the explicit aim of minimizing systemic risk.
C1 [May, Robert M.] Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
   [Haldane, Andrew G.] Bank England, London EC2R 8AH, England.
C3 University of Oxford; Bank of England
RP May, RM (corresponding author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM robert.may@zoo.ox.ac.uk
NR 40
TC 862
Z9 1041
U1 14
U2 462
PU NATURE PUBLISHING 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 20
PY 2011
VL 469
IS 7330
BP 
EP 
DI 10.1038/nature09659
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 708SW
UT WOS:000286385600042
PM 21248842
DA 2026-03-09
ER

PT J
AU Saraux, C
   Le Bohec, C
   Durant, JM
   Viblanc, VA
   Gauthier-Clerc, M
   Beaune, D
   Park, YH
   Yoccoz, NG
   Stenseth, NC
   Le Maho, Y
AF Saraux, Claire
   Le Bohec, Celine
   Durant, Joel M.
   Viblanc, Vincent A.
   Gauthier-Clerc, Michel
   Beaune, David
   Park, Young-Hyang
   Yoccoz, Nigel G.
   Stenseth, Nils C.
   Le Maho, Yvon
TI Reliability of flipper-banded penguins as indicators of climate change
SO NATURE
LA English
DT Article
ID population-dynamics; king penguin; reproduction; survival; behavior
AB In 2007, the Intergovernmental Panel on Climate Change highlighted an urgent need to assess the responses of marine ecosystems to climate change(1). Because they lie in a high-latitude region, the Southern Ocean ecosystems are expected to be strongly affected by global warming. Using top predators of this highly productive ocean(2) (such as penguins) as integrative indicators may help us assess the impacts of climate change on marine ecosystems(3,4). Yet most available information on penguin population dynamics is based on the controversial use of flipper banding. Although some reports have found the effects of flipper bands to be deleterious(5-8), some short-term (one-year) studies have concluded otherwise(9-11), resulting in the continuation of extensive banding schemes and the use of data sets thus collected to predict climate impact on natural populations(12,13). Here we show that banding of free-ranging king penguins (Aptenodytes patagonicus) impairs both survival and reproduction, ultimately affecting population growth rate. Over the course of a 10-year longitudinal study, banded birds produced 39% fewer chicks and had a survival rate 16% lower than non-banded birds, demonstrating a massive long-term impact of banding and thus refuting the assumption that birds will ultimately adapt to being banded(6,12). Indeed, banded birds still arrived later for breeding at the study site and had longer foraging trips even after 10 years. One of our major findings is that responses of flipper-banded penguins to climate variability (that is, changes in sea surface temperature and in the Southern Oscillation index) differ from those of non-banded birds. We show that only long-term investigations may allow an evaluation of the impact of flipper bands and that every major life-history trait can be affected, calling into question the banding schemes still going on. In addition, our understanding of the effects of climate change on marine ecosystems based on flipper-band data should be reconsidered.
C1 [Saraux, Claire; Le Bohec, Celine; Viblanc, Vincent A.; Beaune, David; Le Maho, Yvon] Univ Strasbourg, Inst Pluridisciplinaire Hubert Curien, F-67087 Strasbourg, France.
   [Saraux, Claire; Le Bohec, Celine; Viblanc, Vincent A.; Beaune, David; Le Maho, Yvon] CNRS, UMR7178, F-67037 Strasbourg, France.
   [Saraux, Claire; Le Bohec, Celine; Durant, Joel M.; Stenseth, Nils C.] Univ Oslo, Dept Biol, Ctr Ecol & Evolutionary Synth, N-0316 Oslo, Norway.
   [Saraux, Claire] ENGREF, AgroParisTech, F-75732 Paris, France.
   [Gauthier-Clerc, Michel] Ctr Rech Tour Valat, F-13200 Arles, France.
   [Park, Young-Hyang] Museum Natl Hist Nat, USM LOCEAN 0402, Dept Milieux & Peuplements Aquat, F-75231 Paris, France.
   [Yoccoz, Nigel G.] Univ Tromso, Dept Arctic & Marine Biol, N-9037 Tromso, Norway.
   [Stenseth, Nils C.] Inst Marine Res, Flodevigen Marine Res Stn, N-4817 His, Norway.
C3 Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Oslo; AgroParisTech; Museum National d'Histoire Naturelle (MNHN); UiT The Arctic University of Tromso; Institute of Marine Research - Norway
RP Saraux, C (corresponding author), Univ Strasbourg, Inst Pluridisciplinaire Hubert Curien, 23 Rue Becquerel, F-67087 Strasbourg, France.
EM claire.saraux@c-strasbourg.fr; yvon.lemaho@iphc.cnrs.fr
FU Institut Polaire Francais-Paul-Emile Victor; Fondation Bettencourt-Schueller; Fondation des Treilles; Centre National de la Recherche Scientifique; European Commission; Norwegian Research Council; YGGDRASIL programme
NR 36
TC 165
Z9 179
U1 1
U2 158
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 203
EP 206
DI 10.1038/nature09630
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400036
PM 21228875
DA 2026-03-09
ER

PT J
AU Zaratiegui, M
   Vaughn, MW
   Irvine, DV
   Goto, D
   Watt, S
   Bähler, J
   Arcangioli, B
   Martienssen, RA
AF Zaratiegui, Mikel
   Vaughn, Matthew W.
   Irvine, Danielle V.
   Goto, Derek
   Watt, Stephen
   Baehler, Juerg
   Arcangioli, Benoit
   Martienssen, Robert A.
TI CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR
SO NATURE
LA English
DT Article
ID fission yeast homologs; schizosaccharomyces-pombe; dna-replication; chromosome segregation; fragile sites; protein sap1; recombination; centromere; identification; purification
AB Centromere-binding protein B (CENP-B) is a widely conserved DNA binding factor associated with heterochromatin and centromeric satellite repeats(1). In fission yeast, CENP-B homologues have been shown to silence long terminal repeat (LTR) retrotransposons by recruiting histone deacetylases(2). However, CENP-B factors also have unexplained roles in DNA replication(3,4). Here we show that a molecular function of CENP-B is to promote replication-fork progression through the LTR. Mutants have increased genomic instability caused by replication-fork blockage that depends on the DNA binding factor switch-activating protein 1 (Sap1), which is directly recruited by the LTR. The loss of Sap1-dependent barrier activity allows the unhindered progression of the replication fork, but results in rearrangements deleterious to the retrotransposon. We conclude that retrotransposons influence replication polarity through recruitment of Sap1 and transposition near replication-fork blocks, whereas CENP-B counteracts this activity and promotes fork stability. Our results may account for the role of LTR in fragile sites, and for the association of CENP-B with pericentromeric heterochromatin and tandem satellite repeats.
C1 [Zaratiegui, Mikel; Vaughn, Matthew W.; Irvine, Danielle V.; Goto, Derek; Martienssen, Robert A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Watt, Stephen; Baehler, Juerg] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Watt, Stephen; Baehler, Juerg] UCL Canc Inst, London WC1E 6BT, England.
   [Arcangioli, Benoit] Inst Pasteur, Dynam GenomeUnit, CNRS URA2171, Dept Genomes & Genet, F-75015 Paris, France.
   [Arcangioli, Benoit] Inst Pasteur, Dynam GenomeUnit, CNRS URA2171, Dept Dev Biol, F-75015 Paris, France.
C3 Cold Spring Harbor Laboratory; University of London; University College London; University of London; University College London; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
RP Martienssen, RA (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM martiens@cshl.edu
FU National Institutes of Health [RO1GM076396]; Cancer Research UK [C9546/A6517]; Agence Nationale de la Recherche [ANR-06-BLAN-0271]; National Health and Medical Research Council; Spanish Ministry of Education; Wellcome Trust [095598/Z/11/Z] Funding Source: researchfish; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1025830] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0963400, 0923128] Funding Source: National Science Foundation; Grants-in-Aid for Scientific Research [22115501] Funding Source: KAKEN; Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0271] Funding Source: Agence Nationale de la Recherche (ANR)
NR 30
TC 76
Z9 89
U1 0
U2 21
PU 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 6
PY 2011
VL 469
IS 7328
BP 112
EP 115
DI 10.1038/nature09608
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 702UO
UT WOS:000285921600042
PM 21151105
DA 2026-03-09
ER

PT J
AU Bertrand, R
   Lenoir, J
   Piedallu, C
   Riofrío-Dillon, G
   de Ruffray, P
   Vidal, C
   Pierrat, JC
   Gégout, JC
AF Bertrand, Romain
   Lenoir, Jonathan
   Piedallu, Christian
   Riofrio-Dillon, Gabriela
   de Ruffray, Patrice
   Vidal, Claude
   Pierrat, Jean-Claude
   Gegout, Jean-Claude
TI Changes in plant community composition lag behind climate warming in lowland forests
SO NATURE
LA English
DT Article
ID range shifts; temperature; diversity; impacts
AB Climate change is driving latitudinal and altitudinal shifts in species distribution worldwide(1,2), leading to novel species assemblages(3,4). Lags between these biotic responses and contemporary climate changes have been reported for plants and animals(5). Theoretically, the magnitude of these lags should be greatest in lowland areas, where the velocity of climate change is expected to be much greater than that in highland areas(6). We compared temperature trends to temperatures reconstructed from plant assemblages (observed in 76,634 surveys) over a 44-year period in France (1965-2008). Here we report that forest plant communities had responded to 0.54 degrees C of the effective increase of 1.07 degrees C in highland areas (500-2,600 m above sea level), while they had responded to only 0.02 degrees C of the 1.11 degrees C warming trend in lowland areas. There was a larger temperature lag (by 3.1 times) between the climate and plant community composition in lowland forests than in highland forests. The explanation of such disparity lies in the following properties of lowland, as compared to highland, forests: the higher proportion of species with greater ability for local persistence as the climate warms(7), the reduced opportunity for short-distance escapes(8,9), and the greater habitat fragmentation. Although mountains are currently considered to be among the ecosystems most threatened by climate change (owing to mountaintop extinction), the current inertia of plant communities in lowland forests should also be noted, as it could lead to lowland biotic attrition(10).
C1 [Bertrand, Romain; Piedallu, Christian; Riofrio-Dillon, Gabriela; Pierrat, Jean-Claude; Gegout, Jean-Claude] AgroParisTech, ENGREF, UMR1092, Lab Etud Ressources Foret Bois LERFoB, F-54000 Nancy, France.
   [Bertrand, Romain; Piedallu, Christian; Riofrio-Dillon, Gabriela; Pierrat, Jean-Claude; Gegout, Jean-Claude] INRA, Ctr Nancy, UMR1092, Lab Etud Ressources Foret Bois LERFoB, F-54280 Champenoux, France.
   [Lenoir, Jonathan] Aarhus Univ, Dept Biosci, Ecoinformat & Biodivers Grp, DK-8000 Aarhus C, Denmark.
   [de Ruffray, Patrice] Univ Strasbourg UDS, Inst Biol Mol Plantes IBMP, CNRS, F-67084 Strasbourg, France.
   [Vidal, Claude] Inventaire Forestier Natl, F-45290 Nogent Sur Marne, France.
C3 AgroParisTech; Universite de Lorraine; INRAE; Aarhus University; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS)
RP Bertrand, R (corresponding author), AgroParisTech, ENGREF, UMR1092, Lab Etud Ressources Foret Bois LERFoB, 14 Rue Girardet, F-54000 Nancy, France.
EM romain.bertrand@engref.agroparistech.fr
FU French Institute of Agricultural, Forest and Environmental Engineering (ENGREF, AgroParisTech); National Forest Department (ONF); French Agency for Environment and Energy Management (ADEME); Danish Council for Independent Research - Natural Sciences [272-07-0242]; ADEME; Regional Council of Lorraine
NR 30
TC 721
Z9 823
U1 12
U2 495
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 24
PY 2011
VL 479
IS 7374
BP 517
EP 520
DI 10.1038/nature10548
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 851QI
UT WOS:000297285600048
PM 22012261
DA 2026-03-09
ER

PT J
AU Schmidt, MWI
   Torn, MS
   Abiven, S
   Dittmar, T
   Guggenberger, G
   Janssens, IA
   Kleber, M
   Kögel-Knabner, I
   Lehmann, J
   Manning, DAC
   Nannipieri, P
   Rasse, DP
   Weiner, S
   Trumbore, SE
AF Schmidt, Michael W. I.
   Torn, Margaret S.
   Abiven, Samuel
   Dittmar, Thorsten
   Guggenberger, Georg
   Janssens, Ivan A.
   Kleber, Markus
   Koegel-Knabner, Ingrid
   Lehmann, Johannes
   Manning, David A. C.
   Nannipieri, Paolo
   Rasse, Daniel P.
   Weiner, Steve
   Trumbore, Susan E.
TI Persistence of soil organic matter as an ecosystem property
SO NATURE
LA English
DT Article
ID black carbon; temperature sensitivity; molecular-structure; microbial community; litter decomposition; permafrost carbon; humic substances; nitrogen; stabilization; dynamics
AB Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily-and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.
C1 [Schmidt, Michael W. I.; Abiven, Samuel] Univ Zurich, Dept Geog, CH-8050 Zurich, Switzerland.
   [Torn, Margaret S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Earth Sci, Berkeley, CA 94720 USA.
   [Torn, Margaret S.] Univ Calif Berkeley, Energy & Resources Grp, Berkeley, CA 94720 USA.
   [Dittmar, Thorsten] Carl von Ossietzky Univ Oldenburg, Max Planck Res Grp Marine Geochem, Inst Chem & Biol Marine Environm, D-26129 Oldenburg, Germany.
   [Dittmar, Thorsten] Max Planck Inst Marine Microbiol, Max Planck Res Grp Marine Geochem, D-28359 Bremen, Germany.
   [Guggenberger, Georg] Leibniz Univ Hannover, Inst Soil Sci, D-30419 Hannover, Germany.
   [Janssens, Ivan A.] Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium.
   [Kleber, Markus] Oregon State Univ, Dept Crop & Soil Sci, Corvallis, OR 97331 USA.
   [Koegel-Knabner, Ingrid] Tech Univ Munich, Lehrstuhl Bodenkunde, D-85354 Freising Weihenstephan, Germany.
   [Lehmann, Johannes] Cornell Univ, Dept Crop & Soil Sci, Atkinson Ctr Sustainable Future, Ithaca, NY 14853 USA.
   [Manning, David A. C.] Newcastle Univ, Sch Civil Engn & Geosci, Inst Res Environm & Sustainabil, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Nannipieri, Paolo] Univ Florence, Dept Plant Soil & Environm Sci, I-50144 Florence, Italy.
   [Rasse, Daniel P.] Norwegian Inst Agr & Environm Res, N-1432 As, Norway.
   [Weiner, Steve] Weizmann Inst Sci, IL-76100 Rehovot, Israel.
   [Trumbore, Susan E.] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
C3 University of Zurich; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Max Planck Society; Carl von Ossietzky Universitat Oldenburg; Max Planck Society; Leibniz University Hannover; University of Antwerp; Oregon State University; Technical University of Munich; Cornell University; Newcastle University - UK; University of Florence; Bioforsk; Weizmann Institute of Science; Max Planck Society
RP Schmidt, MWI (corresponding author), Univ Zurich, Dept Geog, CH-8050 Zurich, Switzerland.
EM Michael.Schmidt@geo.uzh.ch; mstorn@lbl.gov
FU European Science Foundation Network MOLTER; US Department of Energy [DE-AC02-05CH11231]; Directorate For Geosciences; Division Of Earth Sciences [0819689] Funding Source: National Science Foundation
NR 100
TC 4628
Z9 5511
U1 204
U2 6146
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 49
EP 56
DI 10.1038/nature10386
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400033
PM 21979045
DA 2026-03-09
ER

PT J
AU Windbichler, N
   Menichelli, M
   Papathanos, PA
   Thyme, SB
   Li, H
   Ulge, UY
   Hovde, BT
   Baker, D
   Monnat, RJ
   Burt, A
   Crisanti, A
AF Windbichler, Nikolai
   Menichelli, Miriam
   Papathanos, Philippos Aris
   Thyme, Summer B.
   Li, Hui
   Ulge, Umut Y.
   Hovde, Blake T.
   Baker, David
   Monnat, Raymond J., Jr.
   Burt, Austin
   Crisanti, Andrea
TI A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
SO NATURE
LA English
DT Article
ID specificity; binding; transmission; derivatives; generation; conversion; protein
AB Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector(4-7). The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations(8). We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose(9). Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions(10) and the homing endonuclease gene I-SceI(11-13), can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.
C1 [Windbichler, Nikolai; Menichelli, Miriam; Papathanos, Philippos Aris; Burt, Austin; Crisanti, Andrea] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
   [Thyme, Summer B.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Thyme, Summer B.; Baker, David] Univ Washington, Grad Program Biomol Struct & Design, Seattle, WA 98195 USA.
   [Li, Hui; Ulge, Umut Y.; Monnat, Raymond J., Jr.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Ulge, Umut Y.; Monnat, Raymond J., Jr.] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA.
   [Hovde, Blake T.; Monnat, Raymond J., Jr.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Burt, Austin] Imperial Coll London, Dept Life Sci, Ascot SL5 7PY, Berks, England.
   [Crisanti, Andrea] Univ Perugia, Dept Expt Med, I-06122 Perugia, Italy.
C3 Imperial College London; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Imperial College London; University of Perugia
RP Crisanti, A (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, S Kensington Campus, London SW7 2AZ, England.
EM a.drcrisanti@imperial.ac.uk
FU Foundation for the National Institutes of Health through Grand Challenges in Global Health initiative; NIH [GM084433, CA133831]; National Cancer Institute [T32CA080416] Funding Source: NIH RePORTER
NR 40
TC 279
Z9 346
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 MAY 12
PY 2011
VL 473
IS 7346
BP 212
EP +
DI 10.1038/nature09937
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200038
PM 21508956
DA 2026-03-09
ER

PT J
AU Ofstad, TA
   Zuker, CS
   Reiser, MB
AF Ofstad, Tyler A.
   Zuker, Charles S.
   Reiser, Michael B.
TI Visual place learning in Drosophila melanogaster
SO NATURE
LA English
DT Article
ID mushroom body; central complex; spatial memory; fruit-fly; behavior; system; expression; paradigm; cells; head
AB The ability of insects to learn and navigate to specific locations in the environment has fascinated naturalists for decades. The impressive navigational abilities of ants, bees, wasps and other insects demonstrate that insects are capable of visual place learning(1-4), but little is known about the underlying neural circuits that mediate these behaviours. Drosophila melanogaster (common fruit fly) is a powerful model organism for dissecting the neural circuitry underlying complex behaviours, from sensory perception to learning and memory. Drosophila can identify and remember visual features such as size, colour and contour orientation(5,6). However, the extent to which they use vision to recall specific locations remains unclear. Here we describe a visual place learning platform and demonstrate that Drosophila are capable of forming and retaining visual place memories to guide selective navigation. By targeted genetic silencing of small subsets of cells in the Drosophila brain, we show that neurons in the ellipsoid body, but not in the mushroom bodies, are necessary for visual place learning. Together, these studies reveal distinct neuroanatomical substrates for spatial versus non-spatial learning, and establish Drosophila as a powerful model for the study of spatial memories. [GRAPHICS] .
C1 [Ofstad, Tyler A.; Zuker, Charles S.; Reiser, Michael B.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Ofstad, Tyler A.; Zuker, Charles S.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci, La Jolla, CA 92093 USA.
   [Zuker, Charles S.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurobiol, La Jolla, CA 92093 USA.
   [Zuker, Charles S.] Columbia Univ, Columbia Coll Phys & Surg, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Zuker, Charles S.] Columbia Univ, Columbia Coll Phys & Surg, Howard Hughes Med Inst, Dept Neurosci, New York, NY 10032 USA.
C3 Howard Hughes Medical Institute; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Howard Hughes Medical Institute; Howard Hughes Medical Institute; Columbia University; Howard Hughes Medical Institute; Columbia University
RP Zuker, CS (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM cz2195@columbia.edu; reiserm@janelia.hhmi.org
FU HHMI
NR 40
TC 308
Z9 372
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 9
PY 2011
VL 474
IS 7350
BP 204
EP U240
DI 10.1038/nature10131
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800048
PM 21654803
DA 2026-03-09
ER

PT J
AU Montpetit, B
   Thomsen, ND
   Helmke, KJ
   Seeliger, MA
   Berger, JM
   Weis, K
AF Montpetit, Ben
   Thomsen, Nathan D.
   Helmke, Kara J.
   Seeliger, Markus A.
   Berger, James M.
   Weis, Karsten
TI A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export
SO NATURE
LA English
DT Article
ID protein dbp5; crystal-structure; structural basis; helicase; complex; domain; eif4a; crystallography; reveals; nup214
AB Superfamily 1 and superfamily 2 RNA helicases are ubiquitous messenger-RNA-protein complex (mRNP) remodelling enzymes that have critical roles in all aspects of RNA metabolism(1,2). The superfamily 2 DEAD-box ATPase Dbp5 (human DDX19) functions in mRNA export and is thought to remodel mRNPs at the nuclear pore complex (NPC)(3-8). Dbp5 is localized to the NPC via an interaction with Nup159 (NUP214 in vertebrates)(3-5,8,9) and is locally activated there by Gle1 together with the small-molecule inositol hexakisphosphate (InsP(6))(10,11). Local activation of Dbp5 at the NPC by Gle1 is essential for mRNA export in vivo(10,12); however, the mechanistic role of Dbp5 in mRNP export is poorly understood and it is not known how Gle1(InsP6) and Nup159 regulate the activity of Dbp5. Here we report, from yeast, structures of Dbp5 in complex with Gle1(InsP6), Nup159/Gle1(InsP6) and RNA. These structures reveal that InsP6 functions as a small-molecule tether for the Gle1-Dbp5 interaction. Surprisingly, the Gle1(InsP6)-Dbp5 complex is structurally similar to another DEAD-box ATPase complex essential for translation initiation, eIF4G-eIF4A, and we demonstrate that Gle1(InsP6) and eIF4G both activate their DEAD-box partner by stimulating RNA release. Furthermore, Gle1(InsP6) relieves Dbp5 autoregulation and cooperates with Nup159 in stabilizing an open Dbp5 intermediate that precludes RNA binding. These findings explain how Gle1(InsP6), Nup159 and Dbp5 collaborate in mRNA export and provide a general mechanism for DEAD-box ATPase regulation by Gle1/eIF4G-like activators.
C1 [Montpetit, Ben; Helmke, Kara J.; Weis, Karsten] Univ Calif Berkeley, Div Cell & Dev Biol, Berkeley, CA 94720 USA.
   [Montpetit, Ben; Thomsen, Nathan D.; Helmke, Kara J.; Seeliger, Markus A.; Berger, James M.; Weis, Karsten] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Montpetit, Ben; Thomsen, Nathan D.; Helmke, Kara J.; Seeliger, Markus A.; Berger, James M.; Weis, Karsten] Univ Calif Berkeley, QB3 Inst, Berkeley, CA 94720 USA.
   [Thomsen, Nathan D.; Seeliger, Markus A.; Berger, James M.] Univ Calif Berkeley, Div Biochem & Mol Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Weis, K (corresponding author), Univ Calif Berkeley, Div Cell & Dev Biol, Berkeley, CA 94720 USA.
EM jmberger@berkeley.edu; kweis@berkeley.edu
FU G Harold and Leila Y Mathers foundation; NIH [R01GM58065, RC1GM91533]; National Institute of General Medical Sciences [T32GM007232] Funding Source: NIH RePORTER
NR 40
TC 209
Z9 242
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 238
EP 242
DI 10.1038/nature09862
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100047
PM 21441902
DA 2026-03-09
ER

PT J
AU De Stefani, D
   Raffaello, A
   Teardo, E
   Szabò, I
   Rizzuto, R
AF De Stefani, Diego
   Raffaello, Anna
   Teardo, Enrico
   Szabo, Ildiko
   Rizzuto, Rosario
TI A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; induced apoptosis; ca2+ channels; colocalization; propagation; activation; dynamics; contacts; feedback; signals
AB Mitochondrial Ca(2+) homeostasis has a key role in the regulation of aerobic metabolism and cell survival(1), but the molecular identity of the Ca(2+) channel, the mitochondrial calcium uniporter(2), is still unknown. Here we have identified in silico a protein (named MCU) that shares tissue distribution with MICU1 (also known as CBARA1), a recently characterized uniporter regulator(3), is present in organisms in which mitochondrial Ca(2+) uptake was demonstrated and whose sequence includes two transmembrane domains. Short interfering RNA (siRNA) silencing of MCU in HeLa cells markedly reduced mitochondrial Ca(2+) uptake. MCU overexpression doubled the matrix Ca(2+) concentration increase evoked by inositol 1,4,5-trisphosphate-generating agonists, thus significantly buffering the cytosolic elevation. The purified MCU protein showed channel activity in planar lipid bilayers, with electrophysiological properties and inhibitor sensitivity of the uniporter. A mutant MCU, in which two negatively charged residues of the putative pore-forming region were replaced, had no channel activity and reduced agonist-dependent matrix Ca(2+) concentration transients when overexpressed in HeLa cells. Overall, these data demonstrate that the 40-kDa protein identified is the channel responsible for ruthenium-red-sensitive mitochondrial Ca(2+) uptake, thus providing a molecular basis for this process of utmost physiological and pathological relevance.
C1 [De Stefani, Diego; Raffaello, Anna; Rizzuto, Rosario] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
   [De Stefani, Diego; Raffaello, Anna; Rizzuto, Rosario] Univ Padua, Inst Neurosci, CNR, I-35121 Padua, Italy.
   [Teardo, Enrico; Szabo, Ildiko] Univ Padua, Dept Biol, Padua, Italy.
C3 University of Padua; Consiglio Nazionale delle Ricerche (CNR); University of Padua; University of Padua
RP Rizzuto, R (corresponding author), Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
EM rosario.rizzuto@unipd.it
FU Italian Ministry of Education, University and Research; European Commission [223576]; National Institutes of Health [1P01AG025532-01A1]; Cariparo Foundation (Padua); Italian Association for Cancer Research (AIRC); Telethon-Italy [GPP1005]
NR 32
TC 1552
Z9 1735
U1 3
U2 154
PU 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 18
PY 2011
VL 476
IS 7360
BP 336
EP U104
DI 10.1038/nature10230
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500039
PM 21685888
DA 2026-03-09
ER

PT J
AU Kau, AL
   Ahern, PP
   Griffin, NW
   Goodman, AL
   Gordon, JI
AF Kau, Andrew L.
   Ahern, Philip P.
   Griffin, Nicholas W.
   Goodman, Andrew L.
   Gordon, Jeffrey I.
TI Human nutrition, the gut microbiome and the immune system
SO NATURE
LA English
DT Article
ID aryl-hydrocarbon receptor; t-cells; small-bowel; intestinal microflora; child undernutrition; insulin-resistance; innate immunity; adipose-tissue; key role; obesity
AB Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.
C1 [Kau, Andrew L.; Ahern, Philip P.; Griffin, Nicholas W.; Goodman, Andrew L.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
C3 Washington University (WUSTL)
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
EM jgordon@wustl.edu
FU National Institutes of Health [DK30292, DK70977, DK078669]; Crohn's and Colitis Foundation of America; Bill and Melinda Gates Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK030292] Funding Source: NIH RePORTER; Crohn&apos;s & Colitis Foundation; Action Medical Research [2158] Funding Source: researchfish
NR 100
TC 2020
Z9 2441
U1 5
U2 1008
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 327
EP 336
DI 10.1038/nature10213
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100036
PM 21677749
DA 2026-03-09
ER

PT J
AU Pei, HD
   Zhang, L
   Luo, KT
   Qin, YX
   Chesi, M
   Fei, F
   Bergsagel, PL
   Wang, LW
   You, ZS
   Lou, ZK
AF Pei, Huadong
   Zhang, Lindsey
   Luo, Kuntian
   Qin, Yuxin
   Chesi, Marta
   Fei, Frances
   Bergsagel, P. Leif
   Wang, Liewei
   You, Zhongsheng
   Lou, Zhenkun
TI MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites
SO NATURE
LA English
DT Article
ID wolf-hirschhorn-syndrome; double-strand breaks; multiple-myeloma; protein; methyltransferase; checkpoint; mdc1; recruitment; repair; domain
AB p53-binding protein 1 (53BP1) is known to be an important mediator of the DNA damage response(1), with dimethylation of histone H4 lysine 20 (H4K20me2) critical to the recruitment of 53BP1 to double-strand breaks (DSBs)(2,3). However, it is not clear how 53BP1 is specifically targeted to the sites of DNA damage, as the overall level of H4K20me2 does not seem to increase following DNA damage. It has been proposed that DNA breaks may cause exposure of methylated H4K20 previously buried within the chromosome; however, experimental evidence for such a model is lacking. Here we found that H4K20 methylation actually increases locally upon the induction of DSBs and that methylation of H4K20 at DSBs is mediated by the histone methyltransferase MMSET (also known as NSD2 or WHSC1) in mammals. Downregulation of MMSET significantly decreases H4K20 methylation at DSBs and the subsequent accumulation of 53BP1. Furthermore, we found that the recruitment of MMSET to DSBs requires the gamma H2AX-MDC1 pathway; specifically, the interaction between the MDC1 BRCT domain and phosphorylated Ser 102 of MMSET. Thus, we propose that a pathway involving gamma H2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment.
C1 [Pei, Huadong; Luo, Kuntian; Lou, Zhenkun] Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA.
   [Zhang, Lindsey; Fei, Frances; You, Zhongsheng] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
   [Qin, Yuxin; Wang, Liewei] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA.
   [Chesi, Marta; Bergsagel, P. Leif] Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA.
C3 Mayo Clinic; Washington University (WUSTL); Mayo Clinic; Mayo Clinic; Mayo Clinic Phoenix
RP Lou, ZK (corresponding author), Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA.
EM lou.zhenkun@mayo.edu
FU Richard Schulze Family Foundation; NIH [CA130996, CA151329]; American Cancer Society [IRG-58-010-52]; Siteman Career Award in Breast Cancer Research
NR 30
TC 340
Z9 408
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 124
EP U144
DI 10.1038/nature09658
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400047
PM 21293379
DA 2026-03-09
ER

PT J
AU Guse, A
   Carroll, CW
   Moree, B
   Fuller, CJ
   Straight, AF
AF Guse, Annika
   Carroll, Christopher W.
   Moree, Ben
   Fuller, Colin J.
   Straight, Aaron F.
TI In vitro centromere and kinetochore assembly on defined chromatin templates
SO NATURE
LA English
DT Article
ID xenopus egg extracts; cenp-a nucleosm; aurora b; histone; complex; phosphorylation; checkpoint; hjurp; dna; organization
AB During cell division, chromosomes are segregated to nascent daughter cells by attaching to the microtubules of the mitotic spindle through the kinetochore. Kinetochores are assembled on a specialized chromatin domain called the centromere, which is characterized by the replacement of nucleosomal histone H3 with the histone H3 variant centromere protein A(CENP-A). CENP-A is essential for centromere and kinetochore formation in all eukaryotes but it is unknown how CENP-A chromatin directs centromere and kinetochore assembly(1). Here we generate synthetic CENP-A chromatin that recapitulates essential steps of centromere and kinetochore assembly in vitro. We show that reconstituted CENP-A chromatin when added to cell-free extracts is sufficient for the assembly of centromere and kinetochore proteins, microtubule binding and stabilization, and mitotic checkpoint function. Using chromatin assembled from histone H3/CENP-A chimaeras, we demonstrate that the conserved carboxy terminus of CENP-A is necessary and sufficient for centromere and kinetochore protein recruitment and function but that the CENP-A targeting domain-required for new CENP-A histone assembly(2)-is not. These data show that two of the primary requirements for accurate chromosome segregation, the assembly of the kinetochore and the propagation of CENP-A chromatin, are specified by different elements in the CENP-A histone. Our unique cell-free system enables complete control and manipulation of the chromatin substrate and thus presents a powerful tool to study centromere and kinetochore assembly.
C1 [Guse, Annika; Carroll, Christopher W.; Moree, Ben; Fuller, Colin J.; Straight, Aaron F.] Stanford Med Sch, Dept Biochem, Stanford, CA 94305 USA.
C3 Stanford University
RP Straight, AF (corresponding author), Stanford Med Sch, Dept Biochem, Beckman 409A, Stanford, CA 94305 USA.
EM astraigh@stanford.edu
FU German Research Foundation (DFG); Helen Hay Whitney Foundation; American Heart Association (AHA); Stanford Graduate Fellowship; National Institutes of Health (NIH) [R01GM074728];  [T32GM007276]; National Institute of General Medical Sciences [R01GM074728, T32GM007276] Funding Source: NIH RePORTER
NR 37
TC 183
Z9 223
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 SEP 15
PY 2011
VL 477
IS 7364
BP 354
EP U136
DI 10.1038/nature10379
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400036
PM 21874020
DA 2026-03-09
ER

PT J
AU Ngo, VN
   Young, RM
   Schmitz, R
   Jhavar, S
   Xiao, WM
   Lim, KH
   Kohlhammer, H
   Xu, WH
   Yang, YD
   Zhao, H
   Shaffer, AL
   Romesser, P
   Wright, G
   Powell, J
   Rosenwald, A
   Muller-Hermelink, HK
   Ott, G
   Gascoyne, RD
   Connors, JM
   Rimsza, LM
   Campo, E
   Jaffe, ES
   Delabie, J
   Smeland, EB
   Fisher, RI
   Braziel, RM
   Tubbs, RR
   Cook, JR
   Weisenburger, DD
   Chan, WC
   Staudt, LM
AF Ngo, Vu N.
   Young, Ryan M.
   Schmitz, Roland
   Jhavar, Sameer
   Xiao, Wenming
   Lim, Kian-Huat
   Kohlhammer, Holger
   Xu, Weihong
   Yang, Yandan
   Zhao, Hong
   Shaffer, Arthur L.
   Romesser, Paul
   Wright, George
   Powell, John
   Rosenwald, Andreas
   Muller-Hermelink, Hans Konrad
   Ott, German
   Gascoyne, Randy D.
   Connors, Joseph M.
   Rimsza, Lisa M.
   Campo, Elias
   Jaffe, Elaine S.
   Delabie, Jan
   Smeland, Erlend B.
   Fisher, Richard I.
   Braziel, Rita M.
   Tubbs, Raymond R.
   Cook, J. R.
   Weisenburger, Denny D.
   Chan, Wing C.
   Staudt, Louis M.
TI Oncogenically active MYD88 mutations in human lymphoma
SO NATURE
LA English
DT Article
ID b-cell lymphoma; nf-kappa-b; tnfaip3 a20; gene; inhibitors; signatures; pathways; survival; subtypes; kinase
AB The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy(1). Constitutive nuclear factor (NF)-kappa B and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling(2,3), and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-kappa B signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-beta. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.
C1 [Ngo, Vu N.; Young, Ryan M.; Schmitz, Roland; Jhavar, Sameer; Lim, Kian-Huat; Kohlhammer, Holger; Xu, Weihong; Yang, Yandan; Zhao, Hong; Shaffer, Arthur L.; Romesser, Paul; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Romesser, Paul] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
   [Wright, George] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA.
   [Rosenwald, Andreas; Muller-Hermelink, Hans Konrad] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
   [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany.
   [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
   [Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
   [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA.
   [Rimsza, Lisa M.; Fisher, Richard I.; Braziel, Rita M.; Tubbs, Raymond R.; Cook, J. R.] SW Oncol Grp, Ann Arbor, MI 48106 USA.
   [Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
   [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Delabie, Jan] Univ Hosp, Rikshosp, Pathol Clin, N-0310 Oslo, Norway.
   [Smeland, Erlend B.] Univ Hosp, Rikshosp, Inst Canc Res, N-0310 Oslo, Norway.
   [Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, N-0310 Oslo, Norway.
   [Fisher, Richard I.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
   [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Tubbs, Raymond R.; Cook, J. R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
   [Weisenburger, Denny D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE 68198 USA.
   [Weisenburger, Denny D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE 68198 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH Center for Information Technology (CIT); Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Wurzburg; Bosch; Robert Bosch Krankenhaus; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; British Columbia Cancer Agency; University of Arizona; Southwest Oncology Group; University of Barcelona; Hospital Clinic de Barcelona; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Oslo; National Hospital Norway; University of Oslo; National Hospital Norway; University of Oslo; University of Rochester; Oregon Health & Science University; Cleveland Clinic Foundation; University of Nebraska System; University of Nebraska Medical Center; University of Nebraska System; University of Nebraska Medical Center
RP Staudt, LM (corresponding author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NCI SPECS [UO1-CA 114778]; Foundation for NIH; Lymphoma/Leukemia Molecular Profiling Project (LLMPP); Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe); National Cancer Institute [P30CA008748, ZIABC011007] Funding Source: NIH RePORTER
CR Compagno M, 2009, NATURE, V459, P717, DOI 10.1038/nature07968
   Davis RE, 2010, NATURE, V463, P88, DOI 10.1038/nature08638
   Davis RE, 2001, J EXP MED, V194, P1861, DOI 10.1084/jem.194.12.1861
   Dierlamm J, 1997, LEUKEMIA, V11, P747, DOI 10.1038/sj.leu.2400635
   Ding BB, 2008, BLOOD, V111, P1515, DOI 10.1182/blood-2007-04-087734
   Ishii KJ, 2006, TRENDS IMMUNOL, V27, P525, DOI 10.1016/j.it.2006.09.002
   Iwasaki A, 2010, SCIENCE, V327, P291, DOI 10.1126/science.1183021
   Jiang ZF, 2006, P NATL ACAD SCI USA, V103, P10961, DOI 10.1073/pnas.0603804103
   Kato M, 2009, NATURE, V459, P712, DOI 10.1038/nature07969
   Lam LT, 2008, BLOOD, V111, P3701, DOI 10.1182/blood-2007-09-111948
   Lam LT, 2005, CLIN CANCER RES, V11, P28
   Lenz G, 2008, NEW ENGL J MED, V359, P2313, DOI 10.1056/NEJMoa0802885
   Lenz G, 2008, P NATL ACAD SCI USA, V105, P13520, DOI 10.1073/pnas.0804295105
   Lenz G, 2008, SCIENCE, V319, P1676, DOI 10.1126/science.1153629
   Lenz G, 2010, NEW ENGL J MED, V362, P1417, DOI 10.1056/NEJMra0807082
   Li CS, 2005, J BIOL CHEM, V280, P26152, DOI 10.1074/jbc.M503262200
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   Novak U, 2009, BLOOD, V113, P4918, DOI 10.1182/blood-2008-08-174110
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   Schmitz R, 2009, J EXP MED, V206, P981, DOI 10.1084/jem.20090528
   Shaffer AL, 2006, IMMUNOL REV, V210, P67, DOI 10.1111/j.0105-2896.2006.00373.x
   Staudt LM, 2010, CSH PERSPECT BIOL, V2, P0, DOI 10.1101/cshperspect.a000109
   Xu YW, 2000, NATURE, V408, P111, DOI 10.1038/35040600
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NR 27
TC 1216
Z9 1465
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 FEB 3
PY 2011
VL 470
IS 7332
BP 115
EP U133
DI 10.1038/nature09671
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400045
PM 21179087
DA 2026-03-09
ER

PT J
AU Hartogh, P
   Lis, DC
   Bockelée-Morvan, D
   de Val-Borro, M
   Biver, N
   Küppers, M
   Emprechtinger, M
   Bergin, EA
   Crovisier, J
   Rengel, M
   Moreno, R
   Szutowicz, S
   Blake, GA
AF Hartogh, Paul
   Lis, Dariusz C.
   Bockelee-Morvan, Dominique
   de Val-Borro, Miguel
   Biver, Nicolas
   Kueppers, Michael
   Emprechtinger, Martin
   Bergin, Edwin A.
   Crovisier, Jacques
   Rengel, Miriam
   Moreno, Raphael
   Szutowicz, Slawomira
   Blake, Geoffrey A.
TI Ocean-like water in the Jupiter-family comet 103P/Hartley 2
SO NATURE
LA English
DT Article
ID heavy bombardment period; giant planets; origin; deuterium; ratios; earth; constraints; delivery; system; gases
AB For decades, the source of Earth's volatiles, especially water with a deuterium-to-hydrogen ratio (D/H) of (1.558 +/- 0.001) x 10(-4), has been a subject of debate. The similarity of Earth's bulk composition to that of meteorites known as enstatite chondrites(1) suggests a dry proto-Earth(2) with subsequent delivery of volatiles(3) by local accretion(4) or impacts of asteroids or comets(5,6). Previous measurements in six comets from the Oort cloud yielded a mean D/H ratio of (2.96 +/- 0.25) x 10(-4). The D/H value in carbonaceous chondrites, (1.4 +/- 0.1) x 10(-4), together with dynamical simulations, led to models in which asteroids were the main source of Earth's water(7), with <= 10 per cent being delivered by comets. Here we report that the D/H ratio in the Jupiter-family comet 103P/Hartley 2, which originated in the Kuiper belt, is (1.61 +/- 0.24) x 10(-4). This result substantially expands the reservoir of Earth ocean-like water to include some comets, and is consistent with the emerging picture of a complex dynamical evolution of the early Solar System(8,9).
C1 [Hartogh, Paul; de Val-Borro, Miguel; Rengel, Miriam] Max Planck Inst Sonnensyst Forsch, D-37191 Katlenburg Lindau, Germany.
   [Lis, Dariusz C.; Emprechtinger, Martin; Blake, Geoffrey A.] CALTECH, Pasadena, CA 91125 USA.
   [Bockelee-Morvan, Dominique; Biver, Nicolas; Crovisier, Jacques; Moreno, Raphael] Univ Paris Diderot, UPMC, CNRS, Observ Paris,LESIA, F-92195 Meudon, France.
   [Kueppers, Michael] European Space Astron Ctr, Rosetta Sci Operat Ctr, Madrid 28691, Spain.
   [Bergin, Edwin A.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Szutowicz, Slawomira] Polish Acad Sci, Space Res Ctr, PL-00716 Warsaw, Poland.
C3 Max Planck Society; California Institute of Technology; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; Universite PSL; Observatoire de Paris; European Space Agency; European Space Astronomy Center; University of Michigan System; University of Michigan; Polish Academy of Sciences; Space Research Centre of the Polish Academy of Sciences
RP Hartogh, P (corresponding author), Max Planck Inst Sonnensyst Forsch, Max Planck Str 2, D-37191 Katlenburg Lindau, Germany.
EM hartogh@mps.mpg.de
FU CEA (France); CNES (France); CNRS (France); ASI (Italy); DLR (Germany); ESA; NASA; JPL/Caltech; NSF
NR 30
TC 360
Z9 391
U1 5
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 13
PY 2011
VL 478
IS 7368
BP 218
EP 220
DI 10.1038/nature10519
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800044
PM 21976024
DA 2026-03-09
ER

PT J
AU Jacquemont, S
   Reymond, A
   Zufferey, F
   Harewood, L
   Walters, RG
   Kutalik, Z
   Martinet, D
   Shen, YP
   Valsesia, A
   Beckmann, ND
   Thorleifsson, G
   Belfiore, M
   Bouquillon, S
   Campion, D
   de Leeuw, N
   de Vries, BBA
   Esko, T
   Fernandez, BA
   Fernández-Aranda, F
   Fernández-Real, JM
   Gratacòs, M
   Guilmatre, A
   Hoyer, J
   Jarvelin, MR
   Kooy, RF
   Kurg, A
   Le Caignec, C
   Männik, K
   Platt, OS
   Sanlaville, D
   Van Haelst, MM
   Gomez, SV
   Walha, F
   Wu, BL
   Yu, YG
   Aboura, A
   Addor, MC
   Alembik, Y
   Antonarakis, SE
   Arveiler, B
   Barth, M
   Bednarek, N
   Béna, F
   Bergmann, S
   Beri, M
   Bernardini, L
   Blaumeiser, B
   Bonneau, D
   Bottani, A
   Boute, O
   Brunner, HG
   Cailley, D
   Callier, P
   Chiesa, J
   Chrast, J
   Coin, L
   Coutton, C
   Cuisset, JM
   Cuvellier, JC
   David, A
   de Freminville, B
   Delobel, B
   Delrue, MA
   Demeer, B
   Descamps, D
   Didelot, G
   Dieterich, K
   Disciglio, V
   Doco-Fenzy, M
   Drunat, S
   Duban-Bedu, B
   Dubourg, C
   Moustafa, JSE
   Elliott, P
   Faas, BHW
   Faivre, L
   Faudet, A
   Fellmann, F
   Ferrarini, A
   Fisher, R
   Flori, E
   Forer, L
   Gaillard, D
   Gerard, M
   Gieger, C
   Gimelli, S
   Gimelli, G
   Grabe, HJ
   Guichet, A
   Guillin, O
   Hartikainen, AL
   Heron, D
   Hippolyte, L
   Holder, M
   Homuth, G
   Isidor, B
   Jaillard, S
   Jaros, Z
   Jiménez-Murcia, S
   Helas, GJ
   Jonveaux, P
   Kaksonen, S
   Keren, B
   Kloss-Brandstätter, A
   Knoers, NVAM
   Koolen, DA
   Kroisel, PM
   Kronenberg, F
   Labalme, A
   Landais, E
   Lapi, E
   Layet, V
   Legallic, S
   Leheup, B
   Leube, B
   Lewis, S
   Lucas, J
   MacDermot, KD
   Magnusson, P
   Marshall, C
   Mathieu-Dramard, M
   McCarthy, MI
   Meitinger, T
   Mencarelli, MA
   Merla, G
   Moerman, A
   Mooser, V
   Morice-Picard, F
   Mucciolo, M
   Nauck, M
   Ndiaye, NC
   Nordgren, A
   Pasquier, L
   Petit, F
   Pfundt, R
   Plessis, G
   Rajcan-Separovic, E
   Ramelli, GP
   Rauch, A
   Ravazzolo, R
   Reis, A
   Renieri, A
   Richart, C
   Ried, JS
   Rieubland, C
   Roberts, W
   Roetzer, KM
   Rooryck, C
   Rossi, M
   Saemundsen, E
   Satre, V
   Schurmann, C
   Sigurdsson, E
   Stavropoulos, DJ
   Stefansson, H
   Tengström, C
   Thorsteinsdóttir, U
   Tinahones, FJ
   Touraine, R
   Vallée, L
   van Binsbergen, E
   Van der Aa, N
   Vincent-Delorme, C
   Visvikis-Siest, S
   Vollenweider, P
   Völzke, H
   Vulto-van Silfhout, AT
   Waeber, G
   Wallgren-Pettersson, C
   Witwicki, RM
   Zwolinksi, S
   Andrieux, J
   Estivill, X
   Gusella, JF
   Gustafsson, O
   Metspalu, A
   Scherer, SW
   Stefansson, K
   Blakemore, AIF
   Beckmann, JS
   Froguel, P
AF Jacquemont, Sebastien
   Reymond, Alexandre
   Zufferey, Flore
   Harewood, Louise
   Walters, Robin G.
   Kutalik, Zoltan
   Martinet, Danielle
   Shen, Yiping
   Valsesia, Armand
   Beckmann, Noam D.
   Thorleifsson, Gudmar
   Belfiore, Marco
   Bouquillon, Sonia
   Campion, Dominique
   de Leeuw, Nicole
   de Vries, Bert B. A.
   Esko, Tonu
   Fernandez, Bridget A.
   Fernandez-Aranda, Fernando
   Manuel Fernandez-Real, Jose
   Gratacos, Monica
   Guilmatre, Audrey
   Hoyer, Juliane
   Jarvelin, Marjo-Riitta
   Kooy, R. Frank
   Kurg, Ants
   Le Caignec, Cedric
   Maennik, Katrin
   Platt, Orah S.
   Sanlaville, Damien
   Van Haelst, Mieke M.
   Villatoro Gomez, Sergi
   Walha, Faida
   Wu, Bai-lin
   Yu, Yongguo
   Aboura, Azzedine
   Addor, Marie-Claude
   Alembik, Yves
   Antonarakis, Stylianos E.
   Arveiler, Benoit
   Barth, Magalie
   Bednarek, Nathalie
   Bena, Frederique
   Bergmann, Sven
   Beri, Mylene
   Bernardini, Laura
   Blaumeiser, Bettina
   Bonneau, Dominique
   Bottani, Armand
   Boute, Odile
   Brunner, Han G.
   Cailley, Dorothee
   Callier, Patrick
   Chiesa, Jean
   Chrast, Jacqueline
   Coin, Lachlan
   Coutton, Charles
   Cuisset, Jean-Marie
   Cuvellier, Jean-Christophe
   David, Albert
   de Freminville, Benedicte
   Delobel, Bruno
   Delrue, Marie-Ange
   Demeer, Benedicte
   Descamps, Dominique
   Didelot, Gerard
   Dieterich, Klaus
   Disciglio, Vittoria
   Doco-Fenzy, Martine
   Drunat, Severine
   Duban-Bedu, Benedicte
   Dubourg, Christele
   Moustafa, Julia S. El-Sayed
   Elliott, Paul
   Faas, Brigitte H. W.
   Faivre, Laurence
   Faudet, Anne
   Fellmann, Florence
   Ferrarini, Alessandra
   Fisher, Richard
   Flori, Elisabeth
   Forer, Lukas
   Gaillard, Dominique
   Gerard, Marion
   Gieger, Christian
   Gimelli, Stefania
   Gimelli, Giorgio
   Grabe, Hans J.
   Guichet, Agnes
   Guillin, Olivier
   Hartikainen, Anna-Liisa
   Heron, Delphine
   Hippolyte, Loyse
   Holder, Muriel
   Homuth, Georg
   Isidor, Bertrand
   Jaillard, Sylvie
   Jaros, Zdenek
   Jimenez-Murcia, Susana
   Helas, Geraldine Joly
   Jonveaux, Philippe
   Kaksonen, Satu
   Keren, Boris
   Kloss-Brandstaetter, Anita
   Knoers, Nine V. A. M.
   Koolen, David A.
   Kroisel, Peter M.
   Kronenberg, Florian
   Labalme, Audrey
   Landais, Emilie
   Lapi, Elisabetta
   Layet, Valerie
   Legallic, Solenn
   Leheup, Bruno
   Leube, Barbara
   Lewis, Suzanne
   Lucas, Josette
   MacDermot, Kay D.
   Magnusson, Pall
   Marshall, Christian
   Mathieu-Dramard, Michele
   McCarthy, Mark I.
   Meitinger, Thomas
   Mencarelli, Maria Antonietta
   Merla, Giuseppe
   Moerman, Alexandre
   Mooser, Vincent
   Morice-Picard, Fanny
   Mucciolo, Mafalda
   Nauck, Matthias
   Ndiaye, Ndeye Coumba
   Nordgren, Ann
   Pasquier, Laurent
   Petit, Florence
   Pfundt, Rolph
   Plessis, Ghislaine
   Rajcan-Separovic, Evica
   Ramelli, Gian Paolo
   Rauch, Anita
   Ravazzolo, Roberto
   Reis, Andre
   Renieri, Alessandra
   Richart, Cristobal
   Ried, Janina S.
   Rieubland, Claudine
   Roberts, Wendy
   Roetzer, Katharina M.
   Rooryck, Caroline
   Rossi, Massimiliano
   Saemundsen, Evald
   Satre, Veronique
   Schurmann, Claudia
   Sigurdsson, Engilbert
   Stavropoulos, Dimitri J.
   Stefansson, Hreinn
   Tengstrom, Carola
   Thorsteinsdottir, Unnur
   Tinahones, Francisco J.
   Touraine, Renaud
   Vallee, Louis
   van Binsbergen, Ellen
   Van der Aa, Nathalie
   Vincent-Delorme, Catherine
   Visvikis-Siest, Sophie
   Vollenweider, Peter
   Voelzke, Henry
   Vulto-van Silfhout, Anneke T.
   Waeber, Gerard
   Wallgren-Pettersson, Carina
   Witwicki, Robert M.
   Zwolinksi, Simon
   Andrieux, Joris
   Estivill, Xavier
   Gusella, James F.
   Gustafsson, Omar
   Metspalu, Andres
   Scherer, Stephen W.
   Stefansson, Kari
   Blakemore, Alexandra I. F.
   Beckmann, Jacques S.
   Froguel, Philippe
TI Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
SO NATURE
LA English
DT Article
ID copy number variation; body-mass index; dependent probe amplification; circular binary segmentation; time quantitative pcr; hidden-markov model; snp genotyping data; failure-to-thrive; relative quantification; metabolic syndrome
AB Both obesity and being underweight have been associated with increased mortality(1,2). Underweight, defined as a body mass index (BMI) <= 18.5 kg per m(2) in adults and <= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive(3-5), feeding and eating disorder and/or anorexia nervosa(6,7). In contrast to obesity, few genetic variants underlying these clinical conditions have been reported(8,9). We previously showed that hemizygosity of a similar to 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities(10). Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.
C1 [Jacquemont, Sebastien; Zufferey, Flore; Martinet, Danielle; Beckmann, Noam D.; Belfiore, Marco; Addor, Marie-Claude; Fellmann, Florence; Ferrarini, Alessandra; Hippolyte, Loyse; Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Reymond, Alexandre; Harewood, Louise; Walha, Faida; Chrast, Jacqueline; Didelot, Gerard; Witwicki, Robert M.] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Walters, Robin G.; Van Haelst, Mieke M.; Coin, Lachlan; Moustafa, Julia S. El-Sayed; Blakemore, Alexandra I. F.; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London W12 0NN, England.
   [Kutalik, Zoltan; Valsesia, Armand; Bergmann, Sven; Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Kutalik, Zoltan; Valsesia, Armand; Bergmann, Sven] Univ Lausanne, Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Shen, Yiping; Platt, Orah S.; Wu, Bai-lin; Yu, Yongguo] Childrens Hosp Boston, Boston, MA 02115 USA.
   [Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Valsesia, Armand] Univ Lausanne, Ludwig Inst Canc Res, CH-1015 Lausanne, Switzerland.
   [Thorleifsson, Gudmar; Stefansson, Hreinn; Thorsteinsdottir, Unnur; Gustafsson, Omar; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Bouquillon, Sonia; Andrieux, Joris] CHRU Lille, Hop Jeanne de Flandre, Med Genet Lab, F-59000 Lille, France.
   [Campion, Dominique; Guilmatre, Audrey; Guillin, Olivier; Legallic, Solenn] Univ Rouen, INSERM U614, F-76000 Rouen, France.
   [Campion, Dominique; Guilmatre, Audrey; Guillin, Olivier; Legallic, Solenn] Ctr Hosp Rouvray, F-76000 Rouen, France.
   [de Leeuw, Nicole; de Vries, Bert B. A.; Brunner, Han G.; Faas, Brigitte H. W.; Koolen, David A.; Pfundt, Rolph; Vulto-van Silfhout, Anneke T.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
   [de Leeuw, Nicole; de Vries, Bert B. A.; Brunner, Han G.; Faas, Brigitte H. W.; Koolen, David A.; Pfundt, Rolph; Vulto-van Silfhout, Anneke T.] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Disorders, NL-6500 HB Nijmegen, Netherlands.
   [Esko, Tonu; Kurg, Ants; Maennik, Katrin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
   [Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
   [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Genet & Med, St John, NF A1B 3V6, Canada.
   [Fernandez-Aranda, Fernando; Jimenez-Murcia, Susana] Univ Hosp Bellvitge IDIBELL, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Dept Psychiat, Barcelona 08907, Spain.
   [Manuel Fernandez-Real, Jose] Hosp Univ Girona Dr Josep Trueta, Dept Diabet Endocrinol & Nutr, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Inst Invest Biomed Girona,Inst Salud Carlos III, Girona 17007, Spain.
   [Gratacos, Monica; Villatoro Gomez, Sergi; Estivill, Xavier] CIBER Epidemiol & Salud Publ CIBERESP, Ctr Genom Regulat CRG UPF, Genes & Dis Program, Barcelona 08003, Catalonia, Spain.
   [Hoyer, Juliane; Reis, Andre] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
   [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Child & Adolescent Hlth, Oulu 90101, Finland.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FIN-90570 Oulu, Finland.
   [Jarvelin, Marjo-Riitta] 90014 Univ Oulu, Univ Oulu, Bioctr Oulu, Oulu, Finland.
   [Kooy, R. Frank; Blaumeiser, Bettina; Van der Aa, Nathalie] Univ Antwerp, Dept Med Genet, B-2650 Antwerp, Belgium.
   [Kooy, R. Frank; Blaumeiser, Bettina; Van der Aa, Nathalie] Univ Antwerp Hosp, B-2650 Antwerp, Belgium.
   [Le Caignec, Cedric; David, Albert; Isidor, Bertrand] CHU Nantes, Serv Genet Med, Nantes, France.
   [Sanlaville, Damien; Labalme, Audrey; Rossi, Massimiliano] CHU Lyon, Hosp Civils Lyon, Serv Cytogenet Constitut, F-69000 Lyon, France.
   [Sanlaville, Damien; Labalme, Audrey; Rossi, Massimiliano] UCBL1, TIGER Team, Neurosci Res Ctr, F-69000 Lyon, France.
   [Van Haelst, Mieke M.; Knoers, Nine V. A. M.; van Binsbergen, Ellen] Univ Med Ctr, Dept Med Genet, NL-3584 EA Utrecht, Netherlands.
   [Wu, Bai-lin] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China.
   [Wu, Bai-lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.
   [Yu, Yongguo] Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China.
   [Aboura, Azzedine; Drunat, Severine; Gerard, Marion] Robert DEBRE Univ Hosp, APHP, Dept Genet, F-75019 Paris, France.
   [Alembik, Yves; Flori, Elisabeth] CHU Strasbourg, Hop Hautepierre, Serv Genet Med, F-67000 Strasbourg, France.
   [Antonarakis, Stylianos E.; Bena, Frederique; Bottani, Armand; Gimelli, Stefania] Univ Hosp Geneva, Serv Genet Med, CH-1205 Geneva, Switzerland.
   [Arveiler, Benoit; Delrue, Marie-Ange; Morice-Picard, Fanny; Rooryck, Caroline] Univ Bordeaux 2, Lab Malad Rares Genet & Metab, F-33076 Bordeaux, France.
   [Arveiler, Benoit; Cailley, Dorothee; Delrue, Marie-Ange; Morice-Picard, Fanny; Rooryck, Caroline] CHU Bordeaux, Serv Genet Med, F-33076 Bordeaux, France.
   [Barth, Magalie; Bonneau, Dominique; Guichet, Agnes] CHU Angers, Serv Genet, F-49933 Angers, France.
   [Bednarek, Nathalie] CHU Hop Alix de Champagne, Serv Pediat, F-51100 Reims, France.
   [Beri, Mylene; Jonveaux, Philippe] CHU Nancy, Genet Lab, F-54511 Vandoeuvre Les Nancy, France.
   [Bernardini, Laura] IRCCS Casa Sollievo della Sofferenza Hosp, Mendel Lab, I-71013 San Giovanni Rotondo, Italy.
   [Boute, Odile; Holder, Muriel; Moerman, Alexandre; Petit, Florence] CHRU Lille, Hop Jeanne de Flandre, Serv Genet Clin, F-59037 Lille, France.
   [Chiesa, Jean] CHU Caremeau, Lab Cytogenet, F-30029 Nimes, France.
   [Coutton, Charles; Satre, Veronique] CHU Grenoble, Lab Genet Chromosom, F-38043 Grenoble, France.
   [Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; Vallee, Louis] CHRU Lille, Hop Roger Salengro, Serv Neurol Pediat, F-59037 Lille, France.
   [de Freminville, Benedicte; Touraine, Renaud] CHU St Etienne, Serv Genet, CHU Hop Nord, F-42055 St Etienne, France.
   [Delobel, Bruno; Duban-Bedu, Benedicte] GHICL, Hop St Vincent de Paul, Ctr Genet Chromosom, F-59160 Lille, France.
   [Demeer, Benedicte; Mathieu-Dramard, Michele] CHRU Amiens, Serv Genet Med, F-80000 Amiens, France.
   [Descamps, Dominique] Ctr Hosp Bethune, F-62408 Bethune, France.
   [Dieterich, Klaus] CHU Grenoble, Serv Genet Clin, F-38043 Grenoble, France.
   [Disciglio, Vittoria; Mencarelli, Maria Antonietta; Mucciolo, Mafalda; Renieri, Alessandra] Univ Siena, Dept Biotechnol, I-53100 Siena, Italy.
   [Doco-Fenzy, Martine; Gaillard, Dominique; Landais, Emilie] CHU REIMS, IFR 53, HMB, Serv Genet, F-51092 Reims, France.
   [Dubourg, Christele; Jaillard, Sylvie] Univ Rennes 1, IFR GFAS 140, UMR CNRS 6061, F-35043 Rennes, France.
   [Dubourg, Christele] CHU, Serv Genet Mol, F-35033 Rennes, France.
   [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
   [Faivre, Laurence] CHU Dijon, Ctr Genet, F-21079 Dijon, France.
   [Faudet, Anne; Keren, Boris] APHP GH Pitie Salpetriere, Dept Genet & Cytogenet, F-75013 Paris, France.
   [Fisher, Richard; Zwolinksi, Simon] Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
   [Forer, Lukas; Kloss-Brandstaetter, Anita; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria.
   [Gieger, Christian; Ried, Janina S.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
   [Gimelli, Giorgio] G Gaslini Inst Children, Lab Citogenet, I-16147 Genoa, Italy.
   [Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, D-17475 Greifswald, Germany.
   [Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, D-18437 Stralsund, Germany.
   [Hartikainen, Anna-Liisa] Univ Oulu, Dept Obstet & Gynecol, Inst Clin Med, FIN-90570 Oulu, Finland.
   [Heron, Delphine] Univ Paris 06, Embryol AP HP, F-75005 Paris, France.
   [Heron, Delphine] Hop La Pitie Salpetriere, Dept Genet Cytogenet, F-75013 Paris, France.
   [Homuth, Georg; Schurmann, Claudia] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany.
   [Jaillard, Sylvie; Lucas, Josette] CHU Rennes, Lab Cytogenet & Biol Cellulaire, F-35033 Rennes, France.
   [Jaros, Zdenek] Landesklinikum Waldviertel Zwettl, Abt Kinder & Jugendheilkunde, A-3910 Zwettl, Austria.
   [Helas, Geraldine Joly] CHU Rouen, Dept Genet, F-76183 Rouen, France.
   [Kaksonen, Satu] Habilitat Unit Folkhalsan, SF-00250 Helsinki, Finland.
   [Knoers, Nine V. A. M.] Univ Med Ctr, Dept Human Genet, NL-3584 EA Utrecht, Netherlands.
   [Kroisel, Peter M.; Roetzer, Katharina M.] Med Univ Graz, Inst Human Genet, A-8010 Graz, Austria.
   [Layet, Valerie] Childrens Hosp Anna Meyer, Med Genet Unit, I-50139 Florence, Italy.
   [Layet, Valerie] Grp Hosp Havre, Unite Genet, F-76600 Le Havre, France.
   [Leheup, Bruno] CHU Nancy, Serv Med Infantile & Genet Clin 3, F-54511 Vandoeuvre Les Nancy, France.
   [Leheup, Bruno] Univ Lorraine UHP Nancy, PRES, F-54511 Vandoeuvre Les Nancy, France.
   [Leube, Barbara] Heinrich Heine Univ Hosp Duesseldorf, Inst Human Genet & Anthropol, D-40001 Dusseldorf, Germany.
   [Lewis, Suzanne] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
   [Lewis, Suzanne] Child & Family Res Inst, Vancouver, BC V6H 3N1, Canada.
   [MacDermot, Kay D.] Northwick Pk & St Marks Hosp, NW Thames Reg Genet Serv, Harrow HA1 3UJ, Middx, England.
   [Magnusson, Pall] Landspitali Univ Hosp, IS-105 Reykjavik, Iceland.
   [Marshall, Christian] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
   [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
   [Meitinger, Thomas] German Res Ctr Environm Hlth, Hemholtz Ctr Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Merla, Giuseppe] IRCCS Casa Sollievo della Sofferenza Hosp, Med Genet Unit, I-71013 San Giovanni Rotondo, Italy.
   [Mooser, Vincent] GlaxoSmithKline R&D, Genet, King Of Prussia, PA 19406 USA.
   [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
   [Ndiaye, Ndeye Coumba; Visvikis-Siest, Sophie] Univ Henri Poincare, Cardiovasc Genet Res Unit, EA4373, F-54000 Nancy, France.
   [Nordgren, Ann] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden.
   [Pasquier, Laurent] CLAD Ouest, Serv Genet, F-35203 Rennes 2, France.
   [Plessis, Ghislaine] CHU Clemenceau, Serv Genet, F-14033 Caen, France.
   [Rajcan-Separovic, Evica] Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 4H4, Canada.
   [Rajcan-Separovic, Evica] Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada.
   [Ramelli, Gian Paolo] Osped San Giovanni Bellinzona, Div Pediat, CH-6500 Bellinzona, Switzerland.
   [Rauch, Anita] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland.
   [Ravazzolo, Roberto] Univ Genoa, Dept Pediat, I-16126 Genoa, Italy.
   [Ravazzolo, Roberto] Univ Genoa, G Gaslini Inst, CEBR, I-16126 Genoa, Italy.
   [Richart, Cristobal] Univ Rovira & Virgili, Univ Hosp Juan XXIII, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Dept Internal Med,Inst Salud Carlos III, Tarragona 43005, Spain.
   [Rieubland, Claudine] Univ Bern, Inselspital, Dept Paediat, Div Human Genet, CH-3010 Bern, Switzerland.
   [Roberts, Wendy] Hosp Sick Children, Autism Res Unit, Toronto, ON M5G 1X8, Canada.
   [Saemundsen, Evald] State Diagnost & Counseling Ctr, IS-200 Kopavogur, Iceland.
   [Sigurdsson, Engilbert] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland.
   [Stavropoulos, Dimitri J.] Hosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada.
   [Tengstrom, Carola] Rinnekoti Res Fdn, Genet Serv, SF-02980 Espoo, Finland.
   [Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [Tinahones, Francisco J.] Clin Hosp Virgen de la Victoria, Ciber Fisiopatol Obesidad & Nutr CIBEROBN, Dept Endocrinol & Nutr, Inst Salud Carlos III, Malaga 29010, Spain.
   [Vincent-Delorme, Catherine] CH Arras CHRU Lille, Ctr Malad Rares, F-59000 Lille, France.
   [Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
   [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
   [Wallgren-Pettersson, Carina] Univ Helsinki, Dept Med Genet, Helsinki 00251, Finland.
   [Wallgren-Pettersson, Carina] Folkhalsan Inst Genet, Helsinki 00251, Finland.
   [Gustafsson, Omar] Oslo Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
   [Scherer, Stephen W.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1L7, Canada.
   [Froguel, Philippe] Inst Pasteur, Inst Biol, CNRS 8090, F-59800 Lille, France.
   [Disciglio, Vittoria] Azienda Osped Univ Senese, UOC Genet Med, Siena, Italy.
   [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
C3 University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Imperial College London; University of Lausanne; Swiss Institute of Bioinformatics; University of Lausanne; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Ludwig Institute for Cancer Research; University of Lausanne; Decode Genetics; Universite de Lille; CHU Lille; Universite de Rouen Normandie; Institut National de la Sante et de la Recherche Medicale (Inserm); Radboud University Nijmegen; Radboud University Nijmegen; University of Tartu; University of Tartu; Memorial University Newfoundland; University of Barcelona; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge University Hospital; CIBER - Centro de Investigacion Biomedica en Red; CIBEROBN; CIBER - Centro de Investigacion Biomedica en Red; CIBEROBN; Universitat de Girona; Girona University Hospital Dr. Josep Trueta; Institut d'Investigacio Biomedica de Girona (IDIBGI); Instituto de Salud Carlos III; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; University of Erlangen Nuremberg; Imperial College London; Finland National Institute for Health & Welfare; University of Oulu; University of Oulu; University of Antwerp; University of Antwerp; Nantes Universite; CHU de Nantes; CHU Lyon; Universite Lyon 1; Institut National de la Sante et de la Recherche Medicale (Inserm); Utrecht University; Utrecht University Medical Center; Fudan University; Fudan University; Shanghai Jiao Tong University; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Ambroise-Pare - APHP; Universite Paris Cite; Hopital Universitaire Robert-Debre - APHP; Hopital Universitaire Hotel-Dieu - APHP; CHU Strasbourg; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of Geneva; Universite de Bordeaux; Universite de Bordeaux; CHU Bordeaux; Universite d'Angers; Centre Hospitalier Universitaire d'Angers; CHU de Reims; CHU de Nancy; IRCCS Casa Sollievo Della Sofferenza; Istituto CSS Mendel; Universite de Lille; CHU Lille; Universite de Montpellier; CHU de Nimes; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CHU Grenoble Alpes; Universite de Lille; CHU Lille; CHU de St Etienne; Universite de Picardie Jules Verne (UPJV); CHU Amiens; CHU Grenoble Alpes; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); University of Siena; CHU de Reims; Universite de Reims Champagne-Ardenne; Universite de Rennes; CHU Rennes; Imperial College London; Universite Bourgogne Europe; CHU Dijon Bourgogne; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite; Newcastle University - UK; Medical University of Innsbruck; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Genoa; IRCCS Istituto Giannina Gaslini; Universitat Greifswald; Universitat Greifswald; University of Oulu; Sorbonne Universite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite; Universitat Greifswald; CHU Rennes; Universite de Rennes; Universite de Rouen Normandie; CHU de Rouen; Utrecht University; Utrecht University Medical Center; Medical University of Graz; University of Florence; Azienda Ospedaliera Universitaria (AOU) MEYER; CHU de Nancy; Universite de Lorraine; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; University of British Columbia; Child & Family Research Institute; Imperial College London; Landspitali National University Hospital; University of Toronto; Hospital for Sick Children (SickKids); University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; IRCCS Casa Sollievo Della Sofferenza; GlaxoSmithKline; Glaxosmithkline USA; Universitat Greifswald; Universite de Lorraine; Karolinska Institutet; CHU de Caen NORMANDIE; University of British Columbia; Child & Family Research Institute; Regional Hospital of Bellinzona & Valleys, San Giovanni; University of Zurich; University of Genoa; University of Genoa; IRCCS Istituto Giannina Gaslini; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBEROBN; Universitat Rovira i Virgili; University of Bern; University Hospital of Bern; University of Toronto; Hospital for Sick Children (SickKids); Landspitali National University Hospital; University of Toronto; Hospital for Sick Children (SickKids); University of Iceland; Instituto de Salud Carlos III; CIBER - Centro de Investigacion Biomedica en Red; CIBEROBN; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Universitat Greifswald; University of Helsinki; University of Oslo; University of Toronto; Hospital for Sick Children (SickKids); Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite de Lille; Institut Pasteur Lille; University of Siena; University Hospital of Siena; Technical University of Munich
RP Beckmann, JS (corresponding author), CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
EM Jacques.Beckmann@chuv.ch
FU Leenaards Foundation; Jerome Lejeune Foundation; Telethon Action Suisse Foundation; Swiss National Science Foundation; European Commission [037627, QLG1-CT-2000-01643]; Ludwig Institute for Cancer Research; Swiss Institute of Bioinformatics; Imperial College Department of Medicine; Comprehensive Biomedical Research Centre; Imperial College Healthcare NHS Trust; National Institute for Health Research; Wellcome Trust; Medical Research Council; Instituto de Salud Carlos III (ISCIII)-FIS; German Mental Retardation Network; German Federal Ministry of Education and Research [NGFNplus 01GS08160]; European Union [PI081714, PS09/01778, 201413, 245536, HEALTH-2007-2.2.1-10-223423]; Belgian National Fund for Scientific Research, Flanders; Dutch Organisation for Health Research and Development (ZON-MW) [917-86-319]; Hersenstichting Nederland (B.B.A.d.V.); Chinese National Natural Science Foundation [81000346]; Simons Foundation Autism Research Initiative; Autism Speaks; NIH [GM061354, MH071425]; Oesterreichische Nationalbank (OENB) [13059]; Children's Tumor Foundation; Harvard Medical School; Fudan University; Chinese National '973' project on Population and Health [2010CB529601]; Science and Technology Council of Shanghai [09JC1402400]; Michael Smith Foundation for Health; CIHR [MOP 74502]; Estonian Government [SF0180142s08, SF0180026s09, SF0180027s10]; Helmholtz Zentrum Munich; State of Bavaria; German National Genome Research Network [01GS0823]; German Federal Ministry of Education and Research (BMBF); Munich Center of Health Sciences (MC Health, LMUinnovativ); Genome Canada; McLaughlin Centre; Academy of Finland [104781, 120315, 129269, 1114194]; University Hospital Oulu; Biocenter; University of Oulu, Finland [75617]; NHLBI [5R01HL087679-02, 1RL1MH083268-01]; NIH/NIMH [5R01MH63706:02]; ENGAGE project; Medical Research Council, UK [G0500539, G0600705]; Academy of Finland; Biocentrum Helsinki;  [SAF2008-02278];  [HEALTH-F4-2007-201413]; MRC [G0801056, G0600705] Funding Source: UKRI; Medical Research Council [G0801056B, G0600705, G0801056] Funding Source: researchfish
NR 61
TC 356
Z9 406
U1 1
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 6
PY 2011
VL 478
IS 7367
BP 97
EP U111
DI 10.1038/nature10406
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400042
PM 21881559
DA 2026-03-09
ER

PT J
AU Laepple, T
   Werner, M
   Lohmann, G
AF Laepple, Thomas
   Werner, Martin
   Lohmann, Gerrit
TI Synchronicity of Antarctic temperatures and local solar insolation on orbital timescales
SO NATURE
LA English
DT Article
ID vostok ice core; southern-hemisphere; climate sensitivity; records; co2; accumulation; seasonality; cycles; ocean; rise
AB The Milankovitch theory states that global climate variability on orbital timescales from tens to hundreds of thousands of years is dominated by the summer insolation at high northern latitudes(1,2). The supporting evidence includes reconstructed air temperatures in Antarctica that are nearly in phase with boreal summer insolation and out of phase with local summer insolation(3-5). Antarctic climate is therefore thought to be driven by northern summer insolation(5). A clear mechanism that links the two hemispheres on orbital timescales is, however, missing. We propose that key Antarctic temperature records derived from ice cores are biased towards austral winter because of a seasonal cycle in snow accumulation. Using present-day estimates of this bias in the 'recorder' system, here we show that the local insolation can explain the orbital component of the temperature record without having to invoke a link to the Northern Hemisphere. Therefore, the Antarctic ice-core-derived temperature record, one of the best-dated records of the late Pleistocene temperature evolution, cannot be used to support or contradict the Milankovitch hypothesis that global climate changes are driven by Northern Hemisphere summer insolation variations.
C1 [Laepple, Thomas; Werner, Martin; Lohmann, Gerrit] Alfred Wegener Inst Polar & Marine Res, Bremerhaven, Germany.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Laepple, T (corresponding author), Alfred Wegener Inst Polar & Marine Res, Bremerhaven, Germany.
EM thomas.laepple@awi.de
NR 32
TC 67
Z9 75
U1 1
U2 39
PU 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 3
PY 2011
VL 471
IS 7336
BP 91
EP 94
DI 10.1038/nature09825
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100040
PM 21368830
DA 2026-03-09
ER

PT J
AU Bi, DP
   Zhang, J
   Chakraborty, B
   Behringer, RP
AF Bi, Dapeng
   Zhang, Jie
   Chakraborty, Bulbul
   Behringer, R. P.
TI Jamming by shear
SO NATURE
LA English
DT Article
AB A broad class of disordered materials including foams, glassy molecular systems, colloids and granular materials can form jammed states. A jammed system can resist small stresses without deforming irreversibly, whereas unjammed systems flow under any applied stresses. The broad applicability of the Liu-Nagel jamming concept(1,2) has attracted intensive theoretical and modelling interest but has prompted less experimental effort(1-6). In the Liu-Nagel framework, jammed states of athermal systems exist only above a certain critical density. Although numerical simulations for particles that do not experience friction broadly support this idea(7-13), the nature of the jamming transition for frictional grains is less clear(14-17). Here we show that jamming of frictional, disk-shaped grains can be induced by the application of shear stress at densities lower than the critical value, at which isotropic (shear-free) jamming occurs. These jammed states have a much richer phenomenology than the isotropic jammed states: for small applied shear stresses, the states are fragile, with a strong force network that percolates only in one direction. A minimum shear stress is needed to create robust, shear-jammed states with a strong force network percolating in all directions. The transitions from unjammed to fragile states and from fragile to shear-jammed states are controlled by the fraction of force-bearing grains. The fractions at which these transitions occur are statistically independent of the density. Jammed states with densities lower than the critical value have an anisotropic fabric (contact network). The minimum anisotropy of shear-jammed states vanishes as the density approaches the critical value from below, in a manner reminiscent of an order-disorder transition.
C1 [Zhang, Jie; Behringer, R. P.] Duke Univ, Dept Phys, Durham, NC 27708 USA.
   [Zhang, Jie] Indiana Univ Purdue Univ, Dept Phys, Ft Wayne, IN 46805 USA.
   [Zhang, Jie] Shanghai Jiao Tong Univ, Dept Phys, Shanghai 200240, Peoples R China.
   [Zhang, Jie] Shanghai Jiao Tong Univ, Inst Nat Sci, Shanghai 200240, Peoples R China.
   [Bi, Dapeng; Chakraborty, Bulbul] Brandeis Univ, Martin Fisher Sch Phys, Waltham, MA 02454 USA.
C3 Duke University; Purdue University System; Indiana University Purdue University Fort Wayne; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Brandeis University
RP Behringer, RP (corresponding author), Duke Univ, Dept Phys, Durham, NC 27708 USA.
EM bob@phy.duke.edu
FU US NSF [DMR-0905880, DMR-0906908, NSF-0835571]; US ARO [W911NF-07-1-1031]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0905880] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [0906908] Funding Source: National Science Foundation
NR 30
TC 568
Z9 681
U1 14
U2 356
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 355
EP 358
DI 10.1038/nature10667
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000048
PM 22170683
DA 2026-03-09
ER

PT J
AU Laguette, N
   Sobhian, B
   Casartelli, N
   Ringeard, M
   Chable-Bessia, C
   Ségéral, E
   Yatim, A
   Emiliani, S
   Schwartz, O
   Benkirane, M
AF Laguette, Nadine
   Sobhian, Bijan
   Casartelli, Nicoletta
   Ringeard, Mathieu
   Chable-Bessia, Christine
   Segeral, Emmanuel
   Yatim, Ahmad
   Emiliani, Stephane
   Schwartz, Olivier
   Benkirane, Monsef
TI SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx
SO NATURE
LA English
DT Article
ID gamma-induced protein; innate immunity; infection; inhibition; target; domain
AB The primate lentivirus auxiliary protein Vpx counteracts an unknown restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection(1-6). Here we identify SAMHD1 as this restriction factor. SAMHD1 is a protein involved in Aicardi-Goutieres syndrome, a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response(7). We show that Vpx induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in non-permissive cell lines alleviates HIV-1 restriction and is associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibits HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction is abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increases the susceptibility of monocytic-derived dendritic cells to infection. Our results demonstrate that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle.
C1 [Laguette, Nadine; Sobhian, Bijan; Ringeard, Mathieu; Chable-Bessia, Christine; Yatim, Ahmad; Benkirane, Monsef] CNRS, Inst Genet Humaine, Lab Virol Mol, UPR1142, F-34000 Montpellier, France.
   [Casartelli, Nicoletta; Schwartz, Olivier] CNRS, Inst Pasteur, Virus & Immun Unit, URA 3015, Paris, France.
   [Segeral, Emmanuel; Emiliani, Stephane] Univ Paris 05, CNRS, Inst Cochin, UMR 8104,INSERM,U567, Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Benkirane, M (corresponding author), CNRS, Inst Genet Humaine, Lab Virol Mol, UPR1142, F-34000 Montpellier, France.
EM nadine.laguette@igh.cnrs.fr; monsef.benkirane@igh.cnrs.fr
FU ERC [250333]; Sidaction; ANRS; FRM 'equipe labellisee'; CNRS/region Languedoc Roussillon; European FP7 [201412]; Institut Pasteur; European Research Council (ERC) [250333] Funding Source: European Research Council (ERC)
NR 27
TC 1260
Z9 1507
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 654
EP U132
DI 10.1038/nature10117
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300042
PM 21613998
DA 2026-03-09
ER

PT J
AU Dominguez, G
   Wilkins, G
   Thiemens, MH
AF Dominguez, Gerardo
   Wilkins, Gautam
   Thiemens, Mark H.
TI The Soret effect and isotopic fractionation in high-temperature silicate melts
SO NATURE
LA English
DT Article
ID thermal-diffusion; molecular-dynamics; evaporation; liquids; systems; sio2
AB Diffusion in condensed phases is a ubiquitous but poorly understood phenomenon. For example, chemical diffusion, which is the transport of matter associated with chemical concentration gradients (Fick's law), is treated as a separate process from thermal transport (the Soret effect), which is mass transport induced by temperature gradients. In the past few years, large variations in the proportions of isotopes of Mg, Ca, Fe, Si and O found in silicate melts subject to thermal gradients have been found(1-3), but no physical mechanism has been proposed. Here we present a model of diffusion in natural condensed systems that explains both the chemical and isotopic fractionation of Mg, Ca and Fe in high-temperature geochemical melts. Despite the high temperatures associated with these melts (T > 1,000 degrees C), we find that consideration of the quantum-mechanical zero-point energy of diffusing species is essential for understanding diffusion at the isotopic level. Our model explains thermal and chemical mass transport as manifestations of the same underlying diffusion mechanism. This work promises to provide insights into mass-transport phenomena (diffusion and evaporation) and associated isotopic fractionations in a wide range of natural condensed systems, including the atmospheric water cycle(1,2), geological and geochemical systems(3-6) and the early Solar System(4). This work might also be relevant to studies of mass transport in biological(7,8) and nanotechnological condensed systems(9).
C1 [Dominguez, Gerardo; Thiemens, Mark H.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Wilkins, Gautam] Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA.
C3 University of California System; University of California San Diego; University of California System; University of California Berkeley
RP Dominguez, G (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM gdominguez@ucsd.edu
FU University of California; NASA [NNX07AM66G, NNX08AI15G]; NASA [NNX08AI15G, 100846] Funding Source: Federal RePORTER
NR 30
TC 71
Z9 79
U1 1
U2 80
PU 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 5
PY 2011
VL 473
IS 7345
BP 70
EP U134
DI 10.1038/nature09911
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300032
PM 21508959
DA 2026-03-09
ER

PT J
AU Vijaykrishna, D
   Smith, GJD
   Pybus, OG
   Zhu, HC
   Bhatt, S
   Poon, LLM
   Riley, S
   Bahl, J
   Ma, SK
   Cheung, CL
   Perera, RAPM
   Chen, HL
   Shortridge, KF
   Webby, RJ
   Webster, RG
   Guan, Y
   Peiris, JSM
AF Vijaykrishna, Dhanasekaran
   Smith, Gavin J. D.
   Pybus, Oliver G.
   Zhu, Huachen
   Bhatt, Samir
   Poon, Leo L. M.
   Riley, Steven
   Bahl, Justin
   Ma, Siu K.
   Cheung, Chung L.
   Perera, Ranawaka A. P. M.
   Chen, Honglin
   Shortridge, Kennedy F.
   Webby, Richard J.
   Webster, Robert G.
   Guan, Yi
   Peiris, J. S. Malik
TI Long-term evolution and transmission dynamics of swine influenza A virus
SO NATURE
LA English
DT Article
ID pigs; reassortment; emergence; origins; china; h9n2
AB Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease(1) and occasionally give rise to human pandemics(2), including that caused by the H1N1/2009 virus(3,4). The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic(4). Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.
C1 [Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Zhu, Huachen; Poon, Leo L. M.; Bahl, Justin; Ma, Siu K.; Cheung, Chung L.; Perera, Ranawaka A. P. M.; Chen, Honglin; Shortridge, Kennedy F.; Webster, Robert G.; Guan, Yi; Peiris, J. S. Malik] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China.
   [Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Zhu, Huachen; Poon, Leo L. M.; Bahl, Justin; Ma, Siu K.; Cheung, Chung L.; Perera, Ranawaka A. P. M.; Chen, Honglin; Shortridge, Kennedy F.; Webster, Robert G.; Guan, Yi; Peiris, J. S. Malik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China.
   [Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Zhu, Huachen; Bahl, Justin; Chen, Honglin; Shortridge, Kennedy F.; Guan, Yi] Shantou Univ, Coll Med, Int Inst Infect & Immun, Shantou, Guangdong, Peoples R China.
   [Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Bahl, Justin] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Lab Virus Evolut, Singapore 169857, Singapore.
   [Pybus, Oliver G.; Bhatt, Samir] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Riley, Steven] Univ Hong Kong, Li Ka Shing Fac Med, Dept Community Med, Pokfulam, Hong Kong, Peoples R China.
   [Riley, Steven] Univ Hong Kong, Li Ka Shing Fac Med, Sch Publ Hlth, Pokfulam, Hong Kong, Peoples R China.
   [Webby, Richard J.; Webster, Robert G.] St Jude Childrens Res Hosp, Dept Infect Dis, Div Virol, Memphis, TN 38015 USA.
   [Peiris, J. S. Malik] Univ Hong Kong, HKU Pasteur Res Ctr, Pokfulam, Hong Kong, Peoples R China.
C3 University of Hong Kong; University of Hong Kong; Shantou University; National University of Singapore; University of Oxford; University of Hong Kong; University of Hong Kong; St Jude Children's Research Hospital; University of Hong Kong
RP Guan, Y (corresponding author), Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China.
EM yguan@hkucc.hku.hk; malik@hkucc.hku.hk
FU National Institute of Allergy and Infectious Diseases (NIAID) [HHSN26600700005C]; University Grants Commission of the Hong Kong SAR Government [AoE/M-12/06]; Royal Society of London; UK COSI; Agency for Science, Technology and Research; Ministry of Health, Singapore; BBSRC [BB/H014306/1] Funding Source: UKRI; MRC [MC_G0902096] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H014306/1] Funding Source: researchfish; Medical Research Council [G0600719B, MC_G0902096] Funding Source: researchfish
NR 32
TC 210
Z9 250
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 MAY 26
PY 2011
VL 473
IS 7348
BP 519
EP U263
DI 10.1038/nature10004
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 768QM
UT WOS:000290951300042
PM 21614079
DA 2026-03-09
ER

PT J
AU Penkman, KEH
   Preece, RC
   Bridgland, DR
   Keen, DH
   Meijer, T
   Parfitt, SA
   White, TS
   Collins, MJ
AF Penkman, Kirsty E. H.
   Preece, Richard C.
   Bridgland, David R.
   Keen, David H.
   Meijer, Tom
   Parfitt, Simon A.
   White, Tom S.
   Collins, Matthew J.
TI A chronological framework for the British Quaternary based on Bithynia opercula
SO NATURE
LA English
DT Article
ID pleistocene; middle; geochronology; occupation; fraction; britain; systems; europe; record
AB Marine and ice-core records show that the Earth has experienced a succession of glacials and interglacials during the Quaternary (last similar to 2.6 million years), although it is often difficult to correlate fragmentary terrestrial records with specific cycles. Aminostratigraphy is a method potentially able to link terrestrial sequences to the marine isotope stages (MIS) of the deep-sea record(1,2). We have used new methods of extraction and analysis of amino acids, preserved within the calcitic opercula of the freshwater gastropod Bithynia, to provide the most comprehensive data set for the British Pleistocene based on a single dating technique. A total of 470 opercula from 74 sites spanning the entire Quaternary are ranked in order of relative age based on the extent of protein degradation, using aspartic acid/asparagine (Asx), glutamic acid/glutamine (Glx), serine (Ser), alanine (Ala) and valine (Val). This new aminostratigraphy is consistent with the stratigraphical relationships of stratotypes, sites with independent geochronology, biostratigraphy and terrace stratigraphy(3-6). The method corroborates the existence of four interglacial stages between the Anglian (MIS 12) and the Holocene in the terrestrial succession. It establishes human occupation of Britain in most interglacial stages after MIS 15, but supports the notion of human absence during the Last Interglacial (MIS 5e)(7). Suspicions that the treeless 'optimum of the Upton Warren interstadial' at Isleworth pre-dates MIS 3 are confirmed. This new aminostratigraphy provides a robust framework against which climatic, biostratigraphical and archaeological models can be tested.
C1 [Penkman, Kirsty E. H.; Collins, Matthew J.] Univ York, BioArCh, Dept Archaeol, York YO10 5DD, N Yorkshire, England.
   [Penkman, Kirsty E. H.; Collins, Matthew J.] Univ York, Dept Chem, BioArCh, York YO10 5DD, N Yorkshire, England.
   [Preece, Richard C.; White, Tom S.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Bridgland, David R.] Univ Durham, Dept Geog, Durham DH1 3LE, England.
   [Keen, David H.] Univ Birmingham, Inst Archaeol & Antiqu, Birmingham B15 2TT, W Midlands, England.
   [Meijer, Tom] Netherlands Ctr Biodivers, Cainozo Mollusca, NL-2300 RA Leiden, Netherlands.
   [Parfitt, Simon A.] UCL, Inst Archaeol, London WC1H 0PY, England.
   [Parfitt, Simon A.] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England.
C3 University of York - UK; University of York - UK; University of Cambridge; Durham University; University of Birmingham; Naturalis Biodiversity Center; University of London; University College London; Natural History Museum London
RP Penkman, KEH (corresponding author), Univ York, BioArCh, Dept Archaeol, York YO10 5DD, N Yorkshire, England.
EM kirsty.penkman@york.ac.uk
FU English Heritage, NERC; Wellcome Trust [GR076905MA]; Leverhulme Trust; EPSRC [EP/I001514/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/I001514/1] Funding Source: researchfish
NR 30
TC 129
Z9 137
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 AUG 25
PY 2011
VL 476
IS 7361
BP 446
EP 449
DI 10.1038/nature10305
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400035
PM 21804567
DA 2026-03-09
ER

PT J
AU Sigal, A
   Kim, JT
   Balazs, AB
   Dekel, E
   Mayo, A
   Milo, R
   Baltimore, D
AF Sigal, Alex
   Kim, Jocelyn T.
   Balazs, Alejandro B.
   Dekel, Erez
   Mayo, Avi
   Milo, Ron
   Baltimore, David
TI Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; lymphoid-tissue; target-cells; infection; dynamics; recombination; lymphocytes; reservoirs; viremia; haart
AB Latency and ongoing replication(1) have both been proposed to explain the drug-insensitive human immunodeficiency virus (HIV) reservoir maintained during antiretroviral therapy. Here we explore a novel mechanism for ongoing HIV replication in the face of antiretroviral drugs. We propose a model whereby multiple infections(2,3) per cell lead to reduced sensitivity to drugs without requiring drug-resistant mutations, and experimentally validate the model using multiple infections per cell by cell-free HIV in the presence of the drug tenofovir. We then examine the drug sensitivity of cell-to-cell spread of HIV(4-7), a mode of HIV transmission that can lead to multiple infection events per target cell(8-10). Infections originating from cell-free virus decrease strongly in the presence of antiretrovirals tenofovir and efavirenz whereas infections involving cell-to-cell spread are markedly less sensitive to the drugs. The reduction in sensitivity is sufficient to keep multiple rounds of infection from terminating in the presence of drugs. We examine replication from cell-to-cell spread in the presence of clinical drug concentrations using a stochastic infection model and find that replication is intermittent, without substantial accumulation of mutations. If cell-to-cell spread has the same properties in vivo, it may have adverse consequences for the immune system(11-13), lead to therapy failure in individuals with risk factors(14), and potentially contribute to viral persistence and hence be a barrier to curing HIV infection.
C1 [Sigal, Alex; Kim, Jocelyn T.; Balazs, Alejandro B.; Baltimore, David] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Kim, Jocelyn T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA.
   [Dekel, Erez; Mayo, Avi] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
   [Milo, Ron] Weizmann Inst Sci, Dept Plant Sci, IL-76100 Rehovot, Israel.
C3 California Institute of Technology; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Weizmann Institute of Science; Weizmann Institute of Science
RP Baltimore, D (corresponding author), CALTECH, Div Biol, Pasadena, CA 91125 USA.
EM baltimo@caltech.edu
FU Human Frontier Science Program [LT00946]; UCLA [T32 AI089398]; amfAR Postdoctoral Research Fellowship [107756-47-RFVA]; Bill & Melinda Gates Foundation; National Institutes of Health [HHSN266200500035C]; National Institute of Allergy and Infectious Diseases; UCLA CFAR Virology Core Lab [P01-AI-28697]; UCSF-GIVI CFAR [P30-AI-27763]
NR 30
TC 445
Z9 515
U1 1
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 1
PY 2011
VL 477
IS 7362
BP 95
EP U100
DI 10.1038/nature10347
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 813XT
UT WOS:000294404300038
PM 21849975
DA 2026-03-09
ER

PT J
AU Goldstone, DC
   Ennis-Adeniran, V
   Hedden, JJ
   Groom, HCT
   Rice, GI
   Christodoulou, E
   Walker, PA
   Kelly, G
   Haire, LF
   Yap, MW
   de Carvalho, LPS
   Stoye, JP
   Crow, YJ
   Taylor, IA
   Webb, M
AF Goldstone, David C.
   Ennis-Adeniran, Valerie
   Hedden, Joseph J.
   Groom, Harriet C. T.
   Rice, Gillian I.
   Christodoulou, Evangelos
   Walker, Philip A.
   Kelly, Geoff
   Haire, Lesley F.
   Yap, Melvyn W.
   de Carvalho, Luiz Pedro S.
   Stoye, Jonathan P.
   Crow, Yanick J.
   Taylor, Ian A.
   Webb, Michelle
TI HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase
SO NATURE
LA English
DT Article
ID aicardi-goutieres-syndrome; human dendritic cells; reverse-transcriptase; dntp triphosphohydrolase; infection; protein; vpx; macrophage; mutations; trex1
AB SAMHD1, an analogue of the murine interferon (IFN)-gamma-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells(2,3) and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction(4-7). SAMHD1 is also associated with Aicardi-Goutieres syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-alpha(8). The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis.
C1 [Goldstone, David C.; Ennis-Adeniran, Valerie; Hedden, Joseph J.; Christodoulou, Evangelos; Walker, Philip A.; Haire, Lesley F.; Taylor, Ian A.] MRC Natl Inst Med Res, Div Mol Struct, London NW7 1AA, England.
   [Groom, Harriet C. T.; Yap, Melvyn W.; Stoye, Jonathan P.] MRC Natl Inst Med Res, Div Virol, London NW7 1AA, England.
   [Rice, Gillian I.; Crow, Yanick J.; Webb, Michelle] Univ Manchester, Cent Manchester Fdn Trust Univ Hosp, Manchester Acad Heath Sci Ctr, Manchester M13 9PT, Lancs, England.
   [Kelly, Geoff] Natl Inst Med Res, MRC Biomed NMR Ctr, London NW7 1AA, England.
   [de Carvalho, Luiz Pedro S.] MRC Natl Inst Med Res, Div Mycobacterial Res, London NW7 1AA, England.
C3 MRC National Institute for Medical Research; MRC National Institute for Medical Research; University of Manchester; MRC National Institute for Medical Research; MRC National Institute for Medical Research
RP Taylor, IA (corresponding author), MRC Natl Inst Med Res, Div Mol Struct, Mill Hill, London NW7 1AA, England.
EM itaylor@nimr.mrc.ac.uk; Michelle.Webb@manchester.ac.uk
FU UK Medical Research Council [U117565647, U117512710]; European Union [241779]; European Leukodystrophy Association; Medical Research Council [MC_UP_A253_1111, MC_U117512710, MC_U117533887, MC_U117565647] Funding Source: researchfish; MRC [MC_U117533887, MC_U117512710, MC_U117565647, MC_UP_A253_1111] Funding Source: UKRI
NR 30
TC 697
Z9 847
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 15
PY 2011
VL 480
IS 7377
BP 379
EP U134
DI 10.1038/nature10623
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PZ
UT WOS:000298033000054
PM 22056990
DA 2026-03-09
ER

PT J
AU Meng, J
   Wang, YQ
   Li, CK
AF Meng, Jin
   Wang, Yuanqing
   Li, Chuankui
TI Transitional mammalian middle ear from a new Cretaceous Jehol eutriconodont
SO NATURE
LA English
DT Article
ID ossified meckels cartilage; evolutionary development; origin; didelphidae
AB The transference of post-dentary jaw elements to the cranium of mammals as auditory ossicles is one of the central topics in evolutionary biology of vertebrates. Homologies of these bones among jawed vertebrates have long been demonstrated by developmental studies; but fossils illuminating this critical transference are sparse and often ambiguous. Here we report the first unambiguous ectotympanic (angular), malleus (articular and prearticular) and incus (quadrate) of an Early Cretaceous eutriconodont mammal from the Jehol Biota, Liaoning, China. The ectotympanic and malleus have lost their direct contact with the dentary bone but still connect the ossified Meckel's cartilage (OMC); we hypothesize that the OMC serves as a stabilizing mechanism bridging the dentary and the detached ossicles during mammalian evolution. This transitional mammalian middle ear narrows the morphological gap between the mandibular middle ear in basal mammaliaforms and the definitive mammalian middle ear (DMME) of extant mammals; it reveals complex changes contributing to the detachment of ear ossicles during mammalian evolution.
C1 [Meng, Jin] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
   [Meng, Jin; Wang, Yuanqing; Li, Chuankui] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
C3 American Museum of Natural History (AMNH); Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS
RP Meng, J (corresponding author), Amer Museum Nat Hist, Div Paleontol, Cent Pk W & 79th St, New York, NY 10024 USA.
EM jmeng@amnh.org
FU Ministry of Science and Technology, China [2006CB806400]; National Science Foundation of China [40121202]; Chinese Academy of Sciences; National Science Foundation of USA [EF-0629811]
NR 46
TC 114
Z9 133
U1 1
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 14
PY 2011
VL 472
IS 7342
BP 181
EP 185
DI 10.1038/nature09921
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 749LR
UT WOS:000289469100034
PM 21490668
DA 2026-03-09
ER

PT J
AU McGrath, PT
   Xu, YF
   Ailion, M
   Garrison, JL
   Butcher, RA
   Bargmann, CI
AF McGrath, Patrick T.
   Xu, Yifan
   Ailion, Michael
   Garrison, Jennifer L.
   Butcher, Rebecca A.
   Bargmann, Cornelia I.
TI Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes
SO NATURE
LA English
DT Article
ID elegans dauer larva; molecular evolution; component; behavior; neurons; food
AB Evolution can follow predictable genetic trajectories(1), indicating that discrete environmental shifts can select for reproducible genetic changes(2-4). Conspecific individuals are an important feature of an animal's environment, and a potential source of selective pressures. Here we show that adaptation of two Caenorhabditis species to growth at high density, a feature common to domestic environments, occurs by reproducible genetic changes to pheromone receptor genes. Chemical communication through pheromones that accumulate during high-density growth causes young nematode larvae to enter the long-lived but non-reproductive dauer stage. Two strains of Caenorhabditis elegans grown at high density have independently acquired multigenic resistance to pheromone-induced dauer formation. In each strain, resistance to the pheromone ascaroside C3 results from a deletion that disrupts the adjacent chemoreceptor genes serpentine receptor class g (srg)-36 and -37. Through misexpression experiments, we show that these genes encode redundant G-protein-coupled receptors for ascaroside C3. Multigenic resistance to dauer formation has also arisen in high-density cultures of a different nematode species, Caenorhabditis briggsae, resulting in part from deletion of an srg gene paralogous to srg-36 and srg-37. These results demonstrate rapid remodelling of the chemoreceptor repertoire as an adaptation to specific environments, and indicate that parallel changes to a common genetic substrate can affect life-history traits across species.
C1 [McGrath, Patrick T.; Xu, Yifan; Garrison, Jennifer L.; Bargmann, Cornelia I.] Rockefeller Univ, Lab Neural Circuits & Behav, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Ailion, Michael] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Butcher, Rebecca A.] Univ Florida, Dept Chem, Gainesville, FL 32611 USA.
C3 Rockefeller University; Howard Hughes Medical Institute; Utah System of Higher Education; University of Utah; State University System of Florida; University of Florida
RP Bargmann, CI (corresponding author), Rockefeller Univ, Lab Neural Circuits & Behav, Howard Hughes Med Inst, New York, NY 10065 USA.
EM cori@rockefeller.edu
FU Damon Runyon Fellowship; Medical Scientist Training Program (MSTP) [GM07739]; Paul and Daisy Soros Fellowship; National Institutes of Health (NIH) [K99 GM092859]; HHMI;  [R00GM87533]; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
NR 36
TC 178
Z9 245
U1 0
U2 66
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2011
VL 477
IS 7364
BP 321
EP U92
DI 10.1038/nature10378
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819TD
UT WOS:000294852400029
PM 21849976
DA 2026-03-09
ER

PT J
AU Skarnes, WC
   Rosen, B
   West, AP
   Koutsourakis, M
   Bushell, W
   Iyer, V
   Mujica, AO
   Thomas, M
   Harrow, J
   Cox, T
   Jackson, D
   Severin, J
   Biggs, P
   Fu, J
   Nefedov, M
   de Jong, PJ
   Stewart, AF
   Bradley, A
AF Skarnes, William C.
   Rosen, Barry
   West, Anthony P.
   Koutsourakis, Manousos
   Bushell, Wendy
   Iyer, Vivek
   Mujica, Alejandro O.
   Thomas, Mark
   Harrow, Jennifer
   Cox, Tony
   Jackson, David
   Severin, Jessica
   Biggs, Patrick
   Fu, Jun
   Nefedov, Michael
   de Jong, Pieter J.
   Stewart, A. Francis
   Bradley, Allan
TI A conditional knockout resource for the genome-wide study of mouse gene function
SO NATURE
LA English
DT Article
ID embryonic stem-cells; homologous recombination; caenorhabditis-elegans; negative selection; rat blastocysts; expression; trap; mice; reporter; vector
AB Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.
C1 [Skarnes, William C.; Rosen, Barry; West, Anthony P.; Koutsourakis, Manousos; Bushell, Wendy; Iyer, Vivek; Mujica, Alejandro O.; Thomas, Mark; Harrow, Jennifer; Cox, Tony; Jackson, David; Severin, Jessica; Biggs, Patrick; Bradley, Allan] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Fu, Jun; Stewart, A. Francis] Tech Univ Dresden, Biotechnol Zentrum, D-01062 Dresden, Germany.
   [Nefedov, Michael; de Jong, Pieter J.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
C3 Wellcome Trust Sanger Institute; Technische Universitat Dresden; Children's Hospital Oakland Research Institute; Children's Hospital Los Angeles
RP Skarnes, WC (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM skarnes@sanger.ac.uk
FU Wellcome Trust Sanger Institute; National Institutes of Health (KOMP) [U01-HG004080]; EU
NR 48
TC 1353
Z9 1610
U1 1
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 337
EP U361
DI 10.1038/nature10163
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100037
PM 21677750
DA 2026-03-09
ER

PT J
AU Vacic, V
   McCarthy, S
   Malhotra, D
   Murray, F
   Chou, HH
   Peoples, A
   Makarov, V
   Yoon, S
   Bhandari, A
   Corominas, R
   Iakoucheva, LM
   Krastoshevsky, O
   Krause, V
   Larach-Walters, V
   Welsh, DK
   Craig, D
   Kelsoe, JR
   Gershon, ES
   Leal, SM
   Aquila, MD
   Morris, DW
   Gill, M
   Corvin, A
   Insel, PA
   McClellan, J
   King, MC
   Karayiorgou, M
   Levy, DL
   DeLisi, LE
   Sebat, J
AF Vacic, Vladimir
   McCarthy, Shane
   Malhotra, Dheeraj
   Murray, Fiona
   Chou, Hsun-Hua
   Peoples, Aine
   Makarov, Vladimir
   Yoon, Seungtai
   Bhandari, Abhishek
   Corominas, Roser
   Iakoucheva, Lilia M.
   Krastoshevsky, Olga
   Krause, Verena
   Larach-Walters, Veronica
   Welsh, David K.
   Craig, David
   Kelsoe, John R.
   Gershon, Elliot S.
   Leal, Suzanne M.
   Aquila, Marie Dell
   Morris, Derek W.
   Gill, Michael
   Corvin, Aiden
   Insel, Paul A.
   McClellan, Jon
   King, Mary-Claire
   Karayiorgou, Maria
   Levy, Deborah L.
   DeLisi, Lynn E.
   Sebat, Jonathan
TI Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia
SO NATURE
LA English
DT Article
ID vasoactive-intestinal-peptide; microdeletions; 7q
AB Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders(1). Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs.
C1 [Vacic, Vladimir; McCarthy, Shane; Malhotra, Dheeraj; Bhandari, Abhishek; Sebat, Jonathan] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 12824 USA.
   [Vacic, Vladimir] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
   [Malhotra, Dheeraj; Chou, Hsun-Hua; Bhandari, Abhishek; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA USA.
   [Malhotra, Dheeraj; Chou, Hsun-Hua; Bhandari, Abhishek; Corominas, Roser; Iakoucheva, Lilia M.; Welsh, David K.; Kelsoe, John R.; Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA USA.
   [Murray, Fiona; Aquila, Marie Dell; Insel, Paul A.] Univ Calif San Diego, Dept Med, La Jolla, CA USA.
   [Murray, Fiona; Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA USA.
   [Peoples, Aine; Morris, Derek W.; Gill, Michael; Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin 2, Ireland.
   [Peoples, Aine; Morris, Derek W.; Gill, Michael; Corvin, Aiden] Trinity Coll Dublin, Dept Psychiat, Dublin 2, Ireland.
   [Makarov, Vladimir; Yoon, Seungtai] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY 10029 USA.
   [Makarov, Vladimir; Yoon, Seungtai] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Krastoshevsky, Olga; Krause, Verena; Levy, Deborah L.] McLean Hosp, Belmont, MA 02478 USA.
   [Larach-Walters, Veronica] Univ Andres Bello, Fac Med, Santiago, Chile.
   [Welsh, David K.; Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA.
   [Welsh, David K.] Univ Calif San Diego, Ctr Chronobiol, La Jolla, CA USA.
   [Craig, David] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA.
   [Kelsoe, John R.; Sebat, Jonathan] Univ Calif San Diego, Inst Genom Med, La Jolla, CA USA.
   [Gershon, Elliot S.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
   [Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77025 USA.
   [Aquila, Marie Dell] Univ Calif San Diego, Div Med Genet, La Jolla, CA USA.
   [McClellan, Jon] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
   [King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [King, Mary-Claire] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Karayiorgou, Maria] Columbia Univ, Dept Psychiat, New York, NY 10027 USA.
   [DeLisi, Lynn E.] Boston VA Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA.
   [DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton, MA 02301 USA.
   [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA USA.
C3 Cold Spring Harbor Laboratory; Columbia University; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Trinity College Dublin; Trinity College Dublin; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; McLean Hospital; Universidad Andres Bello; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA San Diego Healthcare System; University of California System; University of California San Diego; Translational Genomics Research Institute; University of California System; University of California San Diego; University of Chicago; Baylor College of Medicine; University of California System; University of California San Diego; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Columbia University; Harvard University; University of California System; University of California San Diego
RP Sebat, J (corresponding author), Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 12824 USA.
EM jsebat@ucsd.edu
FU Beyster family foundation; NIH [MH076431, HG04222, MH071523, MH083989, GM66232, HL091061, MH082945, MH061399, MH044245]; NARSAD; Wellcome Trust [072894/Z/03/Z]; Science Foundation Ireland [08INIB1916]; Sidney R. Baer, Jr Foundation; Essel Foundation; Veterans Administration
NR 30
TC 266
Z9 317
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 24
PY 2011
VL 471
IS 7339
BP 499
EP 503
DI 10.1038/nature09884
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200059
PM 21346763
DA 2026-03-09
ER

PT J
AU Houck-Loomis, B
   Durney, MA
   Salguero, C
   Shankar, N
   Nagle, JM
   Goff, SP
   D'Souza, VM
AF Houck-Loomis, Brian
   Durney, Michael A.
   Salguero, Carolina
   Shankar, Neelaabh
   Nagle, Julia M.
   Goff, Stephen P.
   D'Souza, Victoria M.
TI An equilibrium-dependent retroviral mRNA switch regulates translational recoding
SO NATURE
LA English
DT Article
ID murine leukemia-virus; gag-termination codon; read-through; gene-expression; internal loops; nmr structure; pseudoknot; nucleotides; suppression; readthrough
AB Most retroviruses require translational recoding of a viral messenger RNA stop codon to maintain a precise ratio of structural (Gag) and enzymatic (Pol) proteins during virus assembly(1,2). Pol is expressed exclusively as a Gag-Pol fusion either by ribosomal frameshifting or by read-through of the gag stop codon(3). Both of these mechanisms occur infrequently and only affect 5-10% of translating ribosomes, allowing the virus to maintain the critical Gag to Gag-Pol ratio(4-8). Although it is understood that the frequency of the recoding event is regulated by cis RNA motifs, no mechanistic explanation is currently available for how the critical protein ratio is maintained. Here we present the NMR structure of the murine leukaemia virus recoding signal and show that a protonation-dependent switch occurs to induce the active conformation. The equilibrium is such that at physiological pH the active, read-through permissive conformation is populated at approximately 6%: a level that correlates with in vivo protein quantities. The RNA functions by a highly sensitive, chemo-mechanical coupling tuned to ensure an optimal read-through frequency. Similar observations for a frameshifting signal indicate that this novel equilibrium-based mechanism may have a general role in translational recoding.
C1 [Durney, Michael A.; Salguero, Carolina; Shankar, Neelaabh; Nagle, Julia M.; D'Souza, Victoria M.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Houck-Loomis, Brian; Goff, Stephen P.] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
C3 Harvard University; Columbia University; Howard Hughes Medical Institute
RP D'Souza, VM (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM dsouza@mcb.harvard.edu
FU NCI/NIH [R37 CA30488]
NR 28
TC 113
Z9 144
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 DEC 22
PY 2011
VL 480
IS 7378
BP 561
EP U193
DI 10.1038/nature10657
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 865NQ
UT WOS:000298318000069
PM 22121021
DA 2026-03-09
ER

PT J
AU Jiang, FG
   Ramanathan, A
   Miller, MT
   Tang, GQ
   Gale, M
   Patel, SS
   Marcotrigiano, J
AF Jiang, Fuguo
   Ramanathan, Anand
   Miller, Matthew T.
   Tang, Guo-Qing
   Gale, Michael, Jr.
   Patel, Smita S.
   Marcotrigiano, Joseph
TI Structural basis of RNA recognition and activation by innate immune receptor RIG-I
SO NATURE
LA English
DT Article
ID cooperative binding; adapter protein; nucleotide; mechanism; helicases; ligand; domain; atp
AB Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp(1) and by polyuridine sequences(2,3). Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer(4,5). The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM.
C1 [Jiang, Fuguo; Miller, Matthew T.; Marcotrigiano, Joseph] Rutgers State Univ, Dept Chem & Chem Biol, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
   [Ramanathan, Anand; Tang, Guo-Qing; Patel, Smita S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
   [Gale, Michael, Jr.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
C3 Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; University of Washington; University of Washington Seattle
RP Marcotrigiano, J (corresponding author), Rutgers State Univ, Dept Chem & Chem Biol, Ctr Adv Biotechnol & Med, 679 Hoes Lane W, Piscataway, NJ 08854 USA.
EM patelss@umdnj.edu; jmarco@cabm.rutgers.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-98CH10886, DE-AC02-06CH11357]; NSF; NIH/NIGMS through NSF [DMR-0936384]; NIH/NCRR [RR-01646]; NIH [GM55310, AI080659]
NR 41
TC 361
Z9 466
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 NOV 17
PY 2011
VL 479
IS 7373
BP 423
EP U184
DI 10.1038/nature10537
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 848OA
UT WOS:000297059700051
PM 21947008
DA 2026-03-09
ER

PT J
AU Nusinow, DA
   Helfer, A
   Hamilton, EE
   King, JJ
   Imaizumi, T
   Schultz, TF
   Farré, EM
   Kay, SA
AF Nusinow, Dmitri A.
   Helfer, Anne
   Hamilton, Elizabeth E.
   King, Jasmine J.
   Imaizumi, Takato
   Schultz, Thomas F.
   Farre, Eva M.
   Kay, Steve A.
TI The ELF4-ELF3-LUX complex links the circadian clock to diurnal control of hypocotyl growth
SO NATURE
LA English
DT Article
ID quantitative-analysis; artificial micrornas; functional genomics; protein; elf3; transcription; component; encodes; time; coincidence
AB The circadian clock is required for adaptive responses to daily and seasonal changes in environmental conditions(1-3). Light and the circadian clock interact to consolidate the phase of hypocotyl cell elongation to peak at dawn under diurnal cycles in Arabidopsis thaliana(4-7). Here we identify a protein complex (called the evening complex)-composed of the proteins encoded by EARLY FLOWERING 3 (ELF3), ELF4 and the transcription-factor-encoding gene LUX ARRHYTHMO (LUX; also known as PHYTOCLOCK 1)-that directly regulates plant growth(8-12). ELF3 is both necessary and sufficient to form a complex between ELF4 and LUX, and the complex is diurnally regulated, peaking at dusk. ELF3, ELF4 and LUX are required for the proper expression of the growth-promoting transcription factors encoded by PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5 (also known as PHYTOCHROME INTERACTING FACTOR 3-LIKE 6) under diurnal conditions(4,6,13). LUX targets the complex to the promoters of PIF4 and PIF5 in vivo. Mutations in PIF4 and/or PIF5 are epistatic to the loss of the ELF4-ELF3-LUX complex, suggesting that regulation of PIF4 and PIF5 is a crucial function of the complex. Therefore, the evening complex underlies the molecular basis for circadian gating of hypocotyl growth in the early evening.
C1 [Nusinow, Dmitri A.; Helfer, Anne; Hamilton, Elizabeth E.; King, Jasmine J.; Imaizumi, Takato; Schultz, Thomas F.; Farre, Eva M.; Kay, Steve A.] Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
   [Nusinow, Dmitri A.; Helfer, Anne; Hamilton, Elizabeth E.; King, Jasmine J.; Kay, Steve A.] Univ Calif San Diego, Ctr Chronobiol, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego
RP Kay, SA (corresponding author), Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM skay@ucsd.edu
FU University of California, San Diego; Chancellor's Undergraduate Research Scholarship; European Molecular Biology Organization [ALTF 236-2005]; National Science Foundation [IBN-0416762]; National Institutes of Health [NRSA GM083585, NRSA GM080930, R01 GM79712, R01 GM50006, GM67837]; National Institute of General Medical Sciences [R01GM079712, R01GM050006] Funding Source: NIH RePORTER
NR 43
TC 731
Z9 853
U1 8
U2 292
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 398
EP U161
DI 10.1038/nature10182
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200047
PM 21753751
DA 2026-03-09
ER

PT J
AU Morgan, JA
   LeCain, DR
   Pendall, E
   Blumenthal, DM
   Kimball, BA
   Carrillo, Y
   Williams, DG
   Heisler-White, J
   Dijkstra, FA
   West, M
AF Morgan, Jack A.
   LeCain, Daniel R.
   Pendall, Elise
   Blumenthal, Dana M.
   Kimball, Bruce A.
   Carrillo, Yolima
   Williams, David G.
   Heisler-White, Jana
   Dijkstra, Feike A.
   West, Mark
TI C4 grasses prosper as carbon dioxide eliminates desiccation in warmed semi-arid grassland
SO NATURE
LA English
DT Article
ID atmospheric co2; water relations; elevated co2; climate; north; responses; ecosystem; drought; impact; future
AB Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand(1-3). Rising CO2 may counter that trend by improving plant water-use efficiency(4,5). However, it is not clear how important this CO2-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO2 also leads to higher plant biomass, and therefore greater transpirational surface(2,6,7). Furthermore, although warming is predicted to favour warm-season, C-4 grasses, rising CO2 should favour C-3, or cool-season plants(8). Here we show in a semi-arid grassland that elevated CO2 can completely reverse the desiccating effects of moderate warming. Although enrichment of air to 600 p. p. m. v. CO2 increased soil water content (SWC), 1.5/3.0 degrees C day/night warming resulted in desiccation, such that combined CO2 enrichment and warming had no effect on SWC relative to control plots. As predicted, elevated CO2 favoured C-3 grasses and enhanced stand productivity, whereas warming favoured C-4 grasses. Combined warming and CO2 enrichment stimulated above-ground growth of C-4 grasses in 2 of 3 years when soil moisture most limited plant productivity. The results indicate that in a warmer, CO2-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected.
C1 [Morgan, Jack A.; LeCain, Daniel R.; Blumenthal, Dana M.; Dijkstra, Feike A.; West, Mark] USDA ARS, Rangeland Resources Res Unit, Ft Collins, CO 80526 USA.
   [Morgan, Jack A.; LeCain, Daniel R.; Blumenthal, Dana M.; Dijkstra, Feike A.; West, Mark] USDA ARS, No Plains Area, Ft Collins, CO 80526 USA.
   [Pendall, Elise; Carrillo, Yolima; Williams, David G.; Heisler-White, Jana] Univ Wyoming, Dept Bot, Laramie, WY 82071 USA.
   [Pendall, Elise; Carrillo, Yolima; Williams, David G.; Heisler-White, Jana] Univ Wyoming, Program Ecol, Laramie, WY 82071 USA.
   [Kimball, Bruce A.] ARS, US Arid Land Agr Res Ctr, USDA, Maricopa, AZ 85238 USA.
   [Dijkstra, Feike A.] Univ Sydney, Fac Agr Food & Nat Resources, Sydney, NSW 2006, Australia.
C3 United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); University of Wyoming; University of Wyoming; United States Department of Agriculture (USDA); University of Sydney
RP Morgan, JA (corresponding author), USDA ARS, Rangeland Resources Res Unit, Ft Collins, CO 80526 USA.
EM jack.morgan@ars.usda.gov
FU US Department of Agriculture; US Department of Agriculture-Cooperative State Research, Education, and Extension Service [2008-35107-18655]; US Department of Energy's Office of Science (Biological and Environmental Research) through the Western Regional Center of the National Institute for Climatic Change Research at Northern Arizona University; National Science Foundation [1021559]; Direct For Biological Sciences; Division Of Environmental Biology [1021559, 1027319, 0823405] Funding Source: National Science Foundation
NR 28
TC 418
Z9 479
U1 7
U2 413
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 202
EP U101
DI 10.1038/nature10274
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900035
PM 21814202
DA 2026-03-09
ER

PT J
AU Jellinek, AM
   Bercovici, D
AF Jellinek, A. Mark
   Bercovici, David
TI Seismic tremors and magma wagging during explosive volcanism
SO NATURE
LA English
DT Article
ID new-zealand; source mechanism; arenal volcano; costa-rica; eruption; ruapehu; flow
AB Volcanic tremor is a ubiquitous feature of explosive eruptions. This oscillation persists for minutes to weeks and is characterized by a remarkably narrow band of frequencies from about 0.5 Hz to 7 Hz (refs 1-4). Before major eruptions, tremor can occur in concert with increased gas flux and related ground deformation(5-7). Volcanic tremor is thus of particular value for eruption forecasting(6,8). Most models for volcanic tremor rely on specific properties of the geometry, structure and constitution of volcanic conduits as well as the gas content of the erupting magma. Because neither the initial structure nor the evolution of the magma-conduit system will be the same from one volcano to the next, it is surprising that tremor characteristics are so consistent among different volcanoes. Indeed, this universality of tremor properties remains a major enigma. Here we employ the contemporary view that silicic magma rises in the conduit as a columnar plug surrounded by a highly vesicular annulus of sheared bubbles(9,10). We demonstrate that, for most geologically relevant conditions, the magma column will oscillate or 'wag' against the restoring 'gas-spring' force of the annulus at observed tremor frequencies. In contrast to previous models, the magma-wagging oscillation is relatively insensitive to the conduit structure and geometry, which explains the narrow band of tremor frequencies observed around the world. Moreover, the model predicts that as an eruption proceeds there will be an upward drift in both the maximum frequency and the total signal frequency bandwidth, the nature of which depends on the explosivity of the eruption, as is often observed.
C1 [Jellinek, A. Mark] Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z4, Canada.
   [Bercovici, David] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
C3 University of British Columbia; Yale University
RP Jellinek, AM (corresponding author), Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z4, Canada.
EM mjellinek@eos.ubc.ca
FU Canadian Institute for Advanced Research; NSERC; National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1015229, 1344538] Funding Source: National Science Foundation
NR 30
TC 81
Z9 91
U1 0
U2 37
PU 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 24
PY 2011
VL 470
IS 7335
BP 522
EP U109
DI 10.1038/nature09828
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900039
PM 21350484
DA 2026-03-09
ER

PT J
AU Raj, L
   Ide, T
   Gurkar, AU
   Foley, M
   Schenone, M
   Li, XY
   Tolliday, NJ
   Golub, TR
   Carr, SA
   Shamji, AF
   Stern, AM
   Mandinova, A
   Schreiber, SL
   Lee, SW
AF Raj, Lakshmi
   Ide, Takao
   Gurkar, Aditi U.
   Foley, Michael
   Schenone, Monica
   Li, Xiaoyu
   Tolliday, Nicola J.
   Golub, Todd R.
   Carr, Steven A.
   Shamji, Alykhan F.
   Stern, Andrew M.
   Mandinova, Anna
   Schreiber, Stuart L.
   Lee, Sam W.
TI RETRACTED: Selective killing of cancer cells by a small molecule targeting the stress response to ROS (Retracted article. See vol. 561, pg. 420, 2018)
SO NATURE
LA English
DT Article; Retracted Publication
ID human tumor-cells; apoptosis; gene; mechanisms; induction; oncogene; proteins; enzymes; death
AB Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage)(1). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells(2). Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress(3-5).
C1 [Raj, Lakshmi; Ide, Takao; Gurkar, Aditi U.; Mandinova, Anna; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
   [Raj, Lakshmi; Ide, Takao; Gurkar, Aditi U.; Mandinova, Anna; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Foley, Michael; Schenone, Monica; Li, Xiaoyu; Tolliday, Nicola J.; Golub, Todd R.; Carr, Steven A.; Shamji, Alykhan F.; Stern, Andrew M.; Mandinova, Anna; Schreiber, Stuart L.; Lee, Sam W.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Lee, SW (corresponding author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM amandinova@partners.org; stuart_schreiber@harvard.edu; swlee@partners.org
FU NIH [CA142805, CA127247, CA085681, CA080058]; National Cancer Institute's Initiative for Chemical Genetics [N01-CO-12400]; Cancer Target Discovery and Development Network [5 RC2 CA148399-02]; National Institutes of Health [RL1HG004671, RL1CA133834, RL1GM084437, UL1RR024924]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 27
TC 899
Z9 1040
U1 3
U2 379
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP 231
EP 234
DI 10.1038/nature10167
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500051
PM 21753854
DA 2026-03-09
ER

PT J
AU Chatterjee, A
   Abeydeera, ND
   Bale, S
   Pai, PJ
   Dorrestein, PC
   Russell, DH
   Ealick, SE
   Begley, TP
AF Chatterjee, Abhishek
   Abeydeera, N. Dinuka
   Bale, Shridhar
   Pai, Pei-Jing
   Dorrestein, Pieter C.
   Russell, David H.
   Ealick, Steven E.
   Begley, Tadhg P.
TI Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase
SO NATURE
LA English
DT Article
ID escherichia-coli; biosynthesis; enzyme; eukaryotes; gene; identification; protein
AB Thiamine pyrophosphate 1 is an essential cofactor in all living systems(1). Its biosynthesis involves the separate syntheses of the pyrimidine 2 and thiazole 3 precursors, which are then coupled(2). Two biosynthetic routes to the thiamine thiazole have been identified. In prokaryotes, five enzymes act on three substrates to produce the thiazole via a complex oxidative condensation reaction, the mechanistic details of which are now well established(2-6). In contrast, only one gene product is involved in thiazole biosynthesis in eukaryotes (THI4p in Saccharomyces cerevisiae)(7). Here we report the preparation of fully active recombinant wild-type THI4p, the identification of an iron-dependent sulphide transfer reaction from a conserved cysteine residue of the protein to a reaction intermediate and the demonstration that THI4p is a suicide enzyme undergoing only a single turnover.
C1 [Abeydeera, N. Dinuka; Pai, Pei-Jing; Russell, David H.; Begley, Tadhg P.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
   [Chatterjee, Abhishek; Bale, Shridhar; Ealick, Steven E.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Dorrestein, Pieter C.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 Texas A&M University System; Texas A&M University College Station; Cornell University; University of California System; University of California San Diego
RP Begley, TP (corresponding author), Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
EM see3@cornell.edu; begley@chem.tamu.edu
FU NIH [DK44083]; Robert E. Welch Foundation [A-0034, DK67081]; NSF [DBI0821700]
NR 25
TC 135
Z9 157
U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 542
EP U146
DI 10.1038/nature10503
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200049
PM 22031445
DA 2026-03-09
ER

PT J
AU van Dijk, EL
   Chen, CL
   d'Aubenton-Carafa, Y
   Gourvennec, S
   Kwapisz, M
   Roche, V
   Bertrand, C
   Silvain, M
   Legoix-Né, P
   Loeillet, S
   Nicolas, A
   Thermes, C
   Morillon, A
AF van Dijk, E. L.
   Chen, C. L.
   d'Aubenton-Carafa, Y.
   Gourvennec, S.
   Kwapisz, M.
   Roche, V.
   Bertrand, C.
   Silvain, M.
   Legoix-Ne, P.
   Loeillet, S.
   Nicolas, A.
   Thermes, C.
   Morillon, A.
TI XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; pervasive transcription; bidirectional promoters; eukaryotic genome; s. cerevisiae; methylation; polymerase; chromatin; decay; xrn1
AB Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability(1,2). Large ncRNAs interact with histone modifiers' and are involved in cancer development(6), X-chromosome inactivation(7) and autosomal gene imprinting(8). However, despite recent evidence showing that pervasive transcription is more widespread than previously thought(9), only a few examples mediating gene regulation in eukaryotes have been described(10). In Saccharomyces cerevisiae, the bona-fide regulatory ncRNAs are destabilized by the Xrn1 5'-3' RNA exonudease(11,12) (also known as Kem1), but the genome-wide characterization of the entire regulatory ncRNA family remains elusive. Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1-sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames. These transcripts are polyadenylated and RNA polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. Notably, RNAP II chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs. These genes show an unusual bias for H3K4me3 marks and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S. cerevisiae.
C1 [van Dijk, E. L.; Chen, C. L.; d'Aubenton-Carafa, Y.; Silvain, M.; Thermes, C.; Morillon, A.] CNRS, Ctr Genet Mol, UPR 3404, F-91198 Gif Sur Yvette, France.
   [Gourvennec, S.; Kwapisz, M.; Roche, V.; Bertrand, C.; Morillon, A.] Univ Paris 06, CNRS, UMR3244, Inst Curie,ncRNA,Ctr Rech, F-75248 Paris 05, France.
   [Legoix-Ne, P.] Inst Curie, NGS Platform, F-75248 Paris 05, France.
C3 Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; UNICANCER; Institut Curie; Sorbonne Universite; UNICANCER; Universite PSL; Institut Curie
RP Morillon, A (corresponding author), CNRS, Ctr Genet Mol, UPR 3404, Ave Terrasse, F-91198 Gif Sur Yvette, France.
EM thermes@cgm.cnrs-gif.fr; antonin.morillon@curie.fr
FU Canceropole Ile de France; ANR "REGULncRNA"; ERC "EPIncRNA"; FRM fellowship
NR 35
TC 285
Z9 344
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 JUL 7
PY 2011
VL 475
IS 7354
BP 114
EP U139
DI 10.1038/nature10118
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300056
PM 21697827
DA 2026-03-09
ER

PT J
AU Zha, S
   Guo, CG
   Boboila, C
   Oksenych, V
   Cheng, HL
   Zhang, Y
   Wesemann, DR
   Yuen, G
   Patel, H
   Goff, PH
   Dubois, RL
   Alt, FW
AF Zha, Shan
   Guo, Chunguang
   Boboila, Cristian
   Oksenych, Valentyn
   Cheng, Hwei-Ling
   Zhang, Yu
   Wesemann, Duane R.
   Yuen, Grace
   Patel, Harin
   Goff, Peter H.
   Dubois, Richard L.
   Alt, Frederick W.
TI ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks
SO NATURE
LA English
DT Article
ID double-strand breaks; genomic instability; v(d)j recombination; histone h2ax; translocations; lymphocytes; cernunnos; mechanism; pathway; mice
AB Classical non-homologous DNA end-joining (NHEJ) is a major mammalian DNA double-strand-break (DSB) repair pathway. Deficiencies for classical NHEJ factors, such as XRCC4, abrogate lymphocyte development, owing to a strict requirement for classical NHEJ to join V(D) J recombination DSB intermediates(1,2). The XRCC4-like factor (XLF; also called NHEJ1) is mutated in certain immunodeficient human patients and has been implicated in classical NHEJ(3-6); however, XLF-deficient mice have relatively normal lymphocyte development and their lymphocytes support normal V(D) J recombination(5). The ataxia telangiectasia-mutated protein (ATM) detects DSBs and activates DSB responses by phosphorylating substrates including histone H2AX(7). However, ATM deficiency causes only modest V(D) J recombination and lymphocyte developmental defects, and H2AX deficiency does not have a measurable impact on these processes(7-9). Here we show that XLF, ATM and H2AX all have fundamental roles in processing and joining DNA ends during V(D) J recombination, but that these roles have been masked by unanticipated functional redundancies. Thus, combined deficiency of ATM and XLF nearly blocks mouse lymphocyte development due to an inability to process and join chromosomal V(D) J recombination DSB intermediates. Combined XLF and ATM deficiency also severely impairs classical NHEJ, but not alternative end-joining, during IgH class switch recombination. Redundant ATM and XLF functions in classical NHEJ are mediated by ATM kinase activity and are not required for extra-chromosomal V(D) J recombination, indicating a role for chromatin-associated ATM substrates. Correspondingly, conditional H2AX inactivation in XLF-deficient pro-B lines leads to V(D) J recombination defects associated with marked degradation of unjoined V(D) J ends, revealing that H2AX has a role in this process.
C1 [Zha, Shan; Guo, Chunguang; Boboila, Cristian; Oksenych, Valentyn; Cheng, Hwei-Ling; Zhang, Yu; Wesemann, Duane R.; Yuen, Grace; Patel, Harin; Goff, Peter H.; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA.
   [Zha, Shan; Guo, Chunguang; Boboila, Cristian; Oksenych, Valentyn; Cheng, Hwei-Ling; Zhang, Yu; Wesemann, Duane R.; Yuen, Grace; Patel, Harin; Goff, Peter H.; Alt, Frederick W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Dubois, Richard L.] Columbia Univ, Inst Canc Genet, Dept Pediat, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Columbia University
RP Alt, FW (corresponding author), Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU NIH [AI076210, AI020047, AI007376]; Cancer Research Institute; AAAI/GlaxoSmithKline; National Institute of Allergy and Infectious Diseases [R01AI020047] Funding Source: NIH RePORTER
NR 26
TC 167
Z9 186
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 13
PY 2011
VL 469
IS 7329
BP 250
EP 254
DI 10.1038/nature09604
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400046
PM 21160472
DA 2026-03-09
ER

PT J
AU Navarro, C
   Abelenda, JA
   Cruz-Oró, E
   Cuéllar, CA
   Tamaki, S
   Silva, J
   Shimamoto, K
   Prat, S
AF Navarro, Cristina
   Abelenda, Jose A.
   Cruz-Oro, Eduard
   Cuellar, Carlos A.
   Tamaki, Shojiro
   Silva, Javier
   Shimamoto, Ko
   Prat, Salome
TI Control of flowering and storage organ formation in potato by FLOWERING LOCUS T
SO NATURE
LA English
DT Article
ID floral induction; ft protein; photoperiodic control; regulate growth; tuber formation; time; gene; signals; hd3a; tuberization
AB Seasonal fluctuations in day length regulate important aspects of plant development such as the flowering transition or, in potato (Solanum tuberosum), the formation of tubers. Day length is sensed by the leaves, which produce a mobile signal transported to the shoot apex or underground stems to induce a flowering transition or, respectively, a tuberization transition. Work in Arabidopsis, tomato and rice (Oryza sativa) identified the mobile FLOWERING LOCUS T (FT) protein as a main component of the long-range 'florigen', or flowering hormone, signal(1-3). Here we show that expression of the Hd3a gene, the FT orthologue in rice, induces strict short-day potato types(4) to tuberize in long days. Tuber induction is graft transmissible and the Hd3a-GFP protein is detected in the stolons of grafted plants, transport of the fusion protein thus correlating with tuber formation. We provide evidence showing that the potato floral and tuberization transitions are controlled by two different FT-like paralogues (StSP3D and StSP6A) that respond to independent environmental cues, and show that an autorelay mechanism involving CONSTANS modulates expression of the tuberization-control StSP6A gene.
C1 [Navarro, Cristina; Abelenda, Jose A.; Cruz-Oro, Eduard; Cuellar, Carlos A.; Silva, Javier; Prat, Salome] CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, Madrid 28049, Spain.
   [Tamaki, Shojiro; Shimamoto, Ko] Nara Inst Sci & Technol, Plant Mol Genet Lab, Ikoma 6300101, Japan.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); Nara Institute of Science & Technology
RP Prat, S (corresponding author), CSIC, Ctr Nacl Biotecnol, Dept Genet Mol Plantas, Calle Darwin 3, Madrid 28049, Spain.
EM sprat@cnb.csic.es
FU Spanish MCyT; EU-SOL European Union; JSPS; CSIC; MEXT of Japan
NR 39
TC 552
Z9 655
U1 10
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 OCT 6
PY 2011
VL 478
IS 7367
BP 119
EP U132
DI 10.1038/nature10431
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 829JN
UT WOS:000295575400046
PM 21947007
DA 2026-03-09
ER

PT J
AU Matsunaga, N
   Kawadu, T
   Nishiyama, S
   Nagayama, T
   Kobayashi, N
   Tamura, M
   Bono, G
   Feast, MW
   Nagata, T
AF Matsunaga, Noriyuki
   Kawadu, Takahiro
   Nishiyama, Shogo
   Nagayama, Takahiro
   Kobayashi, Naoto
   Tamura, Motohide
   Bono, Giuseppe
   Feast, Michael W.
   Nagata, Tetsuya
TI Three classical Cepheid variable stars in the nuclear bulge of the Milky Way
SO NATURE
LA English
DT Article
ID galactic-center; formation history; period distribution; disk galaxy; population; pc; pseudobulges; variability; distance; models
AB The nuclear bulge is a region with a radius of about 200 parsecs around the centre of the Milky Way(1). It contains stars with ages(2-4) ranging from a few million years to over a billion years, yet its star-formation history and the triggering process for star formation remain to be resolved. Recently, episodic star formation, powered by changes in the gas content, has been suggested(5). Classical Cepheid variable stars have pulsation periods that decrease with increasing age(6), so it is possible to probe the star-formation history on the basis of the distribution of their periods(7,8). Here we report the presence of three classical Cepheids in the nuclear bulge with pulsation periods of approximately 20 days, within 40 parsecs (projected distance) of the central black hole. No Cepheids with longer or shorter periods were found. We infer that there was a period about 25 million years ago, and possibly lasting until recently, in which star formation increased relative to the period of 30-70 million years ago.
C1 [Matsunaga, Noriyuki; Kobayashi, Naoto] Univ Tokyo, Inst Astron, Kiso Observ, Kiso, Nagano 3970101, Japan.
   [Kawadu, Takahiro; Nagata, Tetsuya] Kyoto Univ, Dept Astron, Sakyo Ku, Kyoto 6068502, Japan.
   [Nishiyama, Shogo; Tamura, Motohide] Natl Astron Observ Japan, Tokyo 1818588, Japan.
   [Nagayama, Takahiro] Nagoya Univ, Dept Astrophys, Chikusa Ku, Aichi 4648602, Japan.
   [Kobayashi, Naoto] Univ Tokyo, Inst Astron, Tokyo 1810015, Japan.
   [Bono, Giuseppe] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Bono, Giuseppe] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Feast, Michael W.] Univ Cape Town, Dept Astron, Astrophys Cosmol & Grav Ctr, ZA-7701 Rondebosch, South Africa.
   [Feast, Michael W.] S African Astron Observ, ZA-7935 Observatory, South Africa.
C3 University of Tokyo; Kyoto University; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ); Nagoya University; University of Tokyo; University of Rome Tor Vergata; Istituto Nazionale Astrofisica (INAF); University of Cape Town; National Research Foundation - South Africa; South African Astronomical Observatory
RP Matsunaga, N (corresponding author), Univ Tokyo, Inst Astron, Kiso Observ, 10762-30 Mitake, Kiso, Nagano 3970101, Japan.
EM matsunaga@ioa.s.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science (JSPS); National Research Foundation (NRF) of South Africa; Grants-in-Aid for Scientific Research [23840044, 23684005, 21540240] Funding Source: KAKEN
NR 26
TC 86
Z9 88
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 8
PY 2011
VL 477
IS 7363
BP 188
EP 190
DI 10.1038/nature10359
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900030
PM 21866100
DA 2026-03-09
ER

PT J
AU Opitz, CA
   Litzenburger, UM
   Sahm, F
   Ott, M
   Tritschler, I
   Trump, S
   Schumacher, T
   Jestaedt, L
   Schrenk, D
   Weller, M
   Jugold, M
   Guillemin, GJ
   Miller, CL
   Lutz, C
   Radlwimmer, B
   Lehmann, I
   von Deimling, A
   Wick, W
   Platten, M
AF Opitz, Christiane A.
   Litzenburger, Ulrike M.
   Sahm, Felix
   Ott, Martina
   Tritschler, Isabel
   Trump, Saskia
   Schumacher, Theresa
   Jestaedt, Leonie
   Schrenk, Dieter
   Weller, Michael
   Jugold, Manfred
   Guillemin, Gilles J.
   Miller, Christine L.
   Lutz, Christian
   Radlwimmer, Bernhard
   Lehmann, Irina
   von Deimling, Andreas
   Wick, Wolfgang
   Platten, Michael
TI An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
SO NATURE
LA English
DT Article
ID indoleamine 2,3-dioxygenase; tryptophan 2,3-dioxygenase; t-cells; inhibition; kynurenine; differentiation; inflammation; degradation; suppression; pathway
AB Activation of the aryl hydrocarbon receptor (AHR) by environmental xenobiotic toxic chemicals, for instance 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), has been implicated in a variety of cellular processes such as embryogenesis, transformation, tumorigenesis and inflammation. But the identity of an endogenous ligand activating the AHR under physiological conditions in the absence of environmental toxic chemicals is still unknown. Here we identify the tryptophan (Trp) catabolite kynurenine (Kyn) as an endogenous ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver-and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology. TDO-derived Kyn suppresses antitumour immune responses and promotes tumour-cell survival and motility through the AHR in an autocrine/paracrine fashion. The TDO-AHR pathway is active in human brain tumours and is associated with malignant progression and poor survival. Because Kyn is produced during cancer progression and inflammation in the local microenvironment in amounts sufficient for activating the human AHR, these results provide evidence for a previously unidentified pathophysiological function of the AHR with profound implications for cancer and immune biology.
C1 [Opitz, Christiane A.; Litzenburger, Ulrike M.; Ott, Martina; Schumacher, Theresa; Wick, Wolfgang; Platten, Michael] Univ Heidelberg Hosp, Neurol Clin, Dept Neurooncol, D-69120 Heidelberg, Germany.
   [Opitz, Christiane A.; Litzenburger, Ulrike M.; Ott, Martina; Schumacher, Theresa; Wick, Wolfgang; Platten, Michael] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
   [Opitz, Christiane A.; Litzenburger, Ulrike M.; Ott, Martina; Schumacher, Theresa; Platten, Michael] German Canc Res Ctr, Expt Neuroimmunol Unit, D-69120 Heidelberg, Germany.
   [Sahm, Felix; von Deimling, Andreas] Univ Heidelberg Hosp, Inst Pathol, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Sahm, Felix; von Deimling, Andreas] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany.
   [Tritschler, Isabel; Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
   [Trump, Saskia; Lehmann, Irina] UFZ Helmholtz Ctr Environm Res, Dept Environm Immunol, D-04318 Leipzig, Germany.
   [Jestaedt, Leonie] Univ Heidelberg Hosp, Dept Neuroradiol, D-69120 Heidelberg, Germany.
   [Schrenk, Dieter] Univ Kaiserslautern, D-67663 Kaiserslautern, Germany.
   [Jugold, Manfred] German Canc Res Ctr, Small Anim Imaging Ctr, D-69120 Heidelberg, Germany.
   [Guillemin, Gilles J.] Univ New S Wales, Sch Med Sci, Dept Pharmacol, Sydney, NSW 2052, Australia.
   [Miller, Christine L.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21287 USA.
   [Lutz, Christian] Heidelberg Pharma AG, D-68526 Ladenburg, Germany.
   [Radlwimmer, Bernhard] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Wick, Wolfgang] German Canc Res Ctr, Clin Cooperat Unit Neurooncol, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); University of Zurich; University Zurich Hospital; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); Ruprecht Karls University Heidelberg; RPTU University Kaiserslautern; Helmholtz Association; German Cancer Research Center (DKFZ); University of New South Wales Sydney; Johns Hopkins University; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ)
RP Platten, M (corresponding author), Univ Heidelberg Hosp, Neurol Clin, Dept Neurooncol, D-69120 Heidelberg, Germany.
EM m.platten@dkfz-heidelberg.de
FU Helmholtz Association [VH-NG-306]; German Research Foundation [SFB 938 TP K]; Hertie Foundation; Helmholtz Alliance on Systems Biology; DKFZ PhD Program stipend; Heidelberg University Medical Faculty
CR Andersson P, 2002, P NATL ACAD SCI USA, V99, P9990, DOI 10.1073/pnas.152706299
   Apetoh L, 2010, NAT IMMUNOL, V11, P854, DOI 10.1038/ni.1912
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   Munn DH, 2007, J CLIN INVEST, V117, P1147, DOI 10.1172/JCI31178
   NewLink Genetics Corporation, 2008, IDO INH STUD REL REF, V0, P0
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NR 33
TC 1529
Z9 1781
U1 6
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 OCT 13
PY 2011
VL 478
IS 7368
BP 197
EP 203
DI 10.1038/nature10491
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800040
PM 21976023
DA 2026-03-09
ER

PT J
AU Kuhlenkoetter, S
   Wintermeyer, W
   Rodnina, MV
AF Kuhlenkoetter, Stephan
   Wintermeyer, Wolfgang
   Rodnina, Marina V.
TI Different substrate-dependent transition states in the active site of the ribosome
SO NATURE
LA English
DT Article
ID peptide-bond formation; translation termination; transferase reaction; release factors; transfer-rna; 70s ribosome; ggq motif; rf2; catalysis; insights
AB The active site of the ribosome, the peptidyl transferase centre, catalyses two reactions, namely, peptide bond formation between peptidyl-tRNA and aminoacyl-tRNA as well as the release-factor-dependent hydrolysis of peptidyl-tRNA. Unlike peptide bond formation, peptide release is strongly impaired by mutations of nucleotides within the active site, in particular by base exchanges at position A2602 (refs 1, 2). The 2'-OH group of A76 of the peptidyl-tRNA substrate seems to have a key role in peptide release(3). According to computational analysis(4), the 2'-OH may take part in a concerted 'proton shuttle' by which the leaving group is protonated, in analogy to similar current models of peptide bond formation(4-6). Here we report kinetic solvent isotope effects and proton inventories (reaction rates measured in buffers with increasing content of deuterated water, D(2)O) of the two reactions catalysed by the active site of the Escherichia coli ribosome. The transition state of the release factor 2 (RF2)-dependent hydrolysis reaction is characterized by the rate-limiting formation of a single strong hydrogen bond. This finding argues against a concerted proton shuttle in the transition state of the hydrolysis reaction. In comparison, the proton inventory for peptide bond formation indicates the rate-limiting formation of three hydrogen bonds with about equal contributions, consistent with a concerted eight-membered proton shuttle in the transition state(5). Thus, the ribosome supports different rate-limiting transition states for the two reactions that take place in the peptidyl transferase centre.
C1 [Kuhlenkoetter, Stephan; Wintermeyer, Wolfgang; Rodnina, Marina V.] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany.
C3 Max Planck Society
RP Rodnina, MV (corresponding author), Max Planck Inst Biophys Chem, Am Fassberg 11, D-37077 Gottingen, Germany.
EM rodnina@mpibpc.mpg.de
FU Deutsche Forschungsgemeinschaft
NR 29
TC 71
Z9 89
U1 0
U2 37
PU 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 18
PY 2011
VL 476
IS 7360
BP 351
EP U124
DI 10.1038/nature10247
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500042
PM 21804565
DA 2026-03-09
ER

PT J
AU Dwyer, CA
   Stevenson, DJ
   Nimmo, F
AF Dwyer, C. A.
   Stevenson, D. J.
   Nimmo, F.
TI A long-lived lunar dynamo driven by continuous mechanical stirring
SO NATURE
LA English
DT Article
ID core dynamo; moon; precession; magnetism; evolution; history; body
AB Lunar rocks contain a record of an ancient magnetic field that seems to have persisted for more than 400 million years(1,2) and which has been attributed to a lunar dynamo(3,4). Models of conventional dynamos driven by thermal or compositional convection have had difficulty reproducing the existence and apparently long duration of the lunar dynamo(5-7). Here we investigate an alternative mechanism of dynamo generation: continuous mechanical stirring arising from the differential motion, due to Earth-driven precession of the lunar spin axis, between the solid silicate mantle and the liquid core beneath(8,9). We show that the fluid motions and the power required to drive a dynamo operating continuously for more than one billion years and generating a magnetic field that had an intensity of more than one microtesla 4.2 billion years ago(3) are readily obtained by mechanical stirring. The magnetic field is predicted to decrease with time and to shut off naturally when the Moon recedes far enough from Earth that the dissipated power is insufficient to drive a dynamo; in our nominal model, this occurred at about 48 Earth radii (2.7 billion years ago). Thus, lunar palaeomagnetic measurements may be able to constrain the poorly known early orbital evolution of the Moon. This mechanism may also be applicable to dynamos in other bodies, such as large asteroids.
C1 [Dwyer, C. A.; Nimmo, F.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Stevenson, D. J.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
C3 University of California System; University of California Santa Cruz; California Institute of Technology
RP Dwyer, CA (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, 1156 High St, Santa Cruz, CA 95064 USA.
EM cadwyer@ucsc.edu
NR 30
TC 138
Z9 149
U1 1
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 10
PY 2011
VL 479
IS 7372
BP 212
EP U84
DI 10.1038/nature10564
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 861PD
UT WOS:000298030800038
PM 22071766
DA 2026-03-09
ER

PT J
AU Yun, BW
   Feechan, A
   Yin, MH
   Saidi, NBB
   Le Bihan, T
   Yu, M
   Moore, JW
   Kang, JG
   Kwon, E
   Spoel, SH
   Pallas, JA
   Loake, GJ
AF Yun, Byung-Wook
   Feechan, Angela
   Yin, Minghui
   Saidi, Noor B. B.
   Le Bihan, Thierry
   Yu, Manda
   Moore, John W.
   Kang, Jeong-Gu
   Kwon, Eunjung
   Spoel, Steven H.
   Pallas, Jacqueline A.
   Loake, Gary J.
TI S-nitrosylation of NADPH oxidase regulates cell death in plant immunity
SO NATURE
LA English
DT Article
ID nitric-oxide; disease-resistance; salicylic-acid; hypersensitive response; superoxide-production; arabidopsis-thaliana; structure prediction; defense; tobacco; gene
AB Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes(1,2), but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide(3,4) and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes(5). Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection(3,5,6). However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.
C1 [Yun, Byung-Wook; Feechan, Angela; Yin, Minghui; Saidi, Noor B. B.; Yu, Manda; Moore, John W.; Kang, Jeong-Gu; Kwon, Eunjung; Spoel, Steven H.; Loake, Gary J.] Univ Edinburgh, Sch Biol Sci, Inst Mol Plant Sci, Edinburgh EH9 3JH, Midlothian, Scotland.
   [Saidi, Noor B. B.] Univ Putra, Dept Cell & Mol Biol, Serdang 43400, Malaysia.
   [Le Bihan, Thierry] Univ Edinburgh, Ctr Syst Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
   [Pallas, Jacqueline A.] Syngenta, Trait Res, Bracknell RG42 6EY, Berks, England.
C3 University of Edinburgh; Universiti Putra Malaysia; University of Edinburgh; Syngenta
RP Loake, GJ (corresponding author), Univ Edinburgh, Sch Biol Sci, Inst Mol Plant Sci, Kings Bldg, Edinburgh EH9 3JH, Midlothian, Scotland.
EM gloake@ed.ac.uk
FU Biotechnology and Biological Sciences Research Council (BBSRC) [BB/D011809/1]; Physical Sciences Research Council (EPSRC); Darwin Trust; EPSRC [BB/D019621/1]; Ministry of Education Malaysia; Torrance Scholarship; BBSRC [BB/D019621/1, BB/D011809/1, BB/H000984/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H000984/1, BB/D019621/1, BB/D011809/1] Funding Source: researchfish
NR 39
TC 565
Z9 620
U1 4
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 OCT 13
PY 2011
VL 478
IS 7368
BP 264
EP U161
DI 10.1038/nature10427
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832DT
UT WOS:000295782800055
PM 21964330
DA 2026-03-09
ER

PT J
AU Helmink, BA
   Tubbs, AT
   Dorsett, Y
   Bednarski, JJ
   Walker, LM
   Feng, ZH
   Sharma, GG
   McKinnon, PJ
   Zhang, JR
   Bassing, CH
   Sleckman, BP
AF Helmink, Beth A.
   Tubbs, Anthony T.
   Dorsett, Yair
   Bednarski, Jeffrey J.
   Walker, Laura M.
   Feng, Zhihui
   Sharma, Girdhar G.
   McKinnon, Peter J.
   Zhang, Junran
   Bassing, Craig H.
   Sleckman, Barry P.
TI H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes
SO NATURE
LA English
DT Article
ID double-strand breaks; v(d)j recombination; genomic stability; histone h2ax; mrn complex; mdc1; nbs1; chromatin; damage; proteins
AB DNA double-strand breaks (DSBs) are generated by the recombination activating gene (RAG) endonuclease in all developing lymphocytes as they assemble antigen receptor genes(1). DNA cleavage by RAG occurs only at the G1 phase of the cell cycle and generates two hairpin-sealed DNA (coding) ends that require nucleolytic opening before their repair by classical non-homologous end-joining (NHEJ)(1-3). Although there are several cellular nucleases that could perform this function, only the Artemis nuclease is able to do so efficiently(2,3). Here, in vivo, we show that in murine cells the histone protein H2AX prevents nucleases other than Artemis from processing hairpin-sealed coding ends; in the absence of H2AX, CtIP can efficiently promote the hairpin opening and resection of DNA ends generated by RAG cleavage. This CtIP-mediated resection is inhibited by gamma-H2AX and by MDC-1 (mediator of DNA damage checkpoint 1), which binds to gamma-H2AX in chromatin flanking DNA DSBs. Moreover, the ataxia telangiectasia mutated (ATM) kinase activates antagonistic pathways that modulate this resection. CtIP DNA end resection activity is normally limited to cells at post-replicative stages of the cell cycle, in which it is essential for homology-mediated repair(4,5). In G1-phase lymphocytes, DNA ends that are processed by CtIP are not efficiently joined by classical NHEJ and the joints that do form frequently use micro-homologies and show significant chromosomal deletions. Thus, H2AX preserves the structural integrity of broken DNA ends in G1-phase lymphocytes, thereby preventing these DNA ends from accessing repair pathways that promote genomic instability.
C1 [Helmink, Beth A.; Tubbs, Anthony T.; Dorsett, Yair; Bednarski, Jeffrey J.; Walker, Laura M.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Bednarski, Jeffrey J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Feng, Zhihui; Sharma, Girdhar G.; Zhang, Junran] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA.
   [McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA.
   [Bassing, Craig H.] Univ Penn, Sch Med,Ctr Childhood Canc Res, Childrens Hosp Philadelphia,Dept Pathol & Lab Med, Abramson Family Canc Res Inst,Div Canc Pathobiol, Philadelphia, PA 19104 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); St Jude Children's Research Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia
RP Sleckman, BP (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM sleckman@wustl.edu
FU National Institutes of Health (NIH) [AI074953, AI47829, CA136470, CA125195, CA21765, NS37956, T32 HD007499]; Children's Discovery Institute; National Cancer Institute [P01CA096832, P30CA021765] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI074953, R01AI047829] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS037956] Funding Source: NIH RePORTER
NR 33
TC 118
Z9 148
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 13
PY 2011
VL 469
IS 7329
BP 245
EP 249
DI 10.1038/nature09585
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400045
PM 21160476
DA 2026-03-09
ER

PT J
AU Kang, HJ
   Kawasawa, YI
   Cheng, F
   Zhu, Y
   Xu, XM
   Li, MF
   Sousa, AMM
   Pletikos, M
   Meyer, KA
   Sedmak, G
   Guennel, T
   Shin, Y
   Johnson, MB
   Krsnik, Z
   Mayer, S
   Fertuzinhos, S
   Umlauf, S
   Lisgo, SN
   Vortmeyer, A
   Weinberger, DR
   Mane, S
   Hyde, TM
   Huttner, A
   Reimers, M
   Kleinman, JE
   Sestan, N
AF Kang, Hyo Jung
   Kawasawa, Yuka Imamura
   Cheng, Feng
   Zhu, Ying
   Xu, Xuming
   Li, Mingfeng
   Sousa, Andre M. M.
   Pletikos, Mihovil
   Meyer, Kyle A.
   Sedmak, Goran
   Guennel, Tobias
   Shin, Yurae
   Johnson, Matthew B.
   Krsnik, Zeljka
   Mayer, Simone
   Fertuzinhos, Sofia
   Umlauf, Sheila
   Lisgo, Steven N.
   Vortmeyer, Alexander
   Weinberger, Daniel R.
   Mane, Shrikant
   Hyde, Thomas M.
   Huttner, Anita
   Reimers, Mark
   Kleinman, Joel E.
   Sestan, Nenad
TI Spatio-temporal transcriptome of the human brain
SO NATURE
LA English
DT Article
ID gene-expression; pyramidal neurons; life-span; insights; differentiation; tbr1; neuroligins; projections; mutations; evolution
AB Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.
C1 [Kang, Hyo Jung; Kawasawa, Yuka Imamura; Cheng, Feng; Zhu, Ying; Xu, Xuming; Li, Mingfeng; Sousa, Andre M. M.; Pletikos, Mihovil; Meyer, Kyle A.; Sedmak, Goran; Shin, Yurae; Johnson, Matthew B.; Krsnik, Zeljka; Mayer, Simone; Fertuzinhos, Sofia; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
   [Kang, Hyo Jung; Kawasawa, Yuka Imamura; Cheng, Feng; Zhu, Ying; Xu, Xuming; Li, Mingfeng; Sousa, Andre M. M.; Pletikos, Mihovil; Meyer, Kyle A.; Sedmak, Goran; Shin, Yurae; Johnson, Matthew B.; Krsnik, Zeljka; Mayer, Simone; Fertuzinhos, Sofia; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
   [Sousa, Andre M. M.] Univ Porto, Abel Salazar Biomed Sci Inst, Grad Program Areas Basic & Appl Biol, P-4099003 Oporto, Portugal.
   [Pletikos, Mihovil; Sedmak, Goran] Univ Zagreb, Sch Med, Croatian Inst Brain Res, Grad Program Neurosci, Zagreb 10000, Croatia.
   [Guennel, Tobias; Reimers, Mark] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA.
   [Mayer, Simone] Int Max Planck Res Sch Mol Biol, Msc PhD Mol Biol Program, D-37077 Gottingen, Germany.
   [Umlauf, Sheila; Mane, Shrikant] Yale Univ, Sch Med, Yale Ctr Genome Anal, New Haven, CT 06510 USA.
   [Lisgo, Steven N.] Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Vortmeyer, Alexander; Huttner, Anita] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
   [Weinberger, Daniel R.; Hyde, Thomas M.; Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
   [Hyde, Thomas M.] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
C3 Yale University; Yale University; Universidade do Porto; University of Zagreb; Virginia Commonwealth University; Max Planck Society; Yale University; Newcastle University - UK; Yale University; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Johns Hopkins University; Johns Hopkins Medicine
RP Sestan, N (corresponding author), Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
EM nenad.sestan@yale.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD000836]; China Scholarship Council; Portuguese Foundation for Science and Technology; Samsung Scholarship Foundation; German Academic Exchange Service - DAAD; NIDA [DA026119]; US National Institutes of Health [MH081896, MH089929, NS054273]; Kavli Foundation; NARSAD; James S. McDonnell Foundation;  [G0700089];  [GR082557]; MRC [G9900837, G0700089] Funding Source: UKRI; Medical Research Council [G9900837, G0700089] Funding Source: researchfish; National Institute of Mental Health; National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Allergy and Infectious Diseases [R24HD000836] Funding Source: NIH RePORTER
NR 49
TC 1579
Z9 1818
U1 0
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 27
PY 2011
VL 478
IS 7370
BP 483
EP 489
DI 10.1038/nature10523
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 837JI
UT WOS:000296194200036
PM 22031440
DA 2026-03-09
ER

PT J
AU Nègre, N
   Brown, CD
   Ma, LJ
   Bristow, CA
   Miller, SW
   Wagner, U
   Kheradpour, P
   Eaton, ML
   Loriaux, P
   Sealfon, R
   Li, ZR
   Ishii, H
   Spokony, RF
   Chen, J
   Hwang, L
   Cheng, C
   Auburn, RP
   Davis, MB
   Domanus, M
   Shah, PK
   Morrison, CA
   Zieba, J
   Suchy, S
   Senderowicz, L
   Victorsen, A
   Bild, NA
   Grundstad, AJ
   Hanley, D
   MacAlpine, DM
   Mannervik, M
   Venken, K
   Bellen, H
   White, R
   Gerstein, M
   Russell, S
   Grossman, RL
   Ren, B
   Posakony, JW
   Kellis, M
   White, KP
AF Negre, Nicolas
   Brown, Christopher D.
   Ma, Lijia
   Bristow, Christopher Aaron
   Miller, Steven W.
   Wagner, Ulrich
   Kheradpour, Pouya
   Eaton, Matthew L.
   Loriaux, Paul
   Sealfon, Rachel
   Li, Zirong
   Ishii, Haruhiko
   Spokony, Rebecca F.
   Chen, Jia
   Hwang, Lindsay
   Cheng, Chao
   Auburn, Richard P.
   Davis, Melissa B.
   Domanus, Marc
   Shah, Parantu K.
   Morrison, Carolyn A.
   Zieba, Jennifer
   Suchy, Sarah
   Senderowicz, Lionel
   Victorsen, Alec
   Bild, Nicholas A.
   Grundstad, A. Jason
   Hanley, David
   MacAlpine, David M.
   Mannervik, Mattias
   Venken, Koen
   Bellen, Hugo
   White, Robert
   Gerstein, Mark
   Russell, Steven
   Grossman, Robert L.
   Ren, Bing
   Posakony, James W.
   Kellis, Manolis
   White, Kevin P.
TI A cis-regulatory map of the Drosophila genome
SO NATURE
LA English
DT Article
ID transcription factor; enhancers; melanogaster; expression; blastoderm; proteins
AB Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide(1,2) has successfully identified specific subtypes of regulatory elements(3). In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements(4), chromatin states(5), transcription factor binding sites(6-9), RNA polymerase II regulation(8) and insulator elements(10); however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.
C1 [Negre, Nicolas; Brown, Christopher D.; Ma, Lijia; Spokony, Rebecca F.; Davis, Melissa B.; Domanus, Marc; Morrison, Carolyn A.; Zieba, Jennifer; Suchy, Sarah; Senderowicz, Lionel; Victorsen, Alec; Bild, Nicholas A.; Grundstad, A. Jason; Grossman, Robert L.; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, Chicago, IL 60637 USA.
   [Bristow, Christopher Aaron; Kheradpour, Pouya; Sealfon, Rachel; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.
   [Miller, Steven W.; Ishii, Haruhiko; Posakony, James W.] Univ Calif San Diego, Div Biol Sci CDB, La Jolla, CA 92093 USA.
   [Wagner, Ulrich; Li, Zirong; Hwang, Lindsay; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Eaton, Matthew L.] Duke Univ, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC 27710 USA.
   [Loriaux, Paul] Univ Calif San Diego, Signaling Syst Lab, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Chen, Jia; Hanley, David; Grossman, Robert L.] Univ Illinois, Natl Ctr Data Min, Chicago, IL 60607 USA.
   [Cheng, Chao; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Cheng, Chao; Gerstein, Mark] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Cheng, Chao] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Auburn, Richard P.; Russell, Steven] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
   [Auburn, Richard P.; Russell, Steven] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 3EH, England.
   [Shah, Parantu K.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Mannervik, Mattias] Stockholm Univ, Dept Dev Biol, Wenner Gren Inst, Arrhenius Labs E3, S-10691 Stockholm, Sweden.
   [Venken, Koen; Bellen, Hugo] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [White, Robert] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England.
   [Grossman, Robert L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Ren, Bing] Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Ren, Bing] Moores Canc Ctr, La Jolla, CA 92093 USA.
C3 University of Chicago; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of California System; University of California San Diego; Ludwig Institute for Cancer Research; Duke University; University of California System; University of California San Diego; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Yale University; Yale University; Yale University; University of Cambridge; University of Cambridge; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard T.H. Chan School of Public Health; Stockholm University; Baylor College of Medicine; University of Cambridge; University of Chicago
RP White, KP (corresponding author), Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, 900 E 57th St, Chicago, IL 60637 USA.
EM kpwhite@uchicago.edu
FU National Human Genome Research Institute [U01HG004264]; Chicago Biomedical Consortium; Chicago Community Trust; Lilly-Life Sciences Research Foundation; NIH NRSA; Isaac Newton Trust; Department of Energy; NHGRI [U01 HG004279]
NR 27
TC 409
Z9 499
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 527
EP 531
DI 10.1038/nature09990
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200065
PM 21430782
DA 2026-03-09
ER

PT J
AU Li, B
   Piriz, J
   Mirrione, M
   Chung, CH
   Proulx, CD
   Schulz, D
   Henn, F
   Malinow, R
AF Li, Bo
   Piriz, Joaquin
   Mirrione, Martine
   Chung, ChiHye
   Proulx, Christophe D.
   Schulz, Daniela
   Henn, Fritz
   Malinow, Roberto
TI Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
SO NATURE
LA English
DT Article
ID midbrain dopamine neurons; dorsal raphe nucleus; lateral habenula; animal-model; tryptophan depletion; responses; behavior; stress; rat; stimulation
AB The cellular basis of depressive disorders is poorly understood(1). Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (that is, disappointment or anticipation of a negative outcome)(2-4). LHb neurons project to, and modulate, dopamine-rich regions, such as the ventral tegmental area (VTA)(2,5), that control reward-seeking behaviour(6) and participate in depressive disorders(7). Here we show that in two learned helplessness models of depression, excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal's helplessness behaviour and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective for patients who are depressed(8,9), markedly suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behaviour in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.
C1 [Li, Bo; Piriz, Joaquin; Chung, ChiHye; Proulx, Christophe D.; Malinow, Roberto] Univ Calif San Diego, Ctr Neural Circuits & Behav, Dept Neurosci, La Jolla, CA 92093 USA.
   [Li, Bo; Piriz, Joaquin; Chung, ChiHye; Proulx, Christophe D.; Malinow, Roberto] Univ Calif San Diego, Ctr Neural Circuits & Behav, Dept Biol Sci, La Jolla, CA 92093 USA.
   [Li, Bo; Mirrione, Martine; Henn, Fritz] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Mirrione, Martine; Schulz, Daniela; Henn, Fritz] Brookhaven Natl Lab, Upton, NY 11973 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Cold Spring Harbor Laboratory; United States Department of Energy (DOE); Brookhaven National Laboratory
RP Li, B (corresponding author), Univ Calif San Diego, Ctr Neural Circuits & Behav, Dept Neurosci, 9500 Gilman Dr 0634, La Jolla, CA 92093 USA.
EM bli@cshl.edu; rmalinow@ucsd.edu
FU Dana Foundation; National Institute of Mental Health, National Institutes of Health [1R01MH091903-01]; Shiley-Marcos Endowment
NR 34
TC 510
Z9 600
U1 2
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 535
EP U125
DI 10.1038/nature09742
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900042
PM 21350486
DA 2026-03-09
ER

PT J
AU Kim, HJ
   Ruszczycky, MW
   Choi, SH
   Liu, YN
   Liu, HW
AF Kim, Hak Joong
   Ruszczycky, Mark W.
   Choi, Sei-hyun
   Liu, Yung-nan
   Liu, Hung-wen
TI Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn A
SO NATURE
LA English
DT Article
ID diels-alder reaction; macrophomate synthase; saccharopolyspora-spinosa; sugar biosynthesis; mechanism
AB The Diels-Alder reaction is a [4+2] cycloaddition reaction in which a cyclohexene ring is formed between a 1,3-diene and an electron-deficient alkene via a single pericyclic transition state(1). This reaction has been proposed as a key transformation in the biosynthesis of many cyclohexene-containing secondary metabolites(2-5). However, only four purified enzymes have thus far been implicated in biotransformations that are consistent with a Diels-Alder reaction, namely solanapyrone synthase(6), LovB(7,8), macrophomate synthase(9,10), and riboflavin synthase(11,12). Although the stereochemical outcomes of these reactions indicate that the product formation could be enzyme-guided in each case, these enzymes typically demonstrate more than one catalytic activity, leaving their specific influence on the cycloaddition step uncertain. In our studies of the biosynthesis of spinosyn A, a tetracyclic polyketide-derived insecticide from Saccharopolyspora spinosa(13,14), we identified a cyclase, SpnF, that catalyses a transannular [4+2] cycloaddition to form the cyclohexene ring in spinosyn A. Kinetic analysis demonstrates that SpnF specifically accelerates the ring formation reaction with an estimated 500-fold rate enhancement. A second enzyme, SpnL, was also identified as responsible for the final cross-bridging step that completes the tetracyclic core of spinosyn A in a manner consistent with a Rauhut-Currier reaction(15). This work is significant because SpnF represents the first example characterized in vitro of a standalone enzyme solely committed to the catalysis of a [4+2] cycloaddition reaction. In addition, the mode of formation of the complex perhydro-as-indacene moiety in spinosyn A is now fully established.
C1 [Kim, Hak Joong; Choi, Sei-hyun; Liu, Hung-wen] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
   [Ruszczycky, Mark W.; Liu, Yung-nan; Liu, Hung-wen] Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin
RP Liu, HW (corresponding author), Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
EM h.w.liu@mail.utexas.edu
FU National Institutes of Health [GM035906, F32AI082906]; Texas Higher Education Coordination Board [ARP-003658-0093-2007]; Welch Foundation [F-1511]; National Institute of General Medical Sciences [R01GM040541, R01GM035906] Funding Source: NIH RePORTER
NR 29
TC 272
Z9 323
U1 2
U2 210
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 5
PY 2011
VL 473
IS 7345
BP 109
EP 112
DI 10.1038/nature09981
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 759CQ
UT WOS:000290218300041
PM 21544146
DA 2026-03-09
ER

PT J
AU Yusa, K
   Rashid, ST
   Strick-Marchand, H
   Varela, I
   Liu, PQ
   Paschon, DE
   Miranda, E
   Ordóñez, A
   Hannan, NRF
   Rouhani, FJ
   Darche, S
   Alexander, G
   Marciniak, SJ
   Fusaki, N
   Hasegawa, M
   Holmes, MC
   Di Santo, JP
   Lomas, DA
   Bradley, A
   Vallier, L
AF Yusa, Kosuke
   Rashid, S. Tamir
   Strick-Marchand, Helene
   Varela, Ignacio
   Liu, Pei-Qi
   Paschon, David E.
   Miranda, Elena
   Ordonez, Adriana
   Hannan, Nicholas R. F.
   Rouhani, Foad J.
   Darche, Sylvie
   Alexander, Graeme
   Marciniak, Stefan J.
   Fusaki, Noemi
   Hasegawa, Mamoru
   Holmes, Michael C.
   Di Santo, James P.
   Lomas, David A.
   Bradley, Allan
   Vallier, Ludovic
TI Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID efficient; generation; piggybac; genome; induction; complex
AB Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders(1-4). However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications(3,5). The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome(6). Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs)(7) and piggyBac(8,9) technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the alpha(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for alpha(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.
C1 [Yusa, Kosuke; Rouhani, Foad J.; Bradley, Allan] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Rashid, S. Tamir; Hannan, Nicholas R. F.; Rouhani, Foad J.; Vallier, Ludovic] Univ Cambridge, Anne McLaren Lab Regenerat Med, Dept Surg, Cambridge CB2 0SZ, England.
   [Rashid, S. Tamir; Miranda, Elena; Ordonez, Adriana; Marciniak, Stefan J.; Lomas, David A.] Univ Cambridge, Dept Med, Cambridge Inst Med Res, Cambridge CB0 2XY, England.
   [Strick-Marchand, Helene; Darche, Sylvie; Di Santo, James P.] Inst Pasteur, Innate Immun Unit, F-75724 Paris, France.
   [Strick-Marchand, Helene; Darche, Sylvie; Di Santo, James P.] INSERM, U668, F-75724 Paris, France.
   [Varela, Ignacio] CSIC UC SODERCAN, Inst Biomed & Biotecnol Cantabria, Santander 39011, Spain.
   [Liu, Pei-Qi; Paschon, David E.; Holmes, Michael C.] Sangamo BioSci Inc, Richmond, CA 94804 USA.
   [Miranda, Elena] Univ Roma La Sapienza, Dept Biol Biotecnol Charles Darwin, I-00185 Rome, Italy.
   [Alexander, Graeme] Cambridge Univ Hosp NHS Trust, Dept Med, Div Gastroenterol & Hepatol, Cambridge CB2 2QQ, England.
   [Fusaki, Noemi; Hasegawa, Mamoru] DNAVEC Corp, Tsukuba, Ibaraki 3002611, Japan.
   [Fusaki, Noemi] JST, PRESTO, Saitama 3320012, Japan.
C3 Wellcome Trust Sanger Institute; University of Cambridge; University of Cambridge; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Consejo Superior de Investigaciones Cientificas (CSIC); Universidad de Cantabria; CSIC - Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC); Sangamo Therapeutics, Inc.; Sapienza University Rome; DNAVEC Corporation; Japan Science & Technology Agency (JST)
RP Bradley, A (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM abradley@sanger.ac.uk; lv225@cam.ac.uk
FU Wellcome Trust [WT077187]; MRC; Cambridge Hospitals National Institute for Health Research Biomedical Research Center; Papworth NHS Trust; Bill and Melinda Gates Foundation; Inserm; Institut Pasteur; Japan Science and Technology Agency; Japan Society for the Promotion of Science; International Human Frontiers Science Program Organization; Medical Research Council [G0701448, G0901786, G0800784, G0601840, G1000847, G0800784B] Funding Source: researchfish; National Institute for Health Research [CL-2011-14-005] Funding Source: researchfish; MRC [G1000847, G0901786, G0800784, G0601840, G0701448] Funding Source: UKRI
NR 36
TC 517
Z9 631
U1 0
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 OCT 20
PY 2011
VL 478
IS 7369
BP 391
EP +
DI 10.1038/nature10424
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100047
PM 21993621
DA 2026-03-09
ER

PT J
AU Block, BA
   Jonsen, ID
   Jorgensen, SJ
   Winship, AJ
   Shaffer, SA
   Bograd, SJ
   Hazen, EL
   Foley, DG
   Breed, GA
   Harrison, AL
   Ganong, JE
   Swithenbank, A
   Castleton, M
   Dewar, H
   Mate, BR
   Shillinger, GL
   Schaefer, KM
   Benson, SR
   Weise, MJ
   Henry, RW
   Costa, DP
AF Block, B. A.
   Jonsen, I. D.
   Jorgensen, S. J.
   Winship, A. J.
   Shaffer, S. A.
   Bograd, S. J.
   Hazen, E. L.
   Foley, D. G.
   Breed, G. A.
   Harrison, A. -L.
   Ganong, J. E.
   Swithenbank, A.
   Castleton, M.
   Dewar, H.
   Mate, B. R.
   Shillinger, G. L.
   Schaefer, K. M.
   Benson, S. R.
   Weise, M. J.
   Henry, R. W.
   Costa, D. P.
TI Tracking apex marine predator movements in a dynamic ocean
SO NATURE
LA English
DT Article
ID pacific-ocean; bluefin tuna; mortality; habitat; sharks; fish; population; resources; migration; turtles
AB Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems(1-4). Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales(5,6). Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.
C1 [Block, B. A.; Jorgensen, S. J.; Ganong, J. E.; Swithenbank, A.; Castleton, M.; Shillinger, G. L.] Stanford Univ, Hopkins Marine Stn, Dept Biol, Pacific Grove, CA 93950 USA.
   [Jonsen, I. D.; Winship, A. J.; Breed, G. A.] Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
   [Shaffer, S. A.] San Jose State Univ, Dept Biol Sci, San Jose, CA 95192 USA.
   [Bograd, S. J.; Hazen, E. L.; Foley, D. G.] NOAA, SW Fisheries Sci Ctr, Div Environm Res, Pacific Grove, CA 93950 USA.
   [Breed, G. A.; Harrison, A. -L.; Weise, M. J.; Henry, R. W.; Costa, D. P.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Long Marine Lab, Santa Cruz, CA 95060 USA.
   [Dewar, H.] NOAA, SW Fisheries Sci Ctr, Fisheries Res Div, La Jolla, CA 92037 USA.
   [Mate, B. R.] Oregon State Univ, Hatfield Marine Sci Ctr, Newport, OR 97365 USA.
   [Schaefer, K. M.] Interamer Trop Tuna Commiss, La Jolla, CA 92037 USA.
   [Benson, S. R.] NOAA, SW Fisheries Sci Ctr, Protected Resources Div, La Jolla, CA 92037 USA.
C3 Stanford University; Dalhousie University; California State University System; San Jose State University; National Oceanic Atmospheric Admin (NOAA) - USA; University of California System; University of California Santa Cruz; National Oceanic Atmospheric Admin (NOAA) - USA; Oregon State University; National Oceanic Atmospheric Admin (NOAA) - USA
RP Block, BA (corresponding author), Stanford Univ, Hopkins Marine Stn, Dept Biol, Pacific Grove, CA 93950 USA.
EM bblock@stanford.edu
FU Sloan Foundation; Packard Foundation; Moore Foundation; Office of Naval Research; NOAA; E&P Sound and Marine Life JIP under the OGP; Monterey Bay Aquarium Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0838937] Funding Source: National Science Foundation
NR 30
TC 1062
Z9 1229
U1 13
U2 652
PU 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 7
PY 2011
VL 475
IS 7354
BP 86
EP 90
DI 10.1038/nature10082
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300050
PM 21697831
DA 2026-03-09
ER

PT J
AU Avrani, S
   Wurtzel, O
   Sharon, I
   Sorek, R
   Lindell, D
AF Avrani, Sarit
   Wurtzel, Omri
   Sharon, Itai
   Sorek, Rotem
   Lindell, Debbie
TI Genomic island variability facilitates Prochlorococcus-virus coexistence
SO NATURE
LA English
DT Article
ID phage; evolution; bacterial; atlantic; ecotypes; community; resistance; elements
AB Prochlorococcus cyanobacteria are extremely abundant in the oceans, as are the viruses that infect them. How hosts and viruses coexist in nature remains unclear, although the presence of both susceptible and resistant cells may allow this coexistence. Combined whole-genome sequencing and PCR screening technology now enables us to investigate the effect of resistance on genome evolution and the genomic mechanisms behind the long-term coexistence of Prochlorococcus and their viruses. Here we present a genome analysis of 77 substrains selected for resistance to ten viruses, revealing mutations primarily in non-conserved, horizontally transferred genes that localize to a single hypervariable genomic island. Mutations affected viral attachment to the cell surface and imposed a fitness cost to the host, manifested by significantly lower growth rates or a previously unknown mechanism of more rapid infection by other viruses. The mutant genes are generally uncommon in nature yet some carry polymorphisms matching those found experimentally. These data are empirical evidence indicating that viral-attachment genes are preferentially located in genomic islands and that viruses are a selective pressure enhancing the diversity of both island genes and island gene content. This diversity emerges as a genomic mechanism that reduces the effective host population size for infection by a given virus, thus facilitating long-term coexistence between viruses and their hosts in nature.
C1 [Avrani, Sarit; Sharon, Itai; Lindell, Debbie] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
   [Wurtzel, Omri; Sorek, Rotem] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
C3 Technion Israel Institute of Technology; Weizmann Institute of Science
RP Lindell, D (corresponding author), Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
EM dlindell@tx.technion.ac.il
FU European Commission ERC [203406]; ISF [1504/06]; Technion Russell Berrie Nanotechnology Institute; ISF-FIRST [1615/09]; ERC; Azrieli fellowship
NR 34
TC 233
Z9 277
U1 1
U2 97
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 604
EP 608
DI 10.1038/nature10172
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300031
PM 21720364
DA 2026-03-09
ER

PT J
AU Aydin, M
   Verhulst, KR
   Saltzman, ES
   Battle, MO
   Montzka, SA
   Blake, DR
   Tang, Q
   Prather, MJ
AF Aydin, Murat
   Verhulst, Kristal R.
   Saltzman, Eric S.
   Battle, Mark O.
   Montzka, Stephen A.
   Blake, Donald R.
   Tang, Qi
   Prather, Michael J.
TI Recent decreases in fossil-fuel emissions of ethane and methane derived from firn air
SO NATURE
LA English
DT Article
ID variability; budget
AB Methane and ethane are the most abundant hydrocarbons in the atmosphere and they affect both atmospheric chemistry and climate. Both gases are emitted from fossil fuels and biomass burning, whereas methane (CH4) alone has large sources from wetlands, agriculture, landfills and waste water. Here we use measurements in firn (perennial snowpack) air from Greenland and Antarctica to reconstruct the atmospheric variability of ethane (C2H6) during the twentieth century. Ethane levels rose from early in the century until the 1980s, when the trend reversed, with a period of decline over the next 20 years. We find that this variability was primarily driven by changes in ethane emissions from fossil fuels; these emissions peaked in the 1960s and 1970s at 14-16 teragrams per year (1 Tg = 10(12) g) and dropped to 8-10 Tg yr(-1) by the turn of the century. The reduction in fossil-fuel sources is probably related to changes in light hydrocarbon emissions associated with petroleum production and use. The ethane-based fossil-fuel emission history is strikingly different from bottom-up estimates of methane emissions from fossil-fuel use(1,2), and implies that the fossil-fuel source of methane started to decline in the 1980s and probably caused the late twentieth century slow-down in the growth rate of atmospheric methane(3,4).
C1 [Aydin, Murat; Verhulst, Kristal R.; Saltzman, Eric S.; Blake, Donald R.; Tang, Qi; Prather, Michael J.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Battle, Mark O.] Bowdoin Coll, Dept Phys & Astron, Brunswick, ME 04011 USA.
   [Montzka, Stephen A.] Natl Ocean & Atmospher Adm, Earth Syst Res Labs, Global Monitoring Div, Boulder, CO 80305 USA.
C3 University of California System; University of California Irvine; Bowdoin College; National Oceanic Atmospheric Admin (NOAA) - USA
RP Aydin, M (corresponding author), Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
EM maydin@uci.edu
FU National Science Foundation [ANT-0739598, ANT-0440602, ANT-0440509, ARC-0520460]; NASA [NAG58935]; Directorate For Geosciences [0739598] Funding Source: National Science Foundation; Office of Polar Programs (OPP) [0739598] Funding Source: National Science Foundation
NR 30
TC 132
Z9 165
U1 1
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 AUG 11
PY 2011
VL 476
IS 7359
BP 198
EP 201
DI 10.1038/nature10352
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900034
PM 21833087
DA 2026-03-09
ER

PT J
AU Bedding, TR
   Mosser, B
   Huber, D
   Montalbán, J
   Beck, P
   Christensen-Dalsgaard, J
   Elsworth, YP
   García, RA
   Miglio, A
   Stello, D
   White, TR
   De Ridder, J
   Hekker, S
   Aerts, C
   Barban, C
   Belkacem, K
   Broomhall, AM
   Brown, TM
   Buzasi, DL
   Carrier, F
   Chaplin, WJ
   Di Mauro, MP
   Dupret, MA
   Frandsen, S
   Gilliland, RL
   Goupil, MJ
   Jenkins, JM
   Kallinger, T
   Kawaler, S
   Kjeldsen, H
   Mathur, S
   Noels, A
   Aguirre, VS
   Ventura, P
AF Bedding, Timothy R.
   Mosser, Benoit
   Huber, Daniel
   Montalban, Josefina
   Beck, Paul
   Christensen-Dalsgaard, Jorgen
   Elsworth, Yvonne P.
   Garcia, Rafael A.
   Miglio, Andrea
   Stello, Dennis
   White, Timothy R.
   De Ridder, Joris
   Hekker, Saskia
   Aerts, Conny
   Barban, Caroline
   Belkacem, Kevin
   Broomhall, Anne-Marie
   Brown, Timothy M.
   Buzasi, Derek L.
   Carrier, Fabien
   Chaplin, William J.
   Di Mauro, Maria Pia
   Dupret, Marc-Antoine
   Frandsen, Soren
   Gilliland, Ronald L.
   Goupil, Marie-Jo
   Jenkins, Jon M.
   Kallinger, Thomas
   Kawaler, Steven
   Kjeldsen, Hans
   Mathur, Savita
   Noels, Arlette
   Aguirre, Victor Silva
   Ventura, Paolo
TI Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars
SO NATURE
LA English
DT Article
ID solar-like oscillations; stellar oscillations; corot; asteroseismology; kepler; code; mass
AB Red giants are evolved stars that have exhausted the supply of hydrogenin their cores and instead burn hydrogen in a surrounding shell(1,2). Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion(3). Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes(4). Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies(5). Here we report observations of gravity-mode period spacings in red giants(6) that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly similar to 50 seconds) and those that are also burning helium (period spacing similar to 100 to 300 seconds).
C1 [Bedding, Timothy R.; Huber, Daniel; Stello, Dennis; White, Timothy R.] Univ Sydney, Sch Phys, Sydney Inst Astron SIfA, Sydney, NSW 2006, Australia.
   [Mosser, Benoit; Barban, Caroline; Goupil, Marie-Jo] Univ Paris 07, Univ Paris 06, CNRS, LESIA,Observ Paris, F-92195 Meudon, France.
   [Montalban, Josefina; Miglio, Andrea; Dupret, Marc-Antoine; Noels, Arlette] Univ Liege, Inst Astrophys & Geophys, B-4000 Cointe Ougree, Belgium.
   [Beck, Paul; De Ridder, Joris; Aerts, Conny; Carrier, Fabien] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Christensen-Dalsgaard, Jorgen; Frandsen, Soren] Aarhus Univ, Dept Phys & Astron, DASC, DK-8000 Aarhus C, Denmark.
   [Elsworth, Yvonne P.; Miglio, Andrea; Hekker, Saskia; Broomhall, Anne-Marie; Chaplin, William J.] Univ Birmingham, Sch Phys & Astron, Birmingham B15 2TT, W Midlands, England.
   [Garcia, Rafael A.] Univ Paris 07, Ctr Saclay, IRFU SAp, Lab AIM,CEA DSM CNRS, F-91191 Gif Sur Yvette, France.
   [Hekker, Saskia] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 XH Amsterdam, Netherlands.
   [Aerts, Conny] Radboud Univ Nijmegen, Dept Astrophys, IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Belkacem, Kevin] Univ Paris 11, Inst Astrophys Spatiale, UMR 8617, F-91405 Orsay, France.
   [Brown, Timothy M.] Las Cumbres Observ Global Telescope, Goleta, CA 93117 USA.
   [Buzasi, Derek L.] Eureka Sci, Oakland, CA 94602 USA.
   [Di Mauro, Maria Pia] Ist Astrofis Spaziale & Fis Cosm, INAF IASF, I-00133 Rome, Italy.
   [Gilliland, Ronald L.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Jenkins, Jon M.] NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA.
   [Kallinger, Thomas] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Kawaler, Steven] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Mathur, Savita] NCAR, High Altitude Observ, Boulder, CO 80307 USA.
   [Aguirre, Victor Silva] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Ventura, Paolo] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, RM, Italy.
C3 University of Sydney; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; Universite Paris Cite; University of Liege; KU Leuven; Aarhus University; University of Birmingham; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of Amsterdam; Radboud University Nijmegen; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Eureka Scientific; Istituto Nazionale Astrofisica (INAF); Space Telescope Science Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; SETI Institute; University of British Columbia; Iowa State University; National Center Atmospheric Research (NCAR) - USA; Max Planck Society; Istituto Nazionale Astrofisica (INAF)
RP Bedding, TR (corresponding author), Univ Sydney, Sch Phys, Sydney Inst Astron SIfA, Sydney, NSW 2006, Australia.
EM t.bedding@physics.usyd.edu.au
FU NASA's Science Mission Directorate; Australian Research Council; European Community; Netherlands Organisation for Scientific Research (NWO); National Science Foundation; STFC [ST/F002041/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/F002041/1] Funding Source: researchfish
CR AIZENMAN M, 1977, ASTRON ASTROPHYS, V58, P41
   Bedding TR, 2010, ASTROPHYS J LETT, V713, PL176, DOI 10.1088/2041-8205/713/2/L176
   Charbonnel C, 2005, ASTR SOC P, V336, P119
   Christensen-Dalsgaard J, 2004, SOL PHYS, V220, P137, DOI 10.1023/B:SOLA.0000031392.43227.7d
   Christensen-Dalsgaard J, 2008, ASTROPHYS SPACE SCI, V316, P13, DOI 10.1007/s10509-007-9675-5
   De Ridder J, 2009, NATURE, V459, P398, DOI 10.1038/nature08022
   Deheuvels S, 2010, ASTROPHYS SPACE SCI, V328, P259, DOI 10.1007/s10509-009-0216-2
   Dupret MA, 2009, ASTRON ASTROPHYS, V506, P57, DOI 10.1051/0004-6361/200911713
   Dziembowski WA, 2001, MON NOT R ASTRON SOC, V328, P601, DOI 10.1046/j.1365-8711.2001.04894.x
   Girardi L, 1999, MON NOT R ASTRON SOC, V308, P818, DOI 10.1046/j.1365-8711.1999.02746.x
   Gough D, 1986, HYDRODYNAMICAL MAGNE, V0, P117
   Huber D, 2010, ASTROPHYS J, V723, P1607, DOI 10.1088/0004-637X/723/2/1607
   IBEN I, 1968, ASTROPHYS J, V154, P581, DOI 10.1086/149782
   Jenkins JM, 2010, ASTROPHYS J LETT, V713, PL120, DOI 10.1088/2041-8205/713/2/L120
   Kallinger T, 2010, ASTRON ASTROPHYS, V509, P0, DOI 10.1051/0004-6361/200811437
   KJELDSEN H, 1995, ASTRON ASTROPHYS, V293, P87
   Kjeldsen H, 2008, ASTROPHYS J LETT, V683, PL175, DOI 10.1086/591667
   Miglio A, 2008, ASTRON NACHR, V329, P529, DOI 10.1002/asna.200710991
   Miglio A, 2009, ASTRON ASTROPHYS, V503, PL21, DOI 10.1051/0004-6361/200912822
   Montalbán J, 2010, ASTROPHYS J LETT, V721, PL182, DOI 10.1088/2041-8205/721/2/L182
   Mosser B, 2011, ASTRON ASTROPHYS, V525, P0, DOI 10.1051/0004-6361/201015440
   Mosser B, 2009, ASTRON ASTROPHYS, V508, P877, DOI 10.1051/0004-6361/200912944
   Pietrinferni A, 2004, ASTROPHYS J, V612, P168, DOI 10.1086/422498
   SCHWARZSCHILD M, 1962, ASTROPHYS J, V136, P158, DOI 10.1086/147361
   SWEIGART AV, 1978, ASTROPHYS J SUPPL S, V36, P405, DOI 10.1086/190506
   TASSOUL M, 1980, ASTROPHYS J SUPPL S, V43, P469, DOI 10.1086/190678
   Ventura P, 2008, ASTROPHYS SPACE SCI, V316, P93, DOI 10.1007/s10509-007-9672-8
NR 30
TC 517
Z9 559
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 31
PY 2011
VL 471
IS 7340
BP 608
EP 611
DI 10.1038/nature09935
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200036
PM 21455175
DA 2026-03-09
ER

PT J
AU Thuiller, W
   Lavergne, S
   Roquet, C
   Boulangeat, I
   Lafourcade, B
   Araujo, MB
AF Thuiller, Wilfried
   Lavergne, Sebastien
   Roquet, Cristina
   Boulangeat, Isabelle
   Lafourcade, Bruno
   Araujo, Miguel. B.
TI Consequences of climate change on the tree of life in Europe
SO NATURE
LA English
DT Article
ID phylogenetic signal; extinction risk; biodiversity; predictors; traits; niche
AB Many species are projected to become vulnerable to twenty-first-century climate changes(1,2), with consequent effects on the tree of life. If losses were not randomly distributed across the tree of life, climate change could lead to a disproportionate loss of evolutionary history(3-5). Here we estimate the consequences of climate change on the phylogenetic diversities of plant, bird and mammal assemblages across Europe. Using a consensus across ensembles of forecasts for 2020, 2050 and 2080 and high-resolution phylogenetic trees, we show that species vulnerability to climate change clusters weakly across phylogenies. Such phylogenetic signal in species vulnerabilities does not lead to higher loss of evolutionary history than expected with a model of random extinctions. This is because vulnerable species have neither fewer nor closer relatives than the remaining clades. Reductions in phylogenetic diversity will be greater in southern Europe, and gains are expected in regions of high latitude or altitude. However, losses will not be offset by gains and the tree of life faces a trend towards homogenization across the continent.
C1 [Thuiller, Wilfried; Lavergne, Sebastien; Roquet, Cristina; Boulangeat, Isabelle; Lafourcade, Bruno] Univ Grenoble 1, Lab Ecol Alpine, CNRS, UMR 5553, FR-38041 Grenoble 9, France.
   [Araujo, Miguel. B.] CSIC, Natl Museum Nat Sci, Dept Biodivers & Evolutionary Biol, E-28006 Madrid, Spain.
   [Araujo, Miguel. B.] Univ Evora, CIBIO, Rui Nabeiro Biodivers Chair, P-7000 Evora, Portugal.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Universite Savoie Mont Blanc; Consejo Superior de Investigaciones Cientificas (CSIC); University of Evora
RP Thuiller, W (corresponding author), Univ Grenoble 1, Lab Ecol Alpine, CNRS, UMR 5553, BP 53, FR-38041 Grenoble 9, France.
EM wilfried.thuiller@ujf-grenoble.fr
FU EU [GOCE-CT-2007-036866, ANR-2007-BDIV-014]; Fundacion Ramon Areces; Rhone-Alpes region [CPER07-13 CIRA]
NR 26
TC 464
Z9 522
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 FEB 24
PY 2011
VL 470
IS 7335
BP 531
EP 534
DI 10.1038/nature09705
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900041
PM 21326204
DA 2026-03-09
ER

PT J
AU Hamann, K
   Warneken, F
   Greenberg, JR
   Tomasello, M
AF Hamann, Katharina
   Warneken, Felix
   Greenberg, Julia R.
   Tomasello, Michael
TI Collaboration encourages equal sharing in children but not in chimpanzees
SO NATURE
LA English
DT Article
ID distributive justice; cooperation; fairness; behavior; equity
AB Humans actively share resources with one another to a much greater degree than do other great apes, and much human sharing is governed by social norms of fairness and equity(1-3). When in receipt of a windfall of resources, human children begin showing tendencies towards equitable distribution with others at five to seven years of age(4-7). Arguably, however, the primordial situation for human sharing of resources is that which follows cooperative activities such as collaborative foraging, when several individuals must share the spoils of their joint efforts(8-10). Here we show that children of around three years of age share with others much more equitably in collaborative activities than they do in either windfall or parallel-work situations. By contrast, one of humans' two nearest primate relatives, chimpanzees (Pan troglodytes), 'share' (make food available to another individual) just as often whether they have collaborated with them or not. This species difference raises the possibility that humans' tendency to distribute resources equitably may have its evolutionary roots in the sharing of spoils after collaborative efforts.
C1 [Hamann, Katharina; Tomasello, Michael] Max Planck Inst Evolutionary Anthropol, Dept Dev & Comparat Psychol, D-04103 Leipzig, Germany.
   [Warneken, Felix] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
   [Greenberg, Julia R.] Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA.
C3 Max Planck Society; Harvard University; Michigan State University
RP Hamann, K (corresponding author), Max Planck Inst Evolutionary Anthropol, Dept Dev & Comparat Psychol, Deutsch Pl 6, D-04103 Leipzig, Germany.
EM khamann@eva.mpg.de; warneken@wjh.harvard.edu
FU EC [215805]; Academy of Finland (AKA) [215805] Funding Source: Academy of Finland (AKA)
NR 30
TC 269
Z9 321
U1 3
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 18
PY 2011
VL 476
IS 7360
BP 328
EP 331
DI 10.1038/nature10278
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811JV
UT WOS:000294206500037
PM 21775985
DA 2026-03-09
ER

PT J
AU Rinkevich, Y
   Lindau, P
   Ueno, H
   Longaker, MT
   Weissman, IL
AF Rinkevich, Yuval
   Lindau, Paul
   Ueno, Hiroo
   Longaker, Michael T.
   Weissman, Irving L.
TI Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; regulatory elements; blood-cells; mice; limb; expression; skin; recombination; endothelium; precursors
AB The regrowth of amputated limbs and the distal tips of digits represent models of tissue regeneration in amphibians, fish and mice. For decades it had been assumed that limb regeneration derived from the blastema, an undifferentiated pluripotent cell population thought to be derived from mature cells via dedifferentiation. Here we show that a wide range of tissue stem/progenitor cells contribute towards the restoration of the mouse distal digit. Genetic fate mapping and clonal analysis of individual cells revealed that these stem cells are lineage restricted, mimicking digit growth during development. Transplantation of cyan-fluorescent-protein-expressing haematopoietic stem cells, and parabiosis between genetically marked mice, confirmed that the stem/progenitor cells are tissue resident, including the cells involved in angiogenesis. These results, combined with those from appendage regeneration in other vertebrate subphyla, collectively demonstrate that tissue stem cells rather than pluripotent blastema cells are an evolutionarily conserved cellular mode for limb regeneration after amputation.
C1 [Rinkevich, Yuval; Lindau, Paul; Ueno, Hiroo; Longaker, Michael T.; Weissman, Irving L.] Stanford Univ, Sch Med, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Longaker, Michael T.] Stanford Univ, Sch Med, Dept Surg Plast & Reconstruct Surg, Hagey Lab Pediat Regenerat Med, Stanford, CA 94305 USA.
   [Weissman, Irving L.] Stanford Univ, Ludwig Ctr Canc Stem Cell Res, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University
RP Rinkevich, Y (corresponding author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Lorry I Lokey Res Bldg, Stanford, CA 94028 USA.
EM ryuval@stanford.edu
FU California Institute of Regenerative Medicine [RC1 00354]; Smith Family Trust; Oak Foundation; Hagey Laboratory for Pediatric Regenerative Medicine; Human Frontier Science Program (HFSP); Machiah Foundation
NR 46
TC 317
Z9 386
U1 3
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 AUG 25
PY 2011
VL 476
IS 7361
BP 409
EP U53
DI 10.1038/nature10346
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400027
PM 21866153
DA 2026-03-09
ER

PT J
AU Horie, T
   Shinki, R
   Ogura, Y
   Kusakabe, TG
   Satoh, N
   Sasakura, Y
AF Horie, Takeo
   Shinki, Ryoko
   Ogura, Yosuke
   Kusakabe, Takehiro G.
   Satoh, Nori
   Sasakura, Yasunori
TI Ependymal cells of chordate larvae are stem-like cells that form the adult nervous system
SO NATURE
LA English
DT Article
ID ascidian ciona-intestinalis; origin; expression; placodes; genes; brain; identification; transgenesis; networks; insights
AB In ascidian tunicates, the metamorphic transition from larva to adult is accompanied by dynamic changes in the body plan. For instance, the central nervous system (CNS) is subjected to extensive rearrangement because its regulating larval organs are lost and new adult organs are created(1). To understand how the adult CNS is reconstructed, we traced the fate of larval CNS cells during ascidian metamorphosis by using transgenic animals and imaging technologies with photoconvertible fluorescent proteins(2). Here we show that most parts of the ascidian larval CNS, except for the tail nerve cord, are maintained during metamorphosis and recruited to form the adult CNS. We also show that most of the larval neurons disappear and only a subset of cholinergic motor neurons and glutamatergic neurons are retained. Finally, we demonstrate that ependymal cells of the larval CNS contribute to the construction of the adult CNS and that some differentiate into neurons in the adult CNS. An unexpected role of ependymal cells highlighted by this study is that they serve as neural stem-like cells to reconstruct the adult nervous network during chordate metamorphosis. Consequently, the plasticity of non-neuronal ependymal cells and neuronal cells in chordates should be re-examined by future studies(3,4).
C1 [Horie, Takeo; Shinki, Ryoko; Ogura, Yosuke; Sasakura, Yasunori] Univ Tsukuba, Shimoda Marine Res Ctr, Shizuoka 4150025, Japan.
   [Kusakabe, Takehiro G.] Konan Univ, Dept Biol, Kobe, Hyogo 6588501, Japan.
   [Satoh, Nori] Sci & Technol Promot Corp, Okinawa Inst, Marine Genom Unit, Okinawa 9040412, Japan.
C3 University of Tsukuba; Konan University
RP Horie, T (corresponding author), Univ Tsukuba, Shimoda Marine Res Ctr, Shizuoka 4150025, Japan.
EM horie@kurofune.shimoda.tsukuba.ac.jp
FU Japan Society for the Promotion of Science; MEXT; National Institute of Genetics; Grants-in-Aid for Scientific Research [22657023, 21112004, 22310120] Funding Source: KAKEN
NR 33
TC 72
Z9 84
U1 0
U2 16
PU 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 27
PY 2011
VL 469
IS 7331
BP 525
EP U256
DI 10.1038/nature09631
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 711MU
UT WOS:000286596500031
PM 21196932
DA 2026-03-09
ER

PT J
AU Pertel, T
   Hausmann, S
   Morger, D
   Züger, S
   Guerra, J
   Lascano, J
   Reinhard, C
   Santoni, FA
   Uchil, PD
   Chatel, L
   Bisiaux, A
   Albert, ML
   Strambio-De-Castillia, C
   Mothes, W
   Pizzato, M
   Grütter, MG
   Luban, J
AF Pertel, Thomas
   Hausmann, Stephane
   Morger, Damien
   Zueger, Sara
   Guerra, Jessica
   Lascano, Josefina
   Reinhard, Christian
   Santoni, Federico A.
   Uchil, Pradeep D.
   Chatel, Laurence
   Bisiaux, Aurelie
   Albert, Matthew L.
   Strambio-De-Castillia, Caterina
   Mothes, Walther
   Pizzato, Massimo
   Gruetter, Markus G.
   Luban, Jeremy
TI TRIM5 is an innate immune sensor for the retrovirus capsid lattice
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; unanchored polyubiquitin chains; cyclophilin-a; trim5-alpha protein; human-cells; hiv-1; resistance; infection; restriction; recognition
AB TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm(1,2). Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice(3,4) and several reports indicate that TRIM5 has a role in signal transduction(5-7), but the precise mechanism of restriction is unknown(8). Here we demonstrate that TRIM5 promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A (also known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NF kappa B signalling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13-UEV1A-dependent E3 activity of TRIM5 and challenge with retroviruses induces the transcription of AP-1 and NF-kappa B-dependent factors with a magnitude that tracks with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contribute to capsid-specific restriction by TRIM5. Thus, the retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signalling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice.
C1 [Pertel, Thomas; Hausmann, Stephane; Guerra, Jessica; Lascano, Josefina; Reinhard, Christian; Santoni, Federico A.; Strambio-De-Castillia, Caterina; Pizzato, Massimo; Luban, Jeremy] Univ Geneva, Dept Microbiol & Mol Med, CH-1211 Geneva, Switzerland.
   [Morger, Damien; Zueger, Sara; Gruetter, Markus G.] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
   [Uchil, Pradeep D.; Mothes, Walther] Yale Univ, Sect Microbial Pathogenesis, Sch Med, New Haven, CT 06536 USA.
   [Chatel, Laurence] Novimmune SA, CH-1228 Geneva, Switzerland.
   [Bisiaux, Aurelie; Albert, Matthew L.] Inst Pasteur, INSERM, U818, F-75724 Paris, France.
C3 University of Geneva; University of Zurich; Yale University; NovImmune SA; Institut National de la Sante et de la Recherche Medicale (Inserm); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
RP Luban, J (corresponding author), Univ Geneva, Dept Microbiol & Mol Med, CH-1211 Geneva, Switzerland.
EM jeremy.luban@unige.ch
FU NIH [RO1AI59159, R21AI087467]; Swiss National Science Foundation [3100A0-128655, 3100A0-122342]; UZH Forschungskredit [54041402]
NR 27
TC 539
Z9 656
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 APR 21
PY 2011
VL 472
IS 7343
BP 361
EP 365
DI 10.1038/nature09976
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600042
PM 21512573
DA 2026-03-09
ER

PT J
AU Rayner, KJ
   Esau, CC
   Hussain, FN
   McDaniel, AL
   Marshall, SM
   van Gils, JM
   Ray, TD
   Sheedy, FJ
   Goedeke, L
   Liu, XQ
   Khatsenko, OG
   Kaimal, V
   Lees, CJ
   Fernandez-Hernando, C
   Fisher, EA
   Temel, RE
   Moore, KJ
AF Rayner, Katey J.
   Esau, Christine C.
   Hussain, Farah N.
   McDaniel, Allison L.
   Marshall, Stephanie M.
   van Gils, Janine M.
   Ray, Tathagat D.
   Sheedy, Frederick J.
   Goedeke, Leigh
   Liu, Xueqing
   Khatsenko, Oleg G.
   Kaimal, Vivek
   Lees, Cynthia J.
   Fernandez-Hernando, Carlos
   Fisher, Edward A.
   Temel, Ryan E.
   Moore, Kathryn J.
TI Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
SO NATURE
LA English
DT Article
ID cholesterol; microrna-33; intron
AB Cardiovascular disease remains the leading cause of mortality in westernized countries, despite optimum medical therapy to reduce the levels of low-density lipoprotein (LDL)-associated cholesterol. The pursuit of novel therapies to target the residual risk has focused on raising the levels of high-density lipoprotein (HDL)-associated cholesterol in order to exploit its atheroprotective effects(1). MicroRNAs (miRNAs) have emerged as important posttranscriptional regulators of lipid metabolism and are thus a new class of target for therapeutic intervention(2). MicroRNA-33a and microRNA-33b (miR-33a/b) are intronic miRNAs whose encoding regions are embedded in the sterol-response-element-binding protein genes SREBF2 and SREBF1 (refs 3-5), respectively. These miRNAs repress expression of the cholesterol transporter ABCA1, which is a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL levels(3-5) and providing protection against atherosclerosis(6); however, extrapolating these findings to humans is complicated by the fact that mice lack miR-33b, which is present only in the SREBF1 gene of medium and large mammals. Here we show in African green monkeys that systemic delivery of an anti-miRNA oligonucleotide that targets both miR-33a and miR-33b increased hepatic expression of ABCA1 and induced a sustained increase in plasma HDL levels over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in fatty acid oxidation (CROT, CPT1A, HADHB and PRKAA1) and reduced the expression of genes involved in fatty acid synthesis (SREBF1, FASN, ACLY and ACACA), resulting in a marked suppression of the plasma levels of very-low-density lipoprotein (VLDL)-associated triglycerides, a finding that has not previously been observed in mice. These data establish, in a model that is highly relevant to humans, that pharmacological inhibition of miR-33a and miR33b is a promising therapeutic strategy to raise plasma HDL and lower VLDL triglyceride levels for the treatment of dyslipidaemias that increase cardiovascular disease risk.
C1 [Rayner, Katey J.; Hussain, Farah N.; van Gils, Janine M.; Ray, Tathagat D.; Sheedy, Frederick J.; Goedeke, Leigh; Fernandez-Hernando, Carlos; Fisher, Edward A.; Moore, Kathryn J.] NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, Leon H Charney Div Cardiol,Dept Med, New York, NY 10016 USA.
   [Esau, Christine C.; Liu, Xueqing; Khatsenko, Oleg G.; Kaimal, Vivek] Regulus Therapeut, San Diego, CA 92121 USA.
   [McDaniel, Allison L.; Marshall, Stephanie M.; Temel, Ryan E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Sect Lipid Sci, Winston Salem, NC 27157 USA.
   [Lees, Cynthia J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Comparat Med Sect, Winston Salem, NC 27157 USA.
C3 New York University; Ionis Pharmaceuticals, Inc.; Wake Forest University; Wake Forest Baptist Medical Center; Wake Forest University; Wake Forest Baptist Medical Center
RP Moore, KJ (corresponding author), NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, Leon H Charney Div Cardiol,Dept Med, New York, NY 10016 USA.
EM rtemel@wfubmc.edu; kathryn.moore@nyumc.org
FU National Institutes of Health [R01AG02055, R01HL108182, P01HL098055, R01HL084312, R01HL58541, 1P30HL101270, R01HL107953, R00HL088528]; Canadian Institutes of Health Research; National Heart Lung and Blood Institute [R01HL084312] Funding Source: NIH RePORTER
CR Alberti KGMM, 2009, CIRCULATION, V120, P1640, DOI 10.1161/CIRCULATIONAHA.109.192644
   Chyu KY, 2011, CURR ATHEROSCLER REP, V13, P405, DOI 10.1007/s11883-011-0189-9
   Dávalos A, 2011, P NATL ACAD SCI USA, V108, P9232, DOI 10.1073/pnas.1102281108
   Degoma EM, 2011, NAT REV CARDIOL, V8, P266, DOI 10.1038/nrcardio.2010.200
   Fitzgerald ML, 2001, J BIOL CHEM, V276, P15137, DOI 10.1074/jbc.M100474200
   Garber DW, 2000, J LIPID RES, V41, P1020
   Geary RS, 2009, EXPERT OPIN DRUG MET, V5, P381, DOI 10.1517/17425250902877680
   Gerin I, 2010, J BIOL CHEM, V285, P33652, DOI 10.1074/jbc.M110.152090
   Horie T, 2010, P NATL ACAD SCI USA, V107, P17321, DOI 10.1073/pnas.1008499107
   Horton JD, 2002, J CLIN INVEST, V109, P1125, DOI 10.1172/JCI200215593
   Jeyarajah EJ, 2006, CLIN LAB MED, V26, P847, DOI 10.1016/j.cll.2006.07.006
   KIEFT KA, 1991, J LIPID RES, V32, P859
   KORITNIK DL, 1983, J LIPID RES, V24, P1639
   Marquart TJ, 2010, P NATL ACAD SCI USA, V107, P12228, DOI 10.1073/pnas.1005191107
   Moore KJ, 2010, TRENDS ENDOCRIN MET, V21, P699, DOI 10.1016/j.tem.2010.08.008
   Najafi-Shoushtari SH, 2010, SCIENCE, V328, P1566, DOI 10.1126/science.1189123
   Rayner KJ, 2011, J CLIN INVEST, V121, P2921, DOI 10.1172/JCI57275
   Rayner KJ, 2010, SCIENCE, V328, P1570, DOI 10.1126/science.1189862
   Wagner JD, 2006, ILAR J, V47, P259, DOI 10.1093/ilar.47.3.259
   Yvan-Charvet L, 2010, SCIENCE, V328, P1689, DOI 10.1126/science.1189731
NR 20
TC 620
Z9 708
U1 2
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 OCT 20
PY 2011
VL 478
IS 7369
BP 404
EP +
DI 10.1038/nature10486
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100050
PM 22012398
DA 2026-03-09
ER

PT J
AU Smeulders, MJ
   Barends, TRM
   Pol, A
   Scherer, A
   Zandvoort, MH
   Udvarhelyi, A
   Khadem, AF
   Menzel, A
   Hermans, J
   Shoeman, RL
   Wessels, HJCT
   van den Heuvel, LP
   Russ, L
   Schlichting, I
   Jetten, MSM
   den Camp, HJMO
AF Smeulders, Marjan J.
   Barends, Thomas R. M.
   Pol, Arjan
   Scherer, Anna
   Zandvoort, Marcel H.
   Udvarhelyi, Aniko
   Khadem, Ahmad F.
   Menzel, Andreas
   Hermans, John
   Shoeman, Robert L.
   Wessels, Hans J. C. T.
   van den Heuvel, Lambert P.
   Russ, Lina
   Schlichting, Ilme
   Jetten, Mike S. M.
   den Camp, Huub J. M. Op
TI Evolution of a new enzyme for carbon disulphide conversion by an acidothermophilic archaeon
SO NATURE
LA English
DT Article
ID sulfur-compounds; sulfide cos; anhydrase; substrate; model; cs2; macromolecules; consumption; metabolism; scattering
AB Extremophilic organisms require specialized enzymes for their exotic metabolisms. Acid-loving thermophilic Archaea that live in the mudpots of volcanic solfataras obtain their energy from reduced sulphur compounds such as hydrogen sulphide (H2S) and carbon disulphide (CS2)(1,2). The oxidation of these compounds into sulphuric acid creates the extremely acidic environment that characterizes solfataras. The hyperthermophilic Acidianus strain A1-3, which was isolated from the fumarolic, ancient sauna building at the Solfatara volcano (Naples, Italy), was shown to rapidly convert CS2 into H2S and carbon dioxide (CO2), but nothing has been known about the modes of action and the evolution of the enzyme(s) involved. Here we describe the structure, the proposed mechanism and evolution of a CS2 hydrolase from Acidianus A1-3. The enzyme monomer displays a typical beta-carbonic anhydrase fold and active site, yet CO2 is not one of its substrates. Owing to large carboxy-and amino-terminal arms, an unusual hexadecameric catenane oligomer has evolved. This structure results in the blocking of the entrance to the active site that is found in canonical beta-carbonic anhydrases and the formation of a single 15-angstrom-long, highly hydrophobic tunnel that functions as a specificity filter. The tunnel determines the enzyme's substrate specificity for CS2, which is hydrophobic. The transposon sequences that surround the gene encoding this CS2 hydrolase point to horizontal gene transfer as a mechanism for its acquisition during evolution. Our results show how the ancient beta-carbonic anhydrase, which is central to global carbon metabolism, was transformed by divergent evolution into a crucial enzyme in CS2 metabolism.
C1 [Smeulders, Marjan J.; Pol, Arjan; Zandvoort, Marcel H.; Khadem, Ahmad F.; Hermans, John; Russ, Lina; Jetten, Mike S. M.; den Camp, Huub J. M. Op] Radboud Univ Nijmegen, Dept Microbiol, NL-6525 AJ Nijmegen, Netherlands.
   [Barends, Thomas R. M.; Scherer, Anna; Udvarhelyi, Aniko; Shoeman, Robert L.; Schlichting, Ilme] Max Planck Inst Med Res, Dept Biomol Mech, D-69120 Heidelberg, Germany.
   [Menzel, Andreas] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
   [Wessels, Hans J. C. T.; van den Heuvel, Lambert P.] Radboud Univ Nijmegen, Nijmegen Ctr Mitochondrial Disorders, Nijmegen Prote Facil, Dept Lab Med,Med Ctr, NL-6500 HB Nijmegen, Netherlands.
C3 Radboud University Nijmegen; Max Planck Society; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Radboud University Nijmegen
RP Jetten, MSM (corresponding author), Radboud Univ Nijmegen, Dept Microbiol, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.
EM m.jetten@science.ru.nl
FU STW [STW_6353]; Max-Planck Society
NR 51
TC 77
Z9 88
U1 2
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 OCT 20
PY 2011
VL 478
IS 7369
BP 412
EP +
DI 10.1038/nature10464
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835FO
UT WOS:000296021100052
PM 22012399
DA 2026-03-09
ER

PT J
AU Robledo, L
   Childress, L
   Bernien, H
   Hensen, B
   Alkemade, PFA
   Hanson, R
AF Robledo, Lucio
   Childress, Lilian
   Bernien, Hannes
   Hensen, Bas
   Alkemade, Paul F. A.
   Hanson, Ronald
TI High-fidelity projective read-out of a solid-state spin quantum register
SO NATURE
LA English
DT Article
ID single-shot readout; nuclear-spin; electron-spin; diamond; dot; entanglement; coherence
AB Initialization and read-out of coupled quantum systems are essential ingredients for the implementation of quantum algorithms(1,2). Single-shot read-out of the state of a multi-quantum-bit (multi-qubit) register would allow direct investigation of quantum correlations (entanglement), and would give access to further key resources such as quantum error correction and deterministic quantum teleportation(1). Although spins in solids are attractive candidates for scalable quantum information processing, their single-shot detection has been achieved only for isolated qubits(3-6). Here we demonstrate the preparation and measurement of a multi-spin quantum register in a low-temperature solid-state system by implementing resonant optical excitation techniques originally developed in atomic physics. We achieve high-fidelity read-out of the electronic spin associated with a single nitrogen-vacancy centre in diamond, and use this read-out to project up to three nearby nuclear spin qubits onto a well-defined state(7). Conversely, we can distinguish the state of the nuclear spins in a single shot by mapping it onto, and subsequently measuring, the electronic spin(5,8). Finally, we show compatibility with qubit control: we demonstrate initialization, coherent manipulation and single-shot read-out in a single experiment on a two-qubit register, using techniques suitable for extension to larger registers. These results pave the way for a test of Bell's inequalities on solid-state spins and the implementation of measurement-based quantum information protocols.
C1 [Robledo, Lucio; Bernien, Hannes; Hensen, Bas; Alkemade, Paul F. A.; Hanson, Ronald] Delft Univ Technol, Kavli Inst Nanosci Delft, NL-2600 GA Delft, Netherlands.
   [Childress, Lilian] Bates Coll, Dept Phys & Astron, Lewiston, ME 04240 USA.
C3 Delft University of Technology
RP Hanson, R (corresponding author), Delft Univ Technol, Kavli Inst Nanosci Delft, POB 5046, NL-2600 GA Delft, Netherlands.
EM r.hanson@tudelft.nl
FU European Community; Dutch Organization for Fundamental Research on Matter (FOM); European Commission (SOLID); Research Corporation for Science Advancement (RCSA)
NR 32
TC 622
Z9 727
U1 3
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 SEP 29
PY 2011
VL 477
IS 7366
BP 574
EP 578
DI 10.1038/nature10401
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZM
UT WOS:000295320900036
PM 21937989
DA 2026-03-09
ER

PT J
AU Rosenbaum, DM
   Zhang, C
   Lyons, JA
   Holl, R
   Aragao, D
   Arlow, DH
   Rasmussen, SGF
   Choi, HJ
   DeVree, BT
   Sunahara, RK
   Chae, PS
   Gellman, SH
   Dror, RO
   Shaw, DE
   Weis, WI
   Caffrey, M
   Gmeiner, P
   Kobilka, BK
AF Rosenbaum, Daniel M.
   Zhang, Cheng
   Lyons, Joseph A.
   Holl, Ralph
   Aragao, David
   Arlow, Daniel H.
   Rasmussen, Soren G. F.
   Choi, Hee-Jung
   DeVree, Brian T.
   Sunahara, Roger K.
   Chae, Pil Seok
   Gellman, Samuel H.
   Dror, Ron O.
   Shaw, David E.
   Weis, William I.
   Caffrey, Martin
   Gmeiner, Peter
   Kobilka, Brian K.
TI Structure and function of an irreversible agonist-β2 adrenoceptor complex
SO NATURE
LA English
DT Article
ID protein-coupled receptor; crystallizing membrane-proteins; molecular-dynamics simulations; lipidic mesophases; adrenergic-receptor; binding-site; force-fields; rhodopsin; activation; agonists
AB G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs(1), the molecular basis for agonist binding and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered by modest affinities and rapid off-rates of available agonists. Using the inactive structure of the human beta(2) adrenergic receptor (beta(2)AR) as a guide, we designed a beta(2)AR agonist that can be covalently tethered to a specific site on the receptor through a disulphide bond. The covalent beta(2)AR-agonist complex forms efficiently, and is capable of activating a heterotrimeric G protein. We crystallized a covalent agonist-bound beta(2)AR-T4L fusion protein in lipid bilayers through the use of the lipidic mesophase method(2), and determined its structure at 3.5 angstrom resolution. A comparison to the inactive structure and an antibody-stabilized active structure (companion paper(3)) shows how binding events at both the extracellular and intracellular surfaces are required to stabilize an active conformation of the receptor. The structures are in agreement with long-timescale (up to 30 mu s) molecular dynamics simulations showing that an agonist-bound active conformation spontaneously relaxes to an inactive-like conformation in the absence of a G protein or stabilizing antibody.
C1 [Rosenbaum, Daniel M.; Zhang, Cheng; Rasmussen, Soren G. F.; Choi, Hee-Jung; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Lyons, Joseph A.] Univ Limerick, Dept Chem & Environm Sci, Limerick, Ireland.
   [Lyons, Joseph A.; Aragao, David; Caffrey, Martin] Trinity Coll Dublin, Sch Biochem & Immunol, Membrane Struct & Funct Biol Grp, Dublin 2, Ireland.
   [Holl, Ralph; Gmeiner, Peter] Univ Erlangen Nurnberg, Dept Chem & Pharm, D-91052 Erlangan, Germany.
   [Arlow, Daniel H.; Dror, Ron O.; Shaw, David E.] DE Shaw Res, New York, NY 10036 USA.
   [Choi, Hee-Jung; Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [DeVree, Brian T.; Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Chae, Pil Seok; Gellman, Samuel H.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
C3 Stanford University; University of Limerick; Trinity College Dublin; University of Erlangen Nuremberg; D. E. Shaw Research; Stanford University; University of Michigan System; University of Michigan; University of Wisconsin System; University of Wisconsin Madison
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM martin.caffrey@tcd.ie; peter.gmeiner@medchem.uni-erlangen.de; kobilka@stanford.edu
FU National Institutes of Health [NS028471, GM083118, GM56169, P01 GM75913, GM75915, P50GM073210, P60DK-20572]; Mathers Foundation; Lundbeck Foundation; Science Foundation Ireland [07/IN.1/B1836]; FP7 COST Action [CM0902]; Bavaria California Technology Center; University of Michigan; Lundbeck Foundation [R37-2009-3457] Funding Source: researchfish; Science Foundation Ireland (SFI) [07/IN.1/B1836] Funding Source: Science Foundation Ireland (SFI); National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 52
TC 667
Z9 774
U1 1
U2 216
PU NATURE PUBLISHING 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 13
PY 2011
VL 469
IS 7329
BP 236
EP 240
DI 10.1038/nature09665
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 705NO
UT WOS:000286143400043
PM 21228876
DA 2026-03-09
ER

PT J
AU Yartsev, MM
   Witter, MP
   Ulanovsky, N
AF Yartsev, Michael M.
   Witter, Menno P.
   Ulanovsky, Nachum
TI Grid cells without theta oscillations in the entorhinal cortex of bats
SO NATURE
LA English
DT Article
ID spatial representation; echolocating bats; path-integration; cognitive map; interference; frequency; model; rat; periodicity; hippocampus
AB Grid cells provide a neural representation of space, by discharging when an animal traverses through the vertices of a periodic hexagonal grid spanning the environment(1). Although grid cells have been characterized in detail in rats(1-6), the fundamental question of what neural dynamics give rise to the grid structure remains unresolved. Two competing classes of models were proposed: network models, based on attractor dynamics(7-9), and oscillatory interference models, which propose that interference between somatic and dendritic theta-band oscillations (4-10 Hz) in single neurons transforms a temporal oscillation into a spatially periodic grid(10-13). So far, these models could not be dissociated experimentally, because rodent grid cells always co-exist with continuous theta oscillations(4-6,14). Here we used a novel animal model, the Egyptian fruit bat(15,16), to refute the proposed causal link between grids and theta oscillations. On the basis of our previous finding from bat hippocampus, of spatially tuned place cells in the absence of continuous theta oscillations(17), we hypothesized that grid cells in bat medial entorhinal cortex might also exist without theta oscillations. Indeed, we found grid cells in bat medial entorhinal cortex that shared remarkable similarities to rodent grid cells. Notably, the grids existed in the absence of continuous theta-band oscillations, and with almost no theta modulation of grid-cell spiking-both of which are essential prerequisites of the oscillatory interference models. Our results provide a direct demonstration of grid cells in a non-rodent species. Furthermore, they strongly argue against a major class of computational models of grid cells.
C1 [Yartsev, Michael M.; Ulanovsky, Nachum] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
   [Witter, Menno P.] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, NO-7489 Trondheim, Norway.
   [Witter, Menno P.] Norwegian Univ Sci & Technol, Ctr Biol Memory, NO-7489 Trondheim, Norway.
C3 Weizmann Institute of Science; Norwegian University of Science & Technology (NTNU); Norwegian University of Science & Technology (NTNU)
RP Ulanovsky, N (corresponding author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
EM nachum.ulanovsky@weizmann.ac.il
FU Israel Science Foundation; Minerva Foundation; Lev-Zion predoctoral excellence fellowship; Norwegian Research Council; Kavli Foundation
NR 30
TC 273
Z9 330
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 3
PY 2011
VL 479
IS 7371
BP 103
EP 107
DI 10.1038/nature10583
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 840FA
UT WOS:000296422600040
PM 22051680
DA 2026-03-09
ER

PT J
AU Yan, H
   Choe, HS
   Nam, SW
   Hu, YJ
   Das, S
   Klemic, JF
   Ellenbogen, JC
   Lieber, CM
AF Yan, Hao
   Choe, Hwan Sung
   Nam, SungWoo
   Hu, Yongjie
   Das, Shamik
   Klemic, James F.
   Ellenbogen, James C.
   Lieber, Charles M.
TI Programmable nanowire circuits for nanoprocessors
SO NATURE
LA English
DT Article
ID logic; arrays
AB A nanoprocessor constructed from intrinsically nanometre-scale building blocks is an essential component for controlling memory, nanosensors and other functions proposed for nanosystems assembled from the bottom up(1-3). Important steps towards this goal over the past fifteen years include the realization of simple logic gates with individually assembled semiconductor nanowires and carbon nanotubes(1,4-8), but with only 16 devices or fewer and a single function for each circuit. Recently, logic circuits also have been demonstrated that use two or three elements of a one-dimensional memristor array(9), although such passive devices without gain are difficult to cascade. These circuits fall short of the requirements for a scalable, multifunctional nanoprocessor(10,11) owing to challenges in materials, assembly and architecture on the nanoscale. Here we describe the design, fabrication and use of programmable and scalable logic tiles for nanoprocessors that surmount these hurdles. The tiles were built from programmable, non-volatile nanowire transistor arrays. Ge/Si core/shell nanowires(12) coupled to designed dielectric shells yielded single-nanowire, non-volatile field-effect transistors (FETs) with uniform, programmable threshold voltages and the capability to drive cascaded elements. We developed an architecture to integrate the programmable nanowire FETs and define a logic tile consisting of two interconnected arrays with 496 functional configurable FET nodes in an area of similar to 960 mu m(2). The logic tile was programmed and operated first as a full adder with a maximal voltage gain of ten and input-output voltage matching. Then we showed that the same logic tile can be reprogrammed and used to demonstrate full-subtractor, multiplexer, demultiplexer and clocked D-latch functions. These results represent a significant advance in the complexity and functionality of nanoelectronic circuits built from the bottom up with a tiled architecture that could be cascaded to realize fully integrated nanoprocessors with computing, memory and addressing capabilities.
C1 [Yan, Hao; Hu, Yongjie; Lieber, Charles M.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Choe, Hwan Sung] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Nam, SungWoo; Lieber, Charles M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Das, Shamik; Klemic, James F.; Ellenbogen, James C.] Mitre Corp, Nanosyst Grp, Mclean, VA 22102 USA.
C3 Harvard University; Harvard University; Harvard University; MITRE Corporation
RP Das, S (corresponding author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM sdas@mitre.org; cml@cmliris.harvard.edu
FU National Security Science and Engineering Faculty; MITRE Corporation; US government's Nano-Enabled Technology Initiative; MITRE
NR 21
TC 458
Z9 522
U1 4
U2 583
PU NATURE PUBLISHING 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 10
PY 2011
VL 470
IS 7333
BP 240
EP 244
DI 10.1038/nature09749
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200040
PM 21307937
DA 2026-03-09
ER

PT J
AU Merrikh, H
   Machón, C
   Grainger, WH
   Grossman, AD
   Soultanas, P
AF Merrikh, Houra
   Machon, Cristina
   Grainger, William H.
   Grossman, Alan D.
   Soultanas, Panos
TI Co-directional replication-transcription conflicts lead to replication restart
SO NATURE
LA English
DT Article
ID bacillus-subtilis; dna-replication; proteins; pria; localization; initiation; replisome; rep; rna; recombination
AB Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability(1,2). To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication(3). In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10-20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign(2,4-9). Biochemical analyses indicate that head-on encounters(10) are more deleterious than co-directional encounters(8) and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.
C1 [Merrikh, Houra; Grossman, Alan D.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Machon, Cristina; Grainger, William H.; Soultanas, Panos] Univ Nottingham, Sch Chem, Ctr Biomol Sci, Nottingham NG7 2RD, England.
C3 Massachusetts Institute of Technology (MIT); University of Nottingham
RP Grossman, AD (corresponding author), MIT, Dept Biol, Bldg 68-530, Cambridge, MA 02139 USA.
EM adg@mit.edu; Panos.Soultanas@nottingham.ac.uk
FU Biotechnology and Biological Sciences Research Council [BB/E006450/1]; Wellcome Trust [091968/Z/10/Z]; NIH [GM41934, GM093408]; Royal Society; Biotechnology and Biological Sciences Research Council [BB/E006450/1] Funding Source: researchfish; BBSRC [BB/E006450/1] Funding Source: UKRI; Wellcome Trust [091968/Z/10/Z] Funding Source: Wellcome Trust
NR 34
TC 160
Z9 193
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 FEB 24
PY 2011
VL 470
IS 7335
BP 554
EP U147
DI 10.1038/nature09758
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900046
PM 21350489
DA 2026-03-09
ER

PT J
AU Staton, TL
   Lazarevic, V
   Jones, DC
   Lanser, AJ
   Takagi, T
   Ishii, S
   Glimcher, LH
AF Staton, Tracy L.
   Lazarevic, Vanja
   Jones, Dallas C.
   Lanser, Amanda J.
   Takagi, Tsuyoshi
   Ishii, Shunsuke
   Glimcher, Laurie H.
TI Dampening of death pathways by schnurri-2 is essential for T-cell development
SO NATURE
LA English
DT Article
ID negative selection; positive selection; thymocyte development; bh3-only proteins; murine schnurri-2; transgenic mice; bcl-2 family; apoptosis; antigen; bim
AB Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4(+)CD8(+) double-positive thymocytes. Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection)(1). Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. Here we show in mice that repression of TCR-induced death pathways is critical for proper interpretation of positive selecting signals in vivo, and identify schnurri-2 (Shn2; also known as Hivep2) as a crucial death dampener. Our results indicate that Shn2(-/-) double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. Shn2(-/-) double-positive thymocytes are more sensitive to TCR-induced death in vitro and die in response to positive selection interactions in vivo. However, Shn2-deficient thymocytes can be positively selected when TCR-induced death is genetically ablated. Shn2 levels increase after TCR stimulation, indicating that integration of multiple TCR-MHC-peptide interactions may fine-tune the death threshold. Mechanistically, Shn2 functions downstream of TCR proximal signalling compenents to dampen Bax activation and the mitochondrial death pathway. Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation.
C1 [Staton, Tracy L.; Lazarevic, Vanja; Jones, Dallas C.; Lanser, Amanda J.; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Takagi, Tsuyoshi; Ishii, Shunsuke] RIKEN Tsukuba Inst, Mol Genet Lab, Tsukuba, Ibaraki 3050074, Japan.
   [Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Glimcher, Laurie H.] Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA.
C3 Harvard University; Harvard T.H. Chan School of Public Health; RIKEN; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute
RP Glimcher, LH (corresponding author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM lglimche@hsph.harvard.edu
FU National Institutes of Health [AI29673, K99AR055668]; National Cancer Institute [ZIABC011431] Funding Source: NIH RePORTER; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart Lung and Blood Institute; National Institute on Aging; National Institute on Minority Health and Health Disparities; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Institute on Drug Abuse [P30AI060354] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [23659244, 23370079, 22590443, 22125005] Funding Source: KAKEN
NR 30
TC 34
Z9 37
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 7
PY 2011
VL 472
IS 7341
BP 105
EP U138
DI 10.1038/nature09848
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 745VV
UT WOS:000289199400046
PM 21475200
DA 2026-03-09
ER

PT J
AU Qu, XH
   Wen, JD
   Lancaster, L
   Noller, HF
   Bustamante, C
   Tinoco, I
AF Qu, Xiaohui
   Wen, Jin-Der
   Lancaster, Laura
   Noller, Harry F.
   Bustamante, Carlos
   Tinoco, Ignacio, Jr.
TI The ribosome uses two active mechanisms to unwind messenger RNA during translation
SO NATURE
LA English
DT Article
ID secondary structure; single-molecule; translocation; helicases; time; stability; movement; dynamics; receptor
AB The ribosome translates the genetic information encoded in messenger RNA into protein. Folded structures in the coding region of an mRNA represent a kinetic barrier that lowers the peptide elongation rate, as the ribosome must disrupt structures it encounters in the mRNA at its entry site to allow translocation to the next codon. Such structures are exploited by the cell to create diverse strategies for translation regulation, such as programmed frameshifting(1,2), the modulation of protein expression levels-(3,4), ribosome localization(5) and co-translational protein folding(6). Although strand separation activity is inherent to the ribosome, requiring no exogenous helicases(7), its mechanism is still unknown. Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find that the translation rate of identical codons at the decoding centre is greatly influenced by the GC content of folded structures at the mRNA entry site. Furthermore, force applied to the ends of the hairpin to favour its unfolding significantly speeds translation. Quantitative analysis of the force dependence of its helicase activity reveals that the ribosome, unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure: it destabilizes the helical junction at the mRNA entry site by biasing its thermal fluctuations towards the open state, increasing the probability of the ribosome translocating unhindered; and it mechanically pulls apart the mRNA single strands of the closed junction during the conformational changes that accompany ribosome translocation. The second of these mechanisms ensures a minimal basal rate of translation in the cell; specialized, mechanically stable structures are required to stall the ribosome temporarily(1,2). Our results establish a quantitative mechanical basis for understanding the mechanism of regulation of the elongation rate of translation by structured mRNAs.
C1 [Qu, Xiaohui; Wen, Jin-Der; Bustamante, Carlos; Tinoco, Ignacio, Jr.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Qu, Xiaohui; Wen, Jin-Der; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
   [Qu, Xiaohui; Wen, Jin-Der; Bustamante, Carlos] Univ Calif Berkeley, QB3 Inst, Berkeley, CA 94720 USA.
   [Lancaster, Laura; Noller, Harry F.] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Lancaster, Laura; Noller, Harry F.] Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley
RP Tinoco, I (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM carlos@alice.berkeley.edu; intinoco@lbl.gov
FU National Institutes of Health; Human Frontiers Science Program
NR 30
TC 249
Z9 301
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 118
EP 121
DI 10.1038/nature10126
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300057
PM 21734708
DA 2026-03-09
ER

PT J
AU Arumugam, M
   Raes, J
   Pelletier, E
   Le Paslier, D
   Yamada, T
   Mende, DR
   Fernandes, GR
   Tap, J
   Bruls, T
   Batto, JM
   Bertalan, M
   Borruel, N
   Casellas, F
   Fernandez, L
   Gautier, L
   Hansen, T
   Hattori, M
   Hayashi, T
   Kleerebezem, M
   Kurokawa, K
   Leclerc, M
   Levenez, F
   Manichanh, C
   Nielsen, HB
   Nielsen, T
   Pons, N
   Poulain, J
   Qin, JJ
   Sicheritz-Ponten, T
   Tims, S
   Torrents, D
   Ugarte, E
   Zoetendal, EG
   Wang, J
   Guarner, F
   Pedersen, O
   de Vos, WM
   Brunak, S
   Doré, J
   Weissenbach, J
   Ehrlich, SD
   Bork, P
AF Arumugam, Manimozhiyan
   Raes, Jeroen
   Pelletier, Eric
   Le Paslier, Denis
   Yamada, Takuji
   Mende, Daniel R.
   Fernandes, Gabriel R.
   Tap, Julien
   Bruls, Thomas
   Batto, Jean-Michel
   Bertalan, Marcelo
   Borruel, Natalia
   Casellas, Francesc
   Fernandez, Leyden
   Gautier, Laurent
   Hansen, Torben
   Hattori, Masahira
   Hayashi, Tetsuya
   Kleerebezem, Michiel
   Kurokawa, Ken
   Leclerc, Marion
   Levenez, Florence
   Manichanh, Chaysavanh
   Nielsen, H. Bjorn
   Nielsen, Trine
   Pons, Nicolas
   Poulain, Julie
   Qin, Junjie
   Sicheritz-Ponten, Thomas
   Tims, Sebastian
   Torrents, David
   Ugarte, Edgardo
   Zoetendal, Erwin G.
   Wang, Jun
   Guarner, Francisco
   Pedersen, Oluf
   de Vos, Willem M.
   Brunak, Soren
   Dore, Joel
   Weissenbach, Jean
   Ehrlich, S. Dusko
   Bork, Peer
TI Enterotypes of the human gut microbiome
SO NATURE
LA English
DT Article
ID bacterial; diversity; pathways; catalog; genes; mucin
AB Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
C1 [Arumugam, Manimozhiyan; Raes, Jeroen; Yamada, Takuji; Mende, Daniel R.; Fernandes, Gabriel R.; Tap, Julien; Bork, Peer] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Raes, Jeroen] Vrije Univ Brussel VIB, B-1050 Brussels, Belgium.
   [Pelletier, Eric; Le Paslier, Denis; Bruls, Thomas; Poulain, Julie; Ugarte, Edgardo; Weissenbach, Jean] CEA, F-91000 Evry, France.
   [Pelletier, Eric; Le Paslier, Denis; Bruls, Thomas; Weissenbach, Jean] CNRS, UMR8030, F-91000 Evry, France.
   [Pelletier, Eric; Le Paslier, Denis; Bruls, Thomas; Weissenbach, Jean] Univ Evry Val dEssone, F-91000 Evry, France.
   [Fernandes, Gabriel R.] Univ Fed Minas Gerais, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil.
   [Tap, Julien; Batto, Jean-Michel; Leclerc, Marion; Levenez, Florence; Pons, Nicolas; Dore, Joel; Ehrlich, S. Dusko] INRA, F-78350 Jouy En Josas, France.
   [Bertalan, Marcelo; Gautier, Laurent; Nielsen, H. Bjorn; Sicheritz-Ponten, Thomas; Brunak, Soren] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Borruel, Natalia; Casellas, Francesc; Manichanh, Chaysavanh; Guarner, Francisco] Univ Hosp Vall Hebron, Digest Syst Res Unit, Barcelona 08035, Spain.
   [Fernandez, Leyden; Torrents, David] Barcelona Supercomp Ctr, Barcelona 08034, Spain.
   [Hansen, Torben; Nielsen, Trine; Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Sect Metab Genet, Marie Krogh Ctr Metab Res, DK-2100 Copenhagen, Denmark.
   [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark.
   [Hattori, Masahira] Univ Tokyo, Computat Biol Lab Bld, Chiba 2778561, Japan.
   [Hayashi, Tetsuya] Miyazaki Univ, Frontier Sci Res Ctr, Div Bioenvironm Sci, Miyazaki 8891692, Japan.
   [Kleerebezem, Michiel; Tims, Sebastian; Zoetendal, Erwin G.; de Vos, Willem M.] Wageningen Univ, Microbiol Lab, NL-6710 BA Ede, Netherlands.
   [Kurokawa, Ken] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biol Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
   [Qin, Junjie; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Sicheritz-Ponten, Thomas] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark.
   [Torrents, David] Pg Lluis Co 23, ICREA, Barcelona 08010, Spain.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, DK-2200 Copenhagen, Denmark.
   [Pedersen, Oluf] Hagedom Res Inst, DK-2820 Gentofte, Denmark.
   [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark.
   [de Vos, Willem M.] Univ Helsinki, FI-00014 Helsinki, Finland.
   [Bork, Peer] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
C3 European Molecular Biology Laboratory (EMBL); Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; CEA; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); Universite Paris Saclay; Universidade Federal de Minas Gerais; INRAE; Universite Paris Saclay; Technical University of Denmark; Hospital Universitari Vall d'Hebron; Universitat Politecnica de Catalunya; Barcelona Supercomputer Center (BSC-CNS); University of Copenhagen; University of Southern Denmark; University of Tokyo; University of Miyazaki; Wageningen University & Research; Institute of Science Tokyo; Tokyo Institute of Technology; Beijing Genomics Institute (BGI); Technical University of Denmark; ICREA; University of Copenhagen; University of Copenhagen; Aarhus University; University of Helsinki; Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Bork, P (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM dusko.ehrlich@jouy.inra.fr; bork@embl.de
FU European Community [HEALTH-F4-2007-201052]; Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCAMP); Novo Nordisk Foundation; International Science and Technology Cooperation Project in China [0806]; Agence Nationale de la Recherche (ANR); Institute for the encouragement of Scientific Research and Innovation of Brussels (ISRIB); Fund for Scientific Research Flanders (FWO); ICREA Funding Source: Custom; Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish; Grants-in-Aid for Scientific Research [221S0002] Funding Source: KAKEN
NR 40
TC 5517
Z9 6597
U1 24
U2 1933
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 12
PY 2011
VL 473
IS 7346
BP 174
EP 180
DI 10.1038/nature09944
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 762NT
UT WOS:000290487200030
PM 21508958
DA 2026-03-09
ER

PT J
AU Ernst, S
   Kirchner, S
   Krellner, C
   Geibel, C
   Zwicknagl, G
   Steglich, F
   Wirth, S
AF Ernst, S.
   Kirchner, S.
   Krellner, C.
   Geibel, C.
   Zwicknagl, G.
   Steglich, F.
   Wirth, S.
TI Emerging local Kondo screening and spatial coherence in the heavy-fermion metal YbRh2Si2
SO NATURE
LA English
DT Article
ID crystalline electric-field; hidden order; lattice
AB The entanglement of quantum states is both a central concept in fundamental physics and a potential tool for realizing advanced materials and applications. The quantum superpositions underlying entanglement are at the heart of the intricate interplay of localized spin states and itinerant electronic states that gives rise to the Kondo effect in certain dilute magnetic alloys(1). In systems where the density of localized spin states is sufficiently high, they can no longer be treated as non-interacting; if they form a dense periodic array, a Kondo lattice may be established(1). Such a Kondo lattice gives rise to the emergence of charge carriers with enhanced effective masses, but the precise nature of the coherent Kondo state responsible for the generation of these heavy fermions remains highly debated(1-3). Here we use atomic-resolution tunnelling spectroscopy to investigate the low-energy excitations of a generic Kondo lattice system, YbRh2Si2. We find that the hybridization of the conduction electrons with the localized 4f electrons results in a decrease in the tunnelling conductance at the Fermi energy. In addition, we observe unambiguously the crystal-field excitations of the Yb3+ ions. A strongly temperature-dependent peak in the tunnelling conductance is attributed to the Fano resonance(4,5) resulting from tunnelling into the coherent heavy-fermion states that emerge at low temperature. Taken together, these features reveal how quantum coherence develops in heavy 4f-electron Kondo lattices. Our results demonstrate the efficiency of real-space electronic structure imaging for the investigation of strong electronic correlations(6,7), specifically with respect to coherence phenomena, phase coexistence and quantum criticality.
C1 [Ernst, S.; Kirchner, S.; Krellner, C.; Geibel, C.; Steglich, F.; Wirth, S.] Max Planck Inst Chem Phys Solids, D-01187 Dresden, Germany.
   [Kirchner, S.] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
   [Zwicknagl, G.] TU Braunschweig, Inst Math Phys, D-38106 Braunschweig, Germany.
C3 Max Planck Society; Max Planck Society; Braunschweig University of Technology
RP Wirth, S (corresponding author), Max Planck Inst Chem Phys Solids, Nothnitzer Str 40, D-01187 Dresden, Germany.
EM wirth@cpfs.mpg.de
NR 31
TC 145
Z9 163
U1 3
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 362
EP 366
DI 10.1038/nature10148
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100042
PM 21677755
DA 2026-03-09
ER

PT J
AU Jones, MDM
   Forn, I
   Gadelha, C
   Egan, MJ
   Bass, D
   Massana, R
   Richards, TA
AF Jones, Meredith D. M.
   Forn, Irene
   Gadelha, Catarina
   Egan, Martin J.
   Bass, David
   Massana, Ramon
   Richards, Thomas A.
TI Discovery of novel intermediate forms redefines the fungal tree of life
SO NATURE
LA English
DT Article
ID oligonucleotide probes; molecular phylogeny; ribosomal-rna; sequence data; land plants; diversity; evolution; community; eukaryotes; rozella
AB Fungi are the principal degraders of biomass in terrestrial ecosystems and establish important interactions with plants and animals(1-3). However, our current understanding of fungal evolutionary diversity is incomplete(4) and is based upon species amenable to growth in culture(1). These culturable fungi are typically yeast or filamentous forms, bound by a rigid cell wall rich in chitin. Evolution of this body plan was thought critical for the success of the Fungi, enabling them to adapt to heterogeneous habitats and live by osmotrophy: extracellular digestion followed by nutrient uptake(5). Here we investigate the ecology and cell biology of a previously undescribed and highly diverse form of eukaryotic life that branches with the Fungi, using environmental DNA analyses combined with fluorescent detection via DNA probes. This clade is present in numerous ecosystems including soil, freshwater and aquatic sediments. Phylogenetic analyses using multiple ribosomal RNA genes place this clade with Rozella, the putative primary branch of the fungal kingdom(1). Tyramide signal amplification coupled with group-specific fluorescence in situ hybridization reveals that the target cells are small eukaryotes of 3-5 mm in length, capable of forming a microtubule-based flagellum. Co-staining with cell wall markers demonstrates that representatives from the clade do not produce a chitin-rich cell wall during any of the life cycle stages observed and therefore do not conform to the standard fungal body plan(5). We name this highly diverse clade the cryptomycota in anticipation of formal classification.
C1 [Jones, Meredith D. M.; Egan, Martin J.; Richards, Thomas A.] Univ Exeter, Sch Biosci, Exeter EX4 4QD, Devon, England.
   [Jones, Meredith D. M.; Bass, David; Richards, Thomas A.] Nat Hist Museum, Dept Zool, London SW7 5BD, England.
   [Forn, Irene; Massana, Ramon] CSIC, Inst Ciencies Mar, Dept Marine Biol & Oceanog, E-08003 Barcelona, Catalonia, Spain.
   [Gadelha, Catarina] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
   [Egan, Martin J.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 University of Exeter; Natural History Museum London; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); University of Cambridge; Harvard University; Harvard Medical School
RP Richards, TA (corresponding author), Univ Exeter, Sch Biosci, Exeter EX4 4QD, Devon, England.
EM thomr@nhm.ac.uk
FU Leverhulme Trust; Natural Environment Research Council, UK [NE/F011709/1]; Systematics Association; Linnean Society; MICINN [CGL2010-16304]; ERA; NERC [NE/F011709/1] Funding Source: UKRI; Natural Environment Research Council [NE/F011709/1] Funding Source: researchfish
NR 36
TC 312
Z9 366
U1 5
U2 195
PU 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 9
PY 2011
VL 474
IS 7350
BP 200
EP U234
DI 10.1038/nature09984
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800047
PM 21562490
DA 2026-03-09
ER

PT J
AU Isbell, F
   Calcagno, V
   Hector, A
   Connolly, J
   Harpole, WS
   Reich, PB
   Scherer-Lorenzen, M
   Schmid, B
   Tilman, D
   van Ruijven, J
   Weigelt, A
   Wilsey, BJ
   Zavaleta, ES
   Loreau, M
AF Isbell, Forest
   Calcagno, Vincent
   Hector, Andy
   Connolly, John
   Harpole, W. Stanley
   Reich, Peter B.
   Scherer-Lorenzen, Michael
   Schmid, Bernhard
   Tilman, David
   van Ruijven, Jasper
   Weigelt, Alexandra
   Wilsey, Brian J.
   Zavaleta, Erika S.
   Loreau, Michel
TI High plant diversity is needed to maintain ecosystem services
SO NATURE
LA English
DT Article
ID grassland experiment; biomass production; current knowledge; elevated co2; biodiversity; productivity; community; ecology; insurance; stability
AB Biodiversity is rapidly declining worldwide(1), and there is consensus that this can decrease ecosystem functioning and services(2-7). It remains unclear, though, whether few(8) or many(9) of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered(9); however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years(10-14), places(15,16), functions(14,17,18) or environmental change scenarios(12,19-22). Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions(7), many species are needed to maintain multiple functions at multiple times and places in a changing world.
C1 [Isbell, Forest; Calcagno, Vincent; Loreau, Michel] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
   [Hector, Andy; Schmid, Bernhard] Univ Zurich, Inst Evolutionary Biol & Environm Studies, CH-8057 Zurich, Switzerland.
   [Connolly, John] Univ Coll Dublin, UCD Sch Math Sci, Dublin 4, Ireland.
   [Harpole, W. Stanley; Wilsey, Brian J.] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
   [Reich, Peter B.] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Reich, Peter B.] Univ Western Sydney, Hawkesbury Inst Environm, Richmond, NSW 2753, Australia.
   [Scherer-Lorenzen, Michael] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany.
   [Tilman, David] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
   [van Ruijven, Jasper] Wageningen Univ, NL-6700 AA Wageningen, Netherlands.
   [Weigelt, Alexandra] Univ Leipzig, Inst Biol 1, D-04103 Leipzig, Germany.
   [Zavaleta, Erika S.] Univ Calif Santa Cruz, Dept Environm Studies, Santa Cruz, CA 95064 USA.
C3 McGill University; University of Zurich; University College Dublin; Iowa State University; University of Minnesota System; University of Minnesota Twin Cities; Western Sydney University; University of Freiburg; University of Minnesota System; University of Minnesota Twin Cities; Wageningen University & Research; Leipzig University; University of California System; University of California Santa Cruz
RP Isbell, F (corresponding author), McGill Univ, Dept Biol, 1205 Doctor Penfield Ave, Montreal, PQ H3A 1B1, Canada.
EM forest.isbell@gmail.com
FU Swiss SystemsX.ch initiative [IPP-2008/23]; European Commission [ENV-CT95-0008]; Swiss Federal Office for Education and Science [EU-1311]; Deutsche Forschungsgemeinschaft (DFG) [FOR 456]; Friedrich Schiller University of Jena; Max Planck Society; University of Zurich; Swiss National Science Foundation [3100AO-107531]; ETH Zurich; Dutch Organisation for Scientific Research (NWO); EU Commission [852]; Science Foundation Ireland [09/RFP/EOB2546]; US Department of Energy [DOE/DE-FG02-96ER62291]; US National Science Foundation [0322057, LTER DEB 9411972, DEB 0080382, DEB 0620652, LTREB DEB 0716587, DEB 0639417]; Natural Sciences and Engineering Research Council of Canada; Canada Research Chair program; Science Foundation Ireland (SFI) [09/RFP/EOB2546] Funding Source: Science Foundation Ireland (SFI)
NR 34
TC 1228
Z9 1472
U1 37
U2 1834
PU 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 8
PY 2011
VL 477
IS 7363
BP 199
EP U96
DI 10.1038/nature10282
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 816MC
UT WOS:000294603900033
PM 21832994
DA 2026-03-09
ER

