PT J
AU Chang, TC
   Pen, UL
   Bandura, K
   Peterson, JB
AF Chang, Tzu-Ching
   Pen, Ue-Li
   Bandura, Kevin
   Peterson, Jeffrey B.
TI An intensity map of hydrogen 21-cm emission at redshift z ≈ 0.8
SO NATURE
LA English
DT Article
ID galaxy
AB Observations of 21-cm radio emission by neutral hydrogen at redshifts z approximate to 0.5 to similar to 2.5 are expected to provide a sensitive probe of cosmic dark energy(1,2). This is particularly true around the onset of acceleration at z approximate to 1, where traditional optical cosmology becomes very difficult because of the infrared opacity of the atmosphere. Hitherto, 21-cm emission has been detected(3) only to z = 0.24. More distant galaxies generally are too faint for individual detections but it is possible to measure the aggregate emission from many unresolved galaxies in the 'cosmic web'. Here we report a three-dimensional 21-cm intensity field at z=0.53 to 1.12. We then co-add neutral-hydrogen (H I) emission from the volumes surrounding about 10,000 galaxies (from the DEEP2 optical galaxy redshift survey(4)). We detect the aggregate 21-cm glow at a significance of 4s.
C1 [Chang, Tzu-Ching] Acad Sinica, IAA, Taipei 10617, Taiwan.
   [Chang, Tzu-Ching; Pen, Ue-Li] Univ Toronto, CITA, Toronto, ON M5S 3H8, Canada.
   [Bandura, Kevin; Peterson, Jeffrey B.] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
C3 Academia Sinica - Taiwan; University of Toronto; Carnegie Mellon University
RP Chang, TC (corresponding author), Acad Sinica, IAA, POB 23-141, Taipei 10617, Taiwan.
EM tchang@cita.utoronto.ca
FU NSERC; NSF; NRAO
NR 12
TC 332
Z9 386
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 JUL 22
PY 2010
VL 466
IS 7305
BP 463
EP 465
DI 10.1038/nature09187
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200029
PM 20651685
DA 2026-03-09
ER

PT J
AU Sigmund, K
   De Silva, H
   Traulsen, A
   Hauert, C
AF Sigmund, Karl
   De Silva, Hannelore
   Traulsen, Arne
   Hauert, Christoph
TI Social learning promotes institutions for governing the commons
SO NATURE
LA English
DT Article
ID public-goods games; altruistic punishment; costly punishment; cooperation; evolution; reciprocity; advantage; society; humans
AB Theoretical and empirical research highlights the role of punishment in promoting collaborative efforts(1-5). However, both the emergence and the stability of costly punishment are problematic issues. It is not clear how punishers can invade a society of defectors by social learning or natural selection, or how second-order free-riders (who contribute to the joint effort but not to the sanctions) can be prevented from drifting into a coercion-based regime and subverting cooperation. Here we compare the prevailing model of peer-punishment(6-8) with pool-punishment, which consists in committing resources, before the collaborative effort, to prepare sanctions against free-riders. Pool-punishment facilitates the sanctioning of second-order free-riders, because these are exposed even if everyone contributes to the common good. In the absence of such second-order punishment, peer-punishers do better than pool-punishers; but with second-order punishment, the situation is reversed. Efficiency is traded for stability. Neither other-regarding tendencies or preferences for reciprocity and equity, nor group selection or prescriptions from higher authorities, are necessary for the emergence and stability of rudimentary forms of sanctioning institutions regulating common pool resources and enforcing collaborative efforts.
C1 [Sigmund, Karl] Univ Vienna, Fac Math, A-1090 Vienna, Austria.
   [Sigmund, Karl] Int Inst Appl Syst Anal, A-2361 Laxenburg, Austria.
   [De Silva, Hannelore] WU Vienna Univ Econ & Business, A-1090 Vienna, Austria.
   [Traulsen, Arne] Max Planck Inst Evolutionary Biol, D-24306 Plon, Germany.
   [Hauert, Christoph] Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada.
C3 University of Vienna; International Institute for Applied Systems Analysis (IIASA); Vienna University of Economics & Business; Max Planck Society; University of British Columbia
RP Sigmund, K (corresponding author), Univ Vienna, Fac Math, Waehringer Guertel 18, A-1090 Vienna, Austria.
EM karl.sigmund@univie.ac.at
NR 30
TC 454
Z9 491
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 AUG 12
PY 2010
VL 466
IS 7308
BP 861
EP 863
DI 10.1038/nature09203
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100035
PM 20631710
DA 2026-03-09
ER

PT J
AU Eichberger, M
   Schäfer, H
   Krumova, M
   Beyer, M
   Demsar, J
   Berger, H
   Moriena, G
   Sciaini, G
   Miller, RJD
AF Eichberger, Maximilian
   Schaefer, Hanjo
   Krumova, Marina
   Beyer, Markus
   Demsar, Jure
   Berger, Helmuth
   Moriena, Gustavo
   Sciaini, German
   Miller, R. J. Dwayne
TI Snapshots of cooperative atomic motions in the optical suppression of charge density waves
SO NATURE
LA English
DT Article
ID 1t tas2; 1t-tas2; diffraction; electron; bismuth
AB Macroscopic quantum phenomena such as high-temperature superconductivity, colossal magnetoresistance, ferrimagnetism and ferromagnetism arise from a delicate balance of different interactions among electrons, phonons and spins on the nanoscale(1). The study of the interplay among these various degrees of freedom in strongly coupled electron-lattice systems is thus crucial to their understanding and for optimizing their properties. Charge-density-wave (CDW) materials(2), with their inherent modulation of the electron density and associated periodic lattice distortion, represent ideal model systems for the study of such highly cooperative phenomena. With femtosecond time-resolved techniques, it is possible to observe these interactions directly by abruptly perturbing the electronic distribution while keeping track of energy relaxation pathways and coupling strengths among the different subsystems(3-7). Numerous time-resolved experiments have been performed on CDWs(8-13), probing the dynamics of the electronic subsystem. However, the dynamics of the periodic lattice distortion have been only indirectly inferred(14). Here we provide direct atomic-level information on the structural dynamics by using femtosecond electron diffraction(15) to study the quasi two-dimensional CDW system 1T-TaS2. Effectively, we have directly observed the atomic motions that result from the optically induced change in the electronic spatial distribution. The periodic lattice distortion, which has an amplitude of similar to 0.1 angstrom, is suppressed by about 20% on a timescale (similar to 250 femtoseconds) comparable to half the period of the corresponding collective mode. These highly cooperative, electronically driven atomic motions are accompanied by a rapid electron-phonon energy transfer (similar to 350 femtoseconds) and are followed by fast recovery of the CDW (similar to 4 picoseconds). The degree of cooperativity in the observed structural dynamics is remarkable and illustrates the importance of obtaining atomic-level perspectives of the processes directing the physics of strongly correlated systems.
C1 [Moriena, Gustavo; Sciaini, German; Miller, R. J. Dwayne] Univ Toronto, Inst Opt Sci, Toronto, ON M5S 3H6, Canada.
   [Moriena, Gustavo; Sciaini, German; Miller, R. J. Dwayne] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada.
   [Moriena, Gustavo; Sciaini, German; Miller, R. J. Dwayne] Univ Toronto, Dept Phys, Toronto, ON M5S 3H6, Canada.
   [Eichberger, Maximilian; Schaefer, Hanjo; Beyer, Markus; Demsar, Jure] Univ Konstanz, Dept Phys, D-78457 Constance, Germany.
   Univ Konstanz, Ctr Appl Photon, D-78457 Constance, Germany.
   [Eichberger, Maximilian; Schaefer, Hanjo; Beyer, Markus; Demsar, Jure] Univ Konstanz, Zukunftskolleg, D-78457 Constance, Germany.
   [Krumova, Marina] Univ Konstanz, Dept Chem, D-78457 Constance, Germany.
   [Demsar, Jure] Jozef Stefan Inst, Complex Matter Dept, SI-1000 Ljubljana, Slovenia.
   [Berger, Helmuth] Ecole Polytech Fed Lausanne, Dept Phys, CH-1015 Lausanne, Switzerland.
   [Moriena, Gustavo; Sciaini, German; Miller, R. J. Dwayne] Univ Hamburg, Dept Phys, Max Planck Res Dept Struct Dynam, Ctr Free Electron Laser Sci,DESY, D-22607 Hamburg, Germany.
C3 University of Toronto; University of Toronto; University of Toronto; University of Konstanz; University of Konstanz; University of Konstanz; University of Konstanz; Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Hamburg; Max Planck Society; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY)
RP Miller, RJD (corresponding author), Univ Toronto, Inst Opt Sci, Toronto, ON M5S 3H6, Canada.
EM jure.demsar@uni-konstanz.de; dmiller@lphys.chem.utoronto.ca
FU Alexander von Humboldt Foundation; Center for Applied Photonics and Zukunftskolleg at the University of Konstanz; Natural Science and Engineering Research Council of Canada; Canada Foundation for Innovation; Stiftung der Deutschen Wirtschaft; Swiss NSF; NCCR MaNEP
NR 30
TC 379
Z9 428
U1 2
U2 297
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 799
EP 802
DI 10.1038/nature09539
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700040
PM 21107321
DA 2026-03-09
ER

PT J
AU Langley, JA
   Megonigal, JP
AF Langley, J. Adam
   Megonigal, J. Patrick
TI Ecosystem response to elevated CO2 levels limited by nitrogen-induced plant species shift
SO NATURE
LA English
DT Article
ID soil nutrient; climate; competition; limitation; feedbacks; diversity
AB Terrestrial ecosystems gain carbon through photosynthesis and lose it mostly in the form of carbon dioxide (CO2). The extent to which the biosphere can act as a buffer against rising atmospheric CO2 concentration in global climate change projections remains uncertain at the present stage(1-4). Biogeochemical theory predicts that soil nitrogen (N) scarcity may limit natural ecosystem response to elevated CO2 concentration, diminishing the CO2-fertilization effect on terrestrial plant productivity in unmanaged ecosystems(3-7). Recent models have incorporated such carbon-nitrogen interactions and suggest that anthropogenic N sources could help sustain the future CO2-fertilization effect(8,9). However, conclusive demonstration that added N enhances plant productivity in response to CO2-fertilization in natural ecosystems remains elusive. Here we manipulated atmospheric CO2 concentration and soil N availability in a herbaceous brackish wetland where plant community composition is dominated by a C-3 sedge and C-4 grasses, and is capable of responding rapidly to environmental change(10). We found that N addition enhanced the CO2-stimulation of plant productivity in the first year of a multi-year experiment, indicating N-limitation of the CO2 response. But we also found that N addition strongly promotes the encroachment of C-4 plant species that respond less strongly to elevated CO2 concentrations. Overall, we found that the observed shift in the plant community composition ultimately suppresses the CO2-stimulation of plant productivity by the third and fourth years. Although extensive research has shown that global change factors such as elevated CO2 concentrations and N pollution affect plant species differently(11-13), and that they may drive plant community changes(14-17), we demonstrate that plant community shifts can act as a feedback effect that alters the whole ecosystem response to elevated CO2 concentrations. Moreover, we suggest that trade-offs between the abilities of plant taxa to respond positively to different perturbations may constrain natural ecosystem response to global change.
C1 [Langley, J. Adam; Megonigal, J. Patrick] Smithsonian Environm Res Ctr, Edgewater, MD 21037 USA.
   [Langley, J. Adam] Villanova Univ, Dept Biol, Villanova, PA 19084 USA.
C3 Smithsonian Institution; Smithsonian Environmental Research Center; Villanova University
RP Langley, JA (corresponding author), Smithsonian Environm Res Ctr, POB 28, Edgewater, MD 21037 USA.
EM langleya@si.edu
FU USGS [06ERAG0011]; US Department of Energy [DE-FG02-97ER62458]; US Department of Energy's Office of Science (BER) through the Coastal Center of the National Institute of Climate Change Research at Tulane University; Smithsonian Institution; Direct For Biological Sciences; Division Of Environmental Biology [0950080] Funding Source: National Science Foundation
NR 30
TC 199
Z9 240
U1 5
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 JUL 1
PY 2010
VL 466
IS 7302
BP 96
EP 99
DI 10.1038/nature09176
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800041
PM 20596018
DA 2026-03-09
ER

PT J
AU Domazet-Loso, T
   Tautz, D
AF Domazet-Loso, Tomislav
   Tautz, Diethard
TI A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns
SO NATURE
LA English
DT Article
ID conserved embryonic stage; phylotypic stage; gene-expression; developmental hourglass; zebrafish development; life-cycle; evolution; history; search
AB Parallels between phylogeny and ontogeny have been discussed for almost two centuries, and a number of theories have been proposed to explain such patterns(1). Especially elusive is the phylotypic stage, a phase during development where species within a phylum are particularly similar to each other(2-6). Although this has formerly been interpreted as a recapitulation of phylogeny(1), it is now thought to reflect an ontogenetic progression phase(2), where strong constraints on developmental regulation and gene interactions exist(2,3). Several studies have shown that genes expressed during this stage evolve at a slower rate, but it has so far not been possible to derive an unequivocal molecular signature associated with this stage(7-15). Here we use a combination of phylostratigraphy(16) and stage-specific gene expression data to generate a cumulative index that reflects the evolutionary age of the transcriptome at given ontogenetic stages. Using zebrafish ontogeny and adult development as a model, we find that the phylotypic stage does indeed express the oldest transcriptome set and that younger sets are expressed during early and late development, thus faithfully mirroring the hourglass model of morphological divergence(2,3). Reproductively active animals show the youngest transcriptome, with major differences between males and females. Notably, ageing animals express increasingly older genes. Comparisons with similar data sets from flies and nematodes show that this pattern occurs across phyla. Our results indicate that an old transcriptome marks the phylotypic phase and that phylogenetic differences at other ontogenetic stages correlate with the expression of newly evolved genes.
C1 [Domazet-Loso, Tomislav; Tautz, Diethard] Max Planck Inst Evolut Biol, D-24306 Plon, Germany.
   [Domazet-Loso, Tomislav] Rudjer Boskovic Inst, Div Mol Biol, Lab Evolutionary Genet, Zagreb 10002, Croatia.
C3 Max Planck Society; Rudjer Boskovic Institute
RP Domazet-Loso, T (corresponding author), Max Planck Inst Evolut Biol, August Thienemannstr 2, D-24306 Plon, Germany.
EM tdomazet@irb.hr
FU Adris Foundation [49]; Max-Planck Society
NR 32
TC 315
Z9 360
U1 2
U2 92
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 815
EP U107
DI 10.1038/nature09632
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700044
PM 21150997
DA 2026-03-09
ER

PT J
AU Gamo, FJ
   Sanz, LM
   Vidal, J
   de Cozar, C
   Alvarez, E
   Lavandera, JL
   Vanderwall, DE
   Green, DVS
   Kumar, V
   Hasan, S
   Brown, JR
   Peishoff, CE
   Cardon, LR
   Garcia-Bustos, JF
AF Gamo, Francisco-Javier
   Sanz, Laura M.
   Vidal, Jaume
   de Cozar, Cristina
   Alvarez, Emilio
   Lavandera, Jose-Luis
   Vanderwall, Dana E.
   Green, Darren V. S.
   Kumar, Vinod
   Hasan, Samiul
   Brown, James R.
   Peishoff, Catherine E.
   Cardon, Lon R.
   Garcia-Bustos, Jose F.
TI Thousands of chemical starting points for antimalarial lead identification
SO NATURE
LA English
DT Article
ID plasmodium-falciparum; malaria; drugs; sensitivity; discovery; efficacy; kinome; genome
AB Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 mu M concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host-pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease.
C1 [Gamo, Francisco-Javier; Sanz, Laura M.; Vidal, Jaume; de Cozar, Cristina; Alvarez, Emilio; Lavandera, Jose-Luis; Garcia-Bustos, Jose F.] GlaxoSmithKline, Tres Cantos 28760, Spain.
   [Vanderwall, Dana E.] GlaxoSmithKline, Computat & Struct Chem, Res Triangle Pk, NC 27709 USA.
   [Green, Darren V. S.] GlaxoSmithKline, Computat & Struct Chem, Med Res Ctr, Stevenage SG1 2NY, Herts, England.
   [Kumar, Vinod; Hasan, Samiul; Brown, James R.] GlaxoSmithKline, Quantitat Sci, Computat Biol, Collegeville, PA 19426 USA.
   [Peishoff, Catherine E.] GlaxoSmithKline, Computat & Struct Chem, Collegeville, PA 19426 USA.
   [Cardon, Lon R.] GlaxoSmithKline, Quantitat Sci, King Of Prussia, PA 19406 USA.
C3 GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Glaxosmithkline USA
RP Garcia-Bustos, JF (corresponding author), GlaxoSmithKline, Cantos Med Dev Campus,Severo Ochoa 2, Tres Cantos 28760, Spain.
EM jose.f.garcia-bustos@gsk.com
FU Medicines for Malaria Venture
NR 39
TC 823
Z9 949
U1 2
U2 165
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 305
EP U56
DI 10.1038/nature09107
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200031
PM 20485427
DA 2026-03-09
ER

PT J
AU Raaijmakers, MHGP
   Mukherjee, S
   Guo, SQ
   Zhang, SY
   Kobayashi, T
   Schoonmaker, JA
   Ebert, BL
   Al-Shahrour, F
   Hasserjian, RP
   Scadden, EO
   Aung, Z
   Matza, M
   Merkenschlager, M
   Lin, C
   Rommens, JM
   Scadden, DT
AF Raaijmakers, Marc H. G. P.
   Mukherjee, Siddhartha
   Guo, Shangqin
   Zhang, Siyi
   Kobayashi, Tatsuya
   Schoonmaker, Jesse A.
   Ebert, Benjamin L.
   Al-Shahrour, Fatima
   Hasserjian, Robert P.
   Scadden, Edward O.
   Aung, Zinmar
   Matza, Marc
   Merkenschlager, Matthias
   Lin, Charles
   Rommens, Johanna M.
   Scadden, David. T.
TI Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
SO NATURE
LA English
DT Article
ID stem-cell niche; hematopoietic progenitors; differentiation; microenvironment; identification; expression; hedgehog; sbds
AB Mesenchymal cells contribute to the 'stroma' of most normal and malignant tissues, with specific mesenchymal cells participating in the regulatory niches of stem cells. By examining how mesenchymal osteolineage cells modulate haematopoiesis, here we show that deletion of Dicer1 specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of haematopoiesis. Myelodysplasia resulted and acute myelogenous leukaemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Schwachman-Bodian-Diamond syndrome-a human bone marrow failure and leukaemia pre-disposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis.
C1 [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Sch Med, CPZN, Boston, MA 02114 USA.
   [Mukherjee, Siddhartha; Scadden, David. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Kobayashi, Tatsuya] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Lin, Charles] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
   [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Raaijmakers, Marc H. G. P.; Mukherjee, Siddhartha; Guo, Shangqin; Zhang, Siyi; Schoonmaker, Jesse A.; Scadden, Edward O.; Aung, Zinmar; Matza, Marc; Scadden, David. T.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA.
   [Ebert, Benjamin L.; Al-Shahrour, Fatima] Broad Inst, Cambridge, MA 02138 USA.
   [Ebert, Benjamin L.; Al-Shahrour, Fatima] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02115 USA.
   [Merkenschlager, Matthias] Univ London Imperial Coll Sci Technol & Med, Ctr Clin Sci, MRC, Lymphocyte Dev Grp, London W12 0NN, England.
   [Rommens, Johanna M.] Univ Toronto, Program Genet & Genome Biol, Hosp Sick Children, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Imperial College London; University of Toronto; Hospital for Sick Children (SickKids)
RP Raaijmakers, MHGP (corresponding author), Massachusetts Gen Hosp, Ctr Regenerat Med, Room 4265A,185 Cambridge St, Boston, MA 02114 USA.
EM hraaijmakers@partners.org; dscadden@mgh.harvard.edu
FU Dutch Cancer Society; Leukemia & Lymphoma Society; National Institutes of Health; Harvard Stem Cell Institute; Ellison Medical Foundation; Medical Research Council [MC_U120027516] Funding Source: researchfish; MRC [MC_U120027516] Funding Source: UKRI
NR 39
TC 868
Z9 993
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 APR 8
PY 2010
VL 464
IS 7290
BP 852
EP U58
DI 10.1038/nature08851
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300029
PM 20305640
DA 2026-03-09
ER

PT J
AU Verbeeck, J
   Tian, H
   Schattschneider, P
AF Verbeeck, J.
   Tian, H.
   Schattschneider, P.
TI Production and application of electron vortex beams
SO NATURE
LA English
DT Article
ID angular-momentum; laser-beams; dislocations; dichroism; light
AB Vortex beams (also known as beams with a phase singularity) consist of spiralling wavefronts that give rise to angular momentum around the propagation direction. Vortex photon beams are widely used in applications such as optical tweezers to manipulate micrometre-sized particles and in micro-motors to provide angular momentum(1,2), improving channel capacity in optical(3) and radio-wave(4) information transfer, astrophysics(5) and so on(6). Very recently, an experimental realization of vortex beams formed of electrons was demonstrated(7). Here we describe the creation of vortex electron beams, making use of a versatile holographic reconstruction technique in a transmission electron microscope. This technique is a reproducible method of creating vortex electron beams in a conventional electron microscope. We demonstrate how they may be used in electron energy-loss spectroscopy to detect the magnetic state of materials and describe their properties. Our results show that electron vortex beams hold promise for new applications, in particular for analysing and manipulating nanomaterials, and can be easily produced.
C1 [Verbeeck, J.; Tian, H.] Univ Antwerp, B-2020 Antwerp, Belgium.
   [Schattschneider, P.] Vienna Univ Technol, Inst Solid State Phys, A-1040 Vienna, Austria.
   [Schattschneider, P.] Vienna Univ Technol, Univ Serv Ctr Electron Microscopy, A-1040 Vienna, Austria.
C3 University of Antwerp; Technische Universitat Wien; Technische Universitat Wien
RP Verbeeck, J (corresponding author), Univ Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
EM jo.verbeeck@ua.ac.be
FU European Union [026019]; FWO-Vlaanderen [G.0147.06]
NR 20
TC 728
Z9 822
U1 3
U2 561
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 301
EP 304
DI 10.1038/nature09366
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900033
PM 20844532
DA 2026-03-09
ER

PT J
AU Carlsbecker, A
   Lee, JY
   Roberts, CJ
   Dettmer, J
   Lehesranta, S
   Zhou, J
   Lindgren, O
   Moreno-Risueno, MA
   Vatén, A
   Thitamadee, S
   Campilho, A
   Sebastian, J
   Bowman, JL
   Helariutta, Y
   Benfey, PN
AF Carlsbecker, Annelie
   Lee, Ji-Young
   Roberts, Christina J.
   Dettmer, Jan
   Lehesranta, Satu
   Zhou, Jing
   Lindgren, Ove
   Moreno-Risueno, Miguel A.
   Vaten, Anne
   Thitamadee, Siripong
   Campilho, Ana
   Sebastian, Jose
   Bowman, John L.
   Helariutta, Yka
   Benfey, Philip N.
TI Cell signalling by microRNA165/6 directs gene dose-dependent root cell fate
SO NATURE
LA English
DT Article
ID binding-protein hyl1; class iiihd-zip; arabidopsis root; transcription factor; intercellular movement; vascular development; apical meristem; kanadi genes; expression; plants
AB A key question in developmental biology is how cells exchange positional information for proper patterning during organ development. In plant roots the radial tissue organization is highly conserved with a central vascular cylinder in which two water conducting cell types, protoxylem and metaxylem, are patterned centripetally. We show that this patterning occurs through crosstalk between the vascular cylinder and the surrounding endodermis mediated by cell-to-cell movement of a transcription factor in one direction and microRNAs in the other. SHORT ROOT, produced in the vascular cylinder, moves into the endodermis to activate SCARECROW. Together these transcription factors activate MIR165a and MIR166b. Endodermally produced microRNA165/6 then acts to degrade its target mRNAs encoding class III homeodomain-leucine zipper transcription factors in the endodermis and stele periphery. The resulting differential distribution of target mRNA in the vascular cylinder determines xylem cell types in a dosage-dependent manner.
C1 [Carlsbecker, Annelie; Dettmer, Jan; Lehesranta, Satu; Lindgren, Ove; Vaten, Anne; Thitamadee, Siripong; Campilho, Ana; Helariutta, Yka] Univ Helsinki, Inst Biotechnol, Dept Biosci, FIN-00014 Helsinki, Finland.
   [Carlsbecker, Annelie; Roberts, Christina J.] Uppsala Univ, Evolutionary Biol Ctr, Dept Physiol Bot, SE-75236 Uppsala, Sweden.
   [Lee, Ji-Young; Zhou, Jing; Sebastian, Jose] Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA.
   [Lee, Ji-Young; Zhou, Jing] Cornell Univ, Grad Field Plant Biol, Ithaca, NY 14853 USA.
   [Lindgren, Ove] Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia.
   [Moreno-Risueno, Miguel A.; Benfey, Philip N.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Moreno-Risueno, Miguel A.; Benfey, Philip N.] Duke Univ, IGSP Ctr Syst Biol, Durham, NC 27708 USA.
   [Bowman, John L.] Monash Univ, Sch Biol Sci, Melbourne, Vic 3800, Australia.
C3 University of Helsinki; Uppsala University; Cornell University; Boyce Thompson Institute for Plant Research; Cornell University; University of Tartu; Duke University; Duke University; Monash University
RP Helariutta, Y (corresponding author), Univ Helsinki, Inst Biotechnol, Dept Biosci, FIN-00014 Helsinki, Finland.
EM yrjo.helariutta@helsinki.fi; philip.benfey@duke.edu
FU Boyce Thompson Institute; NSF [IOS0818071, NSF DBI-0618969]; Cornell Presidential Life Science Fellowship; NIH [RO1-GM043778]; MICINN, Spanish Government; Academy of Finland; Tekes; ESF; European Molecular Biology Organisation (EMBO) [ALTF 450-2007]; Estonian funding agencies [ETF7361, SF0180071s07]; Nilsson-Ehle Foundation; FORMAS; Carl Trygger's Foundation for Scientific Research; Triad Foundation; Division Of Integrative Organismal Sys; Direct For Biological Sciences [0818071] Funding Source: National Science Foundation
NR 40
TC 689
Z9 799
U1 1
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 MAY 20
PY 2010
VL 465
IS 7296
BP 316
EP 321
DI 10.1038/nature08977
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200033
PM 20410882
DA 2026-03-09
ER

PT J
AU Poliseno, L
   Salmena, L
   Zhang, JW
   Carver, B
   Haveman, WJ
   Pandolfi, PP
AF Poliseno, Laura
   Salmena, Leonardo
   Zhang, Jiangwen
   Carver, Brett
   Haveman, William J.
   Pandolfi, Pier Paolo
TI A coding-independent function of gene and pseudogene mRNAs regulates tumour biology
SO NATURE
LA English
DT Article
ID human genome; micrornas; expression; cancer; transformation; autoimmunity; recognition; signature; reveals; targets
AB The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
C1 [Poliseno, Laura; Salmena, Leonardo; Haveman, William J.; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA.
   [Poliseno, Laura; Salmena, Leonardo; Haveman, William J.; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Pathol, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA.
   [Zhang, Jiangwen] Harvard Univ, FAS Res Comp, Cambridge, MA 02138 USA.
   [Zhang, Jiangwen] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Carver, Brett] Mem Sloan Kettering Canc Ctr, Dept Surg, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University; Memorial Sloan Kettering Cancer Center
RP Pandolfi, PP (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA.
EM ppandolf@bidmc.harvard.edu
FU Istituto Toscano Tumori; American Italian Cancer Foundation; Human Frontier Science Program; Canadian Institutes of Health Research; NIH [R01 CA-82328-09]
NR 52
TC 1959
Z9 2282
U1 0
U2 215
PU NATURE PUBLISHING 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 24
PY 2010
VL 465
IS 7301
BP 1033
EP U90
DI 10.1038/nature09144
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900043
PM 20577206
DA 2026-03-09
ER

PT J
AU Ettwig, KF
   Butler, MK
   Le Paslier, D
   Pelletier, E
   Mangenot, S
   Kuypers, MMM
   Schreiber, F
   Dutilh, BE
   Zedelius, J
   de Beer, D
   Gloerich, J
   Wessels, HJCT
   van Alen, T
   Luesken, F
   Wu, ML
   van de Pas-Schoonen, KT
   den Camp, HJMO
   Janssen-Megens, EM
   Francoijs, KJ
   Stunnenberg, H
   Weissenbach, J
   Jetten, MSM
   Strous, M
AF Ettwig, Katharina F.
   Butler, Margaret K.
   Le Paslier, Denis
   Pelletier, Eric
   Mangenot, Sophie
   Kuypers, Marcel M. M.
   Schreiber, Frank
   Dutilh, Bas E.
   Zedelius, Johannes
   de Beer, Dirk
   Gloerich, Jolein
   Wessels, Hans J. C. T.
   van Alen, Theo
   Luesken, Francisca
   Wu, Ming L.
   van de Pas-Schoonen, Katinka T.
   den Camp, Huub J. M. Op
   Janssen-Megens, Eva M.
   Francoijs, Kees-Jan
   Stunnenberg, Henk
   Weissenbach, Jean
   Jetten, Mike S. M.
   Strous, Marc
TI Nitrite-driven anaerobic methane oxidation by oxygenic bacteria
SO NATURE
LA English
DT Article
ID chlorite dismutase; nitrous-oxide; genome; microsensor; transformation; monooxygenase; enrichment; atmosphere; soils; n2o
AB Only three biological pathways are known to produce oxygen: photosynthesis, chlorate respiration and the detoxification of reactive oxygen species. Here we present evidence for a fourth pathway, possibly of considerable geochemical and evolutionary importance. The pathway was discovered after metagenomic sequencing of an enrichment culture that couples anaerobic oxidation of methane with the reduction of nitrite to dinitrogen. The complete genome of the dominant bacterium, named 'Candidatus Methylomirabilis oxyfera', was assembled. This apparently anaerobic, denitrifying bacterium encoded, transcribed and expressed the well-established aerobic pathway for methane oxidation, whereas it lacked known genes for dinitrogen production. Subsequent isotopic labelling indicated that 'M. oxyfera' bypassed the denitrification intermediate nitrous oxide by the conversion of two nitric oxidemolecules to dinitrogen and oxygen, which was used to oxidize methane. These results extend our understanding of hydrocarbon degradation under anoxic conditions and explain the biochemical mechanism of a poorly understood freshwater methane sink. Because nitrogen oxides were already present on early Earth, our finding opens up the possibility that oxygen was available to microbial metabolism before the evolution of oxygenic photosynthesis.
C1 [Ettwig, Katharina F.; Butler, Margaret K.; van Alen, Theo; Luesken, Francisca; Wu, Ming L.; van de Pas-Schoonen, Katinka T.; den Camp, Huub J. M. Op; Jetten, Mike S. M.; Strous, Marc] Radboud Univ Nijmegen, IWWR, Dept Microbiol, NL-6525 AJ Nijmegen, Netherlands.
   [Le Paslier, Denis; Pelletier, Eric; Mangenot, Sophie; Weissenbach, Jean] CEA Genoscope, F-91057 Evry, France.
   [Le Paslier, Denis; Pelletier, Eric; Weissenbach, Jean] CNRS, UMR 8030, F-91057 Evry, France.
   [Le Paslier, Denis; Pelletier, Eric; Weissenbach, Jean] Univ Evry Val Essonne, F-91057 Evry, France.
   [Kuypers, Marcel M. M.; Schreiber, Frank; Zedelius, Johannes; de Beer, Dirk; Strous, Marc] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
   [Dutilh, Bas E.] Radboud Univ Nijmegen, Med Ctr, Ctr Mol & Biomol Informat, Nijmegen Ctr Mol Life Sci, NL-6525 GA Nijmegen, Netherlands.
   [Gloerich, Jolein; Wessels, Hans J. C. T.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Prote Facil, Dept Lab Med,Lab Genet Endocrine & Metab Dis, NL-6525 GA Nijmegen, Netherlands.
   [Janssen-Megens, Eva M.; Francoijs, Kees-Jan; Stunnenberg, Henk] Radboud Univ Nijmegen, Dept Mol Biol, Nijmegen Ctr Mol Life Sci, NL-6525 GA Nijmegen, Netherlands.
   [Strous, Marc] Univ Bielefeld, Ctr Biotechnol, D-33501 Bielefeld, Germany.
C3 Radboud University Nijmegen; CEA; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); Universite Paris Saclay; Max Planck Society; Radboud University Nijmegen; Radboud University Nijmegen; Radboud University Nijmegen; University of Bielefeld
RP Ettwig, KF (corresponding author), Radboud Univ Nijmegen, IWWR, Dept Microbiol, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.
EM k.ettwig@science.ru.nl; mstrous@mpi-bremen.de
FU Max Planck Society; European Research Council [232937]; Netherlands Organisation for Scientific Research (NWO) [050-71-058]
NR 51
TC 1459
Z9 1755
U1 40
U2 1524
PU NATURE PUBLISHING 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 25
PY 2010
VL 464
IS 7288
BP 543
EP +
DI 10.1038/nature08883
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200038
PM 20336137
DA 2026-03-09
ER

PT J
AU Nicodeme, E
   Jeffrey, KL
   Schaefer, U
   Beinke, S
   Dewell, S
   Chung, CW
   Chandwani, R
   Marazzi, I
   Wilson, P
   Coste, H
   White, J
   Kirilovsky, J
   Rice, CM
   Lora, JM
   Prinjha, RK
   Lee, K
   Tarakhovsky, A
AF Nicodeme, Edwige
   Jeffrey, Kate L.
   Schaefer, Uwe
   Beinke, Soren
   Dewell, Scott
   Chung, Chun-wa
   Chandwani, Rohit
   Marazzi, Ivan
   Wilson, Paul
   Coste, Herve
   White, Julia
   Kirilovsky, Jorge
   Rice, Charles M.
   Lora, Jose M.
   Prinjha, Rab K.
   Lee, Kevin
   Tarakhovsky, Alexander
TI Suppression of inflammation by a synthetic histone mimic
SO NATURE
LA English
DT Article
ID bromodomain protein brd4; transcriptional elongation; gene-expression; binding modules; p-tefb; chromatin; complexes; machines
AB Interaction of pathogens with cells of the immune system results in activation of inflammatory gene expression. This response, although vital for immune defence, is frequently deleterious to the host due to the exaggerated production of inflammatory proteins. The scope of inflammatory responses reflects the activation state of signalling proteins upstream of inflammatory genes as well as signal-induced assembly of nuclear chromatin complexes that support mRNA expression(1-4). Recognition of post-translationally modified histones by nuclear proteins that initiate mRNA transcription and support mRNA elongation is a critical step in the regulation of gene expression(5-10). Here we present a novel pharmacological approach that targets inflammatory gene expression by interfering with the recognition of acetylated histones by the bromodomain and extra terminal domain (BET) family of proteins. We describe a synthetic compound (I-BET) that by 'mimicking' acetylated histones disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis. Our findings suggest that synthetic compounds specifically targeting proteins that recognize post-translationally modified histones can serve as a new generation of immunomodulatory drugs.
C1 [Jeffrey, Kate L.; Schaefer, Uwe; Chandwani, Rohit; Marazzi, Ivan; Tarakhovsky, Alexander] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10065 USA.
   [Nicodeme, Edwige; Coste, Herve; Kirilovsky, Jorge] Ctr Res GSK, F-91140 Villebon Sur Yvette, France.
   [Beinke, Soren; Lora, Jose M.; Prinjha, Rab K.; Lee, Kevin] GlaxoSmithKline, Med Res Ctr, Epinova DPU, Immunoinflammat Ctr Excellence Drug Discovery, Stevenage SG1 2NY, Herts, England.
   [Dewell, Scott] Rockefeller Univ, Genom Resource Ctr, New York, NY 10065 USA.
   [Chung, Chun-wa; Wilson, Paul; White, Julia] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England.
   [Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.
C3 Rockefeller University; GlaxoSmithKline; GlaxoSmithKline; Glaxosmithkline United Kingdom; Rockefeller University; GlaxoSmithKline; Glaxosmithkline United Kingdom; Rockefeller University
RP Tarakhovsky, A (corresponding author), Rockefeller Univ, Lab Lymphocyte Signaling, 1230 York Ave, New York, NY 10065 USA.
EM Kevin.2.Lee@gsk.com; tarakho@rockefeller.edu
FU NIHKL2 Career Development Award; American Italian Cancer Foundation; National Health and Medical Research Council of Australia
NR 27
TC 1312
Z9 1644
U1 2
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1119
EP 1123
DI 10.1038/nature09589
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800062
PM 21068722
DA 2026-03-09
ER

PT J
AU Haga, S
   Hattori, T
   Sato, T
   Sato, K
   Matsuda, S
   Kobayakawa, R
   Sakano, H
   Yoshihara, Y
   Kikusui, T
   Touhara, K
AF Haga, Sachiko
   Hattori, Tatsuya
   Sato, Toru
   Sato, Koji
   Matsuda, Soichiro
   Kobayakawa, Reiko
   Sakano, Hitoshi
   Yoshihara, Yoshihiro
   Kikusui, Takefumi
   Touhara, Kazushige
TI The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor
SO NATURE
LA English
DT Article
ID genes; organization; expression; nucleus; neurons; convergence; projections; pathways; family; peptide
AB Various social behaviours in mice are regulated by chemical signals called pheromones that act through the vomeronasal system(1-3). Exocrine gland-secreting peptide 1 (ESP1) is a 7-kDa peptide that is released intomale tear fluids and stimulates vomeronasal sensory neurons in female mice(4). Here, we describe the molecular and neural mechanisms that are involved in the decoding of ESP1 signals in the vomeronasal system, which leads to behavioural output in female mice. ESP1 is recognized by a specific vomeronasal receptor, V2Rp5, and the ligand-receptor interaction results in sex-specific signal transmission to the amygdaloid and hypothalamic nuclei via the accessory olfactory bulb. Consequently, ESP1 enhances female sexual receptive behaviour upon male mounting (lordosis), allowing successful copulation. In V2Rp5-deficient mice, ESP1 induces neither neural activation nor sexual behaviour. These findings show that ESP1 is a crucial male pheromone that regulates female reproductive behaviour through a specific receptor in the mouse vomeronasal system.
C1 [Haga, Sachiko; Sato, Toru; Sato, Koji; Matsuda, Soichiro; Touhara, Kazushige] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
   [Hattori, Tatsuya; Kikusui, Takefumi] Azabu Univ, Sch Vet Med, Kanagawa 2298501, Japan.
   [Kobayakawa, Reiko] Osaka Biosci Inst, Dept Funct Neurosci, Suita, Osaka 5650874, Japan.
   [Sakano, Hitoshi] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Tokyo 1130032, Japan.
   [Yoshihara, Yoshihiro] RIKEN, Brain Sci Inst, Lab Neurobiol Synapse, Wako, Saitama 3510198, Japan.
C3 University of Tokyo; Azabu University; University of Tokyo; RIKEN
RP Touhara, K (corresponding author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
EM ktouhara@mail.ecc.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, Japan
NR 35
TC 291
Z9 353
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 JUL 1
PY 2010
VL 466
IS 7302
BP 118
EP U136
DI 10.1038/nature09142
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800046
PM 20596023
DA 2026-03-09
ER

PT J
AU Bax, BD
   Chan, PF
   Eggleston, DS
   Fosberry, A
   Gentry, DR
   Gorrec, F
   Giordano, I
   Hann, MM
   Hennessy, A
   Hibbs, M
   Huang, JZ
   Jones, E
   Jones, J
   Brown, KK
   Lewis, CJ
   May, EW
   Saunders, MR
   Singh, O
   Spitzfaden, CE
   Shen, C
   Shillings, A
   Theobald, AJ
   Wohlkonig, A
   Pearson, ND
   Gwynn, MN
AF Bax, Benjamin D.
   Chan, Pan F.
   Eggleston, Drake S.
   Fosberry, Andrew
   Gentry, Daniel R.
   Gorrec, Fabrice
   Giordano, Ilaria
   Hann, Michael M.
   Hennessy, Alan
   Hibbs, Martin
   Huang, Jianzhong
   Jones, Emma
   Jones, Jo
   Brown, Kristin Koretke
   Lewis, Ceri J.
   May, Earl W.
   Saunders, Martin R.
   Singh, Onkar
   Spitzfaden, Claus E.
   Shen, Carol
   Shillings, Anthony
   Theobald, Andrew J.
   Wohlkonig, Alexandre
   Pearson, Neil D.
   Gwynn, Michael N.
TI Type IIA topoisomerase inhibition by a new class of antibacterial agents
SO NATURE
LA English
DT Article
ID infectious-diseases-society; breakage-reunion domain; dna gyrase; crystal-structure; bad bugs; fusion protein; mechanism; cleavage; ia; drugs
AB Despite the success of genomics in identifying new essential bacterial genes, there is a lack of sustainable leads in antibacterial drug discovery to address increasing multidrug resistance. Type IIA topoisomerases cleave and religate DNA to regulate DNA topology and are a major class of antibacterial and anticancer drug targets, yet there is no well developed structural basis for understanding drug action. Here we report the 2.1 angstrom crystal structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically important drug target. The inhibitor 'bridges' the DNA and a transient non-catalytic pocket on the two-fold axis at the GyrA dimer interface, and is close to the active sites and fluoroquinolone binding sites. In the inhibitor complex the active site seems poised to cleave the DNA, with a single metal ion observed between the TOPRIM (topoisomerase/primase) domain and the scissile phosphate. This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.
C1 [Bax, Benjamin D.; Hann, Michael M.; Saunders, Martin R.; Singh, Onkar; Spitzfaden, Claus E.] GlaxoSmithKline, Med Res Ctr, Mol Discovery Res, Stevenage SG1 2NY, Herts, England.
   [Chan, Pan F.; Gentry, Daniel R.; Huang, Jianzhong; May, Earl W.; Shen, Carol; Pearson, Neil D.; Gwynn, Michael N.] GlaxoSmithKline, Infect Dis Ctr Excellence Drug Discovery, Antibacterial Discovery Performance Unit, Collegeville, PA 19426 USA.
   [Eggleston, Drake S.; Fosberry, Andrew; Gorrec, Fabrice; Hibbs, Martin; Jones, Emma; Jones, Jo; Lewis, Ceri J.; Shillings, Anthony; Theobald, Andrew J.] GlaxoSmithKline, Mol Discovery Res, Harlow CM19 5AW, Essex, England.
   [Giordano, Ilaria; Hennessy, Alan; Wohlkonig, Alexandre] GlaxoSmithKline, Med Res Ctr, Antibacterial Discovery Performance Unit, Stevenage SG1 2NY, Herts, England.
   [Brown, Kristin Koretke] GlaxoSmithKline, Mol Discovery Res, Collegeville, PA 19426 USA.
C3 GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline USA
RP Bax, BD (corresponding author), GlaxoSmithKline, Med Res Ctr, Mol Discovery Res, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
EM benjamin.d.bax@gsk.com; mick.gwynn@gsk.com
FU Wellcome Trust Seeding Drug Discovery Initiative; US Department of Defense (DoD) [HDTRA1-07-9-0002]; Joint Science and Technology Office for Chemical and Biological Defense (JSTO-CBD) [HDTRA1-07-9-0002]; Defense Threat Reduction Agency (DTRA); Transformational Medical Technologies (TMT)
NR 53
TC 724
Z9 797
U1 0
U2 198
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 935
EP U51
DI 10.1038/nature09197
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300026
PM 20686482
DA 2026-03-09
ER

PT J
AU Feldser, DM
   Kostova, KK
   Winslow, MM
   Taylor, SE
   Cashman, C
   Whittaker, CA
   Sanchez-Rivera, FJ
   Resnick, R
   Bronson, R
   Hemann, MT
   Jacks, T
AF Feldser, David M.
   Kostova, Kamena K.
   Winslow, Monte M.
   Taylor, Sarah E.
   Cashman, Chris
   Whittaker, Charles A.
   Sanchez-Rivera, Francisco J.
   Resnick, Rebecca
   Bronson, Roderick
   Hemann, Michael T.
   Jacks, Tyler
TI Stage-specific sensitivity to p53 restoration during lung cancer progression
SO NATURE
LA English
DT Article
ID oncogenic k-ras; tumor progression; in-vivo; senescence; proliferation; amplification; expression; mice
AB Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumour suppressor pathways. Personalized cancer therapy that is based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumour suppressors and activation of oncogenes is essential in advanced cancers. Mutations in the p53 tumour-suppressor pathway are common in human cancer and significant efforts towards pharmaceutical reactivation of defective p53 pathways are underway(1-3). Here we show that restoration of p53 in established murine lung tumours leads to significant but incomplete tumour cell loss specifically in malignant adenocarcinomas, but not in adenomas. We define amplification of MAPK signalling as a critical determinant of malignant progression and also a stimulator of Arf tumour-suppressor expression. The response to p53 restoration in this context is critically dependent on the expression of Arf. We propose that p53 not only limits malignant progression by suppressing the acquisition of alterations that lead to tumour progression, but also, in the context of p53 restoration, responds to increased oncogenic signalling to mediate tumour regression. Our observations also underscore that the p53 pathway is not engaged by low levels of oncogene activity that are sufficient for early stages of lung tumour development. These data suggest that restoration of pathways important in tumour progression, as opposed to initiation, may lead to incomplete tumour regression due to the stage-heterogeneity of tumour cell populations.
C1 [Feldser, David M.; Kostova, Kamena K.; Winslow, Monte M.; Taylor, Sarah E.; Cashman, Chris; Whittaker, Charles A.; Sanchez-Rivera, Francisco J.; Resnick, Rebecca; Hemann, Michael T.; Jacks, Tyler] MIT, Dept Biol, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Feldser, David M.; Kostova, Kamena K.; Winslow, Monte M.; Taylor, Sarah E.; Cashman, Chris; Whittaker, Charles A.; Sanchez-Rivera, Francisco J.; Resnick, Rebecca; Hemann, Michael T.; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Bronson, Roderick] Tufts Univ, Boston, MA 02115 USA.
   [Bronson, Roderick] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Tufts University; Harvard University; Harvard Medical School
RP Jacks, T (corresponding author), MIT, Dept Biol, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tjacks@mit.edu
FU National Cancer Institute [P30-CA14051]; American Cancer Society; MIT; Howard Hughes Medical Institute; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 25
TC 242
Z9 292
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 NOV 25
PY 2010
VL 468
IS 7323
BP 572
EP U249
DI 10.1038/nature09535
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200044
PM 21107428
DA 2026-03-09
ER

PT J
AU Montgomery, SB
   Sammeth, M
   Gutierrez-Arcelus, M
   Lach, RP
   Ingle, C
   Nisbett, J
   Guigo, R
   Dermitzakis, ET
AF Montgomery, Stephen B.
   Sammeth, Micha
   Gutierrez-Arcelus, Maria
   Lach, Radoslaw P.
   Ingle, Catherine
   Nisbett, James
   Guigo, Roderic
   Dermitzakis, Emmanouil T.
TI Transcriptome genetics using second generation sequencing in a Caucasian population
SO NATURE
LA English
DT Article
ID rna-seq; regulatory variation; expression; genome; nucleotide; resolution
AB Gene expression is an important phenotype that informs about genetic and environmental effects on cellular state. Many studies have previously identified genetic variants for gene expression phenotypes using custom and commercially available microarrays(1-5). Second generation sequencing technologies are now providing unprecedented access to the fine structure of the transcriptome(6-14). We have sequenced the mRNA fraction of the transcriptome in 60 extended HapMap individuals of European descent and have combined these data with genetic variants from the HapMap3 project(15). We have quantified exon abundance based on read depth and have also developed methods to quantify whole transcript abundance. We have found that approximately 10 million reads of sequencing can provide access to the same dynamic range as arrays with better quantification of alternative and highly abundant transcripts. Correlation with SNPs (small nucleotide polymorphisms) leads to a larger discovery of eQTLs (expression quantitative trait loci) than with arrays. We also detect a substantial number of variants that influence the structure of mature transcripts indicating variants responsible for alternative splicing. Finally, measures of allele-specific expression allowed the identification of rare eQTLs and allelic differences in transcript structure. This analysis shows that high throughput sequencing technologies reveal new properties of genetic effects on the transcriptome and allow the exploration of genetic effects in cellular processes.
C1 [Montgomery, Stephen B.; Gutierrez-Arcelus, Maria; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Montgomery, Stephen B.; Lach, Radoslaw P.; Ingle, Catherine; Nisbett, James; Dermitzakis, Emmanouil T.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Sammeth, Micha; Guigo, Roderic] Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona 08003, Catalonia, Spain.
C3 University of Geneva; Wellcome Trust Sanger Institute; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG)
RP Dermitzakis, ET (corresponding author), Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
EM stephen.montgomery@unige.ch; emmanouil.dermitzakis@unige.ch
FU Wellcome Trust; Louis-Jeantet foundation; Swiss National Science Foundation NCCR; Spanish Ministry of Science and Consolider Ingenio
NR 34
TC 641
Z9 762
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 APR 1
PY 2010
VL 464
IS 7289
BP 773
EP U151
DI 10.1038/nature08903
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000048
PM 20220756
DA 2026-03-09
ER

PT J
AU Neumann, H
   Wang, KH
   Davis, L
   Garcia-Alai, M
   Chin, JW
AF Neumann, Heinz
   Wang, Kaihang
   Davis, Lloyd
   Garcia-Alai, Maria
   Chin, Jason W.
TI Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome
SO NATURE
LA English
DT Article
ID transfer-rna synthetase; expanded genetic-code; escherichia-coli; in-vivo; recombinant proteins; mammalian-cells; messenger-rna; pyrrolysine; suppressors; cyclization
AB The in vivo, genetically programmed incorporation of designer amino acids allows the properties of proteins to be tailored with molecular precision(1). The Methanococcus jannaschii tyrosyl-transfer-RNA synthetase-tRNA(CUA) (MjTyrRS-tRNA(CUA))(2,3) and the Methanosarcina barkeri pyrrolysyl-tRNA synthetase-tRNACUA (MbPylRS-tRNA(CUA))(4-6) orthogonal pairs have been evolved to incorporate a range of unnatural amino acids in response to the amber codon in Escherichia coli(1,6,7). However, the potential of synthetic genetic code expansion is generally limited to the low efficiency incorporation of a single type of unnatural amino acid at a time, because every triplet codon in the universal genetic code is used in encoding the synthesis of the proteome. To encode efficiently many distinct unnatural amino acids into proteins we require blank codons and mutually orthogonal aminoacyl-tRNA synthetase-tRNA pairs that recognize unnatural amino acids and decode the new codons. Here we synthetically evolve an orthogonal ribosome(8,9) (ribo-Q1) that efficiently decodes a series of quadruplet codons and the amber codon, providing several blank codons on an orthogonal messenger RNA, which it specifically translates(8). By creating mutually orthogonal aminoacyl-tRNA synthetase-tRNA pairs and combining them with ribo-Q1 we direct the incorporation of distinct unnatural amino acids in response to two of the new blank codons on the orthogonal mRNA. Using this code, we genetically direct the formation of a specific, redox-insensitive, nanoscale protein cross-link by the bio-orthogonal cycloaddition of encoded azide-and alkyne-containing amino acids(10). Because the synthetase-tRNA pairs used have been evolved to incorporate numerous unnatural amino acids(1,6,7), it will be possible to encode more than 200 unnatural amino acid combinations using this approach. As ribo-Q1 independently decodes a series of quadruplet codons, this work provides foundational technologies for the encoded synthesis and synthetic evolution of unnatural polymers in cells.
C1 [Neumann, Heinz; Wang, Kaihang; Davis, Lloyd; Garcia-Alai, Maria; Chin, Jason W.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Chin, JW (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM chin@mrc-lmb.cam.ac.uk
FU ERC; MRC; Trinity College, Cambridge; Medical Research Council [MC_UP_A024_1008, MC_U105181009] Funding Source: researchfish; MRC [MC_UP_A024_1008, MC_U105181009] Funding Source: UKRI
NR 30
TC 521
Z9 673
U1 1
U2 256
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 441
EP 444
DI 10.1038/nature08817
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100053
PM 20154731
DA 2026-03-09
ER

PT J
AU Guzman, JN
   Sanchez-Padilla, J
   Wokosin, D
   Kondapalli, J
   Ilijic, E
   Schumacker, PT
   Surmeier, DJ
AF Guzman, Jaime N.
   Sanchez-Padilla, Javier
   Wokosin, David
   Kondapalli, Jyothisri
   Ilijic, Ema
   Schumacker, Paul T.
   Surmeier, D. James
TI Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1
SO NATURE
LA English
DT Article
ID calcium-channel blockers; mitochondria; disease; cells; mutations
AB Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta(1) (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss(2), but why these particular neurons should be stressed is a mystery. Here we show, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson's disease.
C1 [Guzman, Jaime N.; Sanchez-Padilla, Javier; Wokosin, David; Ilijic, Ema; Surmeier, D. James] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA.
   [Kondapalli, Jyothisri; Schumacker, Paul T.] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern University; Feinberg School of Medicine
RP Surmeier, DJ (corresponding author), Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA.
EM j-surmeier@northwestern.edu
FU Picower Foundation; Hartman Foundation; Falk Trust; Parkinson's Disease Foundation; NIH [NS047085, NS 054850, K12GM088020, HL35440, RR025355]; DOD [W81XWH-07-1-0170]
NR 33
TC 689
Z9 811
U1 1
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 696
EP U119
DI 10.1038/nature09536
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700041
PM 21068725
DA 2026-03-09
ER

PT J
AU Kaplan, MR
   Schaefer, JM
   Denton, GH
   Barrell, DJA
   Chinn, TJH
   Putnam, AE
   Andersen, BG
   Finkel, RC
   Schwartz, R
   Doughty, AM
AF Kaplan, Michael R.
   Schaefer, Joerg M.
   Denton, George H.
   Barrell, David J. A.
   Chinn, Trevor J. H.
   Putnam, Aaron E.
   Andersen, Bjorn G.
   Finkel, Robert C.
   Schwartz, Roseanne
   Doughty, Alice M.
TI Glacier retreat in New Zealand during the Younger Dryas stadial
SO NATURE
LA English
DT Article
ID antarctic cold reversal; abrupt climate-change; southern alps; atmospheric co2; atlantic; event; ice; fluctuations; seasonality; ocean
AB Millennial-scale cold reversals in the high latitudes of both hemispheres interrupted the last transition from full glacial to interglacial climate conditions. The presence of the Younger Dryas stadial (similar to 12.9 to similar to 11.7 kyr ago) is established throughout much of the Northern Hemisphere, but the global timing, nature and extent of the event are not well established. Evidence in mid to low latitudes of the Southern Hemisphere, in particular, has remained perplexing(1-6). The debate has in part focused on the behaviour of mountain glaciers in New Zealand, where previous research has found equivocal evidence for the precise timing of increased or reduced ice extent(1-3). The interhemispheric behaviour of the climate system during the Younger Dryas thus remains an open question, fundamentally limiting our ability to formulate realistic models of global climate dynamics for this time period. Here we show that New Zealand's glaciers retreated after similar to 13 kyr BP, at the onset of the Younger Dryas, and in general over the subsequent similar to 1.5-kyr period. Our evidence is based on detailed landform mapping, a high-precision Be-10 chronology(7) and reconstruction of former ice extents and snow lines from well-preserved cirque moraines. Our late-glacial glacier chronology matches climatic trends in Antarctica, Southern Ocean behaviour and variations in atmospheric CO2. The evidence points to a distinct warming of the southern mid-latitude atmosphere during the Younger Dryas and a close coupling between New Zealand's cryosphere and southern high-latitude climate. These findings support the hypothesis that extensive winter sea ice and curtailed meridional ocean overturning in the North Atlantic led to a strong interhemispheric thermal gradient(8) during late-glacial times, in turn leading to increased upwelling and CO2 release from the Southern Ocean(9), thereby triggering Southern Hemisphere warming during the northern Younger Dryas.
C1 [Kaplan, Michael R.; Schaefer, Joerg M.; Schwartz, Roseanne] Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Schaefer, Joerg M.] Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
   [Denton, George H.; Putnam, Aaron E.] Univ Maine, Dept Earth Sci, Orono, ME 04469 USA.
   [Denton, George H.; Putnam, Aaron E.] Univ Maine, Climate Change Inst, Orono, ME 04469 USA.
   [Barrell, David J. A.] GNS Sci, Dunedin 9054, New Zealand.
   [Chinn, Trevor J. H.] Alpine & Polar Proc Consultancy, Otago 9382, New Zealand.
   [Andersen, Bjorn G.] Univ Oslo, Dept Geosci, N-0316 Oslo, Norway.
   [Finkel, Robert C.] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 95064 USA.
   [Finkel, Robert C.] CEREGE, F-13545 Aix En Provence 4, France.
   [Doughty, Alice M.] Victoria Univ Wellington, Antarctic Res Ctr, Wellington 6140, New Zealand.
   [Doughty, Alice M.] Victoria Univ Wellington, Sch Earth Sci, Wellington 6140, New Zealand.
C3 Columbia University; Columbia University; University of Maine System; University of Maine Orono; University of Maine System; University of Maine Orono; Earth Sciences New Zealand; GNS Science - New Zealand; University of Oslo; University of California System; University of California Berkeley; Aix-Marseille Universite; Victoria University Wellington; Victoria University Wellington
RP Kaplan, MR (corresponding author), Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM mkaplan@ldeo.columbia.edu
FU Gary C. Comer Science and Education Foundation; National Oceanographic and Atmospheric Administration; National Science Foundation [EAR-0745781, 0936077, 0823521]; Foundation for Research, Science and Technology [CO5X0701]; Directorate For Geosciences; Division Of Earth Sciences [0823521] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [0823693] Funding Source: National Science Foundation
NR 30
TC 145
Z9 163
U1 1
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 SEP 9
PY 2010
VL 467
IS 7312
BP 194
EP 197
DI 10.1038/nature09313
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300031
PM 20829791
DA 2026-03-09
ER

PT J
AU Gurumurthy, S
   Xie, SZ
   Alagesan, B
   Kim, J
   Yusuf, RZ
   Saez, B
   Tzatsos, A
   Ozsolak, F
   Milos, P
   Ferrari, F
   Park, PJ
   Shirihai, OS
   Scadden, DT
   Bardeesy, N
AF Gurumurthy, Sushma
   Xie, Stephanie Z.
   Alagesan, Brinda
   Kim, Judith
   Yusuf, Rushdia Z.
   Saez, Borja
   Tzatsos, Alexandros
   Ozsolak, Fatih
   Milos, Patrice
   Ferrari, Francesco
   Park, Peter J.
   Shirihai, Orian S.
   Scadden, David T.
   Bardeesy, Nabeel
TI The Lkb1 metabolic sensor maintains haematopoietic stem cell survival
SO NATURE
LA English
DT Article
ID peutz-jeghers-syndrome; glucose-homeostasis; tumor suppression; in-vivo; pathway; kinase; mice; apoptosis; system; energy
AB Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.
C1 [Gurumurthy, Sushma; Xie, Stephanie Z.; Alagesan, Brinda; Kim, Judith; Yusuf, Rushdia Z.; Saez, Borja; Tzatsos, Alexandros; Scadden, David T.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Gurumurthy, Sushma; Xie, Stephanie Z.; Alagesan, Brinda; Kim, Judith; Yusuf, Rushdia Z.; Saez, Borja; Tzatsos, Alexandros; Scadden, David T.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Gurumurthy, Sushma; Xie, Stephanie Z.; Alagesan, Brinda; Kim, Judith; Yusuf, Rushdia Z.; Saez, Borja; Tzatsos, Alexandros; Scadden, David T.; Bardeesy, Nabeel] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Xie, Stephanie Z.; Yusuf, Rushdia Z.; Saez, Borja; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Xie, Stephanie Z.; Yusuf, Rushdia Z.; Saez, Borja; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA.
   [Ozsolak, Fatih; Milos, Patrice] Hel BioSci Corp, Cambridge, MA 02139 USA.
   [Ferrari, Francesco; Park, Peter J.] Childrens Hosp, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Ferrari, Francesco; Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Shirihai, Orian S.] Boston Univ, Med Ctr, Mitochondria ARC, Evans Res Ctr,Dept Med, Boston, MA 02118 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University; 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; Boston University
RP Bardeesy, N (corresponding author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM Scadden.David@MGH.Harvard.edu; Bardeesy.Nabeel@MGH.Harvard.edu
FU NIH [U01 CA141576-01, DK050234]; Ellison Medical Foundation; Massachusetts Biotechnology Research Council
NR 35
TC 320
Z9 382
U1 0
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 659
EP U75
DI 10.1038/nature09572
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700033
PM 21124451
DA 2026-03-09
ER

PT J
AU Kajiwara, Y
   Harii, K
   Takahashi, S
   Ohe, J
   Uchida, K
   Mizuguchi, M
   Umezawa, H
   Kawai, H
   Ando, K
   Takanashi, K
   Maekawa, S
   Saitoh, E
AF Kajiwara, Y.
   Harii, K.
   Takahashi, S.
   Ohe, J.
   Uchida, K.
   Mizuguchi, M.
   Umezawa, H.
   Kawai, H.
   Ando, K.
   Takanashi, K.
   Maekawa, S.
   Saitoh, E.
TI Transmission of electrical signals by spin-wave interconversion in a magnetic insulator
SO NATURE
LA English
DT Article
ID semiconductors; films
AB The energy bandgap of an insulator is large enough to prevent electron excitation and electrical conduction(1). But in addition to charge, an electron also has spin(2), and the collective motion of spin can propagate-and so transfer a signal-in some insulators(3). This motion is called a spin wave and is usually excited using magnetic fields. Here we show that a spin wave in an insulator can be generated and detected using spin-Hall effects, which enable the direct conversion of an electric signal into a spin wave, and its subsequent transmission through (and recovery from) an insulator over macroscopic distances. First, we show evidence for the transfer of spin angular momentum between an insulator magnet Y3Fe5O12 and a platinum film. This transfer allows direct conversion of an electric current in the platinum film to a spin wave in the Y3Fe5O12 via spin-Hall effects(4-11). Second, making use of the transfer in a Pt/Y3Fe5O12/Pt system, we demonstrate that an electric current in one metal film induces voltage in the other, far distant, metal film. Specifically, the applied electric current is converted into spin angular momentum owing to the spin-Hall effect(7,8,10,11) in the first platinum film; the angular momentum is then carried by a spin wave in the insulating Y3Fe5O12 layer; at the distant platinum film, the spin angular momentum of the spin wave is converted back to an electric voltage. This effect can be switched on and off using a magnetic field. Weak spin damping(3) in Y3Fe5O12 is responsible for its transparency for the transmission of spin angular momentum. This hybrid electrical transmission method potentially offers a means of innovative signal delivery in electrical circuits and devices.
C1 [Kajiwara, Y.; Harii, K.; Takahashi, S.; Ohe, J.; Uchida, K.; Mizuguchi, M.; Ando, K.; Takanashi, K.; Maekawa, S.; Saitoh, E.] Tohoku Univ, Inst Mat Res, Sendai, Miyagi 9808577, Japan.
   [Kajiwara, Y.; Ando, K.; Saitoh, E.] Keio Univ, Dept Appl Phys & Physicoinformat, Yokohama, Kanagawa 2238522, Japan.
   [Harii, K.; Takahashi, S.; Maekawa, S.] Japan Sci & Technol Agcy, CREST, Tokyo 1020075, Japan.
   [Saitoh, E.] Japan Sci & Technol Agcy, PRESTO, Tokyo 1020075, Japan.
   [Umezawa, H.; Kawai, H.] FDK Corp, Shizuoka 4310495, Japan.
C3 Tohoku University; Keio University; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST)
RP Saitoh, E (corresponding author), Tohoku Univ, Inst Mat Res, Sendai, Miyagi 9808577, Japan.
EM saitoheiji@imr.tohoku.ac.jp
FU MEXT, Japan [19048028, C12]; NEDO, Japan; TRF, Japan; Grants-in-Aid for Scientific Research [19048009, 19048028] Funding Source: KAKEN
NR 31
TC 1472
Z9 1621
U1 12
U2 436
PU NATURE PUBLISHING 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 11
PY 2010
VL 464
IS 7286
BP 262
EP U141
DI 10.1038/nature08876
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100043
PM 20220845
DA 2026-03-09
ER

PT J
AU Weerapana, E
   Wang, C
   Simon, GM
   Richter, F
   Khare, S
   Dillon, MBD
   Bachovchin, DA
   Mowen, K
   Baker, D
   Cravatt, BF
AF Weerapana, Eranthie
   Wang, Chu
   Simon, Gabriel M.
   Richter, Florian
   Khare, Sagar
   Dillon, Myles B. D.
   Bachovchin, Daniel A.
   Mowen, Kerri
   Baker, David
   Cravatt, Benjamin F.
TI Quantitative reactivity profiling predicts functional cysteines in proteomes
SO NATURE
LA English
DT Article
ID complex protein mixtures; mass-spectrometry; saccharomyces-cerevisiae; hydrogen-peroxide; crystal-structure; identification; thiol; electrophiles; peptides; residues
AB Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here we describe a proteomics method to profile quantitatively the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyper-reactivity was a rare feature among cysteines and it was found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and is involved in iron-sulphur protein biogenesis. We also demonstrate that quantitative reactivity profiling can form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs.
C1 [Weerapana, Eranthie; Wang, Chu; Simon, Gabriel M.; Bachovchin, Daniel A.; Cravatt, Benjamin F.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Weerapana, Eranthie; Wang, Chu; Simon, Gabriel M.; Dillon, Myles B. D.; Bachovchin, Daniel A.; Mowen, Kerri; Cravatt, Benjamin F.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Richter, Florian; Khare, Sagar; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Richter, Florian; Baker, David] Univ Washington, Interdisciplinary Program Biomol Struct & Design, Seattle, WA 98195 USA.
   [Khare, Sagar; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 Scripps Research Institute; Scripps Research Institute; 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
RP Cravatt, BF (corresponding author), Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
EM cravatt@scripps.edu
FU National Institutes of Health [CA087660, MH084512]; Pfizer; Koshland Graduate Fellowship; National Science Foundation; Skaggs Institute for Chemical Biology
NR 50
TC 1432
Z9 1720
U1 11
U2 495
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 790
EP U79
DI 10.1038/nature09472
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700038
PM 21085121
DA 2026-03-09
ER

PT J
AU Sprinzak, D
   Lakhanpal, A
   LeBon, L
   Santat, LA
   Fontes, ME
   Anderson, GA
   Garcia-Ojalvo, J
   Elowitz, MB
AF Sprinzak, David
   Lakhanpal, Amit
   LeBon, Lauren
   Santat, Leah A.
   Fontes, Michelle E.
   Anderson, Graham A.
   Garcia-Ojalvo, Jordi
   Elowitz, Michael B.
TI Cis-interactions between Notch and Delta generate mutually exclusive signalling states
SO NATURE
LA English
DT Article
ID pattern-formation; cell fate; drosophila; expression; induction; feedback; transactivation; activation; ligands; domain
AB The Notch-Delta signalling pathway allows communication between neighbouring cells during development(1). It has a critical role in the formation of 'fine-grained' patterns, generating distinct cell fates among groups of initially equivalent neighbouring cells and sharply delineating neighbouring regions in developing tissues(2-5). The Delta ligand has been shown to have two activities: it transactivates Notch in neighbouring cells and cis-inhibits Notch in its own cell. However, it remains unclear how Notch integrates these two activities and how the resulting system facilitates pattern formation. Here we report the development of a quantitative time-lapse microscopy platform for analysing Notch-Delta signalling dynamics in individual mammalian cells, with the aim of addressing these issues. By controlling both cis- and trans-Delta concentrations, and monitoring the dynamics of a Notch reporter, we measured the combined cis-trans input-output relationship in the Notch-Delta system. The data revealed a striking difference between the responses of Notch to trans-and cis-Delta: whereas the response to trans-Delta is graded, the response to cis-Delta is sharp and occurs at a fixed threshold, independent of trans-Delta. We developed a simple mathematical model that shows how these behaviours emerge from the mutual inactivation of Notch and Delta proteins in the same cell. This interaction generates an ultrasensitive switch between mutually exclusive sending ( high Delta/low Notch) and receiving (high Notch/low Delta) signalling states. At the multicellular level, this switch can amplify small differences between neighbouring cells even without transcription-mediated feedback. This Notch-Delta signalling switch facilitates the formation of sharp boundaries and lateral-inhibition patterns in models of development, and provides insight into previously unexplained mutant behaviours.
C1 [Sprinzak, David; Lakhanpal, Amit; LeBon, Lauren; Santat, Leah A.; Fontes, Michelle E.; Elowitz, Michael B.] CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA.
   [Sprinzak, David; Lakhanpal, Amit; LeBon, Lauren; Santat, Leah A.; Fontes, Michelle E.; Elowitz, Michael B.] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA.
   [Anderson, Graham A.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Garcia-Ojalvo, Jordi] Univ Politecn Cataluna, Dept Fis & Engn Nucl, E-08222 Terrassa, Spain.
C3 California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology; Stanford University; Universitat Politecnica de Catalunya
RP Elowitz, MB (corresponding author), CALTECH, Howard Hughes Med Inst, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM melowitz@caltech.edu
FU US National Institutes of Health [F32GM77014, GM08042]; Caltech Center for Biological Circuit Design; Packard Foundation; Fannie and John Hertz Foundation; Ministerio de Ciencia e Innovacion (Spain) [FIS2009-13360]; National Institute of General Medical Sciences [T32GM008042] Funding Source: NIH RePORTER
NR 29
TC 472
Z9 594
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 MAY 6
PY 2010
VL 465
IS 7294
BP 86
EP U95
DI 10.1038/nature08959
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900036
PM 20418862
DA 2026-03-09
ER

PT J
AU Qi, XX
   Lan, SY
   Wang, WJ
   Schelde, LM
   Dong, HH
   Wallat, GD
   Ly, H
   Liang, YY
   Dong, CJ
AF Qi, Xiaoxuan
   Lan, Shuiyun
   Wang, Wenjian
   Schelde, Lisa McLay
   Dong, Haohao
   Wallat, Gregor D.
   Ly, Hinh
   Liang, Yuying
   Dong, Changjiang
TI Cap binding and immune evasion revealed by Lassa nucleoprotein structure
SO NATURE
LA English
DT Article
ID crystal-structure; virus nucleoprotein; l-protein; dendritic cells; rna; trex1; transcription; endonuclease; replication; recognition
AB Lassa virus, the causative agent of Lassa fever, causes thousands of deaths annually and is a biological threat agent, for which there is no vaccine and limited therapy. The nucleoprotein (NP) of Lassa virus has essential roles in viral RNA synthesis and immune suppression, the molecular mechanisms of which are poorly understood. Here we report the crystal structure of Lassa virus NP at 1.80 angstrom resolution, which reveals amino (N)- and carboxy (C)-terminal domains with structures unlike any of the reported viral NPs. The N domain folds into a novel structure with a deep cavity for binding the m7GpppN cap structure that is required for viral RNA transcription, whereas the C domain contains 3'-5' exoribonuclease activity involved in suppressing interferon induction. To our knowledge this is the first X-ray crystal structure solved for an arenaviral NP, which reveals its unexpected functions and indicates unique mechanisms in cap binding and immune evasion. These findings provide great potential for vaccine and drug development.
C1 [Qi, Xiaoxuan; Dong, Haohao; Wallat, Gregor D.; Dong, Changjiang] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.
   [Lan, Shuiyun; Schelde, Lisa McLay; Ly, Hinh; Liang, Yuying] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
   [Wang, Wenjian] Sun Yat Sen Univ, Affiliated Hosp 1, Lab Dept Surg, Guangzhou 510080, Guangdong, Peoples R China.
C3 University of St Andrews; Emory University; Sun Yat Sen University
RP Dong, CJ (corresponding author), Univ St Andrews, Sch Chem, Biomed Sci Res Complex, St Andrews KY16 9ST, Fife, Scotland.
EM hly@emory.edu; yliang5@emory.edu; cd26@st-andrews.ac.uk
FU Southeast Regional Center of Excellence for Emerging Infections and Biodefense [5-U54-AI-057157-06]; Emory University Research Committee (URC); Emory DDRDC [DK64399]; American Cancer Society [RSG-06-162-01-GMC]; NIH [R01AI083409, AI067704];  [5-U19-AI057266-07]; National Institute of Allergy and Infectious Diseases [U19AI057266] Funding Source: NIH RePORTER
NR 50
TC 229
Z9 275
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 DEC 9
PY 2010
VL 468
IS 7325
BP 779
EP U65
DI 10.1038/nature09605
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700036
PM 21085117
DA 2026-03-09
ER

PT J
AU Kim, TK
   Hemberg, M
   Gray, JM
   Costa, AM
   Bear, DM
   Wu, J
   Harmin, DA
   Laptewicz, M
   Barbara-Haley, K
   Kuersten, S
   Markenscoff-Papadimitriou, E
   Kuhl, D
   Bito, H
   Worley, PF
   Kreiman, G
   Greenberg, ME
AF Kim, Tae-Kyung
   Hemberg, Martin
   Gray, Jesse M.
   Costa, Allen M.
   Bear, Daniel M.
   Wu, Jing
   Harmin, David A.
   Laptewicz, Mike
   Barbara-Haley, Kellie
   Kuersten, Scott
   Markenscoff-Papadimitriou, Eirene
   Kuhl, Dietmar
   Bito, Haruhiko
   Worley, Paul F.
   Kreiman, Gabriel
   Greenberg, Michael E.
TI Widespread transcription at neuronal activity-regulated enhancers
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; chip-seq experiments; synapse development; gene; arc/arg3.1; expression; reveals; identification; plasticity; promoters
AB We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified similar to 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.
C1 [Kim, Tae-Kyung; Gray, Jesse M.; Costa, Allen M.; Bear, Daniel M.; Harmin, David A.; Laptewicz, Mike; Markenscoff-Papadimitriou, Eirene; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Hemberg, Martin; Kreiman, Gabriel] Harvard Univ, Childrens Hosp Boston, Dept Ophthalmol, Ctr Brain Sci, Boston, MA 02115 USA.
   [Hemberg, Martin; Kreiman, Gabriel] Harvard Univ, Swartz Ctr Theoret Neurosci, Boston, MA 02115 USA.
   [Wu, Jing; Worley, Paul F.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Harmin, David A.] Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA.
   [Barbara-Haley, Kellie] Childrens Hosp, Mol Genet Core Facil, Boston, MA 02115 USA.
   [Kuersten, Scott] Epictr Biotechnol, Madison, WI 53713 USA.
   [Kuhl, Dietmar] Univ Med Ctr Hamburg Eppendorf UKE, Ctr Mol Neurobiol ZMNH, IMCC, D-20251 Hamburg, Germany.
   [Bito, Haruhiko] Univ Tokyo, Grad Sch Med, Dept Neurochem, Bunkyo Ku, Tokyo 1130033, Japan.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Johns Hopkins University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Hamburg; University Medical Center Hamburg-Eppendorf; University of Tokyo
RP Greenberg, ME (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM michael_greenberg@hms.harvard.edu
FU Nancy Lurie Marks Family Foundation; National Institutes of Health [NS028829, R21EY019710, DP2OD006461, MH-053608]; Lefler postdoctoral fellowship; Jane Coffin Childs Memorial Funds; Helen Hay Whitney postdoctoral fellowship; Children's Hospital Ophthalmology Foundation; Whitehall Foundation; Klingenstein Fund; National Institute of Neurological Disorders and Stroke [R01NS028829] Funding Source: NIH RePORTER
NR 37
TC 1886
Z9 2391
U1 2
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 MAY 13
PY 2010
VL 465
IS 7295
BP 182
EP U65
DI 10.1038/nature09033
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500027
PM 20393465
DA 2026-03-09
ER

PT J
AU Cooper, S
   Khatib, F
   Treuille, A
   Barbero, J
   Lee, J
   Beenen, M
   Leaver-Fay, A
   Baker, D
   Popovic, Z
   Players, F
AF Cooper, Seth
   Khatib, Firas
   Treuille, Adrien
   Barbero, Janos
   Lee, Jeehyung
   Beenen, Michael
   Leaver-Fay, Andrew
   Baker, David
   Popovic, Zoran
   Players, Foldit
TI Predicting protein structures with a multiplayer online game
SO NATURE
LA English
DT Article
AB People exert large amounts of problem-solving effort playing computer games. Simple image-and text-recognition tasks have been successfully 'crowd-sourced' through games(1-3), but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology(4), while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.
C1 [Cooper, Seth; Treuille, Adrien; Barbero, Janos; Beenen, Michael; Popovic, Zoran] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA.
   [Khatib, Firas; Leaver-Fay, Andrew; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Treuille, Adrien; Lee, Jeehyung] Carnegie Mellon Univ, Sch Comp Sci, Pittsburgh, PA 15213 USA.
   [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Carnegie Mellon University; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Popovic, Z (corresponding author), Univ Washington, Dept Comp Sci & Engn, Box 352350, Seattle, WA 98195 USA.
EM dabaker@u.washington.edu; zoran@cs.washington.edu
FU NSF [IIS0811902, 0906026]; DARPA [N00173-08-1-G025]; Howard Hughes Medical Institute; Microsoft; NVIDIA Fellowship; Div Of Biological Infrastructure; Direct For Biological Sciences [0906026] Funding Source: National Science Foundation; Div Of Information & Intelligent Systems; Direct For Computer & Info Scie & Enginr [0811902, 0953985] Funding Source: National Science Foundation
NR 11
TC 816
Z9 1045
U1 18
U2 320
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 756
EP 760
DI 10.1038/nature09304
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500039
PM 20686574
DA 2026-03-09
ER

PT J
AU Sanchez, SE
   Petrillo, E
   Beckwith, EJ
   Zhang, X
   Rugnone, ML
   Hernando, CE
   Cuevas, JC
   Herz, MAG
   Depetris-Chauvin, A
   Simpson, CG
   Brown, JWS
   Cerdán, PD
   Borevitz, JO
   Mas, P
   Ceriani, MF
   Kornblihtt, AR
   Yanovsky, MJ
AF Sanchez, Sabrina E.
   Petrillo, Ezequiel
   Beckwith, Esteban J.
   Zhang, Xu
   Rugnone, Matias L.
   Hernando, C. Esteban
   Cuevas, Juan C.
   Herz, Micaela A. Godoy
   Depetris-Chauvin, Ana
   Simpson, Craig G.
   Brown, John W. S.
   Cerdan, Pablo D.
   Borevitz, Justin O.
   Mas, Paloma
   Fernanda Ceriani, M.
   Kornblihtt, Alberto R.
   Yanovsky, Marcelo J.
TI A methyl transferase links the circadian clock to the regulation of alternative splicing
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; drosophila-melanogaster; reciprocal regulation; arginine methylation; phospholipase-c; gene; methyltransferase; expression; requires; behavior
AB Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day-night cycle(1). Posttranscriptional regulation is emerging as an important component of circadian networks(2-6), but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones(7) and Sm spliceosomal proteins(8,9), links the circadian clock to the control of alternative splicing in plants. Mutations in PRMT5 impair several circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome-wide studies show that PRMT5 contributes to the regulation of many pre-messenger-RNA splicing events, probably by modulating 5'-splice-site recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to the mediation of the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5-1, a mutant affected in the Drosophila melanogaster PRMT5 homologue, and this is associated with alterations in splicing of the core-clock gene period and several clock-associated genes. Our results demonstrate a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.
C1 [Sanchez, Sabrina E.; Rugnone, Matias L.; Hernando, C. Esteban; Yanovsky, Marcelo J.] UBA CONICET, Fac Agron, IFEVA, Buenos Aires, DF, Argentina.
   [Petrillo, Ezequiel; Herz, Micaela A. Godoy; Kornblihtt, Alberto R.] UBA CONICET, FCEyN, IFIBYNE, Buenos Aires, DF, Argentina.
   [Beckwith, Esteban J.; Depetris-Chauvin, Ana; Cerdan, Pablo D.; Fernanda Ceriani, M.; Yanovsky, Marcelo J.] IIBBA CONICET, Fdn Inst Leloir, Buenos Aires, DF, Argentina.
   [Zhang, Xu; Borevitz, Justin O.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Cuevas, Juan C.; Mas, Paloma] Consortium CSIC IRTA UAB, CRAG, Barcelona 08034, Spain.
   [Simpson, Craig G.; Brown, John W. S.] SCRI, Genet Programme, Dundee DD2 5DA, Scotland.
   [Brown, John W. S.] Univ Dundee, SCRI, Div Plant Sci, Dundee DD2 5DA, Scotland.
C3 Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; CONICET UBA; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; CONICET UBA; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Leloir Institute; University of Chicago; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); Centre de Recerca en Agrigenomica (CRAG); University of Barcelona; IRTA; James Hutton Institute; University of Dundee; James Hutton Institute
RP Yanovsky, MJ (corresponding author), UBA CONICET, Fac Agron, IFEVA, C1417DSE, Buenos Aires, DF, Argentina.
EM yanovsky@agro.uba.ar
FU Fundacion Antorchas; Agencia Nacional de Promocion de Ciencia y Tecnologia of Argentina; Consejo Nacional de Investigaciones Cientificas y Tecnicas of Argentina; University of Buenos Aires; European Union Network of Excellence on Alternative Splicing (EURASNET); Ministerio de Educacion y Ciencia; European Young Investigator Awards; EMBO; Proyecto de Investigacion Cientifica y Tecnologica [2006-1249]
NR 45
TC 252
Z9 301
U1 1
U2 83
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 112
EP +
DI 10.1038/nature09470
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900046
PM 20962777
DA 2026-03-09
ER

PT J
AU Chen, CA
   Wang, TY
   Varadharaj, S
   Reyes, LA
   Hemann, C
   Talukder, MAH
   Chen, YR
   Druhan, LJ
   Zweier, JL
AF Chen, Chun-An
   Wang, Tse-Yao
   Varadharaj, Saradhadevi
   Reyes, Levy A.
   Hemann, Craig
   Talukder, M. A. Hassan
   Chen, Yeong-Renn
   Druhan, Lawrence J.
   Zweier, Jay L.
TI S-glutathionylation uncouples eNOS and regulates its cellular and vascular function
SO NATURE
LA English
DT Article
ID nitric-oxide synthase; endothelium-dependent relaxation; superoxide generation; endogenous methylarginines; tetrahydrobiopterin; reductase; oxidation; cells; phosphorylation; glutathiolation
AB Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O-2(center dot-)), which are key mediators of cellular signalling. In the presence of Ca2+/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from L-arginine (L-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH4) and L-Arg(1-3). In the absence of BH4, NO synthesis is abrogated and instead O-2(center dot-) is generated(4-7). While NOS dysfunction occurs in diseases with redox stress, BH4 repletion only partly restores NOS activity and NOS-dependent vasodilation(7). This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation(8,9). Under oxidative stress, S-glutathionylation occurs through thiol-disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione(10,11). Cysteine residues are critical for the maintenance of eNOS function(12,13); we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O-2(center dot-) generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O-2(center dot-) generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol-specific reducing agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS is a pivotal switch providing redox regulation of cellular signalling, endothelial function and vascular tone.
C1 [Chen, Chun-An; Wang, Tse-Yao; Varadharaj, Saradhadevi; Reyes, Levy A.; Hemann, Craig; Talukder, M. A. Hassan; Chen, Yeong-Renn; Druhan, Lawrence J.; Zweier, Jay L.] Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
   [Chen, Chun-An; Wang, Tse-Yao; Varadharaj, Saradhadevi; Reyes, Levy A.; Hemann, Craig; Talukder, M. A. Hassan; Chen, Yeong-Renn; Druhan, Lawrence J.; Zweier, Jay L.] Ohio State Univ, Coll Med, Dept Internal Med, Div Cardiovasc Med, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; University System of Ohio; Ohio State University
RP Zweier, JL (corresponding author), Ohio State Univ, Coll Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
EM jay.zweier@osumc.edu
FU National Institutes of Health [HL63744, HL65608, HL38324, HL83237, HL103846]
NR 42
TC 484
Z9 543
U1 0
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1115
EP U521
DI 10.1038/nature09599
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800061
PM 21179168
DA 2026-03-09
ER

PT J
AU Chen, L
   Park, SM
   Tumanov, AV
   Hau, A
   Sawada, K
   Feig, C
   Turner, JR
   Fu, YX
   Romero, IL
   Lengyel, E
   Peter, ME
AF Chen, Lina
   Park, Sun-Mi
   Tumanov, Alexei V.
   Hau, Annika
   Sawada, Kenjiro
   Feig, Christine
   Turner, Jerrold R.
   Fu, Yang-Xin
   Romero, Iris L.
   Lengyel, Ernst
   Peter, Marcus E.
TI CD95 promotes tumour growth
SO NATURE
LA English
DT Article
ID ovarian-cancer; partial-hepatectomy; cells; receptor; death; proliferation; activation; expression; resistant; mouse
AB CD95 (also called Fas and APO-1) is a prototypical death receptor that regulates tissue homeostasis mainly in the immune system through the induction of apoptosis(1-3). During cancer progression CD95 is frequently downregulated or cells are rendered apoptosis resistant(4,5), raising the possibility that loss of CD95 is part of a mechanism for tumour evasion. However, complete loss of CD95 is rarely seen in human cancers(4) and many cancer cells express large quantities of CD95 and are highly sensitive to CD95-mediated apoptosis in vitro. Furthermore, cancer patients frequently have elevated levels of the physiological ligand for CD95, CD95L(6). These data raise the possibility that CD95 could actually promote the growth of tumours through its non-apoptotic activities(7). Here we show that cancer cells in general, regardless of their CD95 apoptosis sensitivity, depend on constitutive activity of CD95, stimulated by cancer-produced CD95L, for optimal growth. Consistently, loss of CD95 in mouse models of ovarian cancer and liver cancer reduces cancer incidence as well as the size of the tumours. The tumorigenic activity of CD95 is mediated by a pathway involving JNK and Jun. These results demonstrate that CD95 has a growth-promoting role during tumorigenesis and indicate that efforts to inhibit its activity rather than to enhance it should be considered during cancer therapy.
C1 [Chen, Lina; Park, Sun-Mi; Hau, Annika; Feig, Christine; Peter, Marcus E.] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
   [Tumanov, Alexei V.; Turner, Jerrold R.; Fu, Yang-Xin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   [Sawada, Kenjiro; Romero, Iris L.; Lengyel, Ernst] Univ Chicago, Gynecol Oncol Sect, Dept Obstet & Gynecol, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago
RP Peter, ME (corresponding author), Northwestern Univ, Feinberg Sch Med, 303 E Super St, Chicago, IL 60611 USA.
EM m-peter@northwestern.edu
FU NCI [CA112240, CA11182]; Crohn's and Colitis Foundation of America [CCFA 1661]; Burroughs Wellcome Fund; Ovarian Cancer Research Fund; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD000849] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK068271, R01DK061931] Funding Source: NIH RePORTER
NR 30
TC 318
Z9 355
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 492
EP 496
DI 10.1038/nature09075
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700038
PM 20505730
DA 2026-03-09
ER

PT J
AU Schmid, MC
   Mrowka, SW
   Turchi, J
   Saunders, RC
   Wilke, M
   Peters, AJ
   Ye, FQ
   Leopold, DA
AF Schmid, Michael C.
   Mrowka, Sylwia W.
   Turchi, Janita
   Saunders, Richard C.
   Wilke, Melanie
   Peters, Andrew J.
   Ye, Frank Q.
   Leopold, David A.
TI Blindsight depends on the lateral geniculate nucleus
SO NATURE
LA English
DT Article
ID visual response property; superior colliculus; area mt; striate cortex; macaque monkey; ganglion-cells; afferent basis; projection; neurons; activation
AB Injury to the primary visual cortex (V1) leads to the loss of visual experience. Nonetheless, careful testing shows that certain visually guided behaviours can persist even in the absence of visual awareness(1-4). The neural circuits supporting this phenomenon, which is often termed blindsight, remain uncertain(4). Here we demonstrate that the thalamic lateral geniculate nucleus (LGN) has a causal role in V1-independent processing of visual information. By comparing functional magnetic resonance imaging (fMRI) and behavioural measures with and without temporary LGN inactivation, we assessed the contribution of the LGN to visual functions of macaque monkeys (Macaca mulatta) with chronic V1 lesions. Before LGN inactivation, high-contrast stimuli presented to the lesion-affected visual field (scotoma) produced significant V1-independent fMRI activation in the extrastriate cortical areas V2, V3, V4, V5/middle temporal (MT), fundus of the superior temporal sulcus (FST) and lateral intraparietal area (LIP) and the animals correctly located the stimuli in a detection task. However, following reversible inactivation of the LGN in the V1-lesioned hemisphere, fMRI responses and behavioural detection were abolished. These results demonstrate that direct LGN projections to the extrastriate cortex have a critical functional contribution to blindsight. They suggest a viable pathway to mediate fast detection during normal vision.
C1 [Schmid, Michael C.; Mrowka, Sylwia W.; Turchi, Janita; Saunders, Richard C.; Wilke, Melanie; Peters, Andrew J.; Leopold, David A.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
   [Ye, Frank Q.; Leopold, David A.] NEI, Neurophysiol Imaging Facil, NIMH, NINDS, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); NIH National Institute of Mental Health (NIMH); NIH National Eye Institute (NEI)
RP Schmid, MC (corresponding author), NIMH, Neuropsychol Lab, 49 Convent Dr, Bethesda, MD 20892 USA.
EM schmidmicha@gmail.com
FU NIMH; NINDS; NEI; National Institute of Mental Health [ZICMH002899, ZIAMH002838, ZIAMH002896] Funding Source: NIH RePORTER
NR 30
TC 257
Z9 296
U1 0
U2 85
PU 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 15
PY 2010
VL 466
IS 7304
BP 373
EP 377
DI 10.1038/nature09179
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100050
PM 20574422
DA 2026-03-09
ER

PT J
AU Sigmundsson, F
   Hreinsdóttir, S
   Hooper, A
   Arnadóttir, T
   Pedersen, R
   Roberts, MJ
   Oskarsson, N
   Auriac, A
   Decriem, J
   Einarsson, P
   Geirsson, H
   Hensch, M
   Ofeigsson, BG
   Sturkell, E
   Sveinbjörnsson, H
   Feigl, KL
AF Sigmundsson, Freysteinn
   Hreinsdottir, Sigrun
   Hooper, Andrew
   Arnadottir, Thora
   Pedersen, Rikke
   Roberts, Matthew J.
   Oskarsson, Niels
   Auriac, Amandine
   Decriem, Judicael
   Einarsson, Pall
   Geirsson, Halldor
   Hensch, Martin
   Ofeigsson, Benedikt G.
   Sturkell, Erik
   Sveinbjornsson, Hjorleifur
   Feigl, Kurt L.
TI Intrusion triggering of the 2010 Eyjafjallajokull explosive eruption
SO NATURE
LA English
DT Article
ID iceland; volcano; deformation; radar; seismicity; california; earthquake; episode; unrest; katla
AB Gradual inflation of magma chambers often precedes eruptions at highly active volcanoes. During such eruptions, rapid deflation occurs as magma flows out and pressure is reduced(1-3). Less is known about the deformation style at moderately active volcanoes, such as Eyjafjallajokull, Iceland, where an explosive summit eruption of trachyandesite beginning on 14 April 2010 caused exceptional disruption to air traffic, closing airspace over much of Europe for days. This eruption was preceded by an effusive flank eruption of basalt from 20 March to 12 April 2010. The 2010 eruptions are the culmination of 18 years of intermittent volcanic unrest(4-9). Here we show that deformation associated with the eruptions was unusual because it did not relate to pressure changes within a single magma chamber. Deformation was rapid before the first eruption (>5 mm per day after 4 March), but negligible during it. Lack of distinct co-eruptive deflation indicates that the net volume of magma drained from shallow depth during this eruption was small; rather, magma flowed from considerable depth. Before the eruption, a similar to 0.05 km(3) magmatic intrusion grew over a period of three months, in a temporally and spatially complex manner, as revealed by GPS (Global Positioning System) geodetic measurements and interferometric analysis of satellite radar images. The second eruption occurred within the ice-capped caldera of the volcano, with explosivity amplified by magma-ice interaction. Gradual contraction of a source, distinct from the pre-eruptive inflation sources, is evident from geodetic data. Eyjafjallajokull's behaviour can be attributed to its off-rift setting with a 'cold' subsurface structure and limited magma at shallow depth, as may be typical for moderately active volcanoes. Clear signs of volcanic unrest signals over years to weeks may indicate reawakening of such volcanoes, whereas immediate short-term eruption precursors may be subtle and difficult to detect.
C1 [Sigmundsson, Freysteinn; Hreinsdottir, Sigrun; Arnadottir, Thora; Pedersen, Rikke; Oskarsson, Niels; Auriac, Amandine; Decriem, Judicael; Einarsson, Pall; Hensch, Martin; Ofeigsson, Benedikt G.] Univ Iceland, Inst Earth Sci, Nord Volcanol Ctr, IS-101 Reykjavik, Iceland.
   [Hooper, Andrew] Delft Univ Technol, Delft Inst Earth Observat & Space Syst, NL-2629 HS Delft, Netherlands.
   [Roberts, Matthew J.; Geirsson, Halldor; Sveinbjornsson, Hjorleifur] Iceland Meteorol Off, IS-150 Reykjavik, Iceland.
   [Sturkell, Erik] Univ Gothenburg, Dept Earth Sci, SE-40530 Gothenburg, Sweden.
   [Feigl, Kurt L.] Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
C3 University of Iceland; Delft University of Technology; University of Gothenburg; University of Wisconsin System; University of Wisconsin Madison
RP Sigmundsson, F (corresponding author), Univ Iceland, Inst Earth Sci, Nord Volcanol Ctr, Sturlugata 7, IS-101 Reykjavik, Iceland.
EM fs@hi.is
FU University of Iceland; US National Science Foundation [EAR 1042103]; Icelandic government
NR 40
TC 335
Z9 370
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 NOV 18
PY 2010
VL 468
IS 7322
BP 426
EP U253
DI 10.1038/nature09558
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100040
PM 21085177
DA 2026-03-09
ER

PT J
AU Scheuermann, JC
   Alonso, AGD
   Oktaba, K
   Ly-Hartig, N
   McGinty, RK
   Fraterman, S
   Wilm, M
   Muir, TW
   Müller, J
AF Scheuermann, Johanna C.
   Alonso, Andres Gaytan de Ayala
   Oktaba, Katarzyna
   Ly-Hartig, Nga
   McGinty, Robert K.
   Fraterman, Sven
   Wilm, Matthias
   Muir, Tom W.
   Mueller, Juerg
TI Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB
SO NATURE
LA English
DT Article
ID group protein complexes; bithorax complex; drosophila; genes; mechanisms; core; trimethylation; ubiquitination; ubiquitylation; hydrolases
AB Polycomb group (PcG) proteins are transcriptional repressors that control processes ranging from the maintenance of cell fate decisions and stem cell pluripotency in animals to the control of flowering time in plants(1-6). In Drosophila, genetic studies identified more than 15 different PcG proteins that are required to repress homeotic (HOX) and other developmental regulator genes in cells where they must stay inactive(1,7,8). Biochemical analyses established that these PcG proteins exist in distinct multiprotein complexes that bind to and modify chromatin of target genes(1-4). Among those, Polycomb repressive complex 1 (PRC1) and the related dRing-associated factors (dRAF) complex contain an E3 ligase activity for monoubiquitination of histone H2A (refs 1-4). Here we show that the uncharacterized Drosophila PcG gene calypso encodes the ubiquitin carboxy-terminal hydrolase BAP1. Biochemically purified Calypso exists in a complex with the PcG protein ASX, and this complex, named Polycomb repressive deubiquitinase (PR-DUB), is bound at PcG target genes in Drosophila. Reconstituted recombinant Drosophila and human PR-DUB complexes remove monoubiquitin from H2A but not from H2B in nucleosomes. Drosophila mutants lacking PR-DUB show a strong increase in the levels of monoubiquitinated H2A. A mutation that disrupts the catalytic activity of Calypso, or absence of the ASX subunit abolishes H2A deubiquitination in vitro and HOX gene repression in vivo. Polycomb gene silencing may thus entail adynamic balance between H2A ubiquitination by PRC1 and dRAF, and H2A deubiquitination by PR-DUB.
C1 [Scheuermann, Johanna C.; Alonso, Andres Gaytan de Ayala; Oktaba, Katarzyna; Ly-Hartig, Nga; Fraterman, Sven; Wilm, Matthias; Mueller, Juerg] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [McGinty, Robert K.; Muir, Tom W.] Rockefeller Univ, New York, NY 10065 USA.
C3 European Molecular Biology Laboratory (EMBL); Rockefeller University
RP Müller, J (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM juerg.mueller@embl.de
FU NIH [RC2CA148354]; EMBL; DFG; National Institute of General Medical Sciences [R01GM086868, T32GM007739] Funding Source: NIH RePORTER
NR 40
TC 657
Z9 749
U1 2
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 243
EP U138
DI 10.1038/nature08966
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500041
PM 20436459
DA 2026-03-09
ER

PT J
AU Rutishauser, U
   Ross, IB
   Mamelak, AN
   Schuman, EM
AF Rutishauser, Ueli
   Ross, Ian B.
   Mamelak, Adam N.
   Schuman, Erin M.
TI Human memory strength is predicted by theta-frequency phase-locking of single neurons
SO NATURE
LA English
DT Article
ID medial temporal-lobe; human hippocampal; action-potentials; dentate gyrus; oscillations; rhythm; retrieval; electroencephalogram; interneurons; activation
AB Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning(1). The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation(2). The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons(3). Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3-8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory(4). Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity.
C1 [Rutishauser, Ueli; Schuman, Erin M.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Schuman, Erin M.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Ross, Ian B.; Mamelak, Adam N.] Huntington Mem Hosp, Epilepsy & Brain Mapping Unit, Dept Neurosurg, Pasadena, CA 91105 USA.
   [Mamelak, Adam N.] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA.
C3 California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology; University of Southern California; Huntington Memorial Hospital; Cedars Sinai Medical Center
RP Schuman, EM (corresponding author), Max Planck Inst Brain Res, Max von Laue Str 3, D-60438 Frankfurt, Germany.
EM schumane@brain.mpg.de
FU Gordon and Betty Moore Foundation; William T. Gimbel Discovery Fund; Howard Hughes Medical Institute
NR 39
TC 475
Z9 573
U1 1
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 903
EP U116
DI 10.1038/nature08860
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300040
PM 20336071
DA 2026-03-09
ER

PT J
AU Ozgul, A
   Childs, DZ
   Oli, MK
   Armitage, KB
   Blumstein, DT
   Olson, LE
   Tuljapurkar, S
   Coulson, T
AF Ozgul, Arpat
   Childs, Dylan Z.
   Oli, Madan K.
   Armitage, Kenneth B.
   Blumstein, Daniel T.
   Olson, Lucretia E.
   Tuljapurkar, Shripad
   Coulson, Tim
TI Coupled dynamics of body mass and population growth in response to environmental change
SO NATURE
LA English
DT Article
ID yellow-bellied marmots; climate-change; natural-selection; life-history; demography; strategy; evolution; survival; models; trait
AB Environmental change has altered the phenology, morphological traits and population dynamics of many species(1,2). However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework(3). Here we investigate the link between phenotypic and demographic responses to environmental change using a new methodology and a long-term (1976-2008) data set from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change made comparable contributions to the observed marked increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments(4,5).
C1 [Ozgul, Arpat; Coulson, Tim] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, Ascot SL5 7PY, Berks, England.
   [Childs, Dylan Z.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Oli, Madan K.] Univ Florida, Dept Wildlife Ecol & Conservat, Gainesville, FL 32611 USA.
   [Armitage, Kenneth B.] Univ Kansas, Dept Ecol & Evolutionary Biol, Lawrence, KS 66045 USA.
   [Blumstein, Daniel T.; Olson, Lucretia E.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Tuljapurkar, Shripad] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
C3 Imperial College London; University of Sheffield; State University System of Florida; University of Florida; University of Kansas; University of California System; University of California Los Angeles; Stanford University
RP Ozgul, A (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, Ascot SL5 7PY, Berks, England.
EM a.ozgul@imperial.ac.uk
FU NERC; Wellcome Trust; NSF; NIH; NIA; NERC [NE/E013015/1, NE/G004390/1, NE/E015921/1] Funding Source: UKRI; Natural Environment Research Council [NE/G004390/1, NE/E015921/1, NE/E013015/1] Funding Source: researchfish; Direct For Biological Sciences; Div Of Biological Infrastructure [0731346] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0754247] Funding Source: National Science Foundation
NR 54
TC 522
Z9 586
U1 7
U2 422
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 482
EP U5
DI 10.1038/nature09210
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200034
PM 20651690
DA 2026-03-09
ER

PT J
AU Dzhindzhev, NS
   Yu, QAD
   Weiskopf, K
   Tzolovsky, G
   Cunha-Ferreira, I
   Riparbelli, M
   Rodrigues-Martins, A
   Bettencourt-Dias, M
   Callaini, G
   Glover, DM
AF Dzhindzhev, Nikola S.
   Yu, Quan D.
   Weiskopf, Kipp
   Tzolovsky, George
   Cunha-Ferreira, Ines
   Riparbelli, Maria
   Rodrigues-Martins, Ana
   Bettencourt-Dias, Monica
   Callaini, Giuliano
   Glover, David M.
TI Asterless is a scaffold for the onset of centriole assembly
SO NATURE
LA English
DT Article
ID polo-box domain; drosophila; duplication; proteins; cytokinesis; biogenesis; sufficient; substrate; embryo; cells
AB Centrioles are found in the centrosome core and, as basal bodies, at the base of cilia and flagella. Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression(1-7). Here we show that the centriolar protein Asterless (Asl; human orthologue CEP152) provides a conserved molecular platform, the amino terminus of which interacts with the cryptic Polo box of Plk4 whereas the carboxy terminus interacts with the centriolar protein Sas-4 (CPAP in humans). Drosophila Asl and human CEP152 are required for the centrosomal loading of Plk4 in Drosophila and CPAP in human cells, respectively. Depletion of Asl or CEP152 caused failure of centrosome duplication; their overexpression led to de novo centriole formation in Drosophila eggs, duplication of free centrosomes in Drosophila embryos, and centrosome amplification in cultured Drosophila and human cells. Overexpression of a Plk4-binding-deficient mutant of Asl prevented centriole duplication in cultured cells and embryos. However, this mutant protein was able to promote microtubule organizing centre (MTOC) formation in both embryos and oocytes. Such MTOCs had pericentriolar material and the centriolar protein Sas-4, but no centrioles at their core. Formation of such acentriolar MTOCs could be phenocopied by overexpression of Sas-4 in oocytes or embryos. Our findings identify independent functions for Asl as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole and organization of pericentriolar material.
C1 [Dzhindzhev, Nikola S.; Yu, Quan D.; Weiskopf, Kipp; Tzolovsky, George; Cunha-Ferreira, Ines; Rodrigues-Martins, Ana; Glover, David M.] Univ Cambridge, Dept Genet, Canc Res UK Cell Cycle Genet Grp, Cambridge CB2 3EH, England.
   [Tzolovsky, George; Riparbelli, Maria; Rodrigues-Martins, Ana; Glover, David M.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal.
   [Riparbelli, Maria; Callaini, Giuliano] Univ Siena, Dipartimento Biol Evolut, I-53100 Siena, Italy.
C3 University of Cambridge; Instituto Gulbenkian de Ciencia; University of Siena
RP Dzhindzhev, NS (corresponding author), Univ Cambridge, Dept Genet, Canc Res UK Cell Cycle Genet Grp, Downing St, Cambridge CB2 3EH, England.
EM nsd23@cam.ac.uk; dmg25@cam.ac.uk
FU Cancer Research UK; Fundacao Calouste Gulbenkian; Fundacao para a Ciencia e Tecnologia (FCT); Royal Society; Cancer Research UK [11431] Funding Source: researchfish
NR 24
TC 244
Z9 296
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 OCT 7
PY 2010
VL 467
IS 7316
BP 714
EP U104
DI 10.1038/nature09445
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500040
PM 20852615
DA 2026-03-09
ER

PT J
AU Duewell, P
   Kono, H
   Rayner, KJ
   Sirois, CM
   Vladimer, G
   Bauernfeind, FG
   Abela, GS
   Franchi, L
   Nuñez, G
   Schnurr, M
   Espevik, T
   Lien, E
   Fitzgerald, KA
   Rock, KL
   Moore, KJ
   Wright, SD
   Hornung, V
   Latz, E
AF Duewell, Peter
   Kono, Hajime
   Rayner, Katey J.
   Sirois, Cherilyn M.
   Vladimer, Gregory
   Bauernfeind, Franz G.
   Abela, George S.
   Franchi, Luigi
   Nunez, Gabriel
   Schnurr, Max
   Espevik, Terje
   Lien, Egil
   Fitzgerald, Katherine A.
   Rock, Kenneth L.
   Moore, Kathryn J.
   Wright, Samuel D.
   Hornung, Veit
   Latz, Eicke
TI NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
SO NATURE
LA English
DT Article
ID low-density-lipoprotein; nalp3 inflammasome; atherosclerotic lesions; massive xanthomatosis; hyperlipidemic mice; apolipoprotein-e; acat inhibition; progression; cells; hypercholesterolemia
AB The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation(1). Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome(2,3), which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1 alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
C1 [Duewell, Peter; Sirois, Cherilyn M.; Vladimer, Gregory; Lien, Egil; Fitzgerald, Katherine A.; Latz, Eicke] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA.
   [Kono, Hajime; Rock, Kenneth L.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA.
   [Duewell, Peter; Schnurr, Max] Univ Munich, Div Gastroenterol, Dept Med, D-80336 Munich, Germany.
   [Rayner, Katey J.; Moore, Kathryn J.] NYU, Leon H Charney Div Cardiol, New York, NY 10016 USA.
   [Rayner, Katey J.; Moore, Kathryn J.; Hornung, Veit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA.
   [Bauernfeind, Franz G.] Univ Bonn, Inst Clin Chem & Pharmacol, D-53127 Bonn, Germany.
   [Latz, Eicke] Univ Bonn, Univ Hosp, Inst Innate Immunol, D-53127 Bonn, Germany.
   [Abela, George S.] Michigan State Univ, Dept Med, Div Cardiol, E Lansing, MI 48824 USA.
   [Franchi, Luigi; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Espevik, Terje; Latz, Eicke] Norwegian Univ Sci & Technol, Inst Canc Res & Mol Med, N-7491 Trondheim, Norway.
   [Wright, Samuel D.] CSL Ltd, Cardiovasc Therapeut, Parkville, Vic 3052, Australia.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; University of Munich; New York University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of Bonn; University of Bonn; Michigan State University; University of Michigan System; University of Michigan; Norwegian University of Science & Technology (NTNU); CSL
RP Latz, E (corresponding author), Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA 01605 USA.
EM eicke.latz@umassmed.edu
FU National Institutes of Health; Deutsche Forschungsgemeinschaft [GK 1202]
NR 28
TC 3234
Z9 3733
U1 10
U2 469
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1357
EP U7
DI 10.1038/nature08938
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000048
PM 20428172
DA 2026-03-09
ER

PT J
AU Nagy, M
   Akos, Z
   Biro, D
   Vicsek, T
AF Nagy, Mate
   Akos, Zsuzsa
   Biro, Dora
   Vicsek, Tamas
TI Hierarchical group dynamics in pigeon flocks
SO NATURE
LA English
DT Article
ID collective behavior; leadership; transition
AB Animals that travel together in groups display a variety of fascinating motion patterns thought to be the result of delicate local interactions among group members(1-3). Although the most informative way of investigating and interpreting collective movement phenomena would be afforded by the collection of high-resolution spatio-temporal data from moving individuals, such data are scarce(4-7) and are virtually non-existent for long-distance group motion within a natural setting because of the associated technological difficulties(8). Here we present results of experiments in which track logs of homing pigeons flying in flocks of up to 10 individuals have been obtained by high-resolution lightweight GPS devices and analysed using a variety of correlation functions inspired by approaches common in statistical physics. We find a well-defined hierarchy among flock members from data concerning leading roles in pairwise interactions, defined on the basis of characteristic delay times between birds' directional choices. The average spatial position of a pigeon within the flock strongly correlates with its place in the hierarchy, and birds respond more quickly to conspecifics perceived primarily through the left eye-both results revealing differential roles for birds that assume different positions with respect to flock-mates. From an evolutionary perspective, our results suggest that hierarchical organization of group flight may be more efficient than an egalitarian one, at least for those flock sizes that permit regular pairwise interactions among group members, during which leader-follower relationships are consistently manifested.
C1 [Nagy, Mate; Akos, Zsuzsa; Vicsek, Tamas] Eotvos Lorand Univ, Dept Biol Phys, H-1117 Budapest, Hungary.
   [Biro, Dora] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Vicsek, Tamas] Hungarian Acad Sci, Stat & Biol Phys Res Grp, H-1117 Budapest, Hungary.
C3 Eotvos Lorand University; University of Oxford; Hungarian Academy of Sciences
RP Vicsek, T (corresponding author), Eotvos Lorand Univ, Dept Biol Phys, Pazmany Peter Setany 1A, H-1117 Budapest, Hungary.
EM vicsek@hal.elte.hu
FU EU; Royal Society; Somerville College, Oxford
NR 30
TC 851
Z9 970
U1 5
U2 373
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 890
EP U99
DI 10.1038/nature08891
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300037
PM 20376149
DA 2026-03-09
ER

PT J
AU König, R
   Stertz, S
   Zhou, Y
   Inoue, A
   Hoffmann, HH
   Bhattacharyya, S
   Alamares, JG
   Tscherne, DM
   Ortigoza, MB
   Liang, YH
   Gao, QS
   Andrews, SE
   Bandyopadhyay, S
   De Jesus, P
   Tu, BP
   Pache, L
   Shih, C
   Orth, A
   Bonamy, G
   Miraglia, L
   Ideker, T
   García-Sastre, A
   Young, JAT
   Palese, P
   Shaw, ML
   Chanda, SK
AF Koenig, Renate
   Stertz, Silke
   Zhou, Yingyao
   Inoue, Atsushi
   Hoffmann, H. -Heinrich
   Bhattacharyya, Suchita
   Alamares, Judith G.
   Tscherne, Donna M.
   Ortigoza, Mila B.
   Liang, Yuhong
   Gao, Qinshan
   Andrews, Shane E.
   Bandyopadhyay, Sourav
   De Jesus, Paul
   Tu, Buu P.
   Pache, Lars
   Shih, Crystal
   Orth, Anthony
   Bonamy, Ghislain
   Miraglia, Loren
   Ideker, Trey
   Garcia-Sastre, Adolfo
   Young, John A. T.
   Palese, Peter
   Shaw, Megan L.
   Chanda, Sumit K.
TI Human host factors required for influenza virus replication
SO NATURE
LA English
DT Article
ID functional genomic screen; protein-kinase-ii; infection; identification; rna
AB Influenza A virus is an RNA virus that encodes up to 11 proteins and this small coding capacity demands that the virus use the host cellular machinery for many aspects of its life cycle(1). Knowledge of these host cell requirements not only informs us of the molecular pathways exploited by the virus but also provides further targets that could be pursued for antiviral drug development. Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication. Within this group, those involved in kinase-regulated signalling, ubiquitination and phosphatase activity are the most highly enriched, and 181 factors assemble into a highly significant host-pathogen interaction network. Moreover, 219 of the 295 factors were confirmed to be required for efficient wild-type influenza virus growth, and further analysis of a subset of genes showed 23 factors necessary for viral entry, including members of the vacuolar ATPase (vATPase) and COPI-protein families, fibroblast growth factor receptor (FGFR) proteins, and glycogen synthase kinase 3 (GSK3)-beta. Furthermore, 10 proteins were confirmed to be involved in post-entry steps of influenza virus replication. These include nuclear import components, proteases, and the calcium/calmodulin-dependent protein kinase (CaM kinase) II beta (CAMK2B). Notably, growth of swine-origin H1N1 influenza virus is also dependent on the identified host factors, and we show that small molecule inhibitors of several factors, including vATPase and CAMK2B, antagonize influenza virus replication.
C1 [Koenig, Renate; Inoue, Atsushi; De Jesus, Paul; Pache, Lars; Shih, Crystal; Chanda, Sumit K.] Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA.
   [Bhattacharyya, Suchita; Young, John A. T.] Salk Inst Biol Studies, Nomis Ctr Immunobiol & Microbial Pathogenesis, La Jolla, CA 92037 USA.
   [Andrews, Shane E.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Stertz, Silke; Hoffmann, H. -Heinrich; Alamares, Judith G.; Tscherne, Donna M.; Ortigoza, Mila B.; Liang, Yuhong; Gao, Qinshan; Garcia-Sastre, Adolfo; Palese, Peter; Shaw, Megan L.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
   [Garcia-Sastre, Adolfo; Palese, Peter] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA.
   [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
   [Zhou, Yingyao; Tu, Buu P.; Orth, Anthony; Bonamy, Ghislain; Miraglia, Loren] Genom Inst, San Diego, CA 92121 USA.
   [Zhou, Yingyao; Tu, Buu P.; Orth, Anthony; Bonamy, Ghislain; Miraglia, Loren] Novartis Res Fdn, San Diego, CA 92121 USA.
   [Bandyopadhyay, Sourav; Ideker, Trey] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Bandyopadhyay, Sourav; Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
C3 Sanford Burnham Prebys Medical Discovery Institute; Salk Institute; Salk Institute; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Novartis; Novartis USA; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Chanda, SK (corresponding author), Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM megan.shaw@mssm.edu; schanda@burnham.org
FU National Institutes of Health (NIH), (Northeast Biodefense Center) [U01 AI1074539, U54 AI057158]; National Institutes of Health (NIH) [HHSN272200900032C, HHSN266200700010C, 1 PO1 AI058113, 1R21AI083673, 1F32AI081428, 1 T32 AI07647, U54 AI057159, 1S10RR09145-01]; German Research Foundation; Mount Sinai Medical Scientist Training Program [T32 GM007280]; Japan Society for the Promotion of Science; NIH-NCI [5R24 CA095823-04]; NSF [DBI-9724504]; National Institute of Allergy and Infectious Diseases [T32AI007647] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007280] Funding Source: NIH RePORTER
NR 29
TC 688
Z9 821
U1 0
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 813
EP 817
DI 10.1038/nature08699
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300041
PM 20027183
DA 2026-03-09
ER

PT J
AU Turner, DB
   Nelson, KA
AF Turner, Daniel B.
   Nelson, Keith A.
TI Coherent measurements of high-order electronic correlations in quantum wells
SO NATURE
LA English
DT Article
ID coulomb correlations; optical-response; spectroscopy; semiconductors; gaas; biexcitons; signatures
AB Strong, long-range Coulomb interactions can lead to correlated motions of multiple charged particles, which can induce important many-body effects in semiconductors. The exciton states formed from correlated electron-hole pairs have been studied extensively(1,2), but basic properties of multiple-exciton correlations-such as coherence times, population lifetimes, binding energies and the number of particles that can be correlated-are largely unknown because they are not spectroscopically accessible from the ground state. Here we present direct observations of high-order coherences in gallium arsenide quantum wells, achieved using two-dimensional multiple-quantum spectroscopy methods in which up to seven successive light fields were used. The measurements were made possible by the combination of a reconfigurable spatial beam-shaper that formed multiple beams in specified geometries and a spatiotemporal pulse-shaper that controlled the relative optical phases and temporal delays among pulses in all the beams. The results reveal triexciton coherences (correlations of three excitons or six particles), whose existence was not obvious because the third exciton spin is unpaired, and the values of their coherence times and binding energies. Rephasing of biexcitons, triexcitons and unbound two-exciton coherences was demonstrated. We also determined that there are no significant unbound correlations of three excitons and no bound or unbound four-exciton (eight-particle) correlations. Thus, the limits, as well as the properties, of many-body correlations in this system were revealed. The measurement methods open a new window into high-order many-body interactions in materials and molecules(3), and the present results should guide ongoing work on first-principles calculations of electronic interactions in semiconductor nanostructures(4).
C1 [Turner, Daniel B.; Nelson, Keith A.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Nelson, KA (corresponding author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM kanelson@mit.edu
FU National Defense Science and Engineering; National Science Foundation [CHE-0616939]
NR 30
TC 171
Z9 190
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1089
EP 1092
DI 10.1038/nature09286
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600036
PM 20740011
DA 2026-03-09
ER

PT J
AU Owen, AM
   Hampshire, A
   Grahn, JA
   Stenton, R
   Dajani, S
   Burns, AS
   Howard, RJ
   Ballard, CG
AF Owen, Adrian M.
   Hampshire, Adam
   Grahn, Jessica A.
   Stenton, Robert
   Dajani, Said
   Burns, Alistair S.
   Howard, Robert J.
   Ballard, Clive G.
TI Putting brain training to the test
SO NATURE
LA English
DT Article
ID spatial working-memory; visuospatial memory; executive functions; fluid intelligence; schizophrenia; deficits; lesions
AB 'Brain training', or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry(1), yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals(2,3) and preschool children(4), and video-game players outperform non-players on some tests of visual attention(5). However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.
C1 [Owen, Adrian M.; Hampshire, Adam; Grahn, Jessica A.] MRC Cognit & Brain Sci Unit, Cambridge CB2 7EF, England.
   [Stenton, Robert; Dajani, Said; Howard, Robert J.; Ballard, Clive G.] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
   [Burns, Alistair S.] Univ Manchester, Manchester M13 9PL, Lancs, England.
   [Burns, Alistair S.] Manchester Acad Hlth Sci Ctr, Manchester M13 9PL, Lancs, England.
C3 University of London; King's College London; University of Manchester; University of Manchester
RP Owen, AM (corresponding author), MRC Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England.
EM adrian.owen@mrc-cbu.cam.ac.uk
FU Medical Research Council [U.1055.01.002.00001.01, U.1055.01.003.00001.01]; Alzheimer's Society (UK); Medical Research Council [MC_U105559847, MC_U105559837] Funding Source: researchfish; MRC [MC_U105559847, MC_U105559837] Funding Source: UKRI
NR 29
TC 750
Z9 886
U1 1
U2 434
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 775
EP U6
DI 10.1038/nature09042
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800044
PM 20407435
DA 2026-03-09
ER

PT J
AU Beavan, J
   Wang, X
   Holden, C
   Wilson, K
   Power, W
   Prasetya, G
   Bevis, M
   Kautoke, R
AF Beavan, J.
   Wang, X.
   Holden, C.
   Wilson, K.
   Power, W.
   Prasetya, G.
   Bevis, M.
   Kautoke, R.
TI Near-simultaneous great earthquakes at Tongan megathrust and outer rise in September 2009
SO NATURE
LA English
DT Article
ID stress transfer; tsunami
AB The Earth's largest earthquakes and tsunamis are usually caused by thrust-faulting earthquakes on the shallow part of the subduction interface between two tectonic plates, where stored elastic energy due to convergence between the plates is rapidly released(1,2). The tsunami that devastated the Samoan and northern Tongan islands on 29 September 2009 was preceded by a globally recorded magnitude-8 normal-faulting earthquake in the outer-rise region, where the Pacific plate bends before entering the subduction zone. Preliminary interpretation suggested that this earthquake was the source of the tsunami(3). Here we show that the outer-rise earthquake was accompanied by a nearly simultaneous rupture of the shallow subduction interface, equivalent to a magnitude-8 earthquake, that also contributed significantly to the tsunami. The subduction interface event was probably a slow earthquake with a rise time of several minutes that triggered the outer-rise event several minutes later. However, we cannot rule out the possibility that the normal fault ruptured first and dynamically triggered the subduction interface event. Our evidence comes from displacements of Global Positioning System stations and modelling of tsunami waves recorded by ocean-bottom pressure sensors, with support from seismic data and tsunami field observations. Evidence of the subduction earthquake in global seismic data is largely hidden because of the earthquake's slow rise time or because its ground motion is disguised by that of the normal-faulting event. Earthquake doublets where subduction interface events trigger large outer-rise earthquakes have been recorded previously(4), but this is the first well-documented example where the two events occur so closely in time and the triggering event might be a slow earthquake. As well as providing information on strain release mechanisms at subduction zones, earthquakes such as this provide a possible mechanism for the occasional large tsunamis generated at the Tonga subduction zone(5), where slip between the plates is predominantly aseismic(6).
C1 [Beavan, J.; Wang, X.; Holden, C.; Wilson, K.; Power, W.; Prasetya, G.] GNS Sci, Lower Hutt 5040, New Zealand.
   [Bevis, M.] Ohio State Univ, Sch Earth Sci, Columbus, OH 43210 USA.
   [Kautoke, R.] Minist Lands Survey Nat Resources & Environm, Nukualofa, Tonga.
C3 Earth Sciences New Zealand; GNS Science - New Zealand; University System of Ohio; Ohio State University
RP Beavan, J (corresponding author), GNS Sci, POB 30368, Lower Hutt 5040, New Zealand.
EM j.beavan@gns.cri.nz; x.wang@gns.cri.nz
NR 29
TC 98
Z9 108
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 AUG 19
PY 2010
VL 466
IS 7309
BP 959
EP U78
DI 10.1038/nature09292
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300031
PM 20725037
DA 2026-03-09
ER

PT J
AU Bzymek, M
   Thayer, NH
   Oh, SD
   Kleckner, N
   Hunter, N
AF Bzymek, Malgorzata
   Thayer, Nathaniel H.
   Oh, Steve D.
   Kleckner, Nancy
   Hunter, Neil
TI Double Holliday junctions are intermediates of DNA break repair
SO NATURE
LA English
DT Article
ID double-strand-break; saccharomyces-cerevisiae; homologous recombination; meiotic recombination; gene conversion; crossing-over; cell-cycle; endonuclease; transition; helicase
AB Repair of DNA double-strand breaks (DSBs) by homologous recombination is crucial for cell proliferation and tumour suppression. However, despite its importance, the molecular intermediates of mitotic DSB repair remain undefined. The double Holliday junction (DHJ), presupposed to be the central intermediate for more than 25 years(1), has only been identified during meiotic recombination(2). Moreover, evidence has accumulated for alternative, DHJ-independent mechanisms(3-6), raising the possibility that DHJs are not formed during DSB repair in mitotically cycling cells. Here we identify intermediates of DSB repair by using a budding-yeast assay system designed to mimic physiological DSB repair. This system uses diploid cells and provides the possibility for allelic recombination either between sister chromatids or between homologues, as well as direct comparison with meiotic recombination at the same locus. In mitotically cycling cells, we detect inter-homologue joint molecule (JM) intermediates whose strand composition and size are identical to those of the canonical DHJ structures observed in meiosis(2). However, in contrast to meiosis, JMs between sister chromatids form in preference to those between homologues. Moreover, JMs seem to represent a minor pathway of DSB repair in mitotic cells, being detected at about tenfold lower levels (per DSB) than during meiotic recombination. Thus, although DHJs are identified as intermediates of DSB-promoted recombination in both mitotic and meiotic cells, their formation is distinctly regulated according to the specific dictates of the two cellular programs.
C1 [Bzymek, Malgorzata; Hunter, Neil] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Hunter, Neil] Univ Calif Davis, Howard Hughes Med Inst, Davis, CA 95616 USA.
   [Hunter, Neil] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Thayer, Nathaniel H.] Univ Washington, Mol & Cellular Biol PhD Program, Seattle, WA 98195 USA.
   [Oh, Steve D.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Oh, Steve D.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
   [Kleckner, Nancy] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 University of California System; University of California Davis; Howard Hughes Medical Institute; University of California System; University of California Davis; University of California System; University of California Davis; University of Washington; University of Washington Seattle; University of California System; University of California San Francisco; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Harvard University
RP Hunter, N (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM nhunter@ucdavis.edu
FU National Institutes of Health (NIH) National Institute of General Medical Sciences [GM025326, GM074223]; National Institute of General Medical Sciences [R01GM074223] Funding Source: NIH RePORTER
NR 30
TC 187
Z9 241
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 937
EP U162
DI 10.1038/nature08868
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300047
PM 20348905
DA 2026-03-09
ER

PT J
AU Haubensak, W
   Kunwar, PS
   Cai, HJ
   Ciocchi, S
   Wall, NR
   Ponnusamy, R
   Biag, J
   Dong, HW
   Deisseroth, K
   Callaway, EM
   Fanselow, MS
   Lüthi, A
   Anderson, DJ
AF Haubensak, Wulf
   Kunwar, Prabhat S.
   Cai, Haijiang
   Ciocchi, Stephane
   Wall, Nicholas R.
   Ponnusamy, Ravikumar
   Biag, Jonathan
   Dong, Hong-Wei
   Deisseroth, Karl
   Callaway, Edward M.
   Fanselow, Michael S.
   Luethi, Andreas
   Anderson, David J.
TI Genetic dissection of an amygdala microcircuit that gates conditioned fear
SO NATURE
LA English
DT Article
ID central extended amygdala; rat central nucleus; bacterial artificial chromosm; neurons in-vitro; periaqueductal gray; neural circuits; basal ganglia; rabies virus; expression; vivo
AB The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-delta (PKC-delta). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-delta(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-delta(-) neurons in CEl. Electrical silencing of PKC-delta(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.
C1 [Haubensak, Wulf; Kunwar, Prabhat S.; Cai, Haijiang; Anderson, David J.] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
   [Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Ciocchi, Stephane; Luethi, Andreas] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Wall, Nicholas R.; Callaway, Edward M.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
   [Ponnusamy, Ravikumar; Fanselow, Michael S.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
   [Ponnusamy, Ravikumar; Fanselow, Michael S.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
   [Biag, Jonathan; Dong, Hong-Wei] Univ Calif Los Angeles, Lab Neuroimaging, Los Angeles, CA 90095 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
C3 California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; Friedrich Miescher Institute for Biomedical Research; Salk Institute; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Stanford University
RP Anderson, DJ (corresponding author), CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
EM wuwei@caltech.edu
FU NIH [1 R01 MH085082-01A1]; Caltech; Human Frontier Science Program; Jane Coffin Childs Memorial Fund for Medical Research; Novartis Research Foundation
NR 53
TC 671
Z9 832
U1 0
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 270
EP U230
DI 10.1038/nature09553
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000044
PM 21068836
DA 2026-03-09
ER

PT J
AU Schülli, TU
   Daudin, R
   Renaud, G
   Vaysset, A
   Geaymond, O
   Pasturel, A
AF Schuelli, T. U.
   Daudin, R.
   Renaud, G.
   Vaysset, A.
   Geaymond, O.
   Pasturel, A.
TI Substrate-enhanced supercooling in AuSi eutectic droplets
SO NATURE
LA English
DT Article
ID liquid-solid growth; molecular-dynamics; nanowire growth; alloy; order; interface; crystallization; epitaxy; metals; gold
AB The phenomenon of supercooling in metals-that is, the preservation of a disordered, fluid phase in a metastable state well below the melting point(1)-has led to speculation that local atomic structure configurations of dense, symmetric, but non-periodic packing act as the main barrier for crystal nucleation(2,3). For liquids in contact with solids, crystalline surfaces induce layering of the adjacent atoms in the liquid(4,5) and may prevent or lower supercooling(6). This seed effect is supposed to depend on the local lateral order adopted in the last atomic layers of the liquid in contact with the crystal. Although it has been suggested that there might be a direct coupling between surface-induced lateral order and supercooling(6), no experimental observation of such lateral ordering at interfaces is available(6). Here we report supercooling in gold-silicon (AuSi) eutectic droplets, enhanced by a Au-induced (6 x 6) reconstruction of the Si(111) substrate. In situ X-ray scattering and ab initio molecular dynamics reveal that pentagonal atomic arrangements of Au atoms at this interface favour a lateral-ordering stabilization process of the liquid phase. This interface-enhanced stabilization of the liquid state shows the importance of the solid-liquid interaction for the structure of the adjacent liquid layers. Such processes are important for present and future technologies, as fluidity and crystallization play a key part in soldering and casting, as well as in processing and controlling chemical reactions for microfluidic devices or during the vapour-liquid-solid growth of semiconductor nanowires.
C1 [Schuelli, T. U.; Daudin, R.; Renaud, G.; Vaysset, A.; Pasturel, A.] CEA, Inst Nanosci & Cryogenie, SP2M, F-38054 Grenoble, France.
   [Schuelli, T. U.] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
   [Geaymond, O.] Inst Neel, CNRS, F-38042 Grenoble, France.
   [Pasturel, A.] SIMAP INPG, F-38402 St Martin Dheres, France.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; European Synchrotron Radiation Facility (ESRF); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS)
RP Schülli, TU (corresponding author), CEA, Inst Nanosci & Cryogenie, SP2M, 17 Rue Martyrs, F-38054 Grenoble, France.
EM schulli@esrf.fr
NR 29
TC 107
Z9 119
U1 1
U2 185
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1174
EP 1177
DI 10.1038/nature08986
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100033
PM 20414305
DA 2026-03-09
ER

PT J
AU Richly, H
   Rocha-Viegas, L
   Ribeiro, JD
   Demajo, S
   Gundem, G
   Lopez-Bigas, N
   Nakagawa, T
   Rospert, S
   Ito, T
   Di Croce, L
AF Richly, Holger
   Rocha-Viegas, Luciana
   Domingues Ribeiro, Joana
   Demajo, Santiago
   Gundem, Gunes
   Lopez-Bigas, Nuria
   Nakagawa, Tekeya
   Rospert, Sabine
   Ito, Takashi
   Di Croce, Luciano
TI Transcriptional activation of polycomb-repressed genes by ZRF1
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; h2a ubiquitination; histone h2b; protein; chromatin; differentiation; monoubiquitination; demethylation; initiation; leukemia
AB Covalent modification of histones is fundamental in orchestrating chromatin dynamics and transcription(1-3). One example of such an epigenetic mark is the mono-ubiquitination of histones, which mainly occurs at histone H2A and H2B(4-6). Ubiquitination of histone H2A has been implicated in polycomb-mediated transcriptional silencing(7-9). However, the precise role of the ubiquitin mark during silencing is still elusive. Here we show in human cell lines that ZRF1 (zuotin-related factor 1) is specifically recruited to histone H2A when it is ubiquitinated at Lys 119 by means of a novel ubiquitin-interacting domain that is located in the evolutionarily conserved zuotin domain. At the onset of differentiation, ZRF1 specifically displaces polycomb-repressive complex 1 (PRC1) from chromatin and facilitates transcriptional activation. A genome-wide mapping of ZRF1, RING1B and H2A-ubiquitin targets revealed its involvement in the regulation of a large set of polycomb target genes, emphasizing the key role ZRF1 has in cell fate decisions. We provide here a model of the molecular mechanism of switching polycomb-repressed genes to an active state.
C1 [Richly, Holger; Rocha-Viegas, Luciana; Domingues Ribeiro, Joana; Demajo, Santiago; Di Croce, Luciano] UPF, CRG, Barcelona 08003, Spain.
   [Gundem, Gunes; Lopez-Bigas, Nuria] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona 08003, Spain.
   [Nakagawa, Tekeya; Ito, Takashi] Nagasaki Univ, Sch Med, Nagasaki 8528523, Japan.
   [Rospert, Sabine] Univ Freiburg, Inst Biochem & Mol Biol ZBMZ, D-79104 Freiburg, Germany.
   [Di Croce, Luciano] PRBB, CRG, ICREA, Barcelona 08003, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Nagasaki University; University of Freiburg; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Barcelona Biomedical Research Park; ICREA
RP Di Croce, L (corresponding author), UPF, CRG, Barcelona 08003, Spain.
EM luciano.dicroce@crg.es
FU Spanish "Ministerio de Educacion y Ciencia'' [BFU2007-63059]; Association for International Cancer Research [10-0177]; AGAUR; Consolider; FEBS fellowship; Fundacao para a Ciencia e Tecnologia; Juan de la Cierva Fellowship; PFIS fellowship;  [FOR967]; ICREA Funding Source: Custom
NR 33
TC 118
Z9 128
U1 2
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1124
EP U533
DI 10.1038/nature09574
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800063
PM 21179169
DA 2026-03-09
ER

PT J
AU Kim, HJ
   Verbinnen, B
   Tang, XL
   Lu, LR
   Cantor, H
AF Kim, Hye-Jung
   Verbinnen, Bert
   Tang, Xiaolei
   Lu, Linrong
   Cantor, Harvey
TI Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance
SO NATURE
LA English
DT Article
ID systemic-lupus-erythematosus; autoimmune-disease; b-cells; suppression; t-helper-2; generation; expansion; il-15; il-21; mice
AB The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses(1). Regulatory T cells (T-reg) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined(2). Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.
C1 [Kim, Hye-Jung; Verbinnen, Bert; Tang, Xiaolei; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   [Kim, Hye-Jung; Verbinnen, Bert; Tang, Xiaolei; Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Lu, Linrong] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Zhejiang University
RP Cantor, H (corresponding author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
EM Harvey_Cantor@dfci.harvard.edu
FU NIH [AI 037562]; Lupus Research Institute; Schecter Research Foundation; National Research Service [DFCI/NCI T32 CA070083, HSPH/NCI T32 CA009382]; Belgian American Educational Foundation; National Institute of Allergy and Infectious Diseases [R01AI037562] Funding Source: NIH RePORTER
NR 23
TC 300
Z9 385
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 SEP 16
PY 2010
VL 467
IS 7313
BP 328
EP U107
DI 10.1038/nature09370
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900039
PM 20844537
DA 2026-03-09
ER

PT J
AU Gross, C
   Zibold, T
   Nicklas, E
   Estève, J
   Oberthaler, MK
AF Gross, C.
   Zibold, T.
   Nicklas, E.
   Esteve, J.
   Oberthaler, M. K.
TI Nonlinear atom interferometer surpasses classical precision limit
SO NATURE
LA English
DT Article
ID standard quantum limit; entanglement; states; spectroscopy
AB Interference is fundamental to wave dynamics and quantum mechanics. The quantum wave properties of particles are exploited in metrology using atom interferometers, allowing for high-precision inertia measurements(1,2). Furthermore, the state-of-the-art time standard is based on an interferometric technique known as Ramsey spectroscopy. However, the precision of an interferometer is limited by classical statistics owing to the finite number of atoms used to deduce the quantity of interest(3). Here we show experimentally that the classical precision limit can be surpassed using nonlinear atom interferometry with a Bose-Einstein condensate. Controlled interactions between the atoms lead to non-classical entangled states within the interferometer; this represents an alternative approach to the use of non-classical input states(4-8). Extending quantum interferometry(9) to the regime of large atom number, we find that phase sensitivity is enhanced by 15 per cent relative to that in an ideal classical measurement. Our nonlinear atomic beam splitter follows the 'one-axis-twisting' scheme(10) and implements interaction control using a narrow Feshbach resonance. We perform noise tomography of the quantum state within the interferometer and detect coherent spin squeezing with a squeezing factor of -8.2 dB (refs 11-15). The results provide information on the many-particle quantum state, and imply the entanglement of 170 atoms(16).
C1 [Gross, C.; Zibold, T.; Nicklas, E.; Esteve, J.; Oberthaler, M. K.] Heidelberg Univ, Kirchhoff Inst Phys, D-69120 Heidelberg, Germany.
C3 Ruprecht Karls University Heidelberg
RP Oberthaler, MK (corresponding author), Heidelberg Univ, Kirchhoff Inst Phys, Neuenheimer Feld 227, D-69120 Heidelberg, Germany.
EM quantum.metrology@matterwave.de
FU Deutsche Forschungsgemeinschaft; German-Israeli Foundation; Heidelberg Center of Quantum Dynamics; ExtreMe Matter Institute; European Commission; Landesgraduiertenforderung Baden-Wurttemberg
NR 30
TC 717
Z9 782
U1 1
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1165
EP 1169
DI 10.1038/nature08919
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100031
PM 20357767
DA 2026-03-09
ER

PT J
AU Janda, CY
   Li, J
   Oubridge, C
   Hernández, H
   Robinson, CV
   Nagai, K
AF Janda, Claudia Y.
   Li, Jade
   Oubridge, Chris
   Hernandez, Helena
   Robinson, Carol V.
   Nagai, Kiyoshi
TI Recognition of a signal peptide by the signal recognition particle
SO NATURE
LA English
DT Article
ID escherichia-coli ribonucleoprotein; crystal-structure; ribosome; sequence; rna; proteins; translocation; contains; subunit; domain
AB Targeting of proteins to appropriate subcellular compartments is a crucial process in all living cells. Secretory and membrane proteins usually contain an amino-terminal signal peptide, which is recognized by the signal recognition particle (SRP) when nascent polypeptide chains emerge from the ribosome. The SRP-ribosome nascent chain complex is then targeted through its GTP-dependent interaction with SRP receptor to the protein-conducting channel on endoplasmic reticulum membrane in eukaryotes or plasma membrane in bacteria. A universally conserved component of SRP (refs 1, 2), SRP54 or its bacterial homologue, fifty-four homologue (Ffh), binds the signal peptides, which have a highly divergent sequence divisible into a positively charged n-region, an h-region commonly containing 8-20 hydrophobic residues and a polar c-region(3-5). No structure has been reported that exemplifies SRP54 binding of any signal sequence. Here we have produced a fusion protein between Sulfolobus solfataricus SRP54 (Ffh) and a signal peptide connected via a flexible linker. This fusion protein oligomerizes in solution through interaction between the SRP54 and signal peptide moieties belonging to different chains, and it is functional, as demonstrated by its ability to bind SRP RNA and SRP receptor FtsY. We present the crystal structure at 3.5 angstrom resolution of an SRP54-signal peptide complex in the dimer, which reveals how a signal sequence is recognized by SRP54.
C1 [Janda, Claudia Y.; Li, Jade; Oubridge, Chris; Nagai, Kiyoshi] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Hernandez, Helena; Robinson, Carol V.] Univ Cambridge, Chem Labs, Cambridge CB2 1EW, England.
C3 MRC Laboratory Molecular Biology; University of Cambridge
RP Nagai, K (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM kn@mrc-lmb.cam.ac.uk
FU Medical Research Council of the UK; HFSP; Medical Research Council [MC_U105184330] Funding Source: researchfish; MRC [MC_U105184330] Funding Source: UKRI
NR 32
TC 168
Z9 207
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 MAY 27
PY 2010
VL 465
IS 7297
BP 507
EP U139
DI 10.1038/nature08870
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700041
PM 20364120
DA 2026-03-09
ER

PT J
AU Eisenegger, C
   Naef, M
   Snozzi, R
   Heinrichs, M
   Fehr, E
AF Eisenegger, C.
   Naef, M.
   Snozzi, R.
   Heinrichs, M.
   Fehr, E.
TI Prejudice and truth about the effect of testosterone on human bargaining behaviour
SO NATURE
LA English
DT Article
ID healthy-young women; prison-inmates; men; dominance; responses; fairness
AB Both biosociological and psychological models, as well as animal research, suggest that testosterone has a key role in social interactions(1-7). Evidence from animal studies in rodents shows that testosterone causes aggressive behaviour towards conspecifics(7). Folk wisdom generalizes and adapts these findings to humans, suggesting that testosterone induces antisocial, egoistic, or even aggressive human behaviours. However, many researchers have questioned this folk hypothesis(1-6), arguing that testosterone is primarily involved in status-related behaviours in challenging social interactions, but causal evidence that discriminates between these views is sparse. Here we show that the sublingual administration of a single dose of testosterone in women causes a substantial increase in fair bargaining behaviour, thereby reducing bargaining conflicts and increasing the efficiency of social interactions. However, subjects who believed that they received testosterone-regardless of whether they actually received it or not-behaved much more unfairly than those who believed that they were treated with placebo. Thus, the folk hypothesis seems to generate a strong negative association between subjects' beliefs and the fairness of their offers, even though testosterone administration actually causes a substantial increase in the frequency of fair bargaining offers in our experiment.
C1 [Eisenegger, C.; Naef, M.; Snozzi, R.; Fehr, E.] Univ Zurich, Inst Empir Res Econ, Lab Social & Neural Syst Res, CH-8006 Zurich, Switzerland.
   [Naef, M.] Univ London, Dept Econ, Egham TW20 0EX, Surrey, England.
   [Heinrichs, M.] Univ Freiburg, Dept Psychol, Lab Biol & Personal Psychol, D-79104 Freiburg, Germany.
C3 University of Zurich; University of London; Royal Holloway University London; University of Freiburg
RP Eisenegger, C (corresponding author), Univ Zurich, Inst Empir Res Econ, Lab Social & Neural Syst Res, CH-8006 Zurich, Switzerland.
EM eisenegger@iew.uzh.ch; efehr@iew.uzh.ch
FU National Center of Competence in Affective Sciences; Neurochoice Project of SystemsX; Swiss National Science Foundation
NR 39
TC 289
Z9 331
U1 0
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 356
EP U104
DI 10.1038/nature08711
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100044
PM 19997098
DA 2026-03-09
ER

PT J
AU Raj, A
   Rifkin, SA
   Andersen, E
   van Oudenaarden, A
AF Raj, Arjun
   Rifkin, Scott A.
   Andersen, Erik
   van Oudenaarden, Alexander
TI Variability in gene expression underlies incomplete penetrance
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; gata-factor; c-elegans; single-cell; transcription; skn-1; endoderm; pop-1; elt-2; differentiation
AB The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.
C1 [Raj, Arjun; Rifkin, Scott A.; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Raj, Arjun; Rifkin, Scott A.; Andersen, Erik; van Oudenaarden, Alexander] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Andersen, Erik] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Princeton University
RP van Oudenaarden, A (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM avano@mit.edu
FU National Institutes of Health (NIH); National Science Foundation [DMS-0603392]; Burroughs-Wellcome Fund; NIH NRSA [5F32GM080966]
NR 50
TC 512
Z9 623
U1 2
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 913
EP U84
DI 10.1038/nature08781
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700038
PM 20164922
DA 2026-03-09
ER

PT J
AU Wu, YK
   Yang, Y
   Ye, S
   Jiang, YX
AF Wu, Yunkun
   Yang, Yi
   Ye, Sheng
   Jiang, Youxing
TI Structure of the gating ring from the human large-conductance Ca2+-gated K+ channel
SO NATURE
LA English
DT Article
ID dependent activation; voltage sensor; lipid-membrane; bkca channel; ion-binding; rck domain; ca2+; sensitivity; mechanism; mg2+
AB Large-conductance Ca2+-gated K+ (BK) channels are essential for many biological processes such as smooth muscle contraction and neurotransmitter release(1-4). This group of channels can be activated synergistically by both voltage and intracellular Ca2+, with the large carboxy-terminal intracellular portion being responsible for Ca2+ sensing(5-13). Here we present the crystal structure of the entire cytoplasmic region of the human BK channel in a Ca2+-free state. The structure reveals four intracellular subunits, each comprising two tandem RCK domains, assembled into a gating ring similar to that seen in the MthK channel 14 and probably representing its physiological assembly. Three Ca2+ binding sites including the Ca2+ bowl are mapped onto the structure based on mutagenesis data. The Ca2+ bowl, located within the second RCK domain, forms an EF-hand-like motif and is strategically positioned close to the assembly interface between two subunits. The other two Ca2+ (or Mg2+) binding sites, Asp 367 and Glu 374/Glu 399, are located on the first RCK domain. The Asp 367 site has high Ca2+ sensitivity and is positioned in the groove between the amino-and carboxyterminal subdomains of RCK1, whereas the low-affinity Mg2+-binding Glu 374/Glu 399 site is positioned on the upper plateau of the gating ring and close to the membrane. Our structure also contains the linker connecting the transmembrane and intracellular domains, allowing us to dock a voltage-gated K+ channel pore of known structure onto the gating ring with reasonable accuracy and generate a structural model for the full BK channel.
C1 [Wu, Yunkun; Yang, Yi; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Wu, Yunkun; Jiang, Youxing] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Ye, Sheng] Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Zhejiang University
RP Jiang, YX (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
EM youxing.jiang@utsouthwestern.edu
FU Howard Hughes Medical Institute; NIH/NIGMS [RO1 GM071621]; Welch Foundation
NR 39
TC 173
Z9 197
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 JUL 15
PY 2010
VL 466
IS 7304
BP 393
EP U148
DI 10.1038/nature09252
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100054
PM 20574420
DA 2026-03-09
ER

PT J
AU Peterson, WM
   Mutel, RL
   Güdel, M
   Goss, WM
AF Peterson, W. M.
   Mutel, R. L.
   Guedel, M.
   Goss, W. M.
TI A large coronal loop in the Algol system
SO NATURE
LA English
DT Article
ID polarization vlbi observations; x-ray; radio-emission; ux-arietis; solar corona; close binary; stars; region; flare; astrometry
AB The close binary Algol system contains a radio-bright KIV sub-giant star in a very close (0.062 astronomical units) and rapid (2.86 day) orbit with a main sequence B8 star. Because the rotation periods of the two stars are tidally locked to the orbital period, the rapid rotation drives a magnetic dynamo. A large body of evidence points to the existence of an extended, complex coronal magnetosphere originating at the cooler K subgiant(1-4). The detailed morphology of the subgiant's corona and its possible interaction with its companion are unknown, though theory predicts that the coronal plasma should be confined in a magnetic loop structure(5), as seen on the Sun. Here we report multi-epoch radio imaging of the Algol system, in which we see a large, persistent coronal loop approximately one subgiant diameter in height, whose base is straddling the subgiant and whose apex is oriented towards the B8 star. This suggests that a persistent asymmetric magnetic field structure is aligned between the two stars. The loop is larger than anticipated theoretically(6,7), but the size may be the result of a magnetic interaction between the two stars.
C1 [Peterson, W. M.; Mutel, R. L.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52240 USA.
   [Guedel, M.] ETH, Inst Astron, CH-8093 Zurich, Switzerland.
   [Goss, W. M.] Natl Radio Astron Observ, Pete V Domenici Sci Operat Ctr, Socorro, NM 87801 USA.
C3 University of Iowa; Swiss Federal Institutes of Technology Domain; ETH Zurich; National Radio Astronomy Observatory (NRAO)
RP Peterson, WM (corresponding author), Univ Iowa, Dept Phys & Astron, Van Allen Hall, Iowa City, IA 52240 USA.
EM bmp@astro.physics.uiowa.edu
FU NRAO [GSSP08-0022]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0908941] Funding Source: National Science Foundation
NR 29
TC 46
Z9 49
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 207
EP 209
DI 10.1038/nature08643
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700030
PM 20075916
DA 2026-03-09
ER

PT J
AU Tormo-Más, MA
   Mir, I
   Shrestha, A
   Tallent, SM
   Campoy, S
   Lasa, I
   Barbé, J
   Novick, RP
   Christie, GE
   Penadés, JR
AF Angeles Tormo-Mas, Maria
   Mir, Ignacio
   Shrestha, Archana
   Tallent, Sandra M.
   Campoy, Susana
   Lasa, Inigo
   Barbe, Jordi
   Novick, Richard P.
   Christie, Gail E.
   Penades, Jose R.
TI Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands
SO NATURE
LA English
DT Article
ID gram-positive bacteria; helper phage; aureus; particles; dutpase; vector; toxin
AB Staphylococcal superantigen-carrying pathogenicity islands (SaPIs) are discrete, chromosomally integrated units of similar to 15 kilobases that are induced by helper phages to excise and replicate. SaPI DNA is then efficiently encapsidated in phage-like infectious particles, leading to extremely high frequencies of intra-as well as intergeneric transfer(1-3). In the absence of helper phage lytic growth, the island is maintained in a quiescent prophage-like state by a global repressor, Stl, which controls expression of most of the SaPI genes(4). Here we show that SaPI derepression is effected by a specific, non-essential phage protein that binds to Stl, disrupting the Stl-DNA complex and thereby initiating the excision-replication-packaging cycle of the island. Because SaPIs require phage proteins to be packaged(5,6), this strategy assures that SaPIs will be transferred once induced. Several different SaPIs are induced by helper phage 80 alpha and, in each case, the SaPI commandeers a different non-essential phage protein for its derepression. The highly specific interactions between different SaPI repressors and helper-phage-encoded anti-repressors represent a remarkable evolutionary adaptation involved in pathogenicity island mobilization.
C1 [Angeles Tormo-Mas, Maria; Mir, Ignacio; Penades, Jose R.] Inst Valenciano Invest Agr, CITA, Segorbe 12400, Castellon, Spain.
   [Shrestha, Archana; Tallent, Sandra M.; Christie, Gail E.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA.
   [Campoy, Susana; Barbe, Jordi] Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain.
   [Lasa, Inigo] Univ Publ Navarra, CSIC, Inst Agrobiotecnol, Navarra 31006, Spain.
   [Novick, Richard P.] NYU, Med Ctr, Skirball Inst Program Mol Pathogenesis, New York, NY 10016 USA.
   [Novick, Richard P.] NYU, Med Ctr, Dept Microbiol, New York, NY 10016 USA.
   [Novick, Richard P.] NYU, Med Ctr, Dept Med, New York, NY 10016 USA.
   [Penades, Jose R.] Univ Cardenal Herrera CEU, Dept Quim Bioquim & Biol Mol, Valencia 46113, Spain.
C3 Instituto Valenciano de Investigaciones Agrarias (IVIA); Virginia Commonwealth University; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-GN-UPNA - Instituto de Agrobiotecnologia (IDAB); Universidad Publica de Navarra; New York University; New York University; New York University; Universidad CEU Cardenal Herrera
RP Penadés, JR (corresponding author), Inst Valenciano Invest Agr, CITA, Apdo 187, Segorbe 12400, Castellon, Spain.
EM penades_jos@gva.es
FU Ministerio de Ciencia e Innovacion (MICINN) [CSD2009-00006, BIO2005-08399-C02-02, BIO2008-05284-C02-02, BIO2008-00642-E/C, BFU2008-01078]; Cardenal Herrera-CEU University [PRCEU-UCH25/08]; Conselleria de Agricultura, Pesca i Alimentacio (CAPiA); Generalitat Valenciana [ACOMP07/258]; Generalitat de Catalunya [2009SGR1106]; NIH [R21AI067654, R01AI022159-23A2]; A. D. Williams Trust; Baruch Foundation Trust
NR 15
TC 147
Z9 176
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 779
EP U7
DI 10.1038/nature09065
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800045
PM 20473284
DA 2026-03-09
ER

PT J
AU Frankel, N
   Davis, GK
   Vargas, D
   Wang, S
   Payre, F
   Stern, DL
AF Frankel, Nicolas
   Davis, Gregory K.
   Vargas, Diego
   Wang, Shu
   Payre, Francois
   Stern, David L.
TI Phenotypic robustness conferred by apparently redundant transcriptional enhancers
SO NATURE
LA English
DT Article
ID regulatory elements; wingless; activation; expression; mutations; evolution; epidermis; hedgehog; dorsal; roles
AB Genes include cis-regulatory regions that contain transcriptional enhancers. Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns(1-4): primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote positions. It has been proposed that the seemingly redundant activity of primary and secondary enhancers contributes to phenotypic robustness(1,5). We tested this hypothesis by generating a deficiency that removes two newly discovered enhancers of shavenbaby (svb, a transcript of the ovo locus), a gene encoding a transcription factor that directs development of Drosophila larval trichomes(6). At optimal temperatures for embryonic development, this deficiency causes minor defects in trichome patterning. In embryos that develop at both low and high extreme temperatures, however, absence of these secondary enhancers leads to extensive loss of trichomes. These temperature-dependent defects can be rescued by a transgene carrying a secondary enhancer driving transcription of the svb cDNA. Finally, removal of one copy of wingless, a gene required for normal trichome patterning(7), causes a similar loss of trichomes only in flies lacking the secondary enhancers. These results support the hypothesis that secondary enhancers contribute to phenotypic robustness in the face of environmental and genetic variability.
C1 [Frankel, Nicolas; Vargas, Diego; Wang, Shu; Stern, David L.] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
   [Frankel, Nicolas; Vargas, Diego; Wang, Shu; Stern, David L.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Davis, Gregory K.] Bryn Mawr Coll, Dept Biol, Bryn Mawr, PA 19010 USA.
   [Payre, Francois] Univ Toulouse, F-31062 Toulouse, France.
   [Payre, Francois] CNRS, UMR5547, Ctr Dev Biol, F-31062 Toulouse, France.
C3 Howard Hughes Medical Institute; Princeton University; Princeton University; Bryn Mawr College; Universite de Toulouse; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Stern, DL (corresponding author), Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
EM dstern@princeton.edu
FU Pew Charitable Trusts; Agence Nationale de la Recherche; NIH [GM063622-06A1]; NSF [IOS-0640339]
NR 26
TC 403
Z9 522
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 490
EP U8
DI 10.1038/nature09158
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200036
PM 20512118
DA 2026-03-09
ER

PT J
AU Pleasance, ED
   Stephens, PJ
   O'Meara, S
   McBride, DJ
   Meynert, A
   Jones, D
   Lin, ML
   Beare, D
   Lau, KW
   Greenman, C
   Varela, I
   Nik-Zainal, S
   Davies, HR
   Ordoñez, GR
   Mudie, LJ
   Latimer, C
   Edkins, S
   Stebbings, L
   Chen, LN
   Jia, MM
   Leroy, C
   Marshall, J
   Menzies, A
   Butler, A
   Teague, JW
   Mangion, J
   Sun, YA
   McLaughlin, SF
   Peckham, HE
   Tsung, EF
   Costa, GL
   Lee, CC
   Minna, JD
   Gazdar, A
   Birney, E
   Rhodes, MD
   McKernan, KJ
   Stratton, MR
   Futreal, PA
   Campbell, PJ
AF Pleasance, Erin D.
   Stephens, Philip J.
   O'Meara, Sarah
   McBride, David J.
   Meynert, Alison
   Jones, David
   Lin, Meng-Lay
   Beare, David
   Lau, King Wai
   Greenman, Chris
   Varela, Ignacio
   Nik-Zainal, Serena
   Davies, Helen R.
   Ordonez, Gonzalo R.
   Mudie, Laura J.
   Latimer, Calli
   Edkins, Sarah
   Stebbings, Lucy
   Chen, Lina
   Jia, Mingming
   Leroy, Catherine
   Marshall, John
   Menzies, Andrew
   Butler, Adam
   Teague, Jon W.
   Mangion, Jonathon
   Sun, Yongming A.
   McLaughlin, Stephen F.
   Peckham, Heather E.
   Tsung, Eric F.
   Costa, Gina L.
   Lee, Clarence C.
   Minna, John D.
   Gazdar, Adi
   Birney, Ewan
   Rhodes, Michael D.
   McKernan, Kevin J.
   Stratton, Michael R.
   Futreal, P. Andrew
   Campbell, Peter J.
TI A small-cell lung cancer genome with complex signatures of tobacco exposure
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; holliday junction resolvase; somatic mutations; cigarette-smoking; p53 mutations; dna-damage; gene; binding; repair; carcinogenesis
AB Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
C1 [Pleasance, Erin D.; Stephens, Philip J.; O'Meara, Sarah; McBride, David J.; Jones, David; Lin, Meng-Lay; Beare, David; Lau, King Wai; Greenman, Chris; Varela, Ignacio; Nik-Zainal, Serena; Davies, Helen R.; Ordonez, Gonzalo R.; Mudie, Laura J.; Latimer, Calli; Edkins, Sarah; Stebbings, Lucy; Chen, Lina; Jia, Mingming; Leroy, Catherine; Marshall, John; Menzies, Andrew; Butler, Adam; Teague, Jon W.; Stratton, Michael R.; Futreal, P. Andrew; Campbell, Peter J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [O'Meara, Sarah; Mangion, Jonathon] Life Technol, Warrington WA3 7QH, Cheshire, England.
   [Meynert, Alison; Birney, Ewan] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Sun, Yongming A.; Rhodes, Michael D.] Life Technol, Foster City, CA 94404 USA.
   [McLaughlin, Stephen F.; Peckham, Heather E.; Tsung, Eric F.; Costa, Gina L.; Lee, Clarence C.; McKernan, Kevin J.] Life Technol, Beverley, MA 01915 USA.
   [Minna, John D.; Gazdar, Adi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
   [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
C3 Wellcome Trust Sanger Institute; Thermo Fisher Scientific; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Thermo Fisher Scientific; Thermo Fisher Scientific; University of Texas System; University of Texas Southwestern Medical Center; University of London; Institute of Cancer Research - UK; University of Cambridge
RP Campbell, PJ (corresponding author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
EM pc8@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; Human Frontiers Science Programme; NCI [NCI P50CA70907]; National Cancer Institute [P50CA070907] Funding Source: NIH RePORTER
NR 43
TC 852
Z9 1150
U1 1
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 184
EP U66
DI 10.1038/nature08629
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700026
PM 20016488
DA 2026-03-09
ER

PT J
AU Zhao, Z
   Andersen, SU
   Ljung, K
   Dolezal, K
   Miotk, A
   Schultheiss, SJ
   Lohmann, JU
AF Zhao, Zhong
   Andersen, Stig U.
   Ljung, Karin
   Dolezal, Karel
   Miotk, Andrej
   Schultheiss, Sebastian J.
   Lohmann, Jan U.
TI Hormonal control of the shoot stem-cell niche
SO NATURE
LA English
DT Article
ID auxin response factors; arabidopsis-thaliana; transcription factor; gene-expression; cytokinin; meristem; wuschel; fate; embryogenesis; biosynthesis
AB The classic phytohormones cytokinin and auxin play essential roles in the maintenance of stem-cell systems embedded in shoot and root meristems, and exhibit complex functional interactions(1-4). Here we show that the activity of both hormones directly converges on the promoters of two A-type ARABIDOPSIS RESPONSE REGULATOR (ARR) genes, ARR7 and ARR15, which are negative regulators of cytokinin signalling(5) and have important meristematic functions(3). Whereas ARR7 and ARR15 expression in the shoot apical meristem (SAM) is induced by cytokinin, auxin has a negative effect, which is, at least in part, mediated by the AUXIN RESPONSE FACTOR5/MONOPTEROS (MP) transcription factor(6). Our results provide a mechanistic framework for hormonal control of the apical stem-cell niche and demonstrate how root and shoot stem-cell systems differ in their response to phytohormones.
C1 [Zhao, Zhong; Miotk, Andrej; Lohmann, Jan U.] Heidelberg Univ, Dept Stem Cell Biol, D-69120 Heidelberg, Germany.
   [Zhao, Zhong; Andersen, Stig U.; Miotk, Andrej; Schultheiss, Sebastian J.; Lohmann, Jan U.] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Ljung, Karin; Dolezal, Karel] Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, S-90183 Umea, Sweden.
   [Dolezal, Karel] Palacky Univ, Lab Growth Regulators, Olomouc 78371, Czech Republic.
   [Dolezal, Karel] Acad Sci Czech Republ, Inst Expt Bot, Olomouc 78371, Czech Republic.
   [Schultheiss, Sebastian J.] Max Planck Gesell, Friedrich Miescher Lab, D-72076 Tubingen, Germany.
C3 Ruprecht Karls University Heidelberg; Max Planck Society; Swedish University of Agricultural Sciences; Umea University; Palacky University Olomouc; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; Max Planck Society; Eberhard Karls University of Tubingen
RP Lohmann, JU (corresponding author), Heidelberg Univ, Dept Stem Cell Biol, D-69120 Heidelberg, Germany.
EM jlohmann@meristemania.org
FU Human Frontier Science Program; EMBO; Carlsberg Foundation; Czech Ministry of Education [MSM 6198959216]; Max Planck Society;  [SFB446]
NR 34
TC 415
Z9 483
U1 4
U2 183
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1089
EP U154
DI 10.1038/nature09126
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900055
PM 20577215
DA 2026-03-09
ER

PT J
AU Chen, YH
   Hu, L
   Punta, M
   Bruni, R
   Hillerich, B
   Kloss, B
   Rost, B
   Love, J
   Siegelbaum, SA
   Hendrickson, WA
AF Chen, Yu-hang
   Hu, Lei
   Punta, Marco
   Bruni, Renato
   Hillerich, Brandan
   Kloss, Brian
   Rost, Burkhard
   Love, James
   Siegelbaum, Steven A.
   Hendrickson, Wayne A.
TI Homologue structure of the SLAC1 anion channel for closing stomata in leaves
SO NATURE
LA English
DT Article
ID abscisic-acid; chloride channel; guard-cell; plasma-membrane; sulfite efflux; protein; selectivity; model; gene; conservation
AB The plant SLAC1 anion channel controls turgor pressure in the aperture-defining guard cells of plant stomata, thereby regulating the exchange of water vapour and photosynthetic gases in response to environmental signals such as drought or high levels of carbon dioxide. Here we determine the crystal structure of a bacterial homologue (Haemophilus influenzae) of SLAC1 at 1.20 angstrom resolution, and use structure-inspired mutagenesis to analyse the conductance properties of SLAC1 channels. SLAC1 is a symmetrical trimer composed from quasi-symmetrical subunits, each having ten transmembrane helices arranged from helical hairpin pairs to form a central five-helix transmembrane pore that is gated by an extremely conserved phenylalanine residue. Conformational features indicate a mechanism for control of gating by kinase activation, and electrostatic features of the pore coupled with electrophysiological characteristics indicate that selectivity among different anions is largely a function of the energetic cost of ion dehydration.
C1 [Chen, Yu-hang; Rost, Burkhard; Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Chen, Yu-hang; Punta, Marco; Bruni, Renato; Hillerich, Brandan; Kloss, Brian; Rost, Burkhard; Love, James; Hendrickson, Wayne A.] New York Struct Biol Ctr, NYCOMPS, New York, NY 10027 USA.
   [Hu, Lei; Siegelbaum, Steven A.] Columbia Univ, Dept Neurosci, New York, NY 10032 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.
   [Siegelbaum, Steven A.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
   [Siegelbaum, Steven A.; Hendrickson, Wayne A.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Technical University of Munich; Technical University of Munich; Columbia University; Howard Hughes Medical Institute; Columbia University; Columbia University
RP Hendrickson, WA (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
EM wayne@convex.hhmi.columbia.edu
FU New York Consortium on Membrane Protein Structure (NYCOMPS) from the NIGMS Protein Structure Initiative
NR 57
TC 125
Z9 144
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 OCT 28
PY 2010
VL 467
IS 7319
BP 1074
EP U157
DI 10.1038/nature09487
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600040
PM 20981093
DA 2026-03-09
ER

PT J
AU Lutes, AA
   Neaves, WB
   Baumann, DP
   Wiegraebe, W
   Baumann, P
AF Lutes, Aracely A.
   Neaves, William B.
   Baumann, Diana P.
   Wiegraebe, Winfried
   Baumann, Peter
TI Sister chromosome pairing maintains heterozygosity in parthenogenetic lizards
SO NATURE
LA English
DT Article
ID cnemidophorus-tesselatus; skin histocompatibility; teiid lizards
AB Although bisexual reproduction has proven to be highly successful, parthenogenetic all-female populations occur frequently in certain taxa, including the whiptail lizards of the genus Aspidoscelis. Allozyme analysis revealed a high degree of fixed heterozygosity in these parthenogenetic species(1,2), supporting the view that they originated from hybridization events between related sexual species. It has remained unclear how the meiotic program is altered to produce diploid eggs while maintaining heterozygosity. Here we show that meiosis commences with twice the number of chromosomes in parthenogenetic versus sexual species, a mechanism that provides the basis for generating gametes with unreduced chromosome content without fundamental deviation from the classic meiotic program. Our observation of synaptonemal complexes and chiasmata demonstrate that a typical meiotic program occurs and that heterozygosity is not maintained by bypassing recombination. Instead, fluorescent in situ hybridization probes that distinguish between homologues reveal that bivalents form between sister chromosomes, the genetically identical products of the first of two premeiotic replication cycles. Sister chromosome pairing provides a mechanism for the maintenance of heterozygosity, which is critical for offsetting the reduced fitness associated with the lack of genetic diversity in parthenogenetic species.
C1 [Lutes, Aracely A.; Neaves, William B.; Baumann, Diana P.; Wiegraebe, Winfried; Baumann, Peter] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Lutes, Aracely A.; Baumann, Peter] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA.
   [Neaves, William B.] Univ Missouri, Sch Med, Kansas City, MO 64110 USA.
   [Baumann, Peter] Howard Hughes Med Inst, Kansas City, MO 64110 USA.
C3 Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center; University of Missouri System; University of Missouri Kansas City; Howard Hughes Medical Institute
RP Baumann, P (corresponding author), Stowers Inst Med Res, Kansas City, MO 64110 USA.
EM peb@stowers.org
FU Stowers Institute for Medical Research; Pew Charitable Trusts
NR 24
TC 97
Z9 115
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 283
EP U164
DI 10.1038/nature08818
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100048
PM 20173738
DA 2026-03-09
ER

PT J
AU Epshtein, V
   Dutta, D
   Wade, J
   Nudler, E
AF Epshtein, Vitaly
   Dutta, Dipak
   Wade, Joseph
   Nudler, Evgeny
TI An allosteric mechanism of Rho-dependent transcription termination
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; escherichia-coli; elongation complex; structural basis; trigger loop; dna hybrid; in-vitro; subunits
AB Rho is the essential RNA helicase that sets the borders between transcription units and adjusts transcriptional yield to translational needs in bacteria(1-3). Although Rho was the first termination factor to be discovered(4), the actual mechanism by which it reaches and disrupts the elongation complex (EC) is unknown. Here we show that the termination-committed Rho molecule associates with RNA polymerase (RNAP) throughout the transcription cycle; that is, it does not require the nascent transcript for initial binding. Moreover, the formation of the RNAP-Rho complex is crucial for termination. We show further that Rho-dependent termination is a two-step process that involves rapid EC inactivation (trap) and a relatively slow dissociation. Inactivation is the critical rate-limiting step that establishes the position of the termination site. The trap mechanism depends on the allosterically induced rearrangement of the RNAP catalytic centre by means of the evolutionarily conserved mobile trigger-loop domain, which is also required for EC dissociation. The key structural and functional similarities, which we found between Rho-dependent and intrinsic (Rho-independent) termination pathways, argue that the allosteric mechanism of termination is general and likely to be preserved for all cellular RNAPs throughout evolution.
C1 [Epshtein, Vitaly; Dutta, Dipak; Nudler, Evgeny] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA.
   [Wade, Joseph] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA.
C3 New York University; State University of New York (SUNY) System; University at Albany, SUNY
RP Nudler, E (corresponding author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA.
EM evgeny.nudler@nyumc.org
FU National Institutes of Health [R01GM58750]
NR 34
TC 158
Z9 191
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 245
EP U136
DI 10.1038/nature08669
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700039
PM 20075920
DA 2026-03-09
ER

PT J
AU Lee, JH
   Fang, L
   Vlahos, E
   Ke, XL
   Jung, YW
   Kourkoutis, LF
   Kim, JW
   Ryan, PJ
   Heeg, T
   Roeckerath, M
   Goian, V
   Bernhagen, M
   Uecker, R
   Hammel, PC
   Rabe, KM
   Kamba, S
   Schubert, J
   Freeland, JW
   Muller, DA
   Fennie, CJ
   Schiffer, P
   Gopalan, V
   Johnston-Halperin, E
   Schlom, DG
AF Lee, June Hyuk
   Fang, Lei
   Vlahos, Eftihia
   Ke, Xianglin
   Jung, Young Woo
   Kourkoutis, Lena Fitting
   Kim, Jong-Woo
   Ryan, Philip J.
   Heeg, Tassilo
   Roeckerath, Martin
   Goian, Veronica
   Bernhagen, Margitta
   Uecker, Reinhard
   Hammel, P. Chris
   Rabe, Karin M.
   Kamba, Stanislav
   Schubert, Juergen
   Freeland, John W.
   Muller, David A.
   Fennie, Craig J.
   Schiffer, Peter
   Gopalan, Venkatraman
   Johnston-Halperin, Ezekiel
   Schlom, Darrell G.
TI A strong ferroelectric ferromagnet created by means of spin-lattice coupling
SO NATURE
LA English
DT Article
ID magnetic-property; oxide; system
AB Ferroelectric ferromagnets are exceedingly rare, fundamentally interesting multiferroic materials that could give rise to new technologies in which the low power and high speed of field-effect electronics are combined with the permanence and routability of voltage-controlled ferromagnetism(1,2). Furthermore, the properties of the few compounds that simultaneously exhibit these phenomena(1-5) are insignificant in comparison with those of useful ferroelectrics or ferromagnets: their spontaneous polarizations or magnetizations are smaller by a factor of 1,000 or more. The same holds for magnetic-or electric-field-induced multiferroics(6-8). Owing to the weak properties of single-phase multiferroics, composite and multilayer approaches involving strain-coupled piezoelectric and magnetostrictive components are the closest to application today(1,2). Recently, however, a new route to ferroelectric ferromagnets was proposed(9) by which magnetically ordered insulators that are neither ferroelectric nor ferromagnetic are transformed into ferroelectric ferromagnets using a single control parameter, strain. The system targeted, EuTiO3, was predicted to exhibit strong ferromagnetism (spontaneous magnetization, similar to 7 Bohr magnetons per Eu) and strong ferroelectricity (spontaneous polarization, similar to 10 mu C cm(-2)) simultaneously under large biaxial compressive strain(9). These values are orders of magnitude higher than those of any known ferroelectric ferromagnet and rival the best materials that are solely ferroelectric or ferromagnetic. Hindered by the absence of an appropriate substrate to provide the desired compression we turned to tensile strain. Here we show both experimentally and theoretically the emergence of a multiferroic state under biaxial tension with the unexpected benefit that even lower strains are required, thereby allowing thicker high-quality crystalline films. This realization of a strong ferromagnetic ferroelectric points the way to high-temperature manifestations of this spin-lattice coupling mechanism(10). Our work demonstrates that a single experimental parameter, strain, simultaneously controls multiple order parameters and is a viable alternative tuning parameter to composition(11) for creating multiferroics.
C1 [Lee, June Hyuk; Heeg, Tassilo; Schlom, Darrell G.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
   [Lee, June Hyuk; Vlahos, Eftihia; Gopalan, Venkatraman] Penn State Univ, Dept Mat Sci & Engn, University Pk, PA 16802 USA.
   [Fang, Lei; Jung, Young Woo; Hammel, P. Chris; Johnston-Halperin, Ezekiel] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Ke, Xianglin; Schiffer, Peter] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
   [Ke, Xianglin; Schiffer, Peter] Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA.
   [Kourkoutis, Lena Fitting; Muller, David A.; Fennie, Craig J.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
   [Kim, Jong-Woo; Ryan, Philip J.; Freeland, John W.] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Roeckerath, Martin] Forschungszentrum Julich, JARA Fundamentals Future Informat Technol, Inst Bio & Nanosyst, D-52425 Julich, Germany.
   [Goian, Veronica; Kamba, Stanislav] Acad Sci Czech Republ, Inst Phys, Prague 18221 8, Czech Republic.
   [Bernhagen, Margitta; Uecker, Reinhard] Leibniz Inst Crystal Growth, D-12489 Berlin, Germany.
   [Rabe, Karin M.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Muller, David A.] Kavli Inst Cornell Nanoscale Sci, Ithaca, NY 14853 USA.
C3 Cornell University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University System of Ohio; Ohio State University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; Helmholtz Association; Julich Research Centre; Czech Academy of Sciences; Institute of Physics of the Czech Academy of Sciences; Leibniz Association; Leibniz Institut fur Kristallzuchtung (IKZ); Rutgers University System; Rutgers University New Brunswick
RP Schlom, DG (corresponding author), Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
EM schlom@cornell.edu
FU National Science Foundation [DMR-0507146]; National Science Foundation through MRSEC [DMR-0520404, DMR-0820404, DMR-0820414]; Czech Science Foundation [202/09/0682]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0820404] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [0820414] Funding Source: National Science Foundation
NR 47
TC 692
Z9 770
U1 6
U2 801
PU NATURE PUBLISHING 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 19
PY 2010
VL 466
IS 7309
BP 954
EP U72
DI 10.1038/nature09331
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300030
PM 20725036
DA 2026-03-09
ER

PT J
AU Pietrzynski, G
   Thompson, IB
   Gieren, W
   Graczyk, D
   Bono, G
   Udalski, A
   Soszynski, I
   Minniti, D
   Pilecki, B
AF Pietrzynski, G.
   Thompson, I. B.
   Gieren, W.
   Graczyk, D.
   Bono, G.
   Udalski, A.
   Soszynski, I.
   Minniti, D.
   Pilecki, B.
TI The dynamical mass of a classical Cepheid variable star in an eclipsing binary system
SO NATURE
LA English
DT Article
ID large-magellanic-cloud; gravitational lensing experiment.; ogle-iii catalog; pulsation; parameters; companion; curves; models; light
AB Stellar pulsation theory provides a means of determining the masses of pulsating classical Cepheid supergiants-it is the pulsation that causes their luminosity to vary. Such pulsational masses are found to be smaller than the masses derived from stellar evolution theory: this is the Cepheid mass discrepancy problem(1,2), for which a solution is missing(3-5). An independent, accurate dynamical mass determination for a classical Cepheid variable star (as opposed to type-II Cepheids, low-mass stars with a very different evolutionary history) in a binary system is needed in order to determine which is correct. The accuracy of previous efforts to establish a dynamical Cepheid mass from Galactic single-lined non-eclipsing binaries was typically about 15-30% (refs 6, 7), which is not good enough to resolve the mass discrepancy problem. In spite of many observational efforts(8,9), no firm detection of a classical Cepheid in an eclipsing double-lined binary has hitherto been reported. Here we report the discovery of a classical Cepheid in a well detached, double-lined eclipsing binary in the Large Magellanic Cloud. We determine the mass to a precision of 1% and show that it agrees with its pulsation mass, providing strong evidence that pulsation theory correctly and precisely predicts the masses of classical Cepheids.
C1 [Pietrzynski, G.; Gieren, W.; Graczyk, D.; Pilecki, B.] Univ Concepcion, Dept Astron, Concepcion, Chile.
   [Pietrzynski, G.; Udalski, A.; Soszynski, I.; Pilecki, B.] Uniwersytetu Warszawskiego, Obserwatorium Astron, PL-00478 Warsaw, Poland.
   [Thompson, I. B.] Carnegie Observ, Pasadena, CA USA.
   [Bono, G.] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Bono, G.] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Minniti, D.] Pontificia Univ Catolica Chile, Dept Astron & Astrofis, Santiago 22, Chile.
C3 Universidad de Concepcion; University of Warsaw; Carnegie Institution for Science; University of Rome Tor Vergata; Istituto Nazionale Astrofisica (INAF); Pontificia Universidad Catolica de Chile
RP Pietrzynski, G (corresponding author), Univ Concepcion, Dept Astron, Casilla 160-C, Concepcion, Chile.
EM pietrzyn@astrouw.edu.pl
FU Chilean Center for Astrophysics FONDAP; BASAL Centro de Astrofisica y Tecnologias Afines (CATA); NSF; Polish Ministry of Science; Foundation for Polish Science (FOCUS, TEAM); GEMINI-CONICYT; European Research Council
NR 19
TC 109
Z9 113
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 NOV 25
PY 2010
VL 468
IS 7323
BP 542
EP 544
DI 10.1038/nature09598
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200037
PM 21107425
DA 2026-03-09
ER

PT J
AU O'Connell, AD
   Hofheinz, M
   Ansmann, M
   Bialczak, RC
   Lenander, M
   Lucero, E
   Neeley, M
   Sank, D
   Wang, H
   Weides, M
   Wenner, J
   Martinis, JM
   Cleland, AN
AF O'Connell, A. D.
   Hofheinz, M.
   Ansmann, M.
   Bialczak, Radoslaw C.
   Lenander, M.
   Lucero, Erik
   Neeley, M.
   Sank, D.
   Wang, H.
   Weides, M.
   Wenner, J.
   Martinis, John M.
   Cleland, A. N.
TI Quantum ground state and single-phonon control of a mechanical resonator
SO NATURE
LA English
DT Article
ID resolved-side-band; cavity; interferometry; oscillator
AB Quantum mechanics provides a highly accurate description of a wide variety of physical systems. However, a demonstration that quantum mechanics applies equally to macroscopic mechanical systems has been a long-standing challenge, hindered by the difficulty of cooling a mechanical mode to its quantum ground state. The temperatures required are typically far below those attainable with standard cryogenic methods, so significant effort has been devoted to developing alternative cooling techniques. Once in the ground state, quantum-limited measurements must then be demonstrated. Here, using conventional cryogenic refrigeration, we show that we can cool a mechanical mode to its quantum ground state by using a microwave-frequency mechanical oscillator-a 'quantum drum'-coupled to a quantum bit, which is used to measure the quantum state of the resonator. We further show that we can controllably create single quantum excitations (phonons) in the resonator, thus taking the first steps to complete quantum control of a mechanical system.
C1 [O'Connell, A. D.; Hofheinz, M.; Ansmann, M.; Bialczak, Radoslaw C.; Lenander, M.; Lucero, Erik; Neeley, M.; Sank, D.; Wang, H.; Weides, M.; Wenner, J.; Martinis, John M.; Cleland, A. N.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Cleland, AN (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM anc@physics.ucsb.edu
FU US National Science Foundation (NSF) [DMR-0605818]; Intelligence Advanced Research Projects [W911NF-04-1-0204]
NR 38
TC 1705
Z9 1966
U1 7
U2 412
PU NATURE PUBLISHING 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 1
PY 2010
VL 464
IS 7289
BP 697
EP 703
DI 10.1038/nature08967
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000034
PM 20237473
DA 2026-03-09
ER

PT J
AU Zheng, W
   Zhao, HY
   Mancera, E
   Steinmetz, LM
   Snyder, M
AF Zheng, Wei
   Zhao, Hongyu
   Mancera, Eugenio
   Steinmetz, Lars M.
   Snyder, Michael
TI Genetic analysis of variation in transcription factor binding in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; expression profiles; filamentous growth; budding yeast; overexpression; regulators; sites; mcm1; map
AB Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity(1,2). Although widespread differences in gene expression among individuals of a species have been observed(3-8), studies to examine the variability of transcription factor binding on a global scale have not been performed, and thus the extent and underlying genetic basis of transcription factor binding diversity is unknown. By mapping differences in transcription factor binding among individuals, here we present the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12-binding profiles were determined using chromatin immunoprecipitation coupled with DNA sequencing in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12-binding variation among individuals, and mapped underlying cis- and trans-acting loci responsible for such variation. We showed that most transcription factor binding variation is cis- linked, and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two transfactors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than ten genes under alpha-factor treatment. Neither of these two genes was previously known to regulate Ste12, and we suggest that they may be mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes, indicating that binding variation is functional. Many of the variable-bound genes are involved in cell wall organization and biogenesis. Overall, these studies identified genetic regulators of molecular diversity among individuals and provide new insights into mechanisms of gene regulation.
C1 [Zheng, Wei; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Zhao, Hongyu] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Zhao, Hongyu] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
   [Mancera, Eugenio; Steinmetz, Lars M.] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany.
   [Snyder, Michael] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 Yale University; Yale University; Yale University; European Molecular Biology Laboratory (EMBL); Stanford University
RP Snyder, M (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM mpsnyder@stanford.edu
FU National Institutes of Health (NIH) [RR19895]
NR 33
TC 132
Z9 172
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 22
PY 2010
VL 464
IS 7292
BP 1187
EP U106
DI 10.1038/nature08934
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100036
PM 20237471
DA 2026-03-09
ER

PT J
AU Jiao, XF
   Xiang, S
   Oh, C
   Martin, CE
   Tong, LA
   Kiledjian, M
AF Jiao, Xinfu
   Xiang, Song
   Oh, ChanSeok
   Martin, Charles E.
   Tong, Liang
   Kiledjian, Megerditch
TI Identification of a quality-control mechanism for mRNA 5′-end capping
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; decapping enzyme; cap methyltransferase; polymerase-ii; yeast-cells; protein; complex; deadenylation; translation; expression
AB The 7-methylguanosine cap structure at the 5' end of eukaryotic messenger RNAs is a critical determinant of their stability and translational efficiency(1-3). It is generally believed that 5'-end capping is a constitutive process that occurs during mRNA maturation and lacks the need for a quality-control mechanism to ensure its fidelity. We recently reported that the yeast Rai1 protein has pyrophosphohydrolase activity towards mRNAs lacking a 5'-end cap(4). Here we show that, in vitro as well as in yeast cells, Rai1 possesses a novel decapping endonuclease activity that can also remove the entire cap structure dinucleotide from an mRNA. This activity is targeted preferentially towards mRNAs with unmethylated caps in contrast to the canonical decapping enzyme, Dcp2, which targets mRNAs with a methylated cap. Capped but unmethylated mRNAs generated in yeast cells with a defect in the methyltransferase gene are more stable in a rai1-gene-disrupted background. Moreover, rai1 Delta yeast cells with wild-type capping enzymes show significant accumulation of mRNAs with 5'-end capping defects under nutritional stress conditions of glucose starvation or amino acid starvation. These findings provide evidence that 5'-end capping is not a constitutive process that necessarily always proceeds to completion and demonstrates that Rai1 has an essential role in clearing mRNAs with aberrant 5'-end caps. We propose that Rai1 is involved in an as yet uncharacterized quality control process that ensures mRNA 5'-end integrity by an aberrant-cap-mediated mRNA decay mechanism.
C1 [Jiao, Xinfu; Oh, ChanSeok; Martin, Charles E.; Kiledjian, Megerditch] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
   [Xiang, Song; Tong, Liang] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
C3 Rutgers University System; Rutgers University New Brunswick; Columbia University
RP Kiledjian, M (corresponding author), Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
EM kiledjian@biology.rutgers.edu
FU National Institutes of Health (NIH) [GM077175, GM67005]; National Institute of General Medical Sciences [R01GM067005] Funding Source: NIH RePORTER
NR 35
TC 136
Z9 161
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 608
EP U137
DI 10.1038/nature09338
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100043
PM 20802481
DA 2026-03-09
ER

PT J
AU Schoof, C
AF Schoof, Christian
TI Ice-sheet acceleration driven by melt supply variability
SO NATURE
LA English
DT Article
ID glacier surge mechanism; subglacial drainage; west greenland; surface melt; water-level; fast-flow; velocity; system; temperature; switzerland
AB Increased ice velocities in Greenland(1) are contributing significantly to eustatic sea level rise. Faster ice flow has been associated with ice-ocean interactions in water-terminating outlet glaciers(2) and with increased surface meltwater supply to the ice-sheet bed inland. Observed correlations between surface melt and ice acceleration(2-6) have raised the possibility of a positive feedback in which surface melting and accelerated dynamic thinning reinforce one another(7), suggesting that overall warming could lead to accelerated mass loss. Here I show that it is not simply mean surface melt(4) but an increase in water input variability(8) that drives faster ice flow. Glacier sliding responds to melt indirectly through changes in basal water pressure(9-11), with observations showing that water under glaciers drains through channels at low pressure or through interconnected cavities at high pressure(12-15). Using a model that captures the dynamic switching(12) between channel and cavity drainage modes, I show that channelization and glacier deceleration rather than acceleration occur above a critical rate of water flow. Higher rates of steady water supply can therefore suppress rather than enhance dynamic thinning(16), indicating that the melt/dynamic thinning feedback is not universally operational. Shortterm increases in water input are, however, accommodated by the drainage system through temporary spikes in water pressure. It is these spikes that lead to ice acceleration, which is therefore driven by strong diurnal melt cycles(4,14) and an increase in rain and surface lake drainage events(8,17,18) rather than an increase in mean melt supply(3,4).
C1 Univ British Columbia, Dept Earth & Ocean Sci, Vancouver, BC V6T 1Z4, Canada.
C3 University of British Columbia
RP Schoof, C (corresponding author), Univ British Columbia, Dept Earth & Ocean Sci, 6339 Stores Rd, Vancouver, BC V6T 1Z4, Canada.
EM cschoof@eos.ubc.ca
FU Canada Research Chairs; NSERC [357193-08]; Canadian Foundation for Climate and Atmospheric Science through the Polar Climate Stability Network
NR 30
TC 519
Z9 613
U1 0
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 DEC 9
PY 2010
VL 468
IS 7325
BP 803
EP 806
DI 10.1038/nature09618
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700041
PM 21150994
DA 2026-03-09
ER

PT J
AU Boeglin, C
   Beaurepaire, E
   Halté, V
   López-Flores, V
   Stamm, C
   Pontius, N
   Dürr, HA
   Bigot, JY
AF Boeglin, C.
   Beaurepaire, E.
   Halte, V.
   Lopez-Flores, V.
   Stamm, C.
   Pontius, N.
   Duerr, H. A.
   Bigot, J. -Y.
TI Distinguishing the ultrafast dynamics of spin and orbital moments in solids
SO NATURE
LA English
DT Article
ID magnetic circular-dichroism; x-ray dichroism; thin-films; anisotropy; nickel; demagnetization; multilayers; transition
AB For an isolated quantum particle, such as an electron, the orbital (L) and spin (S) magnetic moments can change provided that the total angular momentum of the particle is conserved. In condensed matter, an efficient transfer between L and S can occur owing to the spin-orbit interaction, which originates in the relativistic motion of electrons(1). Disentangling the absolute contributions of the orbital and spin angular momenta is challenging, however, as any transfer between the two occurs on femtosecond timescales. Here we investigate such phenomena by using ultrashort optical laser pulses to change the magnetization of a ferromagnetic film(2-7) and then probe its dynamics with circularly polarized femtosecond X-ray pulses(8). Our measurements enable us to disentangle the spin and orbital components of the magnetic moment, revealing different dynamics for L and S. We highlight the important role played by the spin-orbit interaction in the ultrafast laser-induced demagnetization of ferromagnetic films, and show also that the magneto-crystalline anisotropy energy is an important quantity to consider in such processes. Our study provides insights into the dynamics in magnetic systems(9) as well as perspectives for the ultrafast control of information in magnetic recording media(10).
C1 [Boeglin, C.; Beaurepaire, E.; Halte, V.; Lopez-Flores, V.; Bigot, J. -Y.] CNRS, UMR7504, Inst Phys & Chim Mat Strasbourg, F-67034 Strasbourg, France.
   [Boeglin, C.; Beaurepaire, E.; Halte, V.; Lopez-Flores, V.; Bigot, J. -Y.] Univ Strasbourg, F-67034 Strasbourg, France.
   [Stamm, C.; Pontius, N.; Duerr, H. A.] Helmholtz Zentrum Berlin Mat & Energie GmbH, BESSY 2, D-12489 Berlin, Germany.
C3 Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB)
RP Boeglin, C (corresponding author), CNRS, UMR7504, Inst Phys & Chim Mat Strasbourg, 23 Rue Loess, F-67034 Strasbourg, France.
EM christine.boeglin@ipcms.u-strasbg.fr
FU CNRS-PICS; Universite de Strasbourg; EU [R II 3 CT-2004-5060008]; European Research Council [ERC-2009-AdG-20090325, 247452]; US Department of Energy, Office of Basic Energy Sciences; European Research Council (ERC) [247452] Funding Source: European Research Council (ERC)
NR 30
TC 348
Z9 376
U1 2
U2 239
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 458
EP U78
DI 10.1038/nature09070
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700030
PM 20505724
DA 2026-03-09
ER

PT J
AU Popp, C
   Dean, W
   Feng, SH
   Cokus, SJ
   Andrews, S
   Pellegrini, M
   Jacobsen, SE
   Reik, W
AF Popp, Christian
   Dean, Wendy
   Feng, Suhua
   Cokus, Shawn J.
   Andrews, Simon
   Pellegrini, Matteo
   Jacobsen, Steven E.
   Reik, Wolf
TI Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
SO NATURE
LA English
DT Article
ID epigenetic inheritance; demethylation; deaminase; 5-hydroxymethylcytosine; 5-methylcytosine; pluripotent; dynamics; elements
AB Epigenetic reprogramming including demethylation of DNA occurs in mammalian primordial germ cells (PGCs) and in early embryos, and is important for the erasure of imprints and epimutations, and the return to pluripotency(1-9). The extent of this reprogramming and its molecular mechanisms are poorly understood. We previously showed that the cytidine deaminases AID and APOBEC1 can deaminate 5-methylcytosine in vitro and in Escherichia coli, and in the mouse are expressed in tissues in which demethylation occurs(10). Here we profiled DNA methylation throughout the genome by unbiased bisulphite next generation sequencing(11-13) in wild-type and AID-deficient mouse PGCs at embryonic day (E) 13.5. Wild-type PGCs revealed marked genome-wide erasure of methylation to a level below that of methylation deficient (Np95(-/-), also called Uhrf1(-/-)) embryonic stem cells, with female PGCs being less methylated than male ones. By contrast, AID-deficient PGCs were up to three times more methylated than wild-type ones; this substantial difference occurred throughout the genome, with introns, intergenic regions and transposons being relatively more methylated than exons. Relative hypermethylation in AID-deficient PGCs was confirmed by analysis of individual loci in the genome. Our results reveal that erasure of DNA methylation in the germ line is a global process, hence limiting the potential for transgenerational epigenetic inheritance. AID deficiency interferes with genome-wide erasure of DNA methylation patterns, indicating that AID has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals.
C1 [Feng, Suhua; Cokus, Shawn J.; Pellegrini, Matteo; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Popp, Christian; Dean, Wendy; Reik, Wolf] Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB22 3AT, England.
   [Popp, Christian; Dean, Wendy; Reik, Wolf] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
   [Andrews, Simon] Babraham Inst, Bioinformat Grp, Cambridge CB22 3AT, England.
   [Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; University of Cambridge; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; Howard Hughes Medical Institute; University of California System; University of California Los Angeles
RP Jacobsen, SE (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM jacobsen@ucla.edu; wolf.reik@bbsrc.ac.uk
FU BBSRC; MRC; EU NoE The Epigenome; CellCentric; HHMI; NSF; NIH; Biotechnology and Biological Sciences Research Council [BBS/E/B/0000M220, BBS/E/B/0000M982] Funding Source: researchfish; Medical Research Council [G0700098, G0300723B] Funding Source: researchfish; BBSRC [BBS/E/B/0000M220] Funding Source: UKRI; MRC [G0700098] Funding Source: UKRI
NR 30
TC 684
Z9 812
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1101
EP U126
DI 10.1038/nature08829
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400041
PM 20098412
DA 2026-03-09
ER

PT J
AU Robertson, JL
   Kolmakova-Partensky, L
   Miller, C
AF Robertson, Janice L.
   Kolmakova-Partensky, Ludmila
   Miller, Christopher
TI Design, function and structure of a monomeric ClC transporter
SO NATURE
LA English
DT Article
ID exchange transporter; ammonia transport; chloride channel; mechanism; energetics; reveals; amtb
AB Channels and transporters of the ClC family cause the transmembrane movement of inorganic anions in service of a variety of biological tasks, from the unusual-the generation of the kilowatt pulses with which electric fish stun their prey-to the quotidian-the acidification of endosomes, vacuoles and lysosomes(1). The homodimeric architecture of ClC proteins, initially inferred from single-molecule studies of an elasmobranch Cl- channel(2) and later confirmed by crystal structures of bacterial Cl-/H+ antiporters(3,4), is apparently universal. Moreover, the basic machinery that enables ion movement through these proteins-the aqueous pores for anion diffusion in the channels and the ion-coupling chambers that coordinate Cl- and H+ antiport in the transporters-are contained wholly within each subunit of the homodimer. The near-normal function of a bacterial ClC transporter straitjacketed by covalent cross-links across the dimer interface and the behaviour of a concatemeric human homologue argue that the transport cycle resides within each subunit and does not require rigid-body rearrangements between subunits(5,6). However, this evidence is only inferential, and because examples are known in which quaternary rearrangements of extramembrane ClC domains that contribute to dimerization modulate transport activity(7), we cannot declare as definitive a 'parallel-pathways' picture in which the homodimer consists of two singlesubunit transporters operating independently. A strong prediction of such a view is that it should in principle be possible to obtain a monomeric ClC. Here we exploit the known structure of a ClC Cl-/H+ exchanger, ClC-ec1 from Escherichia coli, to design mutants that destabilize the dimer interface while preserving both the structure and the transport function of individual subunits. The results demonstrate that the ClC subunit alone is the basic functional unit for transport and that cross-subunit interaction is not required for Cl-/H+ exchange in ClC transporters.
C1 [Robertson, Janice L.; Kolmakova-Partensky, Ludmila; Miller, Christopher] Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA.
C3 Brandeis University; Howard Hughes Medical Institute
RP Miller, C (corresponding author), Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA.
EM cmiller@brandeis.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [R37 GM031768, R01 GM031768] Funding Source: Medline
NR 30
TC 97
Z9 111
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 844
EP 847
DI 10.1038/nature09556
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700050
PM 21048711
DA 2026-03-09
ER

PT J
AU Zhou, AW
   Carrell, RW
   Murphy, MP
   Wei, ZQ
   Yan, YH
   Stanley, PLD
   Stein, PE
   Pipkin, FB
   Read, RJ
AF Zhou, Aiwu
   Carrell, Robin W.
   Murphy, Michael P.
   Wei, Zhenquan
   Yan, Yahui
   Stanley, Peter L. D.
   Stein, Penelope E.
   Pipkin, Fiona Broughton
   Read, Randy J.
TI A redox switch in angiotensinogen modulates angiotensin release
SO NATURE
LA English
DT Article
ID oxidative stress; nitric-oxide; renin; hypertension; preeclampsia; system; kidney; model
AB Blood pressure is critically controlled by angiotensins(1), which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors(2,3). Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 angstrom resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 angstrom structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.
C1 [Carrell, Robin W.; Stein, Penelope E.] Univ Cambridge, Cambridge Inst Med Res, Dept Med, Cambridge CB2 0XY, England.
   [Zhou, Aiwu; Wei, Zhenquan; Yan, Yahui; Stanley, Peter L. D.; Read, Randy J.] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England.
   [Murphy, Michael P.] MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
   [Pipkin, Fiona Broughton] Univ Nottingham, City Hosp, Dept Obstet & Gynaecol, Nottingham NG5 1PB, England.
C3 University of Cambridge; University of Cambridge; Nottingham University Hospital NHS Trust; Nottingham City Hospital; University of Nottingham
RP Carrell, RW (corresponding author), Univ Cambridge, Cambridge Inst Med Res, Dept Med, Hills Rd, Cambridge CB2 0XY, England.
EM awz20@cam.ac.uk; rwc1000@cam.ac.uk
FU British Heart Foundation; Wellcome Trust; Isaac Newton Trust of the University of Cambridge; UK Medical Research Council with Daresbury SRS; UK Medical Research Council; Diamond Light Source; MRC [MC_U105663142] Funding Source: UKRI; British Heart Foundation [PG/09/072/27945] Funding Source: researchfish; Medical Research Council [MC_U105663142] Funding Source: researchfish
NR 30
TC 172
Z9 202
U1 0
U2 41
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 108
EP 111
DI 10.1038/nature09505
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900045
PM 20927107
DA 2026-03-09
ER

PT J
AU Matsui, T
   Leung, D
   Miyashita, H
   Maksakova, IA
   Miyachi, H
   Kimura, H
   Tachibana, M
   Lorincz, MC
   Shinkai, Y
AF Matsui, Toshiyuki
   Leung, Danny
   Miyashita, Hiroki
   Maksakova, Irina A.
   Miyachi, Hitoshi
   Kimura, Hiroshi
   Tachibana, Makoto
   Lorincz, Matthew C.
   Shinkai, Yoichi
TI Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET
SO NATURE
LA English
DT Article
ID murine leukemia-virus; zinc finger proteins; dna methylation; binding-site; complexes; elements; h3; heterochromatin; retrovirus; mechanism
AB Endogenous retroviruses (ERVs), retrovirus-like elements with long terminal repeats, are widely dispersed in the euchromatic compartment in mammalian cells, comprising similar to 10% of the mouse genome(1). These parasitic elements are responsible for >10% of spontaneous mutations(2). Whereas DNA methylation has an important role in proviral silencing in somatic and germ-lineage cells(3-5), an additional DNA-methylation-independent pathway also functions in embryonal carcinoma and embryonic stem (ES) cells to inhibit transcription of the exogenous gammaretrovirus murine leukaemia virus (MLV)(6-8). Notably, a recent genome-wide study revealed that ERVs are also marked by histone H3 lysine 9 trimethylation (H3K9me3) and H4K20me3 in ES cells but not in mouse embryonic fibroblasts(9). However, the role that these marks have in proviral silencing remains unexplored. Here we show that the H3K9 methyltransferase ESET (also called SETDB1 or KMT1E) and the Kruppel-associated box (KRAB)associated protein 1 (KAP1, also called TRIM28)(10,11) are required for H3K9me3 and silencing of endogenous and introduced retroviruses specifically in mouse ES cells. Furthermore, whereas ESET enzymatic activity is crucial for HP1 binding and efficient proviral silencing, the H4K20 methyltransferases Suv420h1 and Suv420h2 are dispensable for silencing. Notably, in DNA methyltransferase triple knockout (Dnmt1(-/-) Dnmt3a(-/-) Dnmt3b(-/-)) mouse ES cells, ESET and KAP1 binding and ESET-mediated H3K9me3 are maintained and ERVs are minimally derepressed. We propose that a DNA-methylation-independent pathway involving KAP1 and ESET/ESET-mediated H3K9me3 is required for proviral silencing during the period early in embryogenesis when DNA methylation is dynamically reprogrammed.
C1 [Matsui, Toshiyuki; Miyashita, Hiroki; Miyachi, Hitoshi; Tachibana, Makoto; Shinkai, Yoichi] Kyoto Univ, Inst Virus Res, Expt Res Ctr Infect Dis, Sakyo Ku, Kyoto 6068507, Japan.
   [Matsui, Toshiyuki; Miyashita, Hiroki; Tachibana, Makoto; Shinkai, Yoichi] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068507, Japan.
   [Leung, Danny; Maksakova, Irina A.; Lorincz, Matthew C.] Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
   [Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
C3 Kyoto University; Kyoto University; University of British Columbia; University of Osaka
RP Shinkai, Y (corresponding author), Kyoto Univ, Inst Virus Res, Expt Res Ctr Infect Dis, Sakyo Ku, 53 Shogoin,Kawara Cho, Kyoto 6068507, Japan.
EM mlorincz@interchange.ubc.ca; yshinkai@virus.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; CIHR [77805, 92090]; Grants-in-Aid for Scientific Research [19061001, 21570196] Funding Source: KAKEN; Academy of Finland (AKA) [77805] Funding Source: Academy of Finland (AKA)
NR 35
TC 630
Z9 724
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 8
PY 2010
VL 464
IS 7290
BP 927
EP U149
DI 10.1038/nature08858
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300045
PM 20164836
DA 2026-03-09
ER

PT J
AU Torsvik, TH
   Burke, K
   Steinberger, B
   Webb, SJ
   Ashwal, LD
AF Torsvik, Trond H.
   Burke, Kevin
   Steinberger, Bernhard
   Webb, Susan J.
   Ashwal, Lewis D.
TI Diamonds sampled by plumes from the core-mantle boundary
SO NATURE
LA English
DT Article
ID true polar wander; velocity provinces; kimberlites; margins; origin
AB Diamonds are formed under high pressure more than 150 kilometres deep in the Earth's mantle and are brought to the surface mainly by volcanic rocks called kimberlites. Several thousand kimberlites have been mapped on various scales(1-4), but it is the distribution of kimberlites in the very old cratons (stable areas of the continental lithosphere that are more than 2.5 billion years old and 300 kilometres thick or more(5)) that have generated the most interest, because kimberlites from those areas are the major carriers of economically viable diamond resources. Kimberlites, which are themselves derived from depths of more than 150 kilometres, provide invaluable information on the composition of the deep subcontinental mantle lithosphere, and on melting and metasomatic processes at or near the interface with the underlying flowing mantle. Here we use plate reconstructions and tomographic images to show that the edges of the largest heterogeneities in the deepest mantle, stable for at least 200 million years and possibly for 540 million years, seem to have controlled the eruption of most Phanerozoic kimberlites. We infer that future exploration for kimberlites and their included diamonds should therefore be concentrated in continents with old cratons that once overlay these plume-generation zones at the core-mantle boundary.
C1 [Torsvik, Trond H.; Steinberger, Bernhard] Univ Oslo, N-0316 Oslo, Norway.
   [Torsvik, Trond H.; Steinberger, Bernhard] Geol Survey Norway, Ctr Geodynam, N-7491 Trondheim, Norway.
   [Torsvik, Trond H.; Burke, Kevin; Webb, Susan J.; Ashwal, Lewis D.] Univ Witwatersrand, Sch Geosci, ZA-2050 Johannesburg, South Africa.
   [Burke, Kevin] Univ Houston, Dept Geosci, Houston, TX 77204 USA.
   [Steinberger, Bernhard] German Res Ctr Geosci, Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
C3 University of Oslo; Geological Survey of Norway; University of Witwatersrand; University of Houston System; University of Houston; Helmholtz Association; GFZ Helmholtz Centre for Geosciences
RP Torsvik, TH (corresponding author), Univ Oslo, N-0316 Oslo, Norway.
EM trond.torsvik@ngu.no
FU Statoil; Norwegian Research Council
NR 42
TC 424
Z9 481
U1 1
U2 165
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 352
EP U100
DI 10.1038/nature09216
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100045
PM 20631796
DA 2026-03-09
ER

PT J
AU England, PC
   Katz, RF
AF England, Philip C.
   Katz, Richard F.
TI Melting above the anhydrous solidus controls the location of volcanic arcs
SO NATURE
LA English
DT Article
ID mantle; rates; water; extraction; depths; basalt; models; crust; slabs; hot
AB Segregation of magma from the mantle in subduction zones is one of the principal mechanisms for chemical differentiation of the Earth. Fundamental aspects of this system, in particular the processes by which melt forms and travels to the Earth's surface, remain obscure. Systematics in the location of volcanic arcs, the surface expression of this melting, are widely considered to be a clue to processes taking place at depth, but many mutually incompatible interpretations of this clue exist (for example, see refs 1-6). We discriminate between those interpretations by the use of a simple scaling argument derived from a realistic mathematical model of heat transfer in subduction zones. The locations of the arcs cannot be explained by the release of fluids in reactions taking place near the top of the slab. Instead, the sharpness of the volcanic fronts, together with the systematics of their locations, requires that arcs must be located above the place where the boundary defined by the anhydrous solidus makes its closest approach to the trench. We show that heat carried by magma rising from this region is sufficient to modify the thermal structure of the wedge and determine the pathway through which both wet and dry melts reach the surface.
C1 [England, Philip C.; Katz, Richard F.] Dept Earth Sci, Oxford OX1 3AN, England.
RP England, PC (corresponding author), Dept Earth Sci, S Parks Rd, Oxford OX1 3AN, England.
EM philip@earth.ox.ac.uk
FU Natural Environment Research Council [NE/H00081X/1, NER/A/S/2001/01067] Funding Source: researchfish; NERC [NE/H00081X/1] Funding Source: UKRI
NR 38
TC 164
Z9 184
U1 0
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 7
PY 2010
VL 467
IS 7316
BP 700
EP U84
DI 10.1038/nature09417
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500036
PM 20930842
DA 2026-03-09
ER

PT J
AU Zhang, JJ
   Baker, ML
   Schröder, GF
   Douglas, NR
   Reissmann, S
   Jakana, J
   Dougherty, M
   Fu, CJ
   Levitt, M
   Ludtke, SJ
   Frydman, J
   Chiu, W
AF Zhang, Junjie
   Baker, Matthew L.
   Schroeder, Gunnar F.
   Douglas, Nicholai R.
   Reissmann, Stefanie
   Jakana, Joanita
   Dougherty, Matthew
   Fu, Caroline J.
   Levitt, Michael
   Ludtke, Steven J.
   Frydman, Judith
   Chiu, Wah
TI Mechanism of folding chamber closure in a group II chaperonin
SO NATURE
LA English
DT Article
ID particle electron cryomicroscopy; crystal-structure; archaeal chaperonin; molecular chaperones; groel; resolution; protein; reconstruction; aggregation; state
AB Group II chaperonins are essential mediators of cellular protein folding in eukaryotes and archaea. These oligomeric protein machines, similar to 1 megadalton, consist of two back-to-back rings encompassing a central cavity that accommodates polypeptide substrates(1-3). Chaperonin-mediated protein folding is critically dependent on the closure of a built-in lid(4,5), which is triggered by ATP hydrolysis(6). The structural rearrangements and molecular events leading to lid closure are still unknown. Here we report four single particle cryo-electron microscopy (cryo-EM) structures of Mm-cpn, an archaeal group II chaperonin(5,7), in the nucleotide-free (open) and nucleotide-induced (closed) states. The 4.3 angstrom resolution of the closed conformation allowed building of the first ever atomic model directly from the single particle cryo-EM density map, in which we were able to visualize the nucleotide and more than 70% of the side chains. The model of the open conformation was obtained by using the deformable elastic network modelling with the 8 angstrom resolution open-state cryo-EM density restraints. Together, the open and closed structures show how local conformational changes triggered by ATP hydrolysis lead to an alteration of intersubunit contacts within and across the rings, ultimately causing a rocking motion that closes the ring. Our analyses show that there is an intricate and unforeseen set of interactions controlling allosteric communication and inter-ring signalling, driving the conformational cycle of group II chaperonins. Beyond this, we anticipate that our methodology of combining single particle cryo-EM and computational modelling will become a powerful tool in the determination of atomic details involved in the dynamic processes of macromolecular machines in solution.
C1 [Zhang, Junjie; Ludtke, Steven J.; Chiu, Wah] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
   [Zhang, Junjie; Baker, Matthew L.; Jakana, Joanita; Dougherty, Matthew; Fu, Caroline J.; Ludtke, Steven J.; Chiu, Wah] Baylor Coll Med, Natl Ctr Macromol Imaging, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Schroeder, Gunnar F.; Levitt, Michael] Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA.
   [Douglas, Nicholai R.; Reissmann, Stefanie; Frydman, Judith] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Douglas, Nicholai R.; Reissmann, Stefanie; Frydman, Judith] Stanford Univ, BioX Program, Stanford, CA 94305 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Stanford University; Stanford University; Stanford University
RP Chiu, W (corresponding author), Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
EM jfrydman@stanford.edu; wah@bcm.edu
FU National Institutes of Health through the Nanomedicine Development Center Roadmap Initiative; Biomedical Technology Research Center for Structural Biology in National Center for Research Resources; Nanobiology Training Fellowship; National Science Foundation; National Institute of General Medical Sciences [T32GM007276, R01GM079429, R01GM080139] Funding Source: NIH RePORTER
NR 39
TC 172
Z9 203
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 21
PY 2010
VL 463
IS 7279
BP 379
EP U130
DI 10.1038/nature08701
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100049
PM 20090755
DA 2026-03-09
ER

PT J
AU Virtanen, A
   Joutsensaari, J
   Koop, T
   Kannosto, J
   Yli-Pirilä, P
   Leskinen, J
   Mäkelä, JM
   Holopainen, JK
   Pöschl, U
   Kulmala, M
   Worsnop, DR
   Laaksonen, A
AF Virtanen, Annele
   Joutsensaari, Jorma
   Koop, Thomas
   Kannosto, Jonna
   Yli-Pirila, Pasi
   Leskinen, Jani
   Makela, Jyrki M.
   Holopainen, Jarmo K.
   Poeschl, Ulrich
   Kulmala, Markku
   Worsnop, Douglas R.
   Laaksonen, Ari
TI An amorphous solid state of biogenic secondary organic aerosol particles
SO NATURE
LA English
DT Article
ID atmospheric particles; oleic-acid; model; oxidation; climate; chemistry; diffusion; emissions; products; forests
AB Secondary organic aerosol (SOA) particles are formed in the atmosphere from condensable oxidation products of anthropogenic and biogenic volatile organic compounds (VOCs)(1-7). On a global scale, biogenic VOCs account for about 90% of VOC emissions(1,8) and of SOA formation (90 billion kilograms of carbon per year)(1-4). SOA particles can scatter radiation and act as cloud condensation or ice nuclei, and thereby influence the Earth's radiation balance and climate(1,2,5,9,10). They consist of a myriad of different compounds with varying physicochemical properties, and little information is available on the phase state of SOA particles. Gas-particle partitioning models usually assume that SOA particles are liquid(1,5,11), but here we present experimental evidence that they can be solid under ambient conditions. We investigated biogenic SOA particles formed from oxidation products of VOCs in plant chamber experiments and in boreal forests within a few hours after atmospheric nucleation events. On the basis of observed particle bouncing in an aerosol impactor and of electron microscopy we conclude that biogenic SOA particles can adopt an amorphous solid-most probably glassy-state. This amorphous solid state should provoke a rethinking of SOA processes because it may influence the partitioning of semi-volatile compounds, reduce the rate of heterogeneous chemical reactions, affect the particles' ability to accommodate water and act as cloud condensation or ice nuclei, and change the atmospheric lifetime of the particles(12-15). Thus, the results of this study challenge traditional views of the kinetics and thermodynamics of SOA formation and transformation in the atmosphere and their implications for air quality and climate.
C1 [Virtanen, Annele; Kannosto, Jonna; Makela, Jyrki M.] Tampere Univ Technol, Dept Phys, FIN-33101 Tampere, Finland.
   [Joutsensaari, Jorma; Worsnop, Douglas R.; Laaksonen, Ari] Univ Eastern Finland, Dept Math & Phys, Kuopio 70211, Finland.
   [Koop, Thomas] Univ Bielefeld, Dept Chem, D-33615 Bielefeld, Germany.
   [Yli-Pirila, Pasi; Leskinen, Jani; Holopainen, Jarmo K.] Univ Eastern Finland, Dept Environm Sci, Kuopio 70211, Finland.
   [Poeschl, Ulrich] Max Planck Inst Chem, Biogeochem Dept, D-55128 Mainz, Germany.
   [Kulmala, Markku; Worsnop, Douglas R.] Univ Helsinki, Dept Phys, Helsinki 00014, Finland.
   [Kulmala, Markku] Stockholm Univ, Dept Appl Environm Sci, S-10691 Stockholm, Sweden.
   [Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
   [Worsnop, Douglas R.; Laaksonen, Ari] Finnish Meteorol Inst, FIN-00101 Helsinki, Finland.
C3 Tampere University; University of Eastern Finland; University of Bielefeld; University of Eastern Finland; Max Planck Society; University of Helsinki; Stockholm University; Aerodyne Research; Finnish Meteorological Institute
RP Virtanen, A (corresponding author), Tampere Univ Technol, Dept Phys, POB 692, FIN-33101 Tampere, Finland.
EM annele.virtanen@tut.fi; thomas.koop@uni-bielefeld.de
FU Academy of Finland [110763, 111543, 131019, 218115]; Maj and Tor Nessling foundation; Academy of Finland (AKA) [131019, 111543, 218115, 110763] Funding Source: Academy of Finland (AKA)
NR 29
TC 626
Z9 741
U1 7
U2 621
PU 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 14
PY 2010
VL 467
IS 7317
BP 824
EP 827
DI 10.1038/nature09455
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700063
PM 20944744
DA 2026-03-09
ER

PT J
AU Red-Horse, K
   Ueno, H
   Weissman, IL
   Krasnow, MA
AF Red-Horse, Kristy
   Ueno, Hiroo
   Weissman, Irving L.
   Krasnow, Mark A.
TI Coronary arteries form by developmental reprogramming of venous cells
SO NATURE
LA English
DT Article
ID smooth-muscle-cells; endothelial-cells; saphenous-vein; growth-factor; heart; angiogenesis; embryo; mouse; system; differentiation
AB Coronary artery disease is the leading cause of death worldwide. Determining the coronary artery developmental program could aid understanding of the disease and lead to new treatments, but many aspects of the process, including their developmental origin, remain obscure. Here we show, using histological and clonal analysis in mice and cardiac organ culture, that coronary vessels arise from angiogenic sprouts of the sinus venosus-the vein that returns blood to the embryonic heart. Sprouting venous endothelial cells dedifferentiate as they migrate over and invade the myocardium. Invading cells differentiate into arteries and capillaries; cells on the surface redifferentiate into veins. These results show that some differentiated venous cells retain developmental plasticity, and indicate that position-specific cardiac signals trigger their dedifferentiation and conversion into coronary arteries, capillaries and veins. Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart.
C1 [Red-Horse, Kristy; Krasnow, Mark A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Red-Horse, Kristy; Krasnow, Mark A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Ueno, Hiroo; Weissman, Irving L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Krasnow, MA (corresponding author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
EM krasnow@stanford.edu
FU National Institutes of Health [2T32HD007249]
NR 45
TC 428
Z9 527
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 25
PY 2010
VL 464
IS 7288
BP 549
EP U100
DI 10.1038/nature08873
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200039
PM 20336138
DA 2026-03-09
ER

PT J
AU Winter, SE
   Thiennimitr, P
   Winter, MG
   Butler, BP
   Huseby, DL
   Crawford, RW
   Russell, JM
   Bevins, CL
   Adams, LG
   Tsolis, RM
   Roth, JR
   Bäumler, AJ
AF Winter, Sebastian E.
   Thiennimitr, Parameth
   Winter, Maria G.
   Butler, Brian P.
   Huseby, Douglas L.
   Crawford, Robert W.
   Russell, Joseph M.
   Bevins, Charles L.
   Adams, L. Garry
   Tsolis, Renee M.
   Roth, John R.
   Baeumler, Andreas J.
TI Gut inflammation provides a respiratory electron acceptor for Salmonella
SO NATURE
LA English
DT Article
ID enterica serovar typhimurium; intestinal microbiota; serotype typhimurium; virulence factors; hydrogen-sulfide; host; methanethiol; disrupts; disease; mucosa
AB Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen.
C1 [Winter, Sebastian E.; Thiennimitr, Parameth; Winter, Maria G.; Butler, Brian P.; Crawford, Robert W.; Russell, Joseph M.; Bevins, Charles L.; Tsolis, Renee M.; Baeumler, Andreas J.] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
   [Thiennimitr, Parameth] Chiang Mai Univ, Fac Med, Dept Microbiol, Chiang Mai 50000, Thailand.
   [Huseby, Douglas L.; Roth, John R.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Adams, L. Garry] Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med, College Stn, TX 77843 USA.
C3 University of California System; University of California Davis; Chiang Mai University; University of California System; University of California Davis; Texas A&M University System; Texas A&M University College Station
RP Bäumler, AJ (corresponding author), Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
EM ajbaumler@ucdavis.edu
FU Public Health Service [AI040124, AI044170, AI073120, AI076246, AI088122]; Department of Microbiology, Chiang Mai University, Thailand; National Institute of Allergy and Infectious Diseases [R37AI032738, R01AI044170] Funding Source: NIH RePORTER
NR 19
TC 1028
Z9 1285
U1 7
U2 177
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 426
EP 429
DI 10.1038/nature09415
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200035
PM 20864996
DA 2026-03-09
ER

PT J
AU Reyes, R
   Mandelbaum, R
   Seljak, U
   Baldauf, T
   Gunn, JE
   Lombriser, L
   Smith, RE
AF Reyes, Reinabelle
   Mandelbaum, Rachel
   Seljak, Uros
   Baldauf, Tobias
   Gunn, James E.
   Lombriser, Lucas
   Smith, Robert E.
TI Confirmation of general relativity on large scales from weak lensing and galaxy velocities
SO NATURE
LA English
DT Article
ID digital sky survey
AB Although general relativity underlies modern cosmology, its applicability on cosmological length scales has yet to be stringently tested. Such a test has recently been proposed(1), using a quantity, E-G, that combines measures of large-scale gravitational lensing, galaxy clustering and structure growth rate. The combination is insensitive to 'galaxy bias' (the difference between the clustering of visible galaxies and invisible dark matter) and is thus robust to the uncertainty in this parameter. Modified theories of gravity generally predict values of E-G different from the general relativistic prediction because, in these theories, the 'gravitational slip' (the difference between the two potentials that describe perturbations in the gravitational metric) is non-zero, which leads to changes in the growth of structure(2) and the strength of the gravitational lensing effect(3). Here we report that E-G = 0.39 +/- 0.06 on length scales of tens of megaparsecs, in agreement with the general relativistic prediction of E-G approximate to 0.4. The measured value excludes a model(1) within the tensor-vector-scalar gravity theory(4,5), which modifies both Newtonian and Einstein gravity. However, the relatively large uncertainty still permits models within f(R) theory(6), which is an extension of general relativity. A fivefold decrease in uncertainty is needed to rule out these models.
C1 [Reyes, Reinabelle; Mandelbaum, Rachel; Gunn, James E.] Princeton Univ Observ, Princeton, NJ 08544 USA.
   [Seljak, Uros; Baldauf, Tobias; Lombriser, Lucas; Smith, Robert E.] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
   [Seljak, Uros] Univ Calif Berkeley, Dept Phys & Astron, Berkeley, CA 94720 USA.
   [Seljak, Uros] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Seljak, Uros] Ewha Womans Univ, Inst Early Universe, Seoul 120750, South Korea.
C3 Princeton University; University of Zurich; 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; Ewha Womans University
RP Reyes, R (corresponding author), Princeton Univ Observ, Peyton Hall, Princeton, NJ 08544 USA.
EM rreyes@astro.princeton.edu
FU NASA; Space Telescope Science Institute; Swiss National Foundation; German National Academic Foundation
NR 22
TC 268
Z9 293
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 11
PY 2010
VL 464
IS 7286
BP 256
EP 258
DI 10.1038/nature08857
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100041
PM 20220843
DA 2026-03-09
ER

PT J
AU Sun, YJ
   Wu, GK
   Liu, BH
   Li, P
   Zhou, M
   Xiao, Z
   Tao, HW
   Zhang, LI
AF Sun, Yujiao J.
   Wu, Guangying K.
   Liu, Bao-hua
   Li, Pingyang
   Zhou, Mu
   Xiao, Zhongju
   Tao, Huizhong W.
   Zhang, Li I.
TI Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development
SO NATURE
LA English
DT Article
ID primary visual-cortex; receptive-fields; neurons; circuits; rat; representation; selectivity; inputs; maps
AB Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development(1-4). Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency-intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation-inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.
C1 [Sun, Yujiao J.; Wu, Guangying K.; Liu, Bao-hua; Li, Pingyang; Zhou, Mu; Tao, Huizhong W.; Zhang, Li I.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
   [Zhang, Li I.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA.
   [Tao, Huizhong W.] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA.
   [Xiao, Zhongju] So Med Univ, Sch Basic Med Sci, Dept Physiol, Guangzhou 510515, Guangdong, Peoples R China.
C3 University of Southern California; University of Southern California; University of Southern California; Southern Medical University - China
RP Zhang, LI (corresponding author), Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
EM htao@usc.edu; liizhang@usc.edu
FU US National Institutes of Health/National Institute on Deafness and Other Communication Disorders [R01DC008983, R21DC008588]; Searle Scholar Program; Klingenstein Foundation; David and Lucile Packard Foundation; US National Institutes of Health [EY018718, EY019049]; Karl Kirchgessner Foundation; National Natural Science Foundation of China [30730039, 30970982, 30670665]; National Eye Institute [R01EY019049] Funding Source: NIH RePORTER; National Institute on Deafness and Other Communication Disorders [R01DC008983] Funding Source: NIH RePORTER
NR 30
TC 155
Z9 184
U1 2
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 JUN 17
PY 2010
VL 465
IS 7300
BP 927
EP U8
DI 10.1038/nature09079
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500038
PM 20559386
DA 2026-03-09
ER

PT J
AU Wang, F
   Han, Y
   Lim, CS
   Lu, YH
   Wang, J
   Xu, J
   Chen, HY
   Zhang, C
   Hong, MH
   Liu, XG
AF Wang, Feng
   Han, Yu
   Lim, Chin Seong
   Lu, Yunhao
   Wang, Juan
   Xu, Jun
   Chen, Hongyu
   Zhang, Chun
   Hong, Minghui
   Liu, Xiaogang
TI Simultaneous phase and size control of upconversion nanocrystals through lanthanide doping
SO NATURE
LA English
DT Article
ID doped nayf4 nanocrystals; nanoparticles; quality; reduction; emission; ions
AB Doping is a widely applied technological process in materials science that involves incorporating atoms or ions of appropriate elements into host lattices to yield hybrid materials with desirable properties and functions. For nanocrystalline materials, doping is of fundamental importance in stabilizing a specific crystallographic phase(1), modifying electronic properties(2-4), modulating magnetism(5) as well as tuning emission properties(6-9). Here we describe a material system in which doping influences the growth process to give simultaneous control over the crystallographic phase, size and optical emission properties of the resulting nanocrystals. We show that NaYF(4) nanocrystals can be rationally tuned in size (down to ten nanometres), phase (cubic or hexagonal) and upconversion(10-12) emission colour (green to blue) through use of trivalent lanthanide dopant ions introduced at precisely defined concentrations. We use first-principles calculations to confirm that the influence of lanthanide doping on crystal phase and size arises from a strong dependence on the size and dipole polarizability of the substitutional dopant ion. Our results suggest that the doping-induced structural and size transition, demonstrated here in NaYF(4) upconversion nanocrystals, could be extended to other lanthanide-doped nanocrystal systems for applications ranging from luminescent biological labels(12) to volumetric three-dimensional displays(13).
C1 [Wang, Feng; Wang, Juan; Zhang, Chun; Liu, Xiaogang] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore.
   [Han, Yu] King Abdullah Univ Sci & Technol, Div Chem & Life Sci & Engn, Membrane Res Ctr, Thuwal 239556900, Saudi Arabia.
   [Lim, Chin Seong; Hong, Minghui] ASTAR, Data Storage Inst, Opt Mat & Syst Div, Singapore 117608, Singapore.
   [Lu, Yunhao; Zhang, Chun] Natl Univ Singapore, Dept Phys, Singapore 117543, Singapore.
   [Xu, Jun; Chen, Hongyu] Nanyang Technol Univ, Div Chem & Biol Chem, Singapore 637371, Singapore.
   [Hong, Minghui] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117543, Singapore.
C3 National University of Singapore; King Abdullah University of Science & Technology; Agency for Science Technology & Research (A*STAR); A*STAR - Data Storage Institute; National University of Singapore; Nanyang Technological University; National University of Singapore
RP Liu, XG (corresponding author), Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore.
EM chmlx@nus.edu.sg
FU National University of Singapore (NUS); Ministry of Education of Singapore; Singapore-MIT Alliance; Agency for Science, Technology and Research (A*STAR); NUS
NR 30
TC 2986
Z9 3235
U1 61
U2 4072
PU 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 25
PY 2010
VL 463
IS 7284
BP 1061
EP 1065
DI 10.1038/nature08777
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400032
PM 20182508
DA 2026-03-09
ER

PT J
AU Soria, C
   Estermann, FE
   Espantman, KC
   O'Shea, CC
AF Soria, Conrado
   Estermann, Fanny E.
   Espantman, Kristen C.
   O'Shea, Clodagh C.
TI Heterochromatin silencing of p53 target genes by a small viral protein
SO NATURE
LA English
DT Article
ID early region 4; adenovirus mutant; tumor-suppressor; cells; replication; methylation; expression; e1a; transcription; onyx-015
AB The transcription factor p53 (also known as TP53) guards against tumour and virus replication and is inactivated in almost all cancers. p53-activated transcription of target genes is thought to be synonymous with the stabilization of p53 in response to oncogenes and DNA damage. During adenovirus replication, the degradation of p53 by E1B-55k is considered essential for p53 inactivation, and is the basis for p53-selective viral cancer therapies. Here we reveal a dominant epigenetic mechanism that silences p53-activated transcription, irrespective of p53 phosphorylation and stabilization. We show that another adenoviral protein, E4-ORF3, inactivates p53 independently of E1B-55k by forming a nuclear structure that induces de novo H3K9me3 heterochromatin formation at p53 target promoters, preventing p53-DNA binding. This suppressive nuclear web is highly selective in silencing p53 promoters and operates in the backdrop of global transcriptional changes that drive oncogenic replication. These findings are important for understanding how high levels of wild-type p53 might also be inactivated in cancer as well as the mechanisms that induce aberrant epigenetic silencing of tumour-suppressor loci. Our study changes the longstanding definition of how p53 is inactivated in adenovirus infection and provides key insights that could enable the development of true p53-selective oncolytic viral therapies.
C1 [Soria, Conrado; Estermann, Fanny E.; Espantman, Kristen C.; O'Shea, Clodagh C.] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
C3 Salk Institute
RP O'Shea, CC (corresponding author), Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM oshea@salk.edu
FU Alliance of Cancer Gene Therapy; American Cancer Society; Sontag Foundation; Beckman Foundation; National Cancer Institute [R01CA137094]
NR 58
TC 116
Z9 148
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1076
EP U85
DI 10.1038/nature09307
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600033
PM 20740008
DA 2026-03-09
ER

PT J
AU Kwon, ES
   Narasimhan, D
   Yen, K
   Tissenbaum, HA
AF Kwon, Eun-Soo
   Narasimhan, Devi
   Yen, Kelvin
   Tissenbaum, Heidi A.
TI A new DAF-16 isoform regulates longevity
SO NATURE
LA English
DT Article
ID c-elegans daf-16; life-span; caenorhabditis-elegans; stress; gene; insulin/igf-1; resistance
AB The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity(1-5). In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway(2,3,6,7). One of two isoforms(4,5,8), DAF-16a, is known to regulate longevity, stress response and dauer diapause(8-11). However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate IIS-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases, and regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions(6,12), and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the IIS-mediated processes in the context of a whole organism.
C1 [Kwon, Eun-Soo; Narasimhan, Devi; Yen, Kelvin; Tissenbaum, Heidi A.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Tissenbaum, Heidi A.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester
RP Tissenbaum, HA (corresponding author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM heidi.tissenbaum@umassmed.edu
FU National Institutes of Health National Center for Research Resources; National Institute of Aging [AG025891, AG031237]; Glenn Foundation for Medical Research; Ellison Medical Foundation; William Randolph Hearst Foundation
NR 30
TC 153
Z9 204
U1 2
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 498
EP 502
DI 10.1038/nature09184
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200038
PM 20613724
DA 2026-03-09
ER

PT J
AU Shank, EA
   Cecconi, C
   Dill, JW
   Marqusee, S
   Bustamante, C
AF Shank, Elizabeth A.
   Cecconi, Ciro
   Dill, Jesse W.
   Marqusee, Susan
   Bustamante, Carlos
TI The folding cooperativity of a protein is controlled by its chain topology
SO NATURE
LA English
DT Article
ID atomic-force microscopy; t4 lysozyme; single-molecule; fluctuation theorem; conformations; stability; fragment; dna
AB The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communication between these regions is important for catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfolding pathologies(1). How different structural regions of a protein communicate and contribute to a protein's overall energetics and folding, however, is still poorly understood. Here we use a single-molecule optical tweezers approach to induce the selective unfolding of particular regions of T4 lysozyme and monitor the effect on other regions not directly acted on by force. We investigate how the topological organization of a protein (the order of structural elements along the sequence) affects the coupling and folding cooperativity between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes during mechanical unfolding using Crooks' fluctuation theorem. We pull on topological variants (circular permutants) and find that the topological organization of the polypeptide chain critically determines the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding.
C1 [Shank, Elizabeth A.; Cecconi, Ciro; Marqusee, Susan; Bustamante, Carlos] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Shank, Elizabeth A.; Cecconi, Ciro; Dill, Jesse W.; Marqusee, Susan; Bustamante, Carlos] Univ Calif Berkeley, Inst Quantitat Biosci, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
   [Dill, Jesse W.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Bustamante, Carlos] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Howard Hughes Medical Institute; 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 Marqusee, S (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM Marqusee@berkeley.edu; Carlos@alice.berkeley.edu
FU NIH [GM 32543, GM 50945]; NSF; National Institute of General Medical Sciences [R01GM050945, R01GM032543] Funding Source: NIH RePORTER
NR 28
TC 192
Z9 242
U1 0
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 JUN 3
PY 2010
VL 465
IS 7298
BP 637
EP U134
DI 10.1038/nature09021
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000046
PM 20495548
DA 2026-03-09
ER

PT J
AU Fischer, N
   Konevega, AL
   Wintermeyer, W
   Rodnina, MV
   Stark, H
AF Fischer, Niels
   Konevega, Andrey L.
   Wintermeyer, Wolfgang
   Rodnina, Marina V.
   Stark, Holger
TI Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy
SO NATURE
LA English
DT Article
ID elongation-factor-g; escherichia-coli ribosm; messenger-rna; l1 stalk; intermediate states; angstrom resolution; crystal-structure; single ribosm; gtp hydrolysis; hybrid states
AB The translocation step of protein synthesis entails large-scale rearrangements of the ribosome-transfer RNA (tRNA) complex. Here we have followed tRNA movement through the ribosome during translocation by time-resolved single-particle electron cryomicroscopy (cryo-EM). Unbiased computational sorting of cryo-EM images yielded 50 distinct three-dimensional reconstructions, showing the tRNAs in classical, hybrid and various novel intermediate states that provide trajectories and kinetic information about tRNA movement through the ribosome. The structures indicate how tRNA movement is coupled with global and local conformational changes of the ribosome, in particular of the head and body of the small ribosomal subunit, and show that dynamic interactions between tRNAs and ribosomal residues confine the path of the tRNAs through the ribosome. The temperature dependence of ribosome dynamics reveals a surprisingly flat energy landscape of conformational variations at physiological temperature. The ribosome functions as a Brownian machine that couples spontaneous conformational changes driven by thermal energy to directed movement.
C1 [Fischer, Niels; Stark, Holger] Max Planck Inst Biophys Chem, Elect Cryomicroscopy Grp 3D, D-37077 Gottingen, Germany.
   [Konevega, Andrey L.; Wintermeyer, Wolfgang; Rodnina, Marina V.] Max Planck Inst Biophys Chem, Dept Phys Biochem, D-37077 Gottingen, Germany.
   [Konevega, Andrey L.] Petersburg Nucl Phys Inst, Gatchina 188300, Russia.
C3 Max Planck Society; Max Planck Society; National Research Centre - Kurchatov Institute; Petersburg Nuclear Physics Institute
RP Stark, H (corresponding author), Max Planck Inst Biophys Chem, Elect Cryomicroscopy Grp 3D, Fassberg 11, D-37077 Gottingen, Germany.
EM hstark1@gwdg.de
FU Federal Ministry of Education and Research (BMBF), Germany; European Union; state of Lower-Saxony; Volkswagen Foundation, Hannover, Germany; Boehringer-Ingelheim fellowship; Deutsche Forschungsgemeinschaft
NR 44
TC 329
Z9 392
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 JUL 15
PY 2010
VL 466
IS 7304
BP 329
EP 333
DI 10.1038/nature09206
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100040
PM 20631791
DA 2026-03-09
ER

PT J
AU García-Berro, E
   Torres, S
   Althaus, LG
   Renedo, I
   Lorén-Aguilar, P
   Córsico, AH
   Rohrmann, RD
   Salaris, M
   Isern, J
AF Garcia-Berro, Enrique
   Torres, Santiago
   Althaus, Leandro G.
   Renedo, Isabel
   Loren-Aguilar, Pablo
   Corsico, Alejandro H.
   Rohrmann, Rene D.
   Salaris, Maurizio
   Isern, Jordi
TI A white dwarf cooling age of 8 Gyr for NGC 6791 from physical separation processes
SO NATURE
LA English
DT Article
ID monte-carlo simulations; final mass relationship; stellar evolution; ngc-6791; ne-22; population; sequence; crystallization; interiors; mixtures
AB NGC 6791 is a well studied open cluster(1) that it is so close to us that can be imaged down to very faint luminosities(2). The main-sequence turn-off age (similar to 8 Gyr) and the age derived from the termination of the white dwarf cooling sequence (similar to 6 Gyr) are very different. One possible explanation is that as white dwarfs cool, one of the ashes of helium burning, (22)Ne, sinks in the deep interior of these stars(3-5). At lower temperatures, white dwarfs are expected to crystallize and phase separation of the main constituents of the core of a typical white dwarf ((12)C and (16)O) is expected to occur(6,7). This sequence of events is expected to introduce long delays in the cooling times(8,9), but has not hitherto been proven. Here we report that, as theoretically anticipated(5,6), physical separation processes occur in the cores of white dwarfs, resolving the age discrepancy for NGC 6791.
C1 [Garcia-Berro, Enrique; Torres, Santiago; Althaus, Leandro G.; Renedo, Isabel; Loren-Aguilar, Pablo] Univ Politecn Cataluna, Dept Fis Aplicada, Castelldefels 08860, Spain.
   [Garcia-Berro, Enrique; Torres, Santiago; Renedo, Isabel; Loren-Aguilar, Pablo; Isern, Jordi] Inst Estudis Espacials Catalunya, Barcelona 08034, Spain.
   [Althaus, Leandro G.; Corsico, Alejandro H.] Univ Nacl La Plata, Fac Ciencias Astron & Geofis, RA-1900 La Plata, Argentina.
   [Althaus, Leandro G.; Corsico, Alejandro H.] Consejo Nacl Invest Cient & Tecn, Inst Astrofis La Plata CCT La Plata, RA-1900 La Plata, Argentina.
   [Rohrmann, Rene D.] Consejo Nacl Invest Cient & Tecn, Inst Ciencias Astron Tierra & Espacio, RA-5400 San Juan, Argentina.
   [Salaris, Maurizio] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Isern, Jordi] Fac Ciencies, CSIC, Inst Ciencies Espai, Bellaterra 08193, Spain.
C3 Universitat Politecnica de Catalunya; Institut d'Estudis Espacials de Catalunya (IEEC); National University of La Plata; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Liverpool John Moores University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Institut d'Estudis Espacials de Catalunya (IEEC)
RP García-Berro, E (corresponding author), Univ Politecn Cataluna, Dept Fis Aplicada, C Esteve Terrades 5, Castelldefels 08860, Spain.
EM garcia@fa.upc.edu
FU MCINN; AGENCIA; Generalitat de Catalunya; STFC; CONICET; AGAUR of the Generalitat de Catalunya; Science and Technology Facilities Council [ST/H002391/1, PP/E001149/1] Funding Source: researchfish; STFC [ST/H002391/1, PP/E001149/1] Funding Source: UKRI
NR 25
TC 208
Z9 217
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 194
EP 196
DI 10.1038/nature09045
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500029
PM 20463732
DA 2026-03-09
ER

PT J
AU Snodgrass, C
   Tubiana, C
   Vincent, JB
   Sierks, H
   Hviid, S
   Moissl, R
   Boehnhardt, H
   Barbieri, C
   Koschny, D
   Lamy, P
   Rickman, H
   Rodrigo, R
   Carry, B
   Lowry, SC
   Laird, RJM
   Weissman, PR
   Fitzsimmons, A
   Marchi, S
   A'Hearn, M
   Angrilli, F
   Barucci, A
   Bertaux, JL
   Cremonese, G
   Da Deppo, V
   Davidsson, B
   Debei, S
   De Cecco, M
   Fornasier, S
   Gutiérrez, P
   Ip, WH
   Keller, HU
   Knollenberg, J
   Kramm, JR
   Kuehrt, E
   Kueppers, M
   Lara, LM
   Lazzarin, M
   López-Moreno, JJ
   Marzari, F
   Michalik, H
   Naletto, G
   Sabau, L
   Thomas, N
   Wenzel, KP
AF Snodgrass, Colin
   Tubiana, Cecilia
   Vincent, Jean-Baptiste
   Sierks, Holger
   Hviid, Stubbe
   Moissl, Richard
   Boehnhardt, Hermann
   Barbieri, Cesare
   Koschny, Detlef
   Lamy, Philippe
   Rickman, Hans
   Rodrigo, Rafael
   Carry, Benoit
   Lowry, Stephen C.
   Laird, Ryan J. M.
   Weissman, Paul R.
   Fitzsimmons, Alan
   Marchi, Simone
   A'Hearn, M.
   Angrilli, F.
   Barucci, A.
   Bertaux, J. -L.
   Cremonese, G.
   Da Deppo, V.
   Davidsson, B.
   Debei, S.
   De Cecco, M.
   Fornasier, S.
   Gutierrez, P.
   Ip, W. -H.
   Keller, H. U.
   Knollenberg, J.
   Kramm, J. R.
   Kuehrt, E.
   Kueppers, M.
   Lara, L. M.
   Lazzarin, M.
   Lopez-Moreno, J. J.
   Marzari, F.
   Michalik, H.
   Naletto, G.
   Sabau, L.
   Thomas, N.
   Wenzel, K. -P.
TI A collision in 2009 as the origin of the debris trail of asteroid P/2010 A2
SO NATURE
LA English
DT Article
ID belt; history; comets; ejecta; model
AB The peculiar object P/2010 A2 was discovered(1) in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized(2) class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010 A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results(3). The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.
C1 [Snodgrass, Colin; Tubiana, Cecilia; Vincent, Jean-Baptiste; Sierks, Holger; Hviid, Stubbe; Moissl, Richard; Boehnhardt, Hermann; Kramm, J. R.] Max Planck Inst Sonnensyst Forsch, Max Planck Str 2, D-37191 Katlenburg Lindau, Germany.
   [Snodgrass, Colin] European So Observ, Santiago 19, Chile.
   [Barbieri, Cesare; Marchi, Simone; Lazzarin, M.] Univ Padua, Dept Astron, I-35122 Padua, Italy.
   [Koschny, Detlef; Wenzel, K. -P.] European Space Agcy, Res & Sci Support Dept, NL-2201 AZ Noordwijk, Netherlands.
   [Lamy, Philippe] Univ Aix Marseille, CNRS, Lab Astrophys Marseille, UMR6110, F-13388 Marseille 13, France.
   [Rickman, Hans; Davidsson, B.] Uppsala Univ, Dept Astron & Space Sci, S-75120 Uppsala, Sweden.
   [Rickman, Hans] PAS Space Res Ctr, PL-00716 Warsaw, Poland.
   [Rodrigo, Rafael; Gutierrez, P.; Lara, L. M.; Lopez-Moreno, J. J.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [Carry, Benoit; Barucci, A.; Fornasier, S.] Observ Paris, LESIA, F-92195 Meudon, France.
   [Lowry, Stephen C.; Laird, Ryan J. M.] Univ Kent, Ctr Astrophys & Planetary Sci, Canterbury CT2 7NH, Kent, England.
   [Weissman, Paul R.] Jet Prop Lab, Pasadena, CA 91101 USA.
   [Fitzsimmons, Alan] Queens Univ Belfast, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [A'Hearn, M.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Angrilli, F.] Univ Padua, Dept Mech Engn, Via Venezia 1, I-35131 Padua, Italy.
   [Bertaux, J. -L.] LATMOS, CNRS, UVSQ, IPSL, 11 Blvd Alembert, F-78280 Guyancourt, France.
   [Cremonese, G.] Osserv Astron Padova, INAF, Vicolo Osservatorio 5, I-35122 Padua, Italy.
   [Da Deppo, V.] CNR IFN UOS, Padova LUXOR, Via Trasea 7, I-35131 Padua, Italy.
   [De Cecco, M.] Univ Trent, UNITN, Via Mesiano 77, I-38100 Trento, Italy.
   [Ip, W. -H.] Natl Cent Univ, Inst Astron, Chungli 32054, Taiwan.
   [Keller, H. U.; Michalik, H.] TU Braunschweig, Inst Datentech & Kommunikat, Hans Sommer Str 66, D-38106 Braunschweig, Germany.
   [Knollenberg, J.; Kuehrt, E.] DLR Inst Planetary Res, Rutherfordstr 2, D-12489 Berlin, Germany.
   [Kueppers, M.] ESA ESAC, Camino Bajo del Castillo S-N, Madrid 28691, Spain.
   [Marzari, F.] Univ Padua, Dept Phys, Via Marzolo 8, I-35131 Padua, Italy.
   [Naletto, G.] Univ Padua, Dept Informat Engn, Via Gradenigo 6-B, I-35131 Padua, Italy.
   [Sabau, L.] Inst Nacl Tecn Aeroespacial, Carretera Ajalvir PK 4, Madrid 28850, Spain.
   [Thomas, N.] Univ Bern, Abt Weltraumforsch & Planetol, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland.
C3 Max Planck Society; European Southern Observatory; University of Padua; European Space Agency; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Uppsala University; Polish Academy of Sciences; Space Research Centre of the Polish Academy of Sciences; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Universite PSL; Observatoire de Paris; University of Kent; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Queens University Belfast; University System of Maryland; University of Maryland College Park; University of Padua; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Istituto Nazionale Astrofisica (INAF); University of Padua; University of Trento; National Central University; Braunschweig University of Technology; Helmholtz Association; German Aerospace Centre (DLR); European Space Agency; European Space Astronomy Center; University of Padua; University of Padua; University of Bern
RP Snodgrass, C (corresponding author), Max Planck Inst Sonnensyst Forsch, Max Planck Str 2, D-37191 Katlenburg Lindau, Germany.
EM snodgrass@mps.mpg.de
FU ASI; CNES; DLR; Ministerio de Educacion y Ciencia; SNSB; ESA; STFC [PP/E001823/1, ST/H002553/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E001823/1, ST/H002553/1] Funding Source: researchfish
NR 23
TC 93
Z9 100
U1 0
U2 20
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 814
EP 816
DI 10.1038/nature09453
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700060
PM 20944742
DA 2026-03-09
ER

PT J
AU He, XA
   Szewczyk, P
   Karyakin, A
   Evin, M
   Hong, WX
   Zhang, QH
   Chang, G
AF He, Xiao
   Szewczyk, Paul
   Karyakin, Andrey
   Evin, Mariah
   Hong, Wen-Xu
   Zhang, Qinghai
   Chang, Geoffrey
TI Structure of a cation-bound multidrug and toxic compound extrusion transporter
SO NATURE
LA English
DT Article
ID staphylococcus-aureus; diffraction data; database; family; crystallography; resistance; mechanism; model; gene; norm
AB Transporter proteins from the MATE (multidrug and toxic compound extrusion)(1) family are vital in metabolite transport in plants(2,3), directly affecting crop yields worldwide(4). MATE transporters also mediate multiple-drug resistance (MDR) in bacteria and mammals(5), modulating the efficacy of many pharmaceutical drugs used in the treatment of a variety of diseases(6-9). MATE transporters couple substrate transport to electrochemical gradients and are the only remaining class of MDR transporters whose structure has not been determined(10). Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 angstrom, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known MDR transporter. We also report a cation-binding site in close proximity to residues previously deemed critical for transport(11). This conformation probably represents a stage of the transport cycle with high affinity for monovalent cations and low affinity for substrates.
C1 [He, Xiao; Szewczyk, Paul; Karyakin, Andrey; Evin, Mariah; Hong, Wen-Xu; Zhang, Qinghai; Chang, Geoffrey] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Chang, G (corresponding author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd,CB105, La Jolla, CA 92037 USA.
EM gchang@scripps.edu
FU National Institutes of Health [GM70480, GM73197]; Beckman Foundation; Skaggs Chemical Biology Foundation
NR 37
TC 226
Z9 271
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 OCT 21
PY 2010
VL 467
IS 7318
BP 991
EP U139
DI 10.1038/nature09408
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700044
PM 20861838
DA 2026-03-09
ER

PT J
AU Amstrup, SC
   DeWeaver, ET
   Douglas, DC
   Marcot, BG
   Durner, GM
   Bitz, CM
   Bailey, DA
AF Amstrup, Steven C.
   DeWeaver, Eric T.
   Douglas, David C.
   Marcot, Bruce G.
   Durner, George M.
   Bitz, Cecilia M.
   Bailey, David A.
TI Greenhouse gas mitigation can reduce sea-ice loss and increase polar bear persistence
SO NATURE
LA English
DT Article
ID climate-change; 21st-century; system; policy
AB On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue(1-3). That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold(4-6). Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model(7), that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case(3). Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice(6); instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points(5,6,8). Our outcomes indicate that rapid summer ice losses in models(9) and observations(6,10) represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers(3) are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem(11) and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout and beyond the Arctic(12).
C1 [Amstrup, Steven C.; Durner, George M.] US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
   [DeWeaver, Eric T.] Natl Sci Fdn, Arlington, VA 22230 USA.
   [Douglas, David C.] US Geol Survey, Alaska Sci Ctr, Juneau, AK 99801 USA.
   [Marcot, Bruce G.] US Forest Serv, USDA, PNW Res Stn, Portland, OR 97205 USA.
   [Bitz, Cecilia M.] Univ Washington, Seattle, WA 98195 USA.
   [Bailey, David A.] Natl Ctr Atmospher Res, Boulder, CO 80305 USA.
C3 United States Department of the Interior; United States Geological Survey; National Science Foundation (NSF); United States Department of the Interior; United States Geological Survey; United States Department of Agriculture (USDA); United States Forest Service; University of Washington; University of Washington Seattle; National Center Atmospheric Research (NCAR) - USA
RP Amstrup, SC (corresponding author), Polar Bears Int, 810 N Wallace,Suite E,POB 3008, Bozeman, MT 59772 USA.
EM samstrup@pbears.org
FU USGS; USDA Forest Service, Pacific Northwest Research Station; Office of Science (BER), US Department of Energy [ER64735]; National Science Foundation (NSF); NSF Office of Polar Programs [0908675]; Directorate For Geosciences; Office of Polar Programs (OPP) [0908675] Funding Source: National Science Foundation
NR 37
TC 113
Z9 129
U1 0
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 DEC 16
PY 2010
VL 468
IS 7326
BP 955
EP 958
DI 10.1038/nature09653
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600045
PM 21164484
DA 2026-03-09
ER

PT J
AU Thomson, JP
   Skene, PJ
   Selfridge, J
   Clouaire, T
   Guy, J
   Webb, S
   Kerr, ARW
   Deaton, A
   Andrews, R
   James, KD
   Turner, DJ
   Illingworth, R
   Bird, A
AF Thomson, John P.
   Skene, Peter J.
   Selfridge, Jim
   Clouaire, Thomas
   Guy, Jacky
   Webb, Shaun
   Kerr, Alastair R. W.
   Deaton, Aimee
   Andrews, Rob
   James, Keith D.
   Turner, Daniel J.
   Illingworth, Robert
   Bird, Adrian
TI CpG islands influence chromatin structure via the CpG-binding protein Cfp1
SO NATURE
LA English
DT Article
ID h3-lys(4) methyltransferase complex; embryonic stem-cells; de-novo methylation; dna methylation; human trithorax; histone h3; genome; mecp2; identification; domain
AB CpG islands (CGIs) are prominent in the mammalian genome owing to their GC-rich base composition and high density of CpG dinucleotides(1,2). Most human gene promoters are embedded within CGIs that lack DNA methylation and coincide with sites of histone H3 lysine 4 trimethylation (H3K4me3), irrespective of transcriptional activity(3,4). In spite of these intriguing correlations, the functional significance of non-methylated CGI sequences with respect to chromatin structure and transcription is unknown. By performing a search for proteins that are common to all CGIs, here we show high enrichment for Cfp1, which selectively binds to nonmethylated CpGs in vitro(5,6). Chromatin immunoprecipitation of a mono-allelically methylated CGI confirmed that Cfp1 specifically associates with non-methylated CpG sites in vivo. High throughput sequencing of Cfp1-bound chromatin identified a notable concordance with non-methylated CGIs and sites of H3K4me3 in the mouse brain. Levels of H3K4me3 at CGIs were markedly reduced in Cfp1-depleted cells, consistent with the finding that Cfp1 associates with the H3K4 methyltransferase Setd1 (refs 7, 8). To test whether non-methylated CpG-dense sequences are sufficient to establish domains of H3K4me3, we analysed artificial CpG clusters that were integrated into the mouse genome. Despite the absence of promoters, the insertions recruited Cfp1 and created new peaks of H3K4me3. The data indicate that a primary function of non-methylated CGIs is to genetically influence the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins.
C1 [Thomson, John P.; Skene, Peter J.; Selfridge, Jim; Clouaire, Thomas; Guy, Jacky; Webb, Shaun; Kerr, Alastair R. W.; Deaton, Aimee; Illingworth, Robert; Bird, Adrian] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
   [Andrews, Rob; James, Keith D.; Turner, Daniel J.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 University of Edinburgh; Wellcome Trust Sanger Institute
RP Bird, A (corresponding author), Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Michael Swann Bldg,Mayfield Rd, Edinburgh EH9 3JR, Midlothian, Scotland.
EM a.bird@ed.ac.uk
FU Cancer Research UK studentship; Wellcome Trust; Medical Research Council; European Union; MRC [G0800026] Funding Source: UKRI; Medical Research Council [G0800026] Funding Source: researchfish
NR 33
TC 509
Z9 614
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1082
EP U162
DI 10.1038/nature08924
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000047
PM 20393567
DA 2026-03-09
ER

PT J
AU Shin, J
   Bossenz, M
   Chung, Y
   Ma, H
   Byron, M
   Taniguchi-Ishigaki, N
   Zhu, XC
   Jiao, BW
   Hall, LL
   Green, MR
   Jones, SN
   Hermans-Borgmeyer, I
   Lawrence, JB
   Bach, I
AF Shin, JongDae
   Bossenz, Michael
   Chung, Young
   Ma, Hong
   Byron, Meg
   Taniguchi-Ishigaki, Naoko
   Zhu, Xiaochun
   Jiao, Baowei
   Hall, Lisa L.
   Green, Michael R.
   Jones, Stephen N.
   Hermans-Borgmeyer, Irm
   Lawrence, Jeanne B.
   Bach, Ingolf
TI Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice
SO NATURE
LA English
DT Article
ID homeodomain transcription factors; embryonic stem-cells; dosage compensation; lim cofactors; expression; gene; lines; rlim; differentiation; disruption
AB Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X chromosome (Xm)(1,2). Both forms of XCI require the non-coding Xist RNA that coats the inactive X chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X chromosome (Delta m) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Delta m female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.
C1 [Shin, JongDae; Ma, Hong; Taniguchi-Ishigaki, Naoko; Zhu, Xiaochun; Jiao, Baowei; Green, Michael R.; Bach, Ingolf] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Green, Michael R.; Bach, Ingolf] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
   [Zhu, Xiaochun; Green, Michael R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
   [Byron, Meg; Hall, Lisa L.; Jones, Stephen N.; Lawrence, Jeanne B.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA.
   [Bossenz, Michael; Hermans-Borgmeyer, Irm] Univ Hamburg, Ctr Mol Neurobiol, D-20246 Hamburg, Germany.
   [Chung, Young] Stem Cell & Regenerat Med Int Inc, Marlborough, MA 01752 USA.
   [Chung, Young] CHA Univ, Sch Med, Seoul 135081, South Korea.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester; University of Hamburg; Pochon Cha University
RP Bach, I (corresponding author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM ingolf.bach@umassmed.edu
FU National Institutes of Health (National Cancer Institute) [R01CA131158]; National Institute of Diabetes and Digestive and Kidney Diseases [5 P30 DK32520, GM053234]
NR 37
TC 142
Z9 153
U1 0
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 OCT 21
PY 2010
VL 467
IS 7318
BP 977
EP U157
DI 10.1038/nature09457
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700041
PM 20962847
DA 2026-03-09
ER

PT J
AU Dial, OE
   Ashoori, RC
   Pfeiffer, LN
   West, KW
AF Dial, O. E.
   Ashoori, R. C.
   Pfeiffer, L. N.
   West, K. W.
TI Anomalous structure in the single particle spectrum of the fractional quantum Hall effect
SO NATURE
LA English
DT Article
ID 2-dimensional electron-gas; composite fermions; skyrmions; energy; gaps; excitations; crossover; integer; gaas
AB The two-dimensional electron system is a powerful laboratory for investigating the physics of interacting particles. Application of a large magnetic field produces massively degenerate quantum levels known as Landau levels; within a Landau level the kinetic energy of the electrons is suppressed, and electron-electron interactions set the only energy scale(1). Coulomb interactions break the degeneracy of the Landau levels and can cause the electrons to order into complex ground states. Here we observe, in the high energy single particle spectrum of this system, salient and unexpected structure that extends across a wide range of Landau level filling fractions. The structure appears only when the two-dimensional electron system is cooled to very low temperatures, indicating that it arises from delicate ground state correlations. We characterize this structure by its evolution with changing electron density and applied magnetic field, and present two possible models for understanding these observations. Some of the energies of the features agree qualitatively with what might be expected for composite fermions, which have proven effective for interpreting other experiments in this regime. At the same time, a simple model with electrons localized on ordered lattice sites also generates structure similar to that observed in the experiment. Neither of these models alone is sufficient to explain the observations across the entire range of densities measured. The discovery of this unexpected prominent structure in the single particle spectrum of an otherwise thoroughly studied system suggests that there exist core features of the two-dimensional electron system that have yet to be understood.
C1 [Dial, O. E.; Ashoori, R. C.] MIT, Cambridge, MA 02139 USA.
   [Pfeiffer, L. N.; West, K. W.] Alcatel Lucent Bell Labs, Murray Hill, NJ 07974 USA.
C3 Massachusetts Institute of Technology (MIT); Alcatel-Lucent
RP Dial, OE (corresponding author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM dial@alum.mit.edu; ashoori@mit.edu
FU Office of Science of the US Department of Energy
NR 24
TC 35
Z9 43
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 MAR 25
PY 2010
VL 464
IS 7288
BP 566
EP 570
DI 10.1038/nature08941
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200042
PM 20336140
DA 2026-03-09
ER

PT J
AU Liu, W
   Tanasa, B
   Tyurina, OV
   Zhou, TY
   Gassmann, R
   Liu, WT
   Ohgi, KA
   Benner, C
   Garcia-Bassets, I
   Aggarwal, AK
   Desai, A
   Dorrestein, PC
   Glass, CK
   Rosenfeld, MG
AF Liu, Wen
   Tanasa, Bogdan
   Tyurina, Oksana V.
   Zhou, Tian Yuan
   Gassmann, Reto
   Liu, Wei Ting
   Ohgi, Kenneth A.
   Benner, Chris
   Garcia-Bassets, Ivan
   Aggarwal, Aneel K.
   Desai, Arshad
   Dorrestein, Pieter C.
   Glass, Christopher K.
   Rosenfeld, Michael G.
TI PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression
SO NATURE
LA English
DT Article
ID s-phase; chromosome structure; mental-retardation; heat repeats; methylation; identification; stability; binding; protein; genome
AB While reversible histone modifications are linked to an ever-expanding range of biological functions(1-5), the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structuralmaintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.
C1 [Liu, Wen; Tanasa, Bogdan; Tyurina, Oksana V.; Zhou, Tian Yuan; Ohgi, Kenneth A.; Garcia-Bassets, Ivan; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Liu, Wen] Univ Calif San Diego, Grad Program Biol, La Jolla, CA 92093 USA.
   [Tanasa, Bogdan] Scripps Res Inst, Kellogg Sch Sci & Technol, La Jolla, CA 92037 USA.
   [Gassmann, Reto; Desai, Arshad] Univ Calif San Diego, Dept Cellular & Mol Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Liu, Wei Ting; Dorrestein, Pieter C.] Univ Calif San Diego, Dept Chem & Biochem, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
   [Aggarwal, Aneel K.] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
C3 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; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego; Icahn School of Medicine at Mount Sinai
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM mrosenfeld@ucsd.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK039949] Funding Source: NIH RePORTER; Howard Hughes Medical Institute Funding Source: Medline; NCI NIH HHS [R01 CA097134] Funding Source: Medline; NHLBI NIH HHS [R01 HL065445] Funding Source: Medline; NIDDK NIH HHS [R01 DK018477, R37 DK039949, R01 DK039949] Funding Source: Medline; NINDS NIH HHS [R01 NS034934] Funding Source: Medline
NR 42
TC 344
Z9 419
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 JUL 22
PY 2010
VL 466
IS 7305
BP 508
EP U14
DI 10.1038/nature09272
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200040
PM 20622854
DA 2026-03-09
ER

PT J
AU Becker, T
   Loch, G
   Beyer, M
   Zinke, I
   Aschenbrenner, AC
   Carrera, P
   Inhester, T
   Schultze, JL
   Hoch, M
AF Becker, Thomas
   Loch, Gerrit
   Beyer, Marc
   Zinke, Ingo
   Aschenbrenner, Anna C.
   Carrera, Pilar
   Inhester, Therese
   Schultze, Joachim L.
   Hoch, Michael
TI FOXO-dependent regulation of innate immune homeostasis
SO NATURE
LA English
DT Article
ID life-span; drosophila; homolog; metabolism; expression; drosomycin; infection; mutants; chico; toll
AB The innate immune system represents an ancient host defence mechanism that protects against invading microorganisms. An important class of immune effector molecules to fight pathogen infections are antimicrobial peptides (AMPs) that are produced in plants and animals(1). In Drosophila, the induction of AMPs in response to infection is regulated through the activation of the evolutionarily conserved Toll and immune deficiency (IMD) pathways(2). Here we show that AMP activation can be achieved independently of these immunoregulatory pathways by the transcription factor FOXO, a key regulator of stress resistance, metabolism and ageing. In non-infected animals, AMP genes are activated in response to nuclear FOXO activity when induced by starvation, using insulin signalling mutants, or by applying small molecule inhibitors. AMP induction is lost in foxo null mutants but enhanced when FOXO is overexpressed. Expression of AMP genes in response to FOXO activity can also be triggered in animals unable to respond to immune challenges due to defects in both the Toll and IMD pathways. Molecular experiments at the Drosomycin promoter indicate that FOXO directly binds to its regulatory region, thereby inducing its transcription. In vivo studies in Drosophila, but also studies in human lung, gut, kidney and skin cells indicate that a FOXO-dependent regulation of AMPs is evolutionarily conserved. Our results indicate a new mechanism of cross-regulation of metabolism and innate immunity by which AMP genes can be activated under normal physiological conditions in response to the oscillating energy status of cells and tissues. This regulation seems to be independent of the pathogen-responsive innate immunity pathways whose activation is often associated with tissue damage and repair. The sparse production of AMPs in epithelial tissues in response to FOXO may help modulating the defence reaction without harming the host tissues, in particular when animals are suffering from energy shortage or stress.
C1 [Becker, Thomas; Loch, Gerrit; Zinke, Ingo; Aschenbrenner, Anna C.; Carrera, Pilar; Hoch, Michael] Univ Bonn, Dev Genet & Mol Physiol Unit, LIMES Inst, D-53115 Bonn, Germany.
   [Beyer, Marc; Inhester, Therese; Schultze, Joachim L.] Univ Bonn, Mol Immune & Cell Biol Unit, LIMES Inst, D-53115 Bonn, Germany.
C3 University of Bonn; University of Bonn
RP Hoch, M (corresponding author), Univ Bonn, Dev Genet & Mol Physiol Unit, LIMES Inst, Carl Troll Str 31, D-53115 Bonn, Germany.
EM m.hoch@uni-bonn.de
FU DFG [SFBs 645, 704]
NR 30
TC 292
Z9 329
U1 3
U2 73
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 369
EP 373
DI 10.1038/nature08698
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100047
PM 20090753
DA 2026-03-09
ER

PT J
AU Smith, MR
   Caron, JB
AF Smith, Martin R.
   Caron, Jean-Bernard
TI Primitive soft-bodied cephalopods from the Cambrian
SO NATURE
LA English
DT Article
ID burgess shale; british-columbia; mollusk; radula; origin; fossil
AB The exquisite preservation of soft-bodied animals in Burgess Shale-type deposits provides important clues into the early evolution of body plans that emerged during the Cambrian explosion(1). Until now, such deposits have remained silent regarding the early evolution of extant molluscan lineages-in particular the cephalopods. Nautiloids, traditionally considered basal within the cephalopods, are generally depicted as evolving from a creeping Cambrian ancestor whose dorsal shell afforded protection and buoyancy(2). Although nautiloid-like shells occur from the Late Cambrian onwards, the fossil record provides little constraint on this model, or indeed on the early evolution of cephalopods. Here, we reinterpret the problematic Middle Cambrian animal Nectocaris pteryx(3,4) as a primitive (that is, stem-group), non-mineralized cephalopod, based on new material from the Burgess Shale. Together with Nectocaris, the problematic Lower Cambrian taxa Petalilium(5) and (probably) Vetustovermis(6,7) form a distinctive clade, Nectocarididae, characterized by an open axial cavity with paired gills, wide lateral fins, a single pair of long, prehensile tentacles, a pair of non-faceted eyes on short stalks, and a large, flexible anterior funnel. This clade extends the cephalopods' fossil record(2) by over 30 million years, and indicates that primitive cephalopods lacked a mineralized shell, were hyperbenthic, and were presumably carnivorous. The presence of a funnel suggests that jet propulsion evolved in cephalopods before the acquisition of a shell. The explosive diversification of mineralized cephalopods in the Ordovician may have an understated Cambrian 'fuse'.
C1 [Smith, Martin R.; Caron, Jean-Bernard] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3G5, Canada.
   [Smith, Martin R.; Caron, Jean-Bernard] Royal Ontario Museum, Dept Nat Hist, Toronto, ON M5S 2C6, Canada.
C3 University of Toronto; Royal Ontario Museum
RP Caron, JB (corresponding author), Univ Toronto, Dept Ecol & Evolutionary Biol, 25 Harbord St, Toronto, ON M5S 3G5, Canada.
EM jcaron@rom.on.ca
FU Natural Sciences and Engineering Research Council of Canada; University of Toronto
NR 25
TC 58
Z9 65
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 469
EP 472
DI 10.1038/nature09068
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700033
PM 20505727
DA 2026-03-09
ER

PT J
AU Frearson, JA
   Brand, S
   McElroy, SP
   Cleghorn, LAT
   Smid, O
   Stojanovski, L
   Price, HP
   Guther, MLS
   Torrie, LS
   Robinson, DA
   Hallyburton, I
   Mpamhanga, CP
   Brannigan, JA
   Wilkinson, AJ
   Hodgkinson, M
   Hui, R
   Qiu, W
   Raimi, OG
   van Aalten, DMF
   Brenk, R
   Gilbert, IH
   Read, KD
   Fairlamb, AH
   Ferguson, MAJ
   Smith, DF
   Wyatt, PG
AF Frearson, Julie A.
   Brand, Stephen
   McElroy, Stuart P.
   Cleghorn, Laura A. T.
   Smid, Ondrej
   Stojanovski, Laste
   Price, Helen P.
   Guther, M. Lucia S.
   Torrie, Leah S.
   Robinson, David A.
   Hallyburton, Irene
   Mpamhanga, Chidochangu P.
   Brannigan, James A.
   Wilkinson, Anthony J.
   Hodgkinson, Michael
   Hui, Raymond
   Qiu, Wei
   Raimi, Olawale G.
   van Aalten, Daan M. F.
   Brenk, Ruth
   Gilbert, Ian H.
   Read, Kevin D.
   Fairlamb, Alan H.
   Ferguson, Michael A. J.
   Smith, Deborah F.
   Wyatt, Paul G.
TI N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
SO NATURE
LA English
DT Article
ID variant surface glycoprotein; trypanosoma-brucei; african trypanosm; myristoyl-coa; drug target; substrate proteins; endocytosis; leishmania; trafficking; complexes
AB African sleeping sickness or human African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for similar to 30,000 deaths each year. Available treatments for this disease are poor, with unacceptable efficacy and safety profiles, particularly in the late stage of the disease when the parasite has infected the central nervous system. Here we report the validation of a molecular target and the discovery of associated lead compounds with the potential to address this lack of suitable treatments. Inhibition of this target-T. brucei N-myristoyltransferase-leads to rapid killing of trypanosomes both in vitro and in vivo and cures trypanosomiasis in mice. These high-affinity inhibitors bind into the peptide substrate pocket of the enzyme and inhibit protein N-myristoylation in trypanosomes. The compounds identified have promising pharmaceutical properties and represent an opportunity to develop oral drugs to treat this devastating disease. Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis.
C1 [Frearson, Julie A.; Brand, Stephen; McElroy, Stuart P.; Cleghorn, Laura A. T.; Smid, Ondrej; Stojanovski, Laste; Guther, M. Lucia S.; Torrie, Leah S.; Robinson, David A.; Hallyburton, Irene; Mpamhanga, Chidochangu P.; Brenk, Ruth; Gilbert, Ian H.; Read, Kevin D.; Fairlamb, Alan H.; Ferguson, Michael A. J.; Wyatt, Paul G.] Univ Dundee, Div Biol Chem & Drug Discovery, Drug Discovery Unit, Coll Life Sci, Dundee DD1 5EH, Scotland.
   [Raimi, Olawale G.; van Aalten, Daan M. F.] Univ Dundee, Div Mol Microbiol, Coll Life Sci, Dundee DD1 5EH, Scotland.
   [Price, Helen P.; Hodgkinson, Michael; Smith, Deborah F.] Univ York, Dept Biol, Ctr Immunol & Infect, York YO10 5YW, N Yorkshire, England.
   [Brannigan, James A.; Wilkinson, Anthony J.] Univ York, Dept Chem, Struct Biol Lab, York YO10 5YW, N Yorkshire, England.
   [Price, Helen P.; Hodgkinson, Michael; Smith, Deborah F.] Univ York, Hull York Med Sch, York YO10 5YW, N Yorkshire, England.
   [Hui, Raymond; Qiu, Wei] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
C3 University of Dundee; University of Dundee; University of York - UK; University of York - UK; University of Hull; University of York - UK; University of Toronto; Structural Genomics Consortium
RP Wyatt, PG (corresponding author), Univ Dundee, Div Biol Chem & Drug Discovery, Drug Discovery Unit, Coll Life Sci, Dundee DD1 5EH, Scotland.
EM p.g.wyatt@dundee.ac.uk
FU Wellcome Trust [WT077705, WT083481, WT077503, WT085622]; Scottish Funding Council [HR04013]; Translational Biology Theme of SULSA; European Regional Development Fund; Wolfson Foundation; Canadian Institutes for Health Research [1097737]; Canadian Foundation for Innovation and Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation, Merck; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust; MRC [G0900138] Funding Source: UKRI; Medical Research Council [G0900138] Funding Source: researchfish
NR 39
TC 266
Z9 291
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 728
EP U100
DI 10.1038/nature08893
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000038
PM 20360736
DA 2026-03-09
ER

PT J
AU Chodavarapu, RK
   Feng, SH
   Bernatavichute, YV
   Chen, PY
   Stroud, H
   Yu, YC
   Hetzel, JA
   Kuo, F
   Kim, J
   Cokus, SJ
   Casero, D
   Bernal, M
   Huijser, P
   Clark, AT
   Krämer, U
   Merchant, SS
   Zhang, XY
   Jacobsen, SE
   Pellegrini, M
AF Chodavarapu, Ramakrishna K.
   Feng, Suhua
   Bernatavichute, Yana V.
   Chen, Pao-Yang
   Stroud, Hume
   Yu, Yanchun
   Hetzel, Jonathan A.
   Kuo, Frank
   Kim, Jin
   Cokus, Shawn J.
   Casero, David
   Bernal, Maria
   Huijser, Peter
   Clark, Amander T.
   Kraemer, Ute
   Merchant, Sabeeha S.
   Zhang, Xiaoyu
   Jacobsen, Steven E.
   Pellegrini, Matteo
TI Relationship between nucleosome positioning and DNA methylation
SO NATURE
LA English
DT Article
ID genome; organization; plants; resolution; sequence; particle; animals; reveals; h2a.z; marks
AB Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer(1,2). Here we report a genome-wide nucleosome positioning analysis of Arabidopsis thaliana using massively parallel sequencing of mononucleosomes. By combining this data with profiles of DNA methylation at single base resolution, we identified 10-base periodicities in the DNA methylation status of nucleosome-bound DNA and found that nucleosomal DNA was more highly methylated than flanking DNA. These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransferases preferentially target nucleosome-bound DNA. We also observed similar trends in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron-exon and exon-intron boundaries. RNA polymerase II (Pol II) was also enriched on exons relative to introns, consistent with the hypothesis that nucleosome positioning regulates Pol II processivity. DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition.
C1 [Chodavarapu, Ramakrishna K.; Feng, Suhua; Bernatavichute, Yana V.; Chen, Pao-Yang; Stroud, Hume; Hetzel, Jonathan A.; Kuo, Frank; Kim, Jin; Cokus, Shawn J.; Casero, David; Clark, Amander T.; Jacobsen, Steven E.; Pellegrini, Matteo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Bernatavichute, Yana V.; Merchant, Sabeeha S.; Jacobsen, Steven E.; Pellegrini, Matteo] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Yu, Yanchun; Zhang, Xiaoyu] Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA.
   [Bernal, Maria; Kraemer, Ute] Univ Heidelberg, D-69120 Heidelberg, Germany.
   [Huijser, Peter] Max Planck Inst Plant Breeding Res, Dept Mol Plant Genet, D-50829 Cologne, Germany.
   [Clark, Amander T.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
   [Merchant, Sabeeha S.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University System of Georgia; University of Georgia; Ruprecht Karls University Heidelberg; Max Planck Society; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Jacobsen, SE (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM jacobsen@ucla.edu; matteop@mcdb.ucla.edu
FU Department of Energy, Institute for Genomics and Proteomics; NIH [GM07104, GM60398, GM42143]; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research at UCLA; Alexander-von-Humboldt Fellowship; Heisenberg Fellowship; University of Georgia [JR-040]; NSF [0701745]
NR 29
TC 559
Z9 677
U1 0
U2 122
PU 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 15
PY 2010
VL 466
IS 7304
BP 388
EP 392
DI 10.1038/nature09147
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100053
PM 20512117
DA 2026-03-09
ER

PT J
AU Berné, O
   Marcelino, N
   Cernicharo, J
AF Berne, Olivier
   Marcelino, Nuria
   Cernicharo, Jose
TI Waves on the surface of the Orion molecular cloud
SO NATURE
LA English
DT Article
ID h-2 emission; gas; photoevaporation; region; stars
AB Massive stars influence their parental molecular cloud, and it has long been suspected that the development of hydrodynamical instabilities can compress or fragment the cloud(1,2). Identifying such instabilities has proved difficult. It has been suggested that elongated structures (such as the 'pillars of creation'(3)) and other shapes arise because of instabilities(4,5), but alternative explanations are available(6,7). One key signature of an instability is a wave-like structure in the gas, which has hitherto not been seen. Here we report the presence of 'waves' at the surface of the Orion molecular cloud near where massive stars are forming. The waves seem to be a Kelvin-Helmholtz instability that arises during the expansion of the nebula as gas heated and ionized by massive stars is blown over pre-existing molecular gas.
C1 [Berne, Olivier; Marcelino, Nuria; Cernicharo, Jose] CSIC INTA, Ctr Astrobiol, Torrejon De Ardoz 28850, Spain.
   [Berne, Olivier] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Leiden University - Excl LUMC; Leiden University
RP Berné, O (corresponding author), CSIC INTA, Ctr Astrobiol, Carretera Torrejon Ajalvir,Km 4, Torrejon De Ardoz 28850, Spain.
EM berne@strw.leidenuniv.nl
FU NASA
NR 26
TC 52
Z9 57
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 947
EP 949
DI 10.1038/nature09289
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300028
PM 20725034
DA 2026-03-09
ER

PT J
AU Venditti, C
   Meade, A
   Pagel, M
AF Venditti, Chris
   Meade, Andrew
   Pagel, Mark
TI Phylogenies reveal new interpretation of speciation and the Red Queen
SO NATURE
LA English
DT Article
ID evolution; models; extinction; divergence; rates
AB The Red Queen(1) describes a view of nature in which species continually evolve but do not become better adapted. It is one of the more distinctive metaphors of evolutionary biology, but no test of its claim that speciation occurs at a constant rate(2) has ever been made against competing models that can predict virtually identical outcomes, nor has any mechanism been proposed that could cause the constant-rate phenomenon. Here we use 101 phylogenies of animal, plant and fungal taxa to test the constant-rate claim against four competing models. Phylogenetic branch lengths record the amount of time or evolutionary change between successive events of speciation. The models predict the distribution of these lengths by specifying how factors combine to bring about speciation, or by describing how rates of speciation vary throughout a tree. We find that the hypotheses that speciation follows the accumulation of many small events that act either multiplicatively or additively found support in 8% and none of the trees, respectively. A further 8% of trees hinted that the probability of speciation changes according to the amount of divergence from the ancestral species, and 6% suggested speciation rates vary among taxa. By comparison, 78% of the trees fit the simplest model in which new species emerge from single events, each rare but individually sufficient to cause speciation. This model predicts a constant rate of speciation, and provides a new interpretation of the Red Queen: the metaphor of species losing a race against a deteriorating environment is replaced by a view linking speciation to rare stochastic events that cause reproductive isolation. Attempts to understand species-radiations(3) or why some groups have more or fewer species should look to the size of the catalogue of potential causes of speciation shared by a group of closely related organisms rather than to how those causes combine.
C1 [Venditti, Chris; 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 Reading; The Santa Fe Institute
RP Pagel, M (corresponding author), Univ Reading, Sch Biol Sci, Reading RG6 6BX, Berks, England.
EM m.pagel@reading.ac.uk
FU Natural Environment Research Council (NERC), UK; Leverhulme Trust; Natural Environment Research Council [NE/C51992X/1] Funding Source: researchfish
NR 30
TC 122
Z9 132
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 349
EP 352
DI 10.1038/nature08630
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100042
PM 20010607
DA 2026-03-09
ER

PT J
AU Becks, L
   Agrawal, AF
AF Becks, Lutz
   Agrawal, Aneil F.
TI Higher rates of sex evolve in spatially heterogeneous environments
SO NATURE
LA English
DT Article
ID deleterious mutations; recombination; selection; evolution; advantage; increases
AB The evolution and maintenance of sexual reproduction has puzzled biologists for decades(1,2). Although this field is rich in hypotheses(3-5), experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations(6-8); other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination(9,10) and selfing(11). However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory(13-15) predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high-or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs(2). Counter to some alternative theories(16,17) for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations.
C1 [Becks, Lutz; Agrawal, Aneil F.] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada.
   [Becks, Lutz] Univ Cologne, Ctr Biol Sci, Inst Zool, Dept Gen Ecol, D-50931 Cologne, Germany.
C3 University of Toronto; University of Cologne
RP Becks, L (corresponding author), Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada.
EM lutz.becks@utoronto.ca
FU Volkswagen Foundation [I/83 517]; Natural Sciences and Engineering Research Council (Canada)
NR 32
TC 109
Z9 130
U1 1
U2 317
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 89
EP +
DI 10.1038/nature09449
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900041
PM 20944628
DA 2026-03-09
ER

PT J
AU Armitage, JJ
   Collier, JS
   Minshull, TA
AF Armitage, John J.
   Collier, Jenny S.
   Minshull, Tim A.
TI The importance of rift history for volcanic margin formation
SO NATURE
LA English
DT Article
ID small-scale convection; continental margins; northeast atlantic; flood basalts; magmatism; generation; extension; ridges; ocean; sea
AB Rifting and magmatism are fundamental geological processes that shape the surface of our planet. A relationship between the two is widely acknowledged but its precise nature has eluded geoscientists and remained controversial. Largely on the basis of detailed observations from the North Atlantic Ocean, mantle temperature was identified as the primary factor controlling magmatic production 1, with most authors seeking to explain observed variations in volcanic activity at rifted margins in terms of the mantle temperature at the time of break-up(2,3). However, as more detailed observations have been made at other rifted margins worldwide, the validity of this interpretation and the importance of other factors in controlling break-up style have been much debated(4-7). One such observation is from the northwest Indian Ocean, where, despite an unequivocal link between an onshore flood basalt province, continental break-up and a hot-spot track leading to an active ocean island volcano, the associated continental margins show little magmatism(5,8). Here we reconcile these observations by applying a numerical model that accounts explicitly for the effects of earlier episodes of extension. Our approach allows us to directly compare break-up magmatism generated at different locations and so isolate the key controlling factors. We show that the volume of rift-related magmatism generated, both in the northwest Indian Ocean and at the better-known North Atlantic margins, depends not only on the mantle temperature but, to a similar degree, on the rift history. The inherited extensional history can either suppress or enhance melt generation, which can explain previously enigmatic observations.
C1 [Armitage, John J.; Collier, Jenny S.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Minshull, Tim A.] Univ Southampton, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
C3 Imperial College London; University of Southampton; NERC National Oceanography Centre
RP Armitage, JJ (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
EM j.armitage@imperial.ac.uk
FU UK Natural Environment Research Council
NR 29
TC 79
Z9 82
U1 1
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 913
EP 917
DI 10.1038/nature09063
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500035
PM 20559385
DA 2026-03-09
ER

PT J
AU Tong, C
   Li, P
   Wu, NL
   Yan, YZ
   Ying, QL
AF Tong, Chang
   Li, Ping
   Wu, Nancy L.
   Yan, Youzhen
   Ying, Qi-Long
TI Production of p53 gene knockout rats by homologous recombination in embryonic stem cells
SO NATURE
LA English
DT Article
ID mutagenesis; mice; generation; selection
AB The use of homologous recombination to modify genes in embryonic stem (ES) cells provides a powerful means to elucidate gene function and create disease models(1). Application of this technology to engineer genes in rats has not previously been possible because of the absence of germline-competent ES cells in this species. We have recently established authentic rat ES cells(2,3). Here we report the generation of gene knockout rats using the ES-cell-based gene targeting technology. We designed a targeting vector to disrupt the tumour suppressor gene p53 (also known as Tp53) in rat ES cells by means of homologous recombination. p53 gene-targeted rat ES cells can be routinely generated. Furthermore, the p53 gene-targeted mutation in the rat ES-cell genome can transmit through the germ line via ES-cell rat chimaeras to create p53 gene knockout rats. The rat is the most widely used animal model in biological research(4-7). The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provide a powerful new platform for the study of human disease.
C1 [Tong, Chang; Li, Ping; Ying, Qi-Long] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA.
   [Wu, Nancy L.; Yan, Youzhen] Univ So Calif, Keck Sch Med, Norris Canc Ctr Transgen, Knockout Core Facil, Los Angeles, CA 90033 USA.
C3 University of Southern California; University of Southern California
RP Ying, QL (corresponding author), Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA.
EM qying@usc.edu
FU NIH/NCRR [1R01 RR025881]
NR 29
TC 222
Z9 346
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 SEP 9
PY 2010
VL 467
IS 7312
BP 211
EP U98
DI 10.1038/nature09368
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300035
PM 20703227
DA 2026-03-09
ER

PT J
AU Silverstein, TD
   Johnson, RE
   Jain, R
   Prakash, L
   Prakash, S
   Aggarwal, AK
AF Silverstein, Timothy D.
   Johnson, Robert E.
   Jain, Rinku
   Prakash, Louise
   Prakash, Satya
   Aggarwal, Aneel K.
TI Structural basis for the suppression of skin cancers by DNA polymerase η
SO NATURE
LA English
DT Article
ID xeroderma-pigmentosum-variant; crystal-structure; lesion-bypass; nucleotide incorporation; molecular analysis; yeast; mechanism; replication; mutations; template
AB DNA polymerase eta (Pol eta) is unique among eukaryotic polymerases in its proficient ability for error-free replication through ultraviolet-induced cyclobutane pyrimidine dimers, and inactivation of Pol eta (also known as POLH) in humans causes the variant form of xeroderma pigmentosum (XPV). We present the crystal structures of Saccharomyces cerevisiae Pol eta (also known as RAD30) in ternary complex with a cis-syn thymine-thymine (T-T) dimer and with undamaged DNA. The structures reveal that the ability of Pol eta to replicate efficiently through the ultraviolet-induced lesion derives from a simple and yet elegant mechanism, wherein the two Ts of the T-T dimer are accommodated in an active site cleft that is much more open than in other polymerases. We also show by structural, biochemical and genetic analysis that the two Ts are maintained in a stable configuration in the active site via interactions with Gln 55, Arg 73 and Met 74. Together, these features define the basis for Pol eta's action on ultraviolet-damaged DNA that is crucial in suppressing the mutagenic and carcinogenic consequences of sun exposure, thereby reducing the incidence of skin cancers in humans.
C1 [Silverstein, Timothy D.; Jain, Rinku; Aggarwal, Aneel K.] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
   [Johnson, Robert E.; Prakash, Louise; Prakash, Satya] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77755 USA.
C3 Icahn School of Medicine at Mount Sinai; University of Texas System; University of Texas Medical Branch Galveston
RP Aggarwal, AK (corresponding author), Mt Sinai Sch Med, Dept Struct & Chem Biol, Box 1677,1425 Madison Ave, New York, NY 10029 USA.
EM saprakas@utmb.edu; aneel.aggarwal@mssm.edu
FU NIH
NR 31
TC 126
Z9 161
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 JUN 24
PY 2010
VL 465
IS 7301
BP 1039
EP U96
DI 10.1038/nature09104
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900044
PM 20577207
DA 2026-03-09
ER

PT J
AU Tahirov, TH
   Babayeva, ND
   Varzavand, K
   Cooper, JJ
   Sedore, SC
   Price, DH
AF Tahirov, Tahir H.
   Babayeva, Nigar D.
   Varzavand, Katayoun
   Cooper, Jeffrey J.
   Sedore, Stanley C.
   Price, David H.
TI Crystal structure of HIV-1 Tat complexed with human P-TEFb
SO NATURE
LA English
DT Article
ID polymerase-ii transcription; human cyclin t1; dependent kinase regulation; carboxyl-terminal domain; elongation-factor-b; rna-polymerase; mutational analysis; virus-replication; 7sk snrna; in-vitro
AB Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat center dot P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat center dot P-TEFb complex and block HIV replication.
C1 [Tahirov, Tahir H.; Babayeva, Nigar D.] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
   [Varzavand, Katayoun; Cooper, Jeffrey J.; Sedore, Stanley C.; Price, David H.] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA.
C3 University of Nebraska System; University of Nebraska Medical Center; University of Iowa
RP Tahirov, TH (corresponding author), Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
EM ttahirov@unmc.edu
FU NIH [GM35500, AI074392, GM082923]; Department of Health and Human Services [LB506]; 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]; Cancer Center [P30CA036727]; National Cancer Institute [P30CA036727] Funding Source: NIH RePORTER
NR 48
TC 247
Z9 331
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 747
EP U2
DI 10.1038/nature09131
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800037
PM 20535204
DA 2026-03-09
ER

PT J
AU Cuello, LG
   Jogini, V
   Cortes, DM
   Perozo, E
AF Cuello, Luis G.
   Jogini, Vishwanath
   Cortes, D. Marien
   Perozo, Eduardo
TI Structural mechanism of C-type inactivation in K+ channels
SO NATURE
LA English
DT Article
ID shaker potassium channels; selectivity filter; slow inactivation; ion conduction; tetraethylammonium blockade; crystal-structure; open state; kcsa; pore; mutations
AB Interconversion between conductive and non-conductive forms of the K+ channel selectivity filter underlies a variety of gating events, from flicker transitions (at the microsecond timescale) to C-type inactivation (millisecond to second timescale). Here we report the crystal structure of the Streptomyces lividans K+ channel KcsA in its open-inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels 'trapped' in a series of partially open conformations. Five conformer classes were identified with openings ranging from 12 angstrom in closed KcsA (C alpha-C alpha distances at Thr 112) to 32 angstrom when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures indicate a molecular basis for C-type inactivation in K+ channels.
C1 [Perozo, Eduardo] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Perozo, E (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
EM eperozo@uchicago.edu
FU NIH [R01-GM57846]
NR 53
TC 399
Z9 457
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 8
PY 2010
VL 466
IS 7303
BP 203
EP U73
DI 10.1038/nature09153
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800029
PM 20613835
DA 2026-03-09
ER

PT J
AU Pertsinidis, A
   Zhang, YX
   Chu, S
AF Pertsinidis, Alexandros
   Zhang, Yunxiang
   Chu, Steven
TI Subnanometre single-molecule localization, registration and distance measurements
SO NATURE
LA English
DT Article
ID high-resolution colocalization; fluorescence microscopy; e-cadherin; stimulated-emission; diffraction-limit; calcium-binding; homoassociation; precision; tracking; adhesion
AB Remarkable progress in optical microscopy has been made in the measurement of nanometre distances. If diffraction blurs the image of a point object into an Airy disk with a root-mean-squared (r.m.s.) size of s = 0.44 lambda/2NA (similar to 90 nm for light with a wavelength of lambda = 600 nm and an objective lens with a numerical aperture of NA = 1.49), limiting the resolution of the far-field microscope in use to d = 2.4s approximate to 200 nm, additional knowledge about the specimen can be used to great advantage. For example, if the source is known to be two spatially resolved fluorescent molecules, the distance between them is given by the separation of the centres of the two fluorescence images(1). In high-resolution microwave and optical spectroscopy, there are numerous examples where the line centre is determined with a precision of less than 10(-6) of the linewidth. In contrast, in biological applications the brightest single fluorescent emitters can be detected with a signal-to-noise ratio of similar to 100, limiting the centroid localization precision to s(loc) >= 1% (>= 1 nm) of the r.m.s. size, s, of the microscope point spread function (PSF)(2). Moreover, the error in co-localizing two or more single emitters is notably worse, remaining greater than 5-10% (5-10 nm) of the PSF size(3-8). Here we report a distance resolution of s(reg) = 0.50 nm (1 sigma) and an absolute accuracy of s(distance) = 0.77 nm (1 sigma) in a measurement of the separation between differently coloured fluorescent molecules using conventional far-field fluorescence imaging in physiological buffer conditions. The statistical uncertainty in the mean for an ensemble of identical single-molecule samples is limited only by the total number of collected photons, to s(loc) approximate to 0.3 nm, which is similar to 3 x 10(-3) times the size of the optical PSF. Our method may also be used to improve the resolution of many subwavelength, far-field imaging methods such as those based on co-localization of molecules that are stochastically switched on in space(6-8). The improved resolution will allow the structure of large, multisubunit biological complexes in biologically relevant environments to be deciphered at the single-molecule level.
C1 [Pertsinidis, Alexandros; Zhang, Yunxiang; Chu, Steven] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Pertsinidis, Alexandros; Zhang, Yunxiang; Chu, Steven] Univ Calif Berkeley, Calif Inst Quantitat Biosci QB3, Berkeley, CA 94720 USA.
   [Chu, Steven] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Chu, Steven] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Chu, Steven] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
C3 Stanford University; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; 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 Pertsinidis, A (corresponding author), Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
EM pertsin@berkeley.edu; the.secretary@hq.doe.gov
FU National Institutes of Health; National Science Foundation; National Aeronautics and Space Administration; Defense Advanced Research Projects Agency
NR 39
TC 270
Z9 320
U1 2
U2 183
PU 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 29
PY 2010
VL 466
IS 7306
BP 647
EP U11
DI 10.1038/nature09163
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100058
PM 20613725
DA 2026-03-09
ER

PT J
AU Chen, L
   Yang, SY
   Jakoncic, J
   Zhang, JJ
   Huang, XY
AF Chen, Lin
   Yang, Shengyu
   Jakoncic, Jean
   Zhang, J. Jillian
   Huang, Xin-Yun
TI Migrastatin analogues target fascin to block tumour metastasis
SO NATURE
LA English
DT Article
ID cell-migration inhibitors; negative breast-cancer; actin-bundling protein; expression; carcinoma; motility; gene; discovery; filopodia; roles
AB Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces(1,2), and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis(3-6). Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.
C1 [Chen, Lin; Yang, Shengyu; Zhang, J. Jillian; Huang, Xin-Yun] Cornell Univ, Weill Med Coll, Dept Physiol, New York, NY 10065 USA.
   [Jakoncic, Jean] Brookhaven Natl Lab, Natl Synchrotron Light Source, Upton, NY 11973 USA.
C3 Cornell University; Weill Cornell Medicine; United States Department of Energy (DOE); Brookhaven National Laboratory; State University of New York (SUNY) System
RP Huang, XY (corresponding author), Cornell Univ, Weill Med Coll, Dept Physiol, New York, NY 10065 USA.
EM xyhuang@med.cornell.edu
FU National Institutes of Health [CA136837]; Department of Defense [W81XWH-06-1-0362]
NR 36
TC 238
Z9 284
U1 2
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1062
EP U135
DI 10.1038/nature08978
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000043
PM 20393565
DA 2026-03-09
ER

PT J
AU Calsbeek, R
   Cox, RM
AF Calsbeek, Ryan
   Cox, Robert M.
TI Experimentally assessing the relative importance of predation and competition as agents of selection
SO NATURE
LA English
DT Article
ID lizard anolis-carolinensis; natural-populations; sexual-dimorphism; adaptive radiation; island lizards; habitat use; performance; morphology; evolution; behavior
AB Field experiments that measure natural selection in response to manipulations of the selective regime are extremely rare(1), even in systems where the ecological basis of adaptation has been studied extensively. The adaptive radiation of Caribbean Anolis lizards has been studied for decades(2-5), leading to precise predictions about the influence of alternative agents of selection in the wild. Here we present experimental evidence for the relative importance of two putative agents of selection in shaping the adaptive landscape for a classic island radiation. We manipulated whole-island populations of the brown anole lizard, Anolis sagrei, to measure the relative importance of predation versus competition as agents of natural selection. We excluded or included bird and snake predators across six islands that ranged from low to high population densities of lizards, then measured subsequent differences in behaviour and natural selection in each population. Predators altered the lizards' perching behaviour and increased mortality, but predation treatments did not alter selection on phenotypic traits. By contrast, experimentally increasing population density dramatically increased the strength of viability selection favouring large body size, long relative limb length and high running stamina. Our results from A. sagrei are consistent with the hypothesis(6) that intraspecific competition is more important than predation in shaping the selective landscape for traits central to the adaptive radiation of Anolis ecomorphs.
C1 [Calsbeek, Ryan; Cox, Robert M.] Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA.
C3 Dartmouth College
RP Calsbeek, R (corresponding author), Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA.
EM ryan.calsbeek@dartmouth.edu
FU National Science Foundation; Dartmouth College; Division Of Environmental Biology; Direct For Biological Sciences [0816862] Funding Source: National Science Foundation
NR 30
TC 124
Z9 146
U1 1
U2 112
PU 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 3
PY 2010
VL 465
IS 7298
BP 613
EP 616
DI 10.1038/nature09020
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000041
PM 20453837
DA 2026-03-09
ER

PT J
AU Hudson, TJ
   Anderson, W
   Aretz, A
   Barker, AD
   Bell, C
   Bernabé, RR
   Bhan, MK
   Calvo, F
   Eerola, I
   Gerhard, DS
   Guttmacher, A
   Guyer, M
   Hemsley, FM
   Jennings, JL
   Kerr, D
   Klatt, P
   Kolar, P
   Kusuda, J
   Lane, DP
   Laplace, F
   Lu, YY
   Nettekoven, G
   Ozenberger, B
   Peterson, J
   Rao, TS
   Remacle, J
   Schafer, AJ
   Shibata, T
   Stratton, MR
   Vockley, JG
   Watanabe, K
   Yang, HM
   Yuen, MMF
   Knoppers, M
   Bobrow, M
   Cambon-Thomsen, A
   Dressler, LG
   Dyke, SOM
   Joly, Y
   Kato, K
   Kennedy, KL
   Nicolás, P
   Parker, MJ
   Rial-Sebbag, E
   Romeo-Casabona, CM
   Shaw, KM
   Wallace, S
   Wiesner, GL
   Zeps, N
   Lichter, P
   Biankin, AV
   Chabannon, C
   Chin, L
   Clément, B
   de Alava, E
   Degos, F
   Ferguson, ML
   Geary, P
   Hayes, DN
   Johns, AL
   Nakagawa, H
   Penny, R
   Piris, MA
   Sarin, R
   Scarpa, A
   van de Vijver, M
   Futreal, PA
   Aburatani, H
   Bayés, M
   Bowtell, DDL
   Campbell, PJ
   Estivill, X
   Grimmond, SM
   Gut, I
   Hirst, M
   López-Otín, C
   Majumder, P
   Marra, M
   Ning, ZM
   Puente, XS
   Ruan, YJ
   Stunnenberg, HG
   Swerdlow, H
   Velculescu, VE
   Wilson, RK
   Xue, HH
   Yang, L
   Spellman, PT
   Bader, GD
   Boutros, PC
   Flicek, P
   Getz, G
   Guigó, R
   Guo, GW
   Haussler, D
   Heath, S
   Hubbard, TJ
   Jiang, T
   Jones, SM
   Li, QB
   López-Bigas, N
   Luo, RB
   Pearson, JV
   Quesada, V
   Raphael, BJ
   Sander, C
   Speed, TP
   Stuart, JM
   Teague, JW
   Totoki, Y
   Tsunoda, T
   Valencia, A
   Wheeler, DA
   Wu, HL
   Zhao, SC
   Zhou, GY
   Stein, LD
   Lathrop, M
   Ouellette, BFF
   Thomas, G
   Yoshida, T
   Axton, M
   Gunter, C
   McPherson, JD
   Miller, LJ
   Kasprzyk, A
   Zhang, JJ
   Haider, SA
   Wang, JX
   Yung, CK
   Cross, A
   Liang, Y
   Gnaneshan, S
   Guberman, J
   Hsu, J
   Chalmers, DRC
   Hasel, KW
   Kaan, TSH
   Knoppers, BM
   Lowrance, WW
   Masui, T
   Rodriguez, LL
   Vergely, C
   Cloonan, N
   Defazio, A
   Eshleman, JR
   Etemadmoghadam, D
   Gardiner, BA
   Kench, JG
   Sutherland, RL
   Tempero, MA
   Waddell, NJ
   Wilson, PJ
   Gallinger, S
   Tsao, MS
   Shaw, PA
   Petersen, GM
   Mukhopadhyay, D
   DePinho, RA
   Thayer, S
   Muthuswamy, L
   Shazand, K
   Beck, T
   Sam, M
   Timms, L
   Ballin, V
   Ji, JF
   Zhang, XQ
   Chen, F
   Hu, XD
   Yang, Q
   Tian, G
   Zhang, LH
   Xing, XF
   Li, XH
   Zhu, ZG
   Yu, YY
   Yu, J
   Tost, J
   Brennan, P
   Holcatova, I
   Zaridze, D
   Brazma, A
   Egevad, L
   Prokhortchouk, E
   Banks, RE
   Uhlén, M
   Viksna, J
   Ponten, F
   Skryabin, K
   Birney, E
   Borg, A
   Borresen-Dale, AL
   Caldas, C
   Foekens, JA
   Martin, S
   Reis-Filho, JS
   Richardson, AL
   Sotiriou, C
   van't Veer, L
   Birnbaum, D
   Blanche, H
   Boucher, P
   Boyault, S
   Masson-Jacquemier, JD
   Pauporté, I
   Pivot, X
   Vincent-Salomon, A
   Tabone, E
   Theillet, C
   Treilleux, I
   Bioulac-Sage, P
   Decaens, T
   Franco, D
   Gut, M
   Samuel, D
   Zucman-Rossi, J
   Eils, R
   Brors, B
   Korbel, JO
   Korshunov, A
   Landgraf, P
   Lehrach, H
   Pfister, S
   Radlwimmer, B
   Reifenberger, G
   Taylor, MD
   von Kalle, C
   Majumder, PP
   Pederzoli, P
   Lawlor, RT
   Delledonne, M
   Bardelli, A
   Gress, T
   Klimstra, D
   Zamboni, G
   Nakamura, Y
   Miyano, S
   Fujimoto, A
   Campo, E
   de Sanjosé, S
   Montserrat, E
   González-Díaz, M
   Jares, P
   Himmelbaue, H
   Bea, S
   Aparicio, S
   Easton, DF
   Collins, FS
   Compton, CC
   Lander, ES
   Burke, W
   Green, AR
   Hamilton, SR
   Kallioniemi, OP
   Ley, TJ
   Liu, ET
   Wainwright, BJ
AF Hudson, Thomas J.
   Anderson, Warwick
   Aretz, Axel
   Barker, Anna D.
   Bell, Cindy
   Bernabe, Rosa R.
   Bhan, M. K.
   Calvo, Fabien
   Eerola, Iiro
   Gerhard, Daniela S.
   Guttmacher, Alan
   Guyer, Mark
   Hemsley, Fiona M.
   Jennings, Jennifer L.
   Kerr, David
   Klatt, Peter
   Kolar, Patrik
   Kusuda, Jun
   Lane, David P.
   Laplace, Frank
   Lu, Youyong
   Nettekoven, Gerd
   Ozenberger, Brad
   Peterson, Jane
   Rao, T. S.
   Remacle, Jacques
   Schafer, Alan J.
   Shibata, Tatsuhiro
   Stratton, Michael R.
   Vockley, Joseph G.
   Watanabe, Koichi
   Yang, Huanming
   Yuen, Matthew M. F.
   Knoppers, M.
   Bobrow, Martin
   Cambon-Thomsen, Anne
   Dressler, Lynn G.
   Dyke, Stephanie O. M.
   Joly, Yann
   Kato, Kazuto
   Kennedy, Karen L.
   Nicolas, Pilar
   Parker, Michael J.
   Rial-Sebbag, Emmanuelle
   Romeo-Casabona, Carlos M.
   Shaw, Kenna M.
   Wallace, Susan
   Wiesner, Georgia L.
   Zeps, Nikolajs
   Lichter, Peter
   Biankin, Andrew V.
   Chabannon, Christian
   Chin, Lynda
   Clement, Bruno
   de Alava, Enrique
   Degos, Francoise
   Ferguson, Martin L.
   Geary, Peter
   Hayes, D. Neil
   Johns, Amber L.
   Nakagawa, Hidewaki
   Penny, Robert
   Piris, Miguel A.
   Sarin, Rajiv
   Scarpa, Aldo
   van de Vijver, Marc
   Futreal, P. Andrew
   Aburatani, Hiroyuki
   Bayes, Monica
   Bowtell, David D. L.
   Campbell, Peter J.
   Estivill, Xavier
   Grimmond, Sean M.
   Gut, Ivo
   Hirst, Martin
   Lopez-Otin, Carlos
   Majumder, Partha
   Marra, Marco
   Ning, Zemin
   Puente, Xose S.
   Ruan, Yijun
   Stunnenberg, Hendrik G.
   Swerdlow, Harold
   Velculescu, Victor E.
   Wilson, Richard K.
   Xue, Hong H.
   Yang, Liu
   Spellman, Paul T.
   Bader, Gary D.
   Boutros, Paul C.
   Flicek, Paul
   Getz, Gad
   Guigo, Roderic
   Guo, Guangwu
   Haussler, David
   Heath, Simon
   Hubbard, Tim J.
   Jiang, Tao
   Jones, Steven M.
   Li, Qibin
   Lopez-Bigas, Nuria
   Luo, Ruibang
   Pearson, John V.
   Quesada, Victor
   Raphael, Benjamin J.
   Sander, Chris
   Speed, Terence P.
   Stuart, Joshua M.
   Teague, Jon W.
   Totoki, Yasushi
   Tsunoda, Tatsuhiko
   Valencia, Alfonso
   Wheeler, David A.
   Wu, Honglong
   Zhao, Shancen
   Zhou, Guangyu
   Stein, Lincoln D.
   Lathrop, Mark
   Ouellette, B. F. Francis
   Thomas, Gilles
   Yoshida, Teruhiko
   Axton, Myles
   Gunter, Chris
   McPherson, John D.
   Miller, Linda J.
   Kasprzyk, Arek
   Zhang, Junjun
   Haider, Syed A.
   Wang, Jianxin
   Yung, Christina K.
   Cross, Anthony
   Liang, Yong
   Gnaneshan, Saravanamuttu
   Guberman, Jonathan
   Hsu, Jack
   Chalmers, Don R. C.
   Hasel, Karl W.
   Kaan, Terry S. H.
   Knoppers, Bartha M.
   Lowrance, William W.
   Masui, Tohru
   Rodriguez, Laura Lyman
   Vergely, Catherine
   Cloonan, Nicole
   Defazio, Anna
   Eshleman, James R.
   Etemadmoghadam, Dariush
   Gardiner, Brooke A.
   Kench, James G.
   Sutherland, Robert L.
   Tempero, Margaret A.
   Waddell, Nicola J.
   Wilson, Peter J.
   Gallinger, Steve
   Tsao, Ming-Sound
   Shaw, Patricia A.
   Petersen, Gloria M.
   Mukhopadhyay, Debabrata
   DePinho, Ronald A.
   Thayer, Sarah
   Muthuswamy, Lakshmi
   Shazand, Kamran
   Beck, Timothy
   Sam, Michelle
   Timms, Lee
   Ballin, Vanessa
   Ji, Jiafu
   Zhang, Xiuqing
   Chen, Feng
   Hu, Xueda
   Yang, Qi
   Tian, Geng
   Zhang, Lianhai
   Xing, Xiaofang
   Li, Xianghong
   Zhu, Zhenggang
   Yu, Yingyan
   Yu, Jun
   Tost, Joerg
   Brennan, Paul
   Holcatova, Ivana
   Zaridze, David
   Brazma, Alvis
   Egevad, Lars
   Prokhortchouk, Egor
   Banks, Rosamonde Elizabeth
   Uhlen, Mathias
   Viksna, Juris
   Ponten, Fredrik
   Skryabin, Konstantin
   Birney, Ewan
   Borg, Ake
   Borresen-Dale, Anne-Lise
   Caldas, Carlos
   Foekens, John A.
   Martin, Sancha
   Reis-Filho, Jorge S.
   Richardson, Andrea L.
   Sotiriou, Christos
   van't Veer, Laura
   Birnbaum, Daniel
   Blanche, Helene
   Boucher, Pascal
   Boyault, Sandrine
   Masson-Jacquemier, Jocelyne D.
   Pauporte, Iris
   Pivot, Xavier
   Vincent-Salomon, Anne
   Tabone, Eric
   Theillet, Charles
   Treilleux, Isabelle
   Bioulac-Sage, Paulette
   Decaens, Thomas
   Franco, Dominique
   Gut, Marta
   Samuel, Didier
   Zucman-Rossi, Jessica
   Eils, Roland
   Brors, Benedikt
   Korbel, Jan O.
   Korshunov, Andrey
   Landgraf, Pablo
   Lehrach, Hans
   Pfister, Stefan
   Radlwimmer, Bernhard
   Reifenberger, Guido
   Taylor, Michael D.
   von Kalle, Christof
   Majumder, Partha P.
   Pederzoli, Paolo
   Lawlor, Rita T.
   Delledonne, Massimo
   Bardelli, Alberto
   Gress, Thomas
   Klimstra, David
   Zamboni, Giuseppe
   Nakamura, Yusuke
   Miyano, Satoru
   Fujimoto, Akihiro
   Campo, Elias
   de Sanjose, Silvia
   Montserrat, Emili
   Gonzalez-Diaz, Marcos
   Jares, Pedro
   Himmelbaue, Heinz
   Bea, Silvia
   Aparicio, Samuel
   Easton, Douglas F.
   Collins, Francis S.
   Compton, Carolyn C.
   Lander, Eric S.
   Burke, Wylie
   Green, Anthony R.
   Hamilton, Stanley R.
   Kallioniemi, Olli P.
   Ley, Timothy J.
   Liu, Edison T.
   Wainwright, Brandon J.
TI International network of cancer genome projects
SO NATURE
LA English
DT Article
ID somatic mutations; myeloid-leukemia; breast-cancer; gene; pathways; landscapes
AB The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
C1 [Jennings, Jennifer L.; Boutros, Paul C.; Stein, Lincoln D.; Ouellette, B. F. Francis; McPherson, John D.; Kasprzyk, Arek; Zhang, Junjun; Wang, Jianxin; Yung, Christina K.; Cross, Anthony; Liang, Yong; Gnaneshan, Saravanamuttu; Guberman, Jonathan; Hsu, Jack; Muthuswamy, Lakshmi; Shazand, Kamran; Beck, Timothy; Sam, Michelle; Timms, Lee; Ballin, Vanessa] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
   Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
   [Hudson, Thomas J.; Anderson, Warwick] Natl Hlth & Med Res Council, Canberra, ACT 2601, Australia.
   [Aretz, Axel] German Aerosp Ctr DLR, Project Management Agcy, D-53175 Bonn, Germany.
   [Barker, Anna D.; Gerhard, Daniela S.; Vockley, Joseph G.; Shaw, Kenna M.; Compton, Carolyn C.] NCI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Bell, Cindy; Hasel, Karl W.] Genome Canada, Ottawa, ON K2P 1P1, Canada.
   [Bernabe, Rosa R.; Klatt, Peter] Minist Sci & Innovat, Secretariat State Res, Madrid 28027, Spain.
   [Bhan, M. K.; Rao, T. S.] Govt India, Minist Sci & Technol, Dept Biotechnol, New Delhi 110003, India.
   [Calvo, Fabien; Chabannon, Christian; Boucher, Pascal; Pauporte, Iris] Natl Canc Inst, F-92513 Boulogne, France.
   [Eerola, Iiro; Kolar, Patrik; Remacle, Jacques] European Commiss, Hlth Res Directorate, Genom & Syst Biol Unit, B-1049 Brussels, Belgium.
   [Guttmacher, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Rodriguez, Laura Lyman] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Hemsley, Fiona M.; Lane, David P.] Canc Res UK, London WC2A 3PX, England.
   [Kerr, David] Qatar Fdn, Sidra Med & Res Ctr, Doha, Qatar.
   Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England.
   [Kusuda, Jun; Masui, Tohru] Natl Inst Biomed Innovat, Osaka 5670085, Japan.
   [Laplace, Frank] Fed Minist Educ & Res, Div Mol Life Sci, D-11055 Berlin, Germany.
   [Lu, Youyong; Ji, Jiafu; Chen, Feng; Zhang, Lianhai; Xing, Xiaofang; Li, Xianghong] Peking Univ, Sch Oncol, Beijing Canc Inst & Hosp, Beijing 100142, Peoples R China.
   [Nettekoven, Gerd] German Canc Aid, D-53113 Bonn, Germany.
   [Schafer, Alan J.] Wellcome Trust Res Labs, London NW1 2BE, England.
   [Shibata, Tatsuhiro; Totoki, Yasushi; Yoshida, Teruhiko; Zaridze, David] Natl Canc Ctr, Chuo Ku, Tokyo 1040045, Japan.
   [Stratton, Michael R.; Dyke, Stephanie O. M.; Kennedy, Karen L.; Futreal, P. Andrew; Campbell, Peter J.; Ning, Zemin; Swerdlow, Harold; Hubbard, Tim J.; Teague, Jon W.; Martin, Sancha] Hinxton, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Watanabe, Koichi] RIKEN, Yokohama Inst, Kanagawa, Japan.
   [Yang, Huanming; Guo, Guangwu; Jiang, Tao; Li, Qibin; Luo, Ruibang; Wu, Honglong; Zhao, Shancen; Zhou, Guangyu; Zhang, Xiuqing; Hu, Xueda; Yang, Qi; Tian, Geng] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
   [Yuen, Matthew M. F.] Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China.
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   [Knoppers, M.; Wallace, Susan] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada.
   [Bobrow, Martin] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England.
   [Cambon-Thomsen, Anne; Rial-Sebbag, Emmanuelle] Fac Med Toulouse, INSERM, U558, F-31073 Toulouse, France.
   [Dressler, Lynn G.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC 27599 USA.
   [Kato, Kazuto] Kyoto Univ, Grad Sch Biostudies, Inst Integrated Cell Mat Sci, Inst Res Humanities, Kyoto 6068501, Japan.
   [Nicolas, Pilar; Romeo-Casabona, Carlos M.] Univ Deusto, Interuniv Chair Law & Human Genome, Bizkaia 48007, Spain.
   [Parker, Michael J.] Univ Oxford, Ethox Ctr, Oxford OX3 7LF, England.
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   [Wiesner, Georgia L.] Univ Hosp Cleveland, Case Med Ctr, Ctr Human Genet, Cleveland, OH 44106 USA.
   St John God Pathol, Subiaco, WA 6008, Australia.
   Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
   [Zeps, Nikolajs] Univ Western Australia, Sch Surg, Nedlands, WA 6009, Australia.
   [Lichter, Peter; Eils, Roland; Brors, Benedikt; Pfister, Stefan; Radlwimmer, Bernhard] German Canc Res Ctr, D-69120 Heidelberg, Germany.
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   Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia.
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   [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
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   [de Alava, Enrique; Gonzalez-Diaz, Marcos] Univ Salamanca, Ctr Invest Canc, Univ Hosp, Dept Hematol, Salamanca 37007, Spain.
   [Degos, Francoise] Hop Beaujon, F-92110 Clichy, France.
   [Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
   [Geary, Peter] Canadian Tumour Repository Network, Winnipeg, MB R3M 0V5, Canada.
   [Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Lineberger Comprehens Canc Ctr, Dept Internal Med, Chapel Hill, NC 27599 USA.
   [Nakagawa, Hidewaki; Tsunoda, Tatsuhiko; Nakamura, Yusuke; Fujimoto, Akihiro] RIKEN, Ctr Genom Med, Kanagawa 2300045, Japan.
   [Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Piris, Miguel A.] Spanish Natl Canc Res Ctr, Mol Pathol Programme, Madrid 28029, Spain.
   [Sarin, Rajiv] Tata Mem Hosp, Adv Ctr Treatment, Res & Educ Canc, Navi Mumbai 41021, Maharashtra, India.
   [Scarpa, Aldo; Zamboni, Giuseppe] Univ Verona, Dept Pathol, I-37134 Verona, Italy.
   [Scarpa, Aldo; Lawlor, Rita T.] Verona Univ Hosp, Ctr Appl Res Canc ARC NET, I-37134 Verona, Italy.
   [van de Vijver, Marc; van't Veer, Laura] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [van de Vijver, Marc] Acad Med Ctr, NL-1015 AZ Amsterdam, Netherlands.
   [Aburatani, Hiroyuki] Univ Tokyo, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan.
   [Bayes, Monica; Estivill, Xavier; Himmelbaue, Heinz] Pompeu Fabra Univ, Ctr Genom Regulat, Barcelona 08003, Spain.
   [Bayes, Monica] Biomed Res Ctr CIBERESP, Publ Hlth & Epidemiol Network, Barcelona 08003, Catalonia, Spain.
   [Bowtell, David D. L.; Etemadmoghadam, Dariush] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
   [Etemadmoghadam, Dariush] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.
   Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
   [Grimmond, Sean M.; Pearson, John V.; Cloonan, Nicole; Gardiner, Brooke A.; Waddell, Nicola J.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4067, Australia.
   [Gut, Ivo; Heath, Simon; Lathrop, Mark; Tost, Joerg] CEA, DSV, IG Ctr Natl Genotypage, F-91057 Evry, France.
   [Hirst, Martin; Marra, Marco; Jones, Steven M.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Lopez-Otin, Carlos; Puente, Xose S.; Quesada, Victor] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain.
   [Majumder, Partha; Majumder, Partha P.] Natl Inst Biomed Genom, Kalyani 741251, W Bengal, India.
   [McPherson, John D.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
   [Ruan, Yijun; Liu, Edison T.] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore.
   [Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
   [Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
   [Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA.
   [Xue, Hong H.] HKUST, Appl Genom Ctr, Fok Ying Grad Sch, Hong Kong, Hong Kong, Peoples R China.
   [Xue, Hong H.] Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
   [Yang, Liu] Zhejiang Univ, Inst Canc, Hangzhou 310009, Zhejiang, Peoples R China.
   [Spellman, Paul T.] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94510 USA.
   [Bader, Gary D.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
   [Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Flicek, Paul; Brazma, Alvis; Birney, Ewan; Korbel, Jan O.] Hinxton, European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Getz, Gad; Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
   [Getz, Gad] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Guigo, Roderic] Univ Pompeu Fabra, Spanish Natl Bioinformat Inst, Barcelona 08003, Spain.
   Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona 08003, Spain.
   [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Lopez-Bigas, Nuria] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona 08003, Spain.
   [Raphael, Benjamin J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
   [Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Stuart, Joshua M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Spanish Natl Bioinformat Inst, Madrid 28029, Spain.
   [Valencia, Alfonso] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomputing Programme, Madrid 28029, Spain.
   [Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Blanche, Helene; Gut, Marta] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
   [Thomas, Gilles] Univ Lyon 1, F-69622 Villeurbanne, France.
   Fdn Synergie Lyon Canc, F-69008 Lyon, France.
   [Axton, Myles] Natl Genet, New York, NY 10013 USA.
   [Gunter, Chris] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Miller, Linda J.] Nat & Nat Res Journals, New York, NY 10013 USA.
   [Haider, Syed A.] Univ Cambridge, Comp Lab, Cambridge CB3 0FD, England.
   [Chalmers, Don R. C.] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia.
   [Kaan, Terry S. H.] Natl Univ Singapore, Fac Law, Singapore 259776, Singapore.
   [Lowrance, William W.] Consultant Hlth Res Eth & Policy, F-34280 La Grande Motte, France.
   [Vergely, Catherine] Inst Gustave Roussy, ISIS 39, F-94805 Villejuif, France.
   [Defazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia.
   [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia.
   [Eshleman, James R.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
   [Kench, James G.] Univ Sydney, Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2050, Australia.
   [Tempero, Margaret A.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
   [Gallinger, Steve] Toronto Gen Hosp, Dept Gen Surg, Toronto, ON M5G 2C4, Canada.
   [Gallinger, Steve] Samuel Lunenfeld Res Inst, Toronto, ON M5S 1A1, Canada.
   [Tsao, Ming-Sound] Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 2M9, Canada.
   [Tsao, Ming-Sound] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada.
   [Shaw, Patricia A.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
   [Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
   [Mukhopadhyay, Debabrata] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA.
   [Thayer, Sarah] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
   [Zhu, Zhenggang; Yu, Yingyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China.
   [Yu, Jun] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China.
   [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
   [Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12108, Czech Republic.
   [Zaridze, David] NN Blokhin Russian Canc Res Ctr, Dept Epidemiol & Prevent, Moscow 115478, Russia.
   [Egevad, Lars] Karolinska Univ Hosp, Karolinska Inst, SE-17176 Stockholm, Sweden.
   [Prokhortchouk, Egor] Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia.
   [Banks, Rosamonde Elizabeth] St James Univ Hosp, Leeds Inst Mol Med, Canc Res UK Ctr, Leeds LS9 7TF, W Yorkshire, England.
   [Uhlen, Mathias] KTH Royal Inst Technol, Sci Life Lab, SE-10044 Stockholm, Sweden.
   [Viksna, Juris] Univ Latvia, Inst Math & Comp Sci, LV-1459 Riga, Latvia.
   [Ponten, Fredrik] Uppsala Univ, SE-75105 Uppsala, Sweden.
   [Skryabin, Konstantin] Kurchatov Sci Ctr, Moscow 123182, Russia.
   [Borg, Ake] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden.
   [Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, N-0310 Oslo, Norway.
   [Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, N-0316 Oslo, Norway.
   [Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England.
   [Caldas, Carlos] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
   [Foekens, John A.] Josephine Nefkens Inst, Erasmus MC Rotterdam, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands.
   [Foekens, John A.] Canc Genom Ctr, NL-3015 CE Rotterdam, Netherlands.
   [Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
   [Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Boyault, Sandrine; Tabone, Eric; Treilleux, Isabelle] Ctr Leon Berard, F-69373 Lyon, France.
   [Sotiriou, Christos] Inst Jules Bordet, B-1000 Brussels, Belgium.
   [Pivot, Xavier] Hop Jean Minjoz, F-25030 Besancon, France.
   [Vincent-Salomon, Anne] Inst Curie, F-75231 Paris, France.
   [Theillet, Charles] Ctr Val Aurelle, F-34298 Montpellier, France.
   [Bioulac-Sage, Paulette] Hop Pellegrin, F-33076 Bordeaux, France.
   [Decaens, Thomas] Hop Henri Mondor, F-94010 Creteil, France.
   [Decaens, Thomas] INSERM, U955, F-94000 Creteil, France.
   [Franco, Dominique] Hop Antoine Beclere, F-92141 Clamart, France.
   [Samuel, Didier] Hop Paul Brousse, AP HP, Ctr Hepatobilaire, F-94800 Villejuif, France.
   [Samuel, Didier] INSERM, U785, F-94800 Villejuif, France.
   [Zucman-Rossi, Jessica] INSERM, U674, F-75010 Paris, France.
   [Eils, Roland] Heidelberg Univ, D-69120 Heidelberg, Germany.
   [Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69126 Heidelberg, Germany.
   [Korshunov, Andrey] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Landgraf, Pablo] Univ Dusseldorf, Clin Pediat Oncol Hematol & Immunol, D-40225 Dusseldorf, Germany.
   [Lehrach, Hans] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Pfister, Stefan] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany.
   [Reifenberger, Guido] Univ Dusseldorf, Inst Neuropathol, D-40001 Dusseldorf, Germany.
   [Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
   [Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
   [von Kalle, Christof] Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany.
   [von Kalle, Christof] German Canc Res Ctr, Div Translat Oncol, D-69120 Heidelberg, Germany.
   [Pederzoli, Paolo] Univ Hosp Trust Verona, Dept Surg, I-37134 Verona, Italy.
   [Delledonne, Massimo] Univ Verona, Dept Biotechnol, Funct Genom Ctr, I-37134 Verona, Italy.
   [Bardelli, Alberto] Univ Torino, Inst Canc Res & Treatment, Mol Genet Lab, I-10060 Turin, Italy.
   [Bardelli, Alberto] FIRC Inst Mol Oncol, I-20139 Milan, Italy.
   [Gress, Thomas] Univ Marburg, Dept Gastroenterol Endocrinol Metab & Infectiol, D-35043 Marburg, Germany.
   [Klimstra, David] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Nakamura, Yusuke; Miyano, Satoru] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Minato Ku, Tokyo 1088639, Japan.
   Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain.
   [Wilson, Peter J.; de Sanjose, Silvia] Hosp Llobregat, Inst Catala Oncol IDIBELL, Unit Infect & Canc,CIBER Epidemiol & Salud Publ, Canc Epidemiol Res Programme, Lhospitalet De Llobregat 08907, Spain.
   [Aparicio, Samuel] British Columbia Canc Agcy, BC Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Easton, Douglas F.] Univ Cambridge, Dept Primary Care & Oncol, Dept Publ Hlth, Cambridge CB1 8RN, England.
   [Collins, Francis S.] US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Burke, Wylie] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA.
   [Green, Anthony R.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
   [Green, Anthony R.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England.
   [Hamilton, Stanley R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Kallioniemi, Olli P.] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland.
   [Ley, Timothy J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Ley, Timothy J.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Wainwright, Brandon J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
C3 Ontario Institute for Cancer Research; University of Toronto; University of Toronto; University of Toronto; National Health & Medical Research Council (NHMRC) of Australia; Helmholtz Association; German Aerospace Centre (DLR); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Department of Biotechnology (DBT) India; Institut National du Cancer (INCA) France; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Cancer Research UK; Qatar Foundation (QF); Sidra Medical & Research Center; University of Oxford; National Institute of Health Sciences - Japan; Peking University; Chinese Academy of Medical Sciences - Peking Union Medical College; Cancer Institute & Hospital - CAMS; National Cancer Center - Japan; Wellcome Trust Sanger Institute; RIKEN; Beijing Genomics Institute (BGI); Hong Kong University of Science & Technology; McGill University; University of Cambridge; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Institut National de la Sante et de la Recherche Medicale (Inserm); University of North Carolina; University of North Carolina Chapel Hill; Kyoto University; University of Deusto; University of Oxford; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University Hospitals of Cleveland; St John of God Health Care; University of Western Australia; University of Western Australia; Helmholtz Association; German Cancer Research Center (DKFZ); University of New South Wales Sydney; Garvan Institute of Medical Research; NSW Health; Bankstown Lidcombe Hospital; UNICANCER; Institut Paoli-Calmette (IPC); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Universite de Rennes; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Salamanca; 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); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Beaujon - APHP; University of North Carolina; University of North Carolina Chapel Hill; RIKEN; International Genomics Consortium; Centro Nacional de Investigaciones Oncologicas (CNIO); Tata Memorial Centre (TMC); Advance Centre for Treatment, Research & Education in Cancer (ACTREC); Tata Memorial Hospital; University of Verona; Netherlands Cancer Institute; University of Amsterdam; Academic Medical Center Amsterdam; University of Tokyo; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; Peter Maccallum Cancer Center; University of Melbourne; University of Cambridge; University of Queensland; CEA; British Columbia Cancer Agency; University of Oviedo; Instituto Universitario de Oncologia de Asturias; Department of Biotechnology (DBT) India; National Institute of Biomedical Genomics (NIBMG); University of Toronto; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Radboud University Nijmegen; Johns Hopkins University; Johns Hopkins Medicine; Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Hong Kong University of Science & Technology; Hong Kong University of Science & Technology; Zhejiang University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Toronto; University of Toronto; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Pompeu Fabra University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Howard Hughes Medical Institute; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Pompeu Fabra University; Brown University; Brown University; Memorial Sloan Kettering Cancer Center; Walter & Eliza Hall Institute; University of California System; University of California Berkeley; University of California System; University of California Santa Cruz; Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Baylor College of Medicine; Baylor College of Medicine; Foundation Jean Dausset-CEPH; Universite Lyon 1; HudsonAlpha Institute for Biotechnology; University of Cambridge; University of Tasmania; National University of Singapore; UNICANCER; Gustave Roussy; NSW Health; Westmead Hospital; University of Sydney; University of Sydney; Westmead Institute for Medical Research; Johns Hopkins University; Johns Hopkins Medicine; University of Sydney; NSW Health; Royal Prince Alfred Hospital; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of Toronto; University Health Network Toronto; Toronto General Hospital; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University Health Network Toronto; University of Toronto; University of Toronto; University Health Network Toronto; Mayo Clinic; Mayo Clinic; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Shanghai Jiao Tong University; Chinese University of Hong Kong; World Health Organization; International Agency for Research on Cancer (IARC); Charles University Prague; N.N. Blokhin Russian Cancer Research Center; Karolinska Institutet; Karolinska University Hospital; Russian Academy of Sciences; Research Center of Biotechnology RAS; Saint James's University Hospital; University of Leeds; Cancer Research UK; Royal Institute of Technology; University of Latvia; Uppsala University; National Research Centre - Kurchatov Institute; Lund University; University of Oslo; University of Oslo; University of Cambridge; CRUK Cambridge Institute; Cancer Research UK; Erasmus University Rotterdam; Erasmus MC; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; UNICANCER; Centre Leon Berard; Institut Jules Bordet; Universite Marie et Louis Pasteur; CHU Besancon; UNICANCER; Universite PSL; Institut Curie; UNICANCER; Universite de Montpellier; Institut Regional du Cancer Montpellier / Val d'Aurelle (ICM); CHU Bordeaux; Universite de Bordeaux; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Henri-Mondor - APHP; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Antoine-Beclere - APHP; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Paul-Brousse - APHP; Hopital Universitaire Bicetre - APHP; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Ruprecht Karls University Heidelberg; European Molecular Biology Laboratory (EMBL); Ruprecht Karls University Heidelberg; Heinrich Heine University Dusseldorf; Max Planck Society; Ruprecht Karls University Heidelberg; Heinrich Heine University Dusseldorf; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; National Center for Tumor Diseases; Helmholtz Association; German Cancer Research Center (DKFZ); University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; University of Verona; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR); University of Turin; IFOM - FIRC Institute of Molecular Oncology; Philipps University Marburg; Memorial Sloan Kettering Cancer Center; University of Tokyo; University of Barcelona; Hospital Clinic de Barcelona; Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; British Columbia Cancer Agency; University of Cambridge; National Institutes of Health (NIH) - USA; University of Washington; University of Washington Seattle; University of Cambridge; University of Cambridge; University of Texas System; UTMD Anderson Cancer Center; University of Helsinki; Washington University (WUSTL); Washington University (WUSTL); University of Queensland
RP Hudson, TJ (corresponding author), Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
EM tom.hudson@oicr.on.ca
FU National Cancer Institute [P01CA117969, P50CA127003] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [20221009] Funding Source: KAKEN; NCI NIH HHS [P01 CA117969, R21 CA094510, P50 CA127003, P50 CA102701] Funding Source: Medline; NHGRI NIH HHS [R01 HG001806] Funding Source: Medline; NIDDK NIH HHS [K08 DK071329] Funding Source: Medline; Wellcome Trust [093867, 088340, 077198] Funding Source: Medline
NR 35
TC 1706
Z9 1950
U1 6
U2 386
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 993
EP 998
DI 10.1038/nature08987
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000029
PM 20393554
DA 2026-03-09
ER

PT J
AU Melton, C
   Judson, RL
   Blelloch, R
AF Melton, Collin
   Judson, Robert L.
   Blelloch, Robert
TI Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
SO NATURE
LA English
DT Article
ID transcriptional network; dna methylation; c-myc; pluripotency; rna; differentiation; expression; lin-28; nanog; uridylation
AB When embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In the absence of DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to silence self-renewal. Here we show that the introduction of let-7 miRNAs-a family of miRNAs highly expressed in somatic cells-can suppress self-renewal in Dgcr8(-/-) but not wild-type ESCs. Introduction of ESC cell cycle regulating (ESCC) miRNAs into the Dgcr8(-/-) ESCs blocks the capacity of let-7 to suppress self-renewal. Profiling and bioinformatic analyses show that let-7 inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes. Furthermore, inhibition of the let-7 family promotes de-differentiation of somatic cells to induced pluripotent stem cells. Together, these findings show how the ESCC and let-7 miRNAs act through common pathways to alternatively stabilize the self-renewing versus differentiated cell fates.
C1 [Melton, Collin; Judson, Robert L.; Blelloch, Robert] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Program Biomed Sci, Ctr Reprod Sci, San Francisco, CA 94143 USA.
   [Melton, Collin; Judson, Robert L.; Blelloch, Robert] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Blelloch, R (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Program Biomed Sci, Ctr Reprod Sci, San Francisco, CA 94143 USA.
EM blellochr@stemcell.ucsf.edu
FU National Institutes of Health (NIH) [K08 NS48118, R01 NS057221]; California Institute of Regenerative Medicine (CIRM) [RS1-00161, RN2-00906]; American Health Assistance Foundation; Pew Charitable Trust; National Science Foundation (NSF)
NR 49
TC 550
Z9 650
U1 0
U2 87
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 621
EP U45
DI 10.1038/nature08725
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900027
PM 20054295
DA 2026-03-09
ER

PT J
AU Kravitz, AV
   Freeze, BS
   Parker, PRL
   Kay, K
   Thwin, MT
   Deisseroth, K
   Kreitzer, AC
AF Kravitz, Alexxai V.
   Freeze, Benjamin S.
   Parker, Philip R. L.
   Kay, Kenneth
   Thwin, Myo T.
   Deisseroth, Karl
   Kreitzer, Anatol C.
TI Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
SO NATURE
LA English
DT Article
ID subthalamic nucleus; movement-disorders; in-vivo; neurons; interneurons; lesions; models; mice
AB Neural circuits of the basal ganglia are critical for motor planning and action selection(1-3). Two parallel basal ganglia pathways have been described(4), and have been proposed to exert opposing influences on motor function(5-7). According to this classical model, activation of the 'direct' pathway facilitates movement and activation of the 'indirect' pathway inhibits movement. However, more recent anatomical and functional evidence has called into question the validity of this hypothesis(8-10). Because this model has never been empirically tested, the specific function of these circuits in behaving animals remains unknown. Here we report direct activation of basal ganglia circuitry in vivo, using optogenetic control(11-14) of direct-and indirect-pathway medium spiny projection neurons (MSNs), achieved through Cre-dependent viral expression of channelrhodopsin-2 in the striatum of bacterial artificial chromosome transgenic mice expressing Cre recombinase under control of regulatory elements for the dopamine D1 or D2 receptor. Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia and locomotor initiation. Taken together, our findings establish a critical role for basal ganglia circuitry in the bidirectional regulation of motor behaviour and indicate that modulation of direct-pathway circuitry may represent an effective therapeutic strategy for ameliorating parkinsonian motor deficits.
C1 [Kravitz, Alexxai V.; Freeze, Benjamin S.; Parker, Philip R. L.; Kay, Kenneth; Thwin, Myo T.; Kreitzer, Anatol C.] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA.
   [Kreitzer, Anatol C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   [Kreitzer, Anatol C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Parker, Philip R. L.; Kreitzer, Anatol C.] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA.
   [Freeze, Benjamin S.; Kreitzer, Anatol C.] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA.
   [Freeze, Benjamin S.; Kay, Kenneth; Kreitzer, Anatol C.] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Stanford University; Stanford University
RP Kreitzer, AC (corresponding author), Gladstone Inst Neurol Dis, 1650 Owens St, San Francisco, CA 94158 USA.
EM akreitzer@gladstone.ucsf.edu
FU W.M. Keck Foundation; Pew Biomedical Scholars Program; McKnight Foundation; NIH; National Institute of Neurological Disorders and Stroke [R01NS064984] Funding Source: NIH RePORTER
NR 27
TC 1421
Z9 1818
U1 5
U2 390
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 622
EP U7
DI 10.1038/nature09159
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100053
PM 20613723
DA 2026-03-09
ER

PT J
AU Zeng, L
   Zhang, Q
   Li, S
   Plotnikov, AN
   Walsh, MJ
   Zhou, MM
AF Zeng, Lei
   Zhang, Qiang
   Li, Side
   Plotnikov, Alexander N.
   Walsh, Martin J.
   Zhou, Ming-Ming
TI Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b
SO NATURE
LA English
DT Article
ID lysine-4 trimethylation; autoimmune regulator; plant homeodomain; h3; recognition; methylation; bromodomain; nmr; domain; h3k4me3
AB Histone lysine acetylation and methylation have an important role during gene transcription in a chromatin context(1,2). Knowledge concerning the types of protein modules that can interact with acetyl-lysine has so far been limited to bromodomains(1). Recently, a tandem plant homeodomain (PHD) finger(3) (PHD1-PHD2, or PHD12) of human DPF3b, which functions in association with the BAF chromatin remodelling complex to initiate gene transcription during heart and muscle development, was reported to bind histones H3 and H4 in an acetylation-sensitive manner(4), making it the first alternative to bromodomains for acetyl-lysine binding(5). Here we report the structural mechanism of acetylated histone binding by the double PHD fingers of DPF3b. Our three-dimensional solution structures and biochemical analysis of DPF3b highlight the molecular basis of the integrated tandem PHD finger, which acts as one functional unit in the sequence-specific recognition of lysine-14-acetylated histone H3 (H3K14ac). Whereas the interaction with H3 is promoted by acetylation at lysine 14, it is inhibited by methylation at lysine 4, and these opposing influences are important during transcriptional activation of the mouse DPF3b target genes Pitx2 and Jmjd1c. Binding of this tandem protein module to chromatin can thus be regulated by different histone modifications during the initiation of gene transcription.
C1 [Zeng, Lei; Zhang, Qiang; Plotnikov, Alexander N.; Walsh, Martin J.; Zhou, Ming-Ming] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
   [Li, Side; Walsh, Martin J.] Mt Sinai Sch Med, Dept Paediat, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
RP Zhou, MM (corresponding author), Mt Sinai Sch Med, Dept Struct & Chem Biol, 1425 Madison Ave,Box 1677, New York, NY 10029 USA.
EM ming-ming.zhou@mssm.edu
FU National Institutes of Health
NR 30
TC 244
Z9 304
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 258
EP U138
DI 10.1038/nature09139
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800041
PM 20613843
DA 2026-03-09
ER

PT J
AU Bodin, K
   Ellmerich, S
   Kahan, MC
   Tennent, GA
   Loesch, A
   Gilbertson, JA
   Hutchinson, WL
   Mangione, PP
   Gallimore, JR
   Millar, DJ
   Minogue, S
   Dhillon, AP
   Taylor, GW
   Bradwell, AR
   Petrie, A
   Gillmore, JD
   Bellotti, V
   Botto, M
   Hawkins, PN
   Pepys, MB
AF Bodin, Karl
   Ellmerich, Stephan
   Kahan, Melvyn C.
   Tennent, Glenys A.
   Loesch, Andrzej
   Gilbertson, Janet A.
   Hutchinson, Winston L.
   Mangione, Palma P.
   Gallimore, J. Ruth
   Millar, David J.
   Minogue, Shane
   Dhillon, Amar P.
   Taylor, Graham W.
   Bradwell, Arthur R.
   Petrie, Aviva
   Gillmore, Julian D.
   Bellotti, Vittorio
   Botto, Marina
   Hawkins, Philip N.
   Pepys, Mark B.
TI Antibodies to human serum amyloid P component eliminate visceral amyloid deposits
SO NATURE
LA English
DT Article
ID pharmacological depletion; al amyloidosis; complement; fibrils; mice
AB Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries(1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present(1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation(1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous(1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP)(2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.
C1 [Bodin, Karl; Ellmerich, Stephan; Kahan, Melvyn C.; Tennent, Glenys A.; Loesch, Andrzej; Gilbertson, Janet A.; Hutchinson, Winston L.; Mangione, Palma P.; Gallimore, J. Ruth; Millar, David J.; Taylor, Graham W.; Gillmore, Julian D.; Bellotti, Vittorio; Hawkins, Philip N.; Pepys, Mark B.] UCL, Ctr Amyloidosis & Acute Phase Prot, Div Med, London NW3 2PF, England.
   [Mangione, Palma P.; Bellotti, Vittorio] Univ Pavia, Dipartimento Biochim, I-27100 Pavia, Italy.
   [Minogue, Shane] UCL, Ctr Mol Cell Biol, Div Med, London NW3 2PF, England.
   [Dhillon, Amar P.] UCL, Dept Histopathol, London NW3 2PF, England.
   [Bradwell, Arthur R.] Univ Birmingham, Sch Med, Dept Immun & Infect, Birmingham B15 2TT, W Midlands, England.
   [Bradwell, Arthur R.] Binding Site Ltd, Birmingham B14 4ZB, W Midlands, England.
   [Petrie, Aviva] UCL Eastman Dent Inst, Biostat Unit, London WC1X 8LD, England.
   [Botto, Marina] Univ London Imperial Coll Sci Technol & Med, Fac Med, Rheumatol Sect, London W12 0NN, England.
C3 University of London; University College London; University of Pavia; University of London; University College London; University of London; University College London; University of Birmingham; University of London; University College London; Imperial College London
RP Pepys, MB (corresponding author), UCL, Ctr Amyloidosis & Acute Phase Prot, Div Med, Royal Free Campus,Rowland Hill St, London NW3 2PF, England.
EM m.pepys@ucl.ac.uk
FU Medical Research Council [G97900510]; University College London; Erik and Edith Fernstroms Foundation for Medical Research; Swedish Research Council; Medical Research Council [G0901596, G7900510] Funding Source: researchfish; National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [G0800737/1] Funding Source: researchfish; MRC [G0901596, G7900510] Funding Source: UKRI
NR 26
TC 264
Z9 295
U1 0
U2 37
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 93
EP 97
DI 10.1038/nature09494
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900042
PM 20962779
DA 2026-03-09
ER

PT J
AU Humphries, NE
   Queiroz, N
   Dyer, JRM
   Pade, NG
   Musyl, MK
   Schaefer, KM
   Fuller, DW
   Brunnschweiler, JM
   Doyle, TK
   Houghton, JDR
   Hays, GC
   Jones, CS
   Noble, LR
   Wearmouth, VJ
   Southall, EJ
   Sims, DW
AF Humphries, Nicolas E.
   Queiroz, Nuno
   Dyer, Jennifer R. M.
   Pade, Nicolas G.
   Musyl, Michael K.
   Schaefer, Kurt M.
   Fuller, Daniel W.
   Brunnschweiler, Juerg M.
   Doyle, Thomas K.
   Houghton, Jonathan D. R.
   Hays, Graeme C.
   Jones, Catherine S.
   Noble, Leslie R.
   Wearmouth, Victoria J.
   Southall, Emily J.
   Sims, David W.
TI Environmental context explains Levy and Brownian movement patterns of marine predators
SO NATURE
LA English
DT Article
ID flight search patterns; power-law distributions; wandering albatrosses; strategy; behavior; pacific; success; speed; ocean; prey
AB An optimal search theory, the so-called Levy-flight foraging hypothesis(1), predicts that predators should adopt search strategies known as Levy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey(2-4). Empirical studies have generated controversy because the accuracy of statistical methods that have been used to identify Levy behaviour has recently been questioned(5,6). Consequently, whether foragers exhibit Levy flights in the wild remains unclear. Crucially, moreover, it has not been tested whether observed movement patterns across natural landscapes having different expected resource distributions conform to the theory's central predictions. Here we use maximum-likelihood methods to test for Levy patterns in relation to environmental gradients in the largest animal movement data set assembled for this purpose. Strong support was found for Levy search patterns across 14 species of open-ocean predatory fish (sharks, tuna, billfish and ocean sunfish), with some individuals switching between Levy and Brownian movement as they traversed different habitat types. We tested the spatial occurrence of these two principal patterns and found Levy behaviour to be associated with less productive waters (sparser prey) and Brownian movements to be associated with productive shelf or convergence-front habitats (abundant prey). These results are consistent with the Levy-flight foraging hypothesis(1,7), supporting the contention(8,9) that organism search strategies naturally evolved in such a way that they exploit optimal Levy patterns.
C1 [Humphries, Nicolas E.; Queiroz, Nuno; Dyer, Jennifer R. M.; Pade, Nicolas G.; Wearmouth, Victoria J.; Southall, Emily J.; Sims, David W.] Marine Biol Assoc UK, The Lab, Plymouth PL1 2PB, Devon, England.
   [Humphries, Nicolas E.; Sims, David W.] Univ Plymouth, Sch Marine Sci & Engn, Inst Marine, Marine Biol & Ecol Res Ctr, Plymouth PL4 8AA, Devon, England.
   [Queiroz, Nuno] Univ Porto, CIBIO, P-4485668 Vairao, Portugal.
   [Queiroz, Nuno; Pade, Nicolas G.; Jones, Catherine S.; Noble, Leslie R.] Univ Aberdeen, Sch Biol Sci, Inst Biol & Environm Sci, Aberdeen AB24 2TZ, Scotland.
   [Musyl, Michael K.] Univ Hawaii Manoa, Joint Inst Marine & Atmospher Res, Kewalo Res Facil, NOAA Fisheries, Honolulu, HI 96814 USA.
   [Schaefer, Kurt M.; Fuller, Daniel W.] Interamer Trop Tuna Commiss, La Jolla, CA 92037 USA.
   [Brunnschweiler, Juerg M.] ETH, CH-8092 Zurich, Switzerland.
   [Doyle, Thomas K.] Univ Coll Cork, Glucksman Marine Facil, ERI, Coastal & Marine Resources Ctr, Cork, Ireland.
   [Houghton, Jonathan D. R.] Queens Univ Belfast, Ctr Med Biol, Sch Biol Sci, Belfast BT9 7BL, Antrim, North Ireland.
   [Hays, Graeme C.] Swansea Univ, Inst Environm Sustainabil, Dept Pure & Appl Ecol, Swansea SA2 8PP, W Glam, Wales.
C3 Marine Biological Association United Kingdom; University of Plymouth; Universidade do Porto; University of Aberdeen; National Oceanic Atmospheric Admin (NOAA) - USA; University of Hawaii System; University of Hawaii Manoa; Swiss Federal Institutes of Technology Domain; ETH Zurich; University College Cork; Queens University Belfast; Swansea University
RP Sims, DW (corresponding author), Marine Biol Assoc UK, The Lab, Citadel Hill, Plymouth PL1 2PB, Devon, England.
EM dws@mba.ac.uk
FU UK Natural Environment Research Council (NERC); Save Our Seas Foundation; Leverhulme Trust; UK Department for Environment Food and Rural Affairs, Fundacao para a Ciencia e a Tecnologia [SFRH/BD/21354/2005]; UK Royal Society; Fisheries Society of the British Isles; Udaras na Gaeltachta; Taighde Mara Teo; Marine Institute (Ireland); Irish Research Council for Science Engineering and Technology; Shark Foundation Switzerland; University of Aberdeen; PADI Project; Japan Fisheries Agency; US Tuna Foundation; Tagging of Pacific Pelagics programme in the Census of Marine Life; National Oceanic and Atmospheric Administration (US Department of Commerce) [NA37RJ0199, NA67RJ0154]; University of Hawaii [NA37RJ0199, NA67RJ0154]; Royal Society; Marine Biological Association of the UK; UK NERC; Fundação para a Ciência e a Tecnologia [SFRH/BD/21354/2005] Funding Source: FCT; Natural Environment Research Council [mba010004] Funding Source: researchfish; NERC [mba010004] Funding Source: UKRI
NR 29
TC 737
Z9 828
U1 2
U2 296
PU 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 24
PY 2010
VL 465
IS 7301
BP 1066
EP 1069
DI 10.1038/nature09116
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900050
PM 20531470
DA 2026-03-09
ER

PT J
AU Hung, RJ
   Yazdani, U
   Yoon, J
   Wu, H
   Yang, TH
   Gupta, N
   Huang, ZY
   van Berkel, WJH
   Terman, JR
AF Hung, Ruei-Jiun
   Yazdani, Umar
   Yoon, Jimok
   Wu, Heng
   Yang, Taehong
   Gupta, Nidhi
   Huang, Zhiyu
   van Berkel, Willem J. H.
   Terman, Jonathan R.
TI Mical links semaphorins to F-actin disassembly
SO NATURE
LA English
DT Article
ID growth cones; drosophila; collapse; molecule; protein; 3a; microtubules; organization; cytoskeleton; morphology
AB How instructive cues present on the cell surface have their precise effects on the actin cytoskeleton is poorly understood. Semaphorins are one of the largest families of these instructive cues and are widely studied for their effects on cell movement, navigation, angiogenesis, immunology and cancer(1). Semaphorins/collapsins were characterized in part on the basis of their ability to drastically alter actin cytoskeletal dynamics in neuronal processes(2), but despite considerable progress in the identification of semaphorin receptors and their signalling pathways(3), the molecules linking them to the precise control of cytoskeletal elements remain unknown. Recently, highly unusual proteins of the Mical family of enzymes have been found to associate with the cytoplasmic portion of plexins, which are large cell-surface semaphorin receptors, and to mediate axon guidance, synaptogenesis, dendritic pruning and other cell morphological changes(4-7). Mical enzymes perform reduction-oxidation (redox) enzymatic reactions(4,5,8-10) and also contain domains found in proteins that regulate cell morphology(4,11). However, nothing is known of the role of Mical or its redox activity in mediating morphological changes. Here we report that Mical directly links semaphorins and their plexin receptors to the precise control of actin filament (F-actin) dynamics. We found that Mical is both necessary and sufficient for semaphorin-plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical protein and found that it directly binds F-actin and disassembles both individual and bundled actin filaments. We also found that Mical utilizes its redox activity to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown role for specific redox signalling events in actin cytoskeletal regulation. Mical therefore is a novel F-actin-disassembly factor that provides a molecular conduit through which actin reorganization-a hallmark of cell morphological changes including axon navigation-can be precisely achieved spatiotemporally in response to semaphorins.
C1 [Hung, Ruei-Jiun; Yazdani, Umar; Yoon, Jimok; Wu, Heng; Yang, Taehong; Gupta, Nidhi; Huang, Zhiyu; Terman, Jonathan R.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
   [Hung, Ruei-Jiun; Yazdani, Umar; Yoon, Jimok; Wu, Heng; Yang, Taehong; Gupta, Nidhi; Huang, Zhiyu; Terman, Jonathan R.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Hung, Ruei-Jiun; Yazdani, Umar; Yoon, Jimok; Wu, Heng; Yang, Taehong; Gupta, Nidhi; Huang, Zhiyu; Terman, Jonathan R.] Univ Texas SW Med Ctr Dallas, Grad Program Neurosci, Dallas, TX 75390 USA.
   [van Berkel, Willem J. H.] Wageningen Univ, Biochem Lab, NL-6703 HA Wageningen, Netherlands.
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; Wageningen University & Research
RP Terman, JR (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
EM jonathan.terman@utsouthwestern.edu
FU US National Institute of Mental Health [MH085923]; Basil O'Connor Starter Scholar Research Award; National Institute of Mental Health [R01MH085923] Funding Source: NIH RePORTER
NR 30
TC 213
Z9 252
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 823
EP 827
DI 10.1038/nature08724
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300043
PM 20148037
DA 2026-03-09
ER

PT J
AU Baldridge, MT
   King, KY
   Boles, NC
   Weksberg, DC
   Goodell, MA
AF Baldridge, Megan T.
   King, Katherine Y.
   Boles, Nathan C.
   Weksberg, David C.
   Goodell, Margaret A.
TI Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
SO NATURE
LA English
DT Article
ID progenitor cells; identification; homeostasis; deficient; alpha
AB Lymphocytes and neutrophils are rapidly depleted by systemic infection(1). Progenitor cells of the haematopoietic system, such as common myeloid progenitors and common lymphoid progenitors, increase the production of immune cells to restore and maintain homeostasis during chronic infection, but the contribution of haematopoietic stem cells (HSCs) to this process is largely unknown(2). Here we show, using an in vivo mouse model of Mycobacterium avium infection, that an increased proportion of long-term repopulating HSCs proliferate during M. avium infection, and that this response requires interferon-gamma (IFN-gamma) but not interferon-alpha (IFN-alpha) signalling. Thus, the haematopoietic response to chronic bacterial infection involves the activation not only of intermediate blood progenitors but of long-term repopulating HSCs as well. IFN-gamma is sufficient to promote long-term repopulating HSC proliferation in vivo; furthermore, HSCs from IFN-gamma-deficient mice have a lower proliferative rate, indicating that baseline IFN-gamma tone regulates HSC activity. These findings implicate IFN-gamma both as a regulator of HSCs during homeostasis and under conditions of infectious stress. Our studies contribute to a deeper understanding of haematological responses in patients with chronic infections such as HIV/AIDS or tuberculosis(3-5).
C1 [Baldridge, Megan T.; Weksberg, David C.; Goodell, Margaret A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [King, Katherine Y.; Goodell, Margaret A.] Baylor Coll Med, Dept Pediat, Infect Dis Sect, Houston, TX 77030 USA.
   [Boles, Nathan C.; Goodell, Margaret A.] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine
RP Goodell, MA (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM goodell@bcm.edu
FU NIDDK institute of the National Institutes of Health (NIH); Texas Children's Hospital Auxiliary; Simmons Foundation; NHLBI institute of the NIH; NCI institute of the NIH; NIBIB institute of the NIH; National Cancer Institute [P50CA126752] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL092332] Funding Source: NIH RePORTER
NR 32
TC 736
Z9 858
U1 2
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 793
EP U9
DI 10.1038/nature09135
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800048
PM 20535209
DA 2026-03-09
ER

PT J
AU Lee, I
   Obukhov, Y
   Xiang, G
   Hauser, A
   Yang, FY
   Banerjee, P
   Pelekhov, DV
   Hammel, PC
AF Lee, Inhee
   Obukhov, Yuri
   Xiang, Gang
   Hauser, Adam
   Yang, Fengyuan
   Banerjee, Palash
   Pelekhov, Denis V.
   Hammel, P. Chris
TI Nanoscale scanning probe ferromagnetic resonance imaging using localized modes
SO NATURE
LA English
DT Article
ID magnetic-resonance; force microscopy; spin waves; spectrum; disk
AB The discovery of new phenomena in layered and nanostructured magnetic devices is driving rapid growth in nanomagnetics research. Resulting applications such as giant magnetoresistive field sensors and spin torque devices are fuelling advances in information and communications technology, magnetoelectronic sensing and biomedicine(1,2). There is an urgent need for high-resolution magnetic-imaging tools capable of characterizing these complex, often buried, nanoscale structures. Conventional ferromagnetic resonance(3,4) (FMR) provides quantitative information about ferromagnetic materials and interacting multicomponent magnetic structures with spectroscopic precision and can distinguish components of complex bulk samples through their distinctive spectroscopic features. However, it lacks the sensitivity to probe nanoscale volumes and has no imaging capabilities. Here we demonstrate FMR imaging through spin-wave localization. Although the strong interactions in a ferromagnet favour the excitation of extended collective modes, we show that the intense, spatially confined magnetic field of the micromagnetic probe tip used in FMR force microscopy can be used to localize the FMR mode immediately beneath the probe. We demonstrate FMR modes localized within volumes having 200 nm lateral dimensions, and improvements of the approach may allow these dimensions to be decreased to tens of nanometres. Our study shows that this approach is capable of providing the microscopic detail required for the characterization of ferromagnets used in fields ranging from spintronics to biomagnetism. This method is applicable to buried and surface magnets, and, being a resonance technique, measures local internal fields and other magnetic properties with spectroscopic precision.
C1 [Lee, Inhee; Obukhov, Yuri; Xiang, Gang; Hauser, Adam; Yang, Fengyuan; Banerjee, Palash; Pelekhov, Denis V.; Hammel, P. Chris] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University
RP Hammel, PC (corresponding author), Ohio State Univ, Dept Phys, 174 W 18th Ave, Columbus, OH 43210 USA.
EM hammel@mps.ohio-state.edu
FU US Department of Energy [DE-FG02-03ER46054]; U.S. Department of Energy (DOE) [DE-FG02-03ER46054] Funding Source: U.S. Department of Energy (DOE)
NR 24
TC 90
Z9 105
U1 2
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 AUG 12
PY 2010
VL 466
IS 7308
BP 845
EP 848
DI 10.1038/nature09279
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100031
PM 20703302
DA 2026-03-09
ER

PT J
AU Pakmor, R
   Kromer, M
   Röpke, FK
   Sim, SA
   Ruiter, AJ
   Hillebrandt, W
AF Pakmor, Ruediger
   Kromer, Markus
   Roepke, Friedrich K.
   Sim, Stuart A.
   Ruiter, Ashley J.
   Hillebrandt, Wolfgang
TI Sub-luminous type Ia supernovae from the mergers of equal-mass white dwarfs with mass ∼0.9M⊙
SO NATURE
LA English
DT Article
ID star; nucleosynthesis; evolution; models; rates; detonations; explosions; binary; objects; code
AB Type Ia supernovae are thought to result from thermonuclear explosions of carbon-oxygen white dwarf stars(1). Existing models(2) generally explain the observed properties, with the exception of the sub-luminous 1991bg-like supernovae(3). It has long been suspected that the merger of two white dwarfs could give rise to a type Ia event(4,5), but hitherto simulations have failed to produce an explosion(6,7). Here we report a simulation of the merger of two equal-mass white dwarfs that leads to a sub-luminous explosion, although at the expense of requiring a single common-envelope phase, and component masses of similar to 0.9M(circle dot). The light curve is too broad, but the synthesized spectra, red colour and low expansion velocities are all close to what is observed for sub-luminous 1991bg-like events. Although the mass ratios can be slightly less than one and still produce a sub-luminous event, the masses have to be in the range 0.83M(circle dot) to 0.9M(circle dot).
C1 [Pakmor, Ruediger; Kromer, Markus; Roepke, Friedrich K.; Sim, Stuart A.; Ruiter, Ashley J.; Hillebrandt, Wolfgang] Max Planck Inst Astrophys, D-85748 Garching, Germany.
C3 Max Planck Society
RP Pakmor, R (corresponding author), Max Planck Inst Astrophys, Karl Schwarzschild Str 1, D-85748 Garching, Germany.
EM rpakmor@mpa-garching.mpg.de
FU German Research Foundation; Excellence Cluster "Origin and Structure of the Universe''
NR 29
TC 307
Z9 349
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 7
PY 2010
VL 463
IS 7277
BP 61
EP 64
DI 10.1038/nature08642
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900029
PM 20054390
DA 2026-03-09
ER

PT J
AU Zhang, JM
   Adrián, FJ
   Jahnke, W
   Cowan-Jacob, SW
   Li, AG
   Iacob, RE
   Sim, T
   Powers, J
   Dierks, C
   Sun, FX
   Guo, GR
   Ding, Q
   Okram, B
   Choi, Y
   Wojciechowski, A
   Deng, XM
   Liu, GX
   Fendrich, G
   Strauss, A
   Vajpai, N
   Grzesiek, S
   Tuntland, T
   Liu, Y
   Bursulaya, B
   Azam, M
   Manley, PW
   Engen, JR
   Daley, GQ
   Warmuth, M
   Gray, NS
AF Zhang, Jianming
   Adrian, Francisco J.
   Jahnke, Wolfgang
   Cowan-Jacob, Sandra W.
   Li, Allen G.
   Iacob, Roxana E.
   Sim, Taebo
   Powers, John
   Dierks, Christine
   Sun, Fangxian
   Guo, Gui-Rong
   Ding, Qiang
   Okram, Barun
   Choi, Yongmun
   Wojciechowski, Amy
   Deng, Xianming
   Liu, Guoxun
   Fendrich, Gabriele
   Strauss, Andre
   Vajpai, Navratna
   Grzesiek, Stephan
   Tuntland, Tove
   Liu, Yi
   Bursulaya, Badry
   Azam, Mohammad
   Manley, Paul W.
   Engen, John R.
   Daley, George Q.
   Warmuth, Markus
   Gray, Nathanael S.
TI Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors
SO NATURE
LA English
DT Article
ID chronic myeloid-leukemia; cell lung-cancer; kinase-inhibitor; c-abl; tyrosine kinase; lymphoblastic-leukemia; imatinib resistance; selective inhibitor; mutations; dynamics
AB In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
C1 [Adrian, Francisco J.; Li, Allen G.; Dierks, Christine; Sun, Fangxian; Guo, Gui-Rong; Ding, Qiang; Liu, Guoxun; Tuntland, Tove; Liu, Yi; Bursulaya, Badry] Novartis Res Fdn, Dept Chem, Genom Inst, San Diego, CA 92121 USA.
   [Zhang, Jianming; Sim, Taebo; Choi, Yongmun; Wojciechowski, Amy; Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Zhang, Jianming; Sim, Taebo; Powers, John; Choi, Yongmun; Wojciechowski, Amy; Deng, Xianming; Azam, Mohammad; Daley, George Q.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Jahnke, Wolfgang; Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Strauss, Andre; Manley, Paul W.] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland.
   [Iacob, Roxana E.; Engen, John R.] Northwestern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
   [Iacob, Roxana E.; Engen, John R.] Northwestern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA.
   [Sim, Taebo] Korea Inst Sci & Technol, Life Sci Res Div, Seoul 136791, South Korea.
   [Powers, John; Azam, Mohammad; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Powers, John; Azam, Mohammad; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Powers, John; Azam, Mohammad; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Okram, Barun] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
   [Okram, Barun] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Vajpai, Navratna; Grzesiek, Stephan] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
   [Warmuth, Markus] Novartis Inst BioMed Res Inc, Cambridge, MA 02139 USA.
C3 Novartis; Novartis USA; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Novartis; Northwestern University; Northwestern University; Korea Institute of Science & Technology (KIST); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Howard Hughes Medical Institute; Scripps Research Institute; Scripps Research Institute; University of Basel; Novartis; Novartis USA
RP Adrián, FJ (corresponding author), Novartis Res Fdn, Dept Chem, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA.
EM fadrian@gnf.org; markus.warmuth@novartis.com; nathanael_gray@dfci.harvard.edu
FU NCI NIH HHS [R01 CA130876] Funding Source: Medline
NR 41
TC 509
Z9 624
U1 2
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 501
EP U116
DI 10.1038/nature08675
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100042
PM 20072125
DA 2026-03-09
ER

PT J
AU de Bono, JS
   Ashworth, A
AF de Bono, J. S.
   Ashworth, Alan
TI Translating cancer research into targeted therapeutics
SO NATURE
LA English
DT Article
ID circulating tumor-cells; resistant prostate-cancer; progression-free survival; clinical-trial; abiraterone acetate; phase-i; drug; gene; imatinib; inhibition
AB The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.
C1 [de Bono, J. S.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
   [de Bono, J. S.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England.
   [Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Ctr, London SW3 6JB, England.
C3 University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust
RP de Bono, JS (corresponding author), Inst Canc Res, Cotswold Rd, Sutton SM2 5NG, Surrey, England.
EM johann.de-bono@icr.ac.uk; alan.ashworth@icr.ac.uk
FU Breast Cancer Now [BREAST CANCER NOW RESEARCH CENTRE] Funding Source: Medline
NR 70
TC 263
Z9 310
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 543
EP 549
DI 10.1038/nature09339
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100029
PM 20882008
DA 2026-03-09
ER

PT J
AU Terauchi, A
   Johnson-Venkatesh, EM
   Toth, AB
   Javed, D
   Sutton, MA
   Umemori, H
AF Terauchi, Akiko
   Johnson-Venkatesh, Erin M.
   Toth, Anna B.
   Javed, Danish
   Sutton, Michael A.
   Umemori, Hisashi
TI Distinct FGFs promote differentiation of excitatory and inhibitory synapses
SO NATURE
LA English
DT Article
ID presynaptic organizing molecules; synaptic-transmission; growth-factor; brain; interneurons; localization; epilepsy; family
AB The differential formation of excitatory (glutamate-mediated) and inhibitory(GABA-mediated) synapses is a critical step for the proper functioning of the brain. An imbalance in these synapses may lead to various neurological disorders such as autism, schizophrenia, Tourette's syndrome and epilepsy(1-4). Synapses are formed through communication between the appropriate synaptic partners(5-8). However, the molecular mechanisms that mediate the formation of specific synaptic types are not known. Here we show that two members of the fibroblast growth factor (FGF) family, FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. FGF22 and FGF7 are expressed by CA3 pyramidal neurons in the hippocampus. The differentiation of excitatory or inhibitory nerve terminals on dendrites of CA3 pyramidal neurons is specifically impaired in mutants lacking FGF22 or FGF7. These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. FGF22-deficientmice are resistant to epileptic seizures, and FGF7-deficient mice are prone to them, as expected from the alterations in excitatory/inhibitory balance. Differential effects of FGF22 and FGF7 involve both their distinct synaptic localizations and their use of different signalling pathways. These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain.
C1 [Terauchi, Akiko; Johnson-Venkatesh, Erin M.; Toth, Anna B.; Javed, Danish; Sutton, Michael A.; Umemori, Hisashi] Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
   [Sutton, Michael A.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
   [Umemori, Hisashi] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Umemori, H (corresponding author), Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
EM umemoh@umich.edu
FU Ester A. & Joseph Klingenstein Fund; Edward Mallinckrodt Jr Foundation; March of Dimes Foundation; Whitehall Foundation
NR 25
TC 160
Z9 195
U1 2
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 JUN 10
PY 2010
VL 465
IS 7299
BP 783
EP U8
DI 10.1038/nature09041
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800046
PM 20505669
DA 2026-03-09
ER

PT J
AU Finkelstein, IJ
   Visnapuu, ML
   Greene, EC
AF Finkelstein, Ilya J.
   Visnapuu, Mari-Liis
   Greene, Eric C.
TI Single-molecule imaging reveals mechanisms of protein disruption by a DNA translocase
SO NATURE
LA English
DT Article
ID rna-polymerase; recbcd enzyme; replication fork; lac repressor; transcription; binding; replisome; helicase; operator; motor
AB In physiological settings, nucleic-acid translocases must act on substrates occupied by other proteins, and an increasingly appreciated role of translocases is to catalyse protein displacement from RNA andDNA(1-4). However, little is known regarding the inevitable collisions that must occur, and the fate of protein obstacles and the mechanisms by which they are evicted from DNA remain unexplored. Here we sought to establish the mechanistic basis for protein displacement from DNA using RecBCD as a model system. Using nanofabricated curtains of DNA and multicolour single-molecule microscopy, we visualized collisions between a model translocase and different DNA-bound proteins in real time. We show that the DNA translocase RecBCD can disrupt core RNA polymerase, holoenzymes, stalled elongation complexes and transcribing RNA polymerases in either head-to-head or head-to-tail orientations, as well as EcoRI(E111Q), lac repressor and even nucleosomes. RecBCD did not pause during collisions and often pushed proteins thousands of base pairs before evicting them from DNA. We conclude that RecBCD overwhelms obstacles through direct transduction of chemomechanical force with no need for specific protein-protein interactions, and that proteins can be removed from DNA through active disruption mechanisms that act on a transition state intermediate as they are pushed from one nonspecific site to the next.
C1 [Greene, Eric C.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Finkelstein, Ilya J.; Visnapuu, Mari-Liis; Greene, Eric C.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University
RP Greene, EC (corresponding author), Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
EM ecg2108@columbia.edu
FU NIH [F32GM80864, GM074739, GM082848]; Columbia University; Nanoscale Science and Engineering Initiative of the National Science Foundation [CHE-0641523]; New York State Office of Science, Technology, and Academic Research
NR 30
TC 139
Z9 161
U1 0
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 983
EP 987
DI 10.1038/nature09561
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600051
PM 21107319
DA 2026-03-09
ER

PT J
AU Pen, I
   Uller, T
   Feldmeyer, B
   Harts, A
   While, GM
   Wapstra, E
AF Pen, Ido
   Uller, Tobias
   Feldmeyer, Barbara
   Harts, Anna
   While, Geoffrey M.
   Wapstra, Erik
TI Climate-driven population divergence in sex-determining systems
SO NATURE
LA English
DT Article
ID adaptive significance; offspring sex; evolution; ratio; size
AB Sex determination is a fundamental biological process, yet its mechanisms are remarkably diverse(1,2). In vertebrates, sex can be determined by inherited genetic factors or by the temperature experienced during embryonic development(2,3). However, the evolutionary causes of this diversity remain unknown. Here we show that live-bearing lizards at different climatic extremes of the species' distribution differ in their sex-determining mechanisms, with temperature-dependent sex determination in lowlands and genotypic sex determination in highlands. A theoretical model parameterized with field data accurately predicts this divergence in sex-determining systems and the consequence thereof for variation in cohort sex ratios among years. Furthermore, we show that divergent natural selection on sex determination across altitudes is caused by climatic effects on lizard life history and variation in the magnitude of between-year temperature fluctuations. Our results establish an adaptive explanation for intra-specific divergence in sex-determining systems driven by phenotypic plasticity and ecological selection, thereby providing a unifying framework for integrating the developmental, ecological and evolutionary basis for variation in vertebrate sex determination.
C1 [Pen, Ido; Feldmeyer, Barbara; Harts, Anna] Univ Groningen, Theoret Biol Grp, NL-9750 AA Haren, Netherlands.
   [Uller, Tobias] Univ Oxford, Dept Zool, Edward Grey Inst, Oxford OX1 3PS, England.
   [While, Geoffrey M.; Wapstra, Erik] Univ Tasmania, Sch Zool, Hobart, Tas 7001, Australia.
C3 University of Groningen; University of Oxford; University of Tasmania
RP Pen, I (corresponding author), Univ Groningen, Theoret Biol Grp, POB 14, NL-9750 AA Haren, Netherlands.
EM i.r.pen@rug.nl
FU Australian Research Council [DP0877948]; Hermon Slade Foundation; Wenner-Gren Foundations; Australian Research Council [DP0877948] Funding Source: Australian Research Council
NR 28
TC 137
Z9 149
U1 1
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 436
EP U262
DI 10.1038/nature09512
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100042
PM 20981009
DA 2026-03-09
ER

PT J
AU Li, WK
   Schulman, S
   Dutton, RJ
   Boyd, D
   Beckwith, J
   Rapoport, TA
AF Li, Weikai
   Schulman, Sol
   Dutton, Rachel J.
   Boyd, Dana
   Beckwith, Jon
   Rapoport, Tom A.
TI Structure of a bacterial homologue of vitamin K epoxide reductase
SO NATURE
LA English
DT Article
ID disulfide bond formation; active-site; vkorc1; dsbb; model; resistance; conversion; mutations; mechanism; cycle
AB Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain c-carboxylation of many blood coagulation factors. Here, we report the 3.6 angstrom crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins to reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.
C1 [Li, Weikai; Schulman, Sol; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Li, Weikai; Schulman, Sol; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Dutton, Rachel J.; Boyd, Dana; Beckwith, Jon] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; 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 weikai@crystal.harvard.edu; tom_rapoport@hms.harvard.edu
FU NIH; National Institute of General Medical Sciences [GMO41883]; Charles King Trust; National Heart, Lung, and Blood Institute (NIH) [K99, 1K99HL097083]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 43
TC 160
Z9 191
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 28
PY 2010
VL 463
IS 7280
BP 507
EP U123
DI 10.1038/nature08720
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100043
PM 20110994
DA 2026-03-09
ER

PT J
AU Zheng, JM
   Jia, ZC
AF Zheng, Jimin
   Jia, Zongchao
TI Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase
SO NATURE
LA English
DT Article
ID dependent protein-kinase; x-ray analysis; phosphorylation cycle; crystal-structure; phosphatase; substrate; purification; enzyme; crystallization; recognition
AB The Escherichia coli isocitrate dehydrogenase kinase/phosphatase (AceK) is a unique bifunctional enzyme that phosphorylates or dephosphorylates isocitrate dehydrogenase (ICDH) in response to environmental changes, resulting in the inactivation or, respectively, activation of ICDH1. ICDH inactivation short-circuits the Krebs cycle by enabling the glyoxlate bypass(2,3). It was the discovery of AceK and ICDH that established the existence of protein phosphorylation regulation in prokaryotes(1,4). As a 65-kDa protein, AceK is significantly larger than typical eukaryotic protein kinases. Apart from the ATP-binding motif, AceK does not share sequence homology with any eukaryotic protein kinase or phosphatase(5,6). Most intriguingly, AceK possesses the two opposing activities of protein kinase and phosphatase within one protein, and specifically recognizes only intact ICDH7,8. Additionally, AceK has strong ATPase activity(9). It has been shown that AceK kinase, phosphatase and ATPase activities reside at the same site(6,10), although the molecular basis of such multifunctionality and its regulation remains completely unknown. Here we report the structures of AceK and its complex with ICDH. The AceK structure reveals a eukaryotic protein-kinase-like domain containing ATP and a regulatory domain with a novel fold. As an AceK phosphatase activator and kinase inhibitor, AMP is found to bind in an allosteric site between the two AceK domains. An AMP-mediated conformational change exposes and shields ATP, acting as a switch between AceK kinase and phosphatase activities, and ICDH-binding induces further conformational change for AceK activation. The substrate recognition loop of AceK binds to the ICDH dimer, allowing higher-order substrate recognition and interaction, and inducing critical conformational change at the phosphorylation site of ICDH.
C1 [Zheng, Jimin; Jia, Zongchao] Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada.
   [Zheng, Jimin] Beijing Normal Univ, Coll Chem, Beijing 100875, Peoples R China.
C3 Queens University - Canada; Beijing Normal University
RP Jia, ZC (corresponding author), Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada.
EM jia@queensu.ca
FU Canadian Institutes of Health Research
NR 39
TC 64
Z9 76
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 JUN 17
PY 2010
VL 465
IS 7300
BP 961
EP U16
DI 10.1038/nature09088
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500045
PM 20505668
DA 2026-03-09
ER

PT J
AU Doak, DF
   Morris, WF
AF Doak, Daniel F.
   Morris, William F.
TI Demographic compensation and tipping points in climate-induced range shifts
SO NATURE
LA English
DT Article
ID extinction; responses; impacts; plants
AB To persist, species are expected to shift their geographical ranges polewards or to higher elevations as the Earth's climate warms(1-4). However, although many species' ranges have shifted in historical times, many others have not, or have shifted only at the high-latitude or high-elevation limits, leading to range expansions rather than contractions(5-11). Given these idiosyncratic responses to climate warming, and their varied implications for species' vulnerability to climate change, a critical task is to understand why some species have not shifted their ranges, particularly at the equatorial or low-elevation limits, and whether such resilience will last as warming continues. Here we show that compensatory changes in demographic rates are buffering southern populations of two North American tundra plants against the negative effects of a warming climate, slowing their northward range shifts, but that this buffering is unlikely to continue indefinitely. Southern populations of both species showed lower survival and recruitment but higher growth of individual plants, possibly owing to longer, warmer growing seasons. Because of these and other compensatory changes, the population growth rates of southern populations are not at present lower than those of northern ones. However, continued warming may yet prove detrimental, as most demographic rates that improved in moderately warmer years declined in the warmest years, with the potential to drive future population declines. Our results emphasize the need for long-term, range-wide measurement of all population processes to detect demographic compensation and to identify nonlinear responses that may lead to sudden range shifts as climatic tipping points are exceeded.
C1 [Doak, Daniel F.] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
   [Morris, William F.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
C3 University of Wyoming; Duke University
RP Doak, DF (corresponding author), Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
EM ddoak@uwyo.edu
FU NSF [DEB-9806818, DEB-0087096, DEB-0716433]
NR 23
TC 388
Z9 459
U1 3
U2 310
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 21
PY 2010
VL 467
IS 7318
BP 959
EP 962
DI 10.1038/nature09439
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700037
PM 20962844
DA 2026-03-09
ER

PT J
AU Borghetti, J
   Snider, GS
   Kuekes, PJ
   Yang, JJ
   Stewart, DR
   Williams, RS
AF Borghetti, Julien
   Snider, Gregory S.
   Kuekes, Philip J.
   Yang, J. Joshua
   Stewart, Duncan R.
   Williams, R. Stanley
TI 'Memristive' switches enable 'stateful' logic operations via material implication
SO NATURE
LA English
DT Article
ID nm half-pitch; molecular electronics; nanoimprint lithography; crossbar circuits; devices; architecture; fabrication; element
AB The authors of the International Technology Roadmap for Semiconductors(1)-the industry consensus set of goals established for advancing silicon integrated circuit technology-have challenged the computing research community to find new physical state variables (other than charge or voltage), new devices, and new architectures that offer memory and logic functions(1-6) beyond those available with standard transistors. Recently, ultra-dense resistive memory arrays built from various two-terminal semiconductor or insulator thin film devices have been demonstrated(7-12). Among these, bipolar voltage-actuated switches have been identified as physical realizations of 'memristors' or memristive devices, combining the electrical properties of a memory element and a resistor(13,14). Such devices were first hypothesized by Chua in 1971 (ref. 15), and are characterized by one or more state variables(16) that define the resistance of the switch depending upon its voltage history. Here we show that this family of nonlinear dynamical memory devices can also be used for logic operations: we demonstrate that they can execute material implication (IMP), which is a fundamental Boolean logic operation on two variables p and q such that pIMPq is equivalent to (NOTp)ORq. Incorporated within an appropriate circuit(17,18), memristive switches can thus perform 'stateful' logic operations for which the same devices serve simultaneously as gates (logic) and latches(19) (memory) that use resistance instead of voltage or charge as the physical state variable.
C1 [Borghetti, Julien; Snider, Gregory S.; Kuekes, Philip J.; Yang, J. Joshua; Stewart, Duncan R.; Williams, R. Stanley] Hewlett Packard Labs, Palo Alto, CA 94304 USA.
C3 Hewlett-Packard
RP Stewart, DR (corresponding author), Natl Res Council Canada, Steacie Inst Mol Sci, 100 Sussex Dr, Ottawa, ON K1A OR6, Canada.
EM duncan.stewart@nrc.gc.ca; stan.williams@hp.com
NR 29
TC 1582
Z9 1751
U1 12
U2 825
PU NATURE PUBLISHING 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 8
PY 2010
VL 464
IS 7290
BP 873
EP 876
DI 10.1038/nature08940
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300033
PM 20376145
DA 2026-03-09
ER

PT J
AU Coudreuse, D
   Nurse, P
AF Coudreuse, Damien
   Nurse, Paul
TI Driving the cell cycle with a minimal CDK control network
SO NATURE
LA English
DT Article
ID yeast schizosaccharomyces-pombe; b-type cyclin; fission yeast; s-phase; protein-kinase; tyrosine phosphorylation; dependent kinases; genetic-analysis; dna-replication; mitotic control
AB Control of eukaryotic cell proliferation involves an extended regulatory network, the complexity of which has made it difficult to understand the basic principles of the cell cycle. To investigate the core engine of the mitotic cycle we have generated a minimal control network in fission yeast that efficiently sustains cellular reproduction. Here we demonstrate that orderly progression through the major events of the cell cycle can be driven by oscillation of an engineered monomolecular cyclin-dependent protein kinase (CDK) module lacking much of the canonical regulation. We show further that the CDK oscillator acts as the primary organizer of the cell cycle, imposing timing and directionality to a system of two CDK activity thresholds that define independent cell cycle phases. We propose that this simple core architecture forms the basic control of the eukaryotic cell cycle.
C1 [Coudreuse, Damien; Nurse, Paul] Rockefeller Univ, Lab Yeast Genet & Cell Biol, New York, NY 10065 USA.
C3 Rockefeller University
RP Coudreuse, D (corresponding author), Rockefeller Univ, Lab Yeast Genet & Cell Biol, 1230 York Ave, New York, NY 10065 USA.
EM dcoudreuse@rockefeller.edu
FU EMBO [ALTF 899-2007]; Human Frontier Science Program [LT00623/2008]; Breast Cancer Research Foundation; Rockefeller University; Anderson Cancer Center Research at Rockefeller University
NR 67
TC 308
Z9 368
U1 0
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1074
EP U474
DI 10.1038/nature09543
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800052
PM 21179163
DA 2026-03-09
ER

PT J
AU Schramek, D
   Leibbrandt, A
   Sigl, V
   Kenner, L
   Pospisilik, JA
   Lee, HJ
   Hanada, R
   Joshi, PA
   Aliprantis, A
   Glimcher, L
   Pasparakis, M
   Khokha, R
   Ormandy, CJ
   Widschwendter, M
   Schett, G
   Penninger, JM
AF Schramek, Daniel
   Leibbrandt, Andreas
   Sigl, Verena
   Kenner, Lukas
   Pospisilik, John A.
   Lee, Heather J.
   Hanada, Reiko
   Joshi, Purna A.
   Aliprantis, Antonios
   Glimcher, Laurie
   Pasparakis, Manolis
   Khokha, Rama
   Ormandy, Christopher J.
   Widschwendter, Martin
   Schett, Georg
   Penninger, Josef M.
TI Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer
SO NATURE
LA English
DT Article
ID hormone-replacement therapy; estrogen-plus-progestin; stem-cell; postmenopausal women; epithelial-cells; medroxyprogesterone acetate; osteoprotegerin-ligand; receptor activator; gland development; bone metastasis
AB Breast cancer is one of the most common cancers in humans and will on average affect up to one in eight women in their lifetime in the United States and Europe(1). The Women's Health Initiative and the Million Women Study have shown that hormone replacement therapy is associated with an increased risk of incident and fatal breast cancer(2,3). In particular, synthetic progesterone derivatives (progestins) such as medroxyprogesterone acetate (MPA), used in millions of women for hormone replacement therapy and contraceptives, markedly increase the risk of developing breast cancer. Here we show that the in vivo administration of MPA triggers massive induction of the key osteoclast differentiation factor RANKL (receptor activator of NF-kappa B ligand) in mammary-gland epithelial cells. Genetic inactivation of the RANKL receptor RANK in mammary-gland epithelial cells prevents MPA-induced epithelial proliferation, impairs expansion of the CD49f(hi) stem-cell-enriched population, and sensitizes these cells to DNA-damage-induced cell death. Deletion of RANK from the mammary epithelium results in a markedly decreased incidence and delayed onset of MPA-driven mammary cancer. These data show that the RANKL/RANK system controls the incidence and onset of progestin-driven breast cancer.
C1 [Schramek, Daniel; Leibbrandt, Andreas; Sigl, Verena; Pospisilik, John A.; Hanada, Reiko; Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Kenner, Lukas] Med Univ Vienna, A-1090 Vienna, Austria.
   [Lee, Heather J.; Ormandy, Christopher J.] Garvan Inst Med Res, Sydney, NSW 2010, Australia.
   [Joshi, Purna A.; Khokha, Rama] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Aliprantis, Antonios; Glimcher, Laurie] Harvard Univ, Sch Med, Dept Med, Sch Publ Hlth,Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Aliprantis, Antonios; Glimcher, Laurie] MGH MIT, Ragon Inst, Boston, MA 02115 USA.
   [Pasparakis, Manolis] Univ Cologne, Ctr Mol Med CMMC, Inst Genet, D-50674 Cologne, Germany.
   [Pasparakis, Manolis] Univ Cologne, Cologne Excellence Cluster CECAD, D-50674 Cologne, Germany.
   [Widschwendter, Martin] UCL, Dept Gynaecol Oncol, London WC1E 6AU, England.
   [Schett, Georg] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany.
C3 Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Austrian Academy of Sciences; Medical University of Vienna; Garvan Institute of Medical Research; University of Toronto; University Health Network Toronto; Harvard University; Harvard T.H. Chan School of Public Health; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; University of Cologne; University of Cologne; University of London; University College London; University of Erlangen Nuremberg
RP Penninger, JM (corresponding author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
EM josef.penninger@imba.oeaw.ac.at
FU Burroughs Wellcome Fund; National Institutes of Health (NIH) [HD055601]; German Research Council (Deutsche Forschungsgemeinschaft (DFG)) [FOR643, SFB641, SPP1468]; Interdisciplinary Center for Clinical Sciences Erlangen; European Union (EU); National Health and Medical Research Council of Australia; Australian Cancer Research Fund; Cancer Institute New South Wales; EU InflaCare network; University College London (UCL) Hospital/UCL Comprehensive Biomedical Research Centre [152]; Department of Health National Institute for Health Research Biomedical Research Centres; Institute of Molecular Biotechnology; Austrian Ministry of Sciences; Austrian Academy of Sciences; GEN-AU (AustroMouse); European Research Council
NR 41
TC 457
Z9 524
U1 3
U2 63
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 98
EP +
DI 10.1038/nature09387
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900043
PM 20881962
DA 2026-03-09
ER

PT J
AU Nakada, S
   Tai, I
   Panier, S
   Al-Hakim, A
   Iemura, S
   Juang, YC
   O'Donnell, L
   Kumakubo, A
   Munro, M
   Sicheri, F
   Gingras, AC
   Natsume, T
   Suda, T
   Durocher, D
AF Nakada, Shinichiro
   Tai, Ikue
   Panier, Stephanie
   Al-Hakim, Abdallah
   Iemura, Shun-ichiro
   Juang, Yu-Chi
   O'Donnell, Lara
   Kumakubo, Ayako
   Munro, Meagan
   Sicheri, Frank
   Gingras, Anne-Claude
   Natsume, Tohru
   Suda, Toshio
   Durocher, Daniel
TI Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1
SO NATURE
LA English
DT Article
ID double-strand breaks; statistical-model; structural basis; mammalian-cells; repair proteins; binding; complex; enzyme; chains; specificity
AB DNA double-strand breaks (DSBs) pose a potent threat to genome integrity. These lesions also contribute to the efficacy of radiotherapy and many cancer chemotherapeutics. DSBs elicit a signalling cascade that modifies the chromatin surrounding the break, first by ATM-dependent phosphorylation and then by RNF8-, RNF168- and BRCA1-dependent regulatory ubiquitination. Here we report that OTUB1, a deubiquitinating enzyme, is an inhibitor of DSB-induced chromatin ubiquitination. Surprisingly, we found that OTUB1 suppresses RNF168-dependent poly-ubiquitination independently of its catalytic activity. OTUB1 does so by binding to and inhibiting UBC13 (also known as UBE2N), the cognate E2 enzyme for RNF168. This unusual mode of regulation is unlikely to be limited to UBC13 because analysis of OTUB1-associated proteins revealed that OTUB1 binds to E2s of the UBE2D and UBE2E subfamilies. Finally, OTUB1 depletion mitigates the DSB repair defect associated with defective ATM signalling, indicating that pharmacological targeting of the OTUB1-UBC13 interaction might enhance the DNA damage response.
C1 [Panier, Stephanie; Al-Hakim, Abdallah; Juang, Yu-Chi; O'Donnell, Lara; Munro, Meagan; Sicheri, Frank; Gingras, Anne-Claude; Durocher, Daniel] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Nakada, Shinichiro; Tai, Ikue] Keio Univ, Sch Med, Ctr Integrated Med Res, Shinjuku Ku, Tokyo 1608582, Japan.
   [Nakada, Shinichiro; Tai, Ikue; Kumakubo, Ayako; Suda, Toshio] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab Dev Biol,Shinjuku Ku, Tokyo 1608582, Japan.
   [Panier, Stephanie; Sicheri, Frank; Gingras, Anne-Claude; Durocher, Daniel] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Iemura, Shun-ichiro; Natsume, Tohru] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Biol Syst Control Team, Koto Ku, Tokyo 1350064, Japan.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; Keio University; Keio University; University of Toronto; National Institute of Advanced Industrial Science & Technology (AIST)
RP Durocher, D (corresponding author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM snakada@z3.keio.jp; durocher@lunenfeld.ca
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan; MEXT [21870033]; Takeda Science Foundation; Mitsubishi Pharma Research Foundation; Daiwa Anglo-Japanese Foundation; New Energy and Industrial Technology Development Organization (NEDO); Boehringer Ingelheim Fonds; Canadian Institutes of Health Research [MOP10703115, MOP84314]; Grants-in-Aid for Scientific Research [21870033] Funding Source: KAKEN
NR 38
TC 312
Z9 365
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 AUG 19
PY 2010
VL 466
IS 7309
BP 941
EP U59
DI 10.1038/nature09297
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300027
PM 20725033
DA 2026-03-09
ER

PT J
AU Sheu, YJ
   Stillman, B
AF Sheu, Yi-Jun
   Stillman, Bruce
TI The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4
SO NATURE
LA English
DT Article
ID eukaryotic dna-replication; cdk-dependent phosphorylation; budding yeast; cell-cycle; saccharomyces-cerevisiae; complex; cdc7-dbf4; initiation; checkpoint; chromatin
AB Eukaryotic DNA replication uses kinase regulatory pathways to facilitate coordination with other processes during cell division cycles and response to environmental cues. At least two cell cycle-regulated protein kinase systems, the S-phase-specific cyclin-dependent protein kinases (S-CDKs) and the Dbf4-Cdc7 kinase (DDK, Dbf4-dependent protein kinase) are essential activators for initiation of DNA replication(1-5). Although the essential mechanism of CDK activation of DNA replication in Saccharomyces cerevisiae has been established(6,7), exactly how DDK acts has been unclear. Here we show that the amino terminal serine/threonine-rich domain (NSD) of Mcm4 has both inhibitory and facilitating roles in DNA replication control and that the sole essential function of DDK is to relieve an inhibitory activity residing within the NSD. By combining an mcm4 mutant lacking the inhibitory activity with mutations that bypass the requirement for CDKs for initiation of DNA replication, we show that DNA synthesis can occur in G1 phase when CDKs and DDK are limited. However, DDK is still required for efficient S phase progression. In the absence of DDK, CDK phosphorylation at the distal part of the Mcm4 NSD becomes crucial. Moreover, DDK-null cells fail to activate the intra-S-phase checkpoint in the presence of hydroxyurea-induced DNA damage and are unable to survive this challenge. Our studies establish that the eukaryote-specific NSD of Mcm4 has evolved to integrate several protein kinase regulatory signals for progression through S phase.
C1 [Sheu, Yi-Jun; Stillman, Bruce] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory
RP Stillman, B (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM stillman@cshl.edu
FU US National Institute of General Medical Sciences; National Institute of General Medical Sciences [R01GM045436] Funding Source: NIH RePORTER
NR 28
TC 247
Z9 317
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 7
PY 2010
VL 463
IS 7277
BP 113
EP U127
DI 10.1038/nature08647
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900041
PM 20054399
DA 2026-03-09
ER

PT J
AU Yi, CQ
   Jia, GF
   Hou, GH
   Dai, Q
   Zhang, W
   Zheng, GQ
   Jian, X
   Yang, CG
   Cui, QA
   He, CA
AF Yi, Chengqi
   Jia, Guifang
   Hou, Guanhua
   Dai, Qing
   Zhang, Wen
   Zheng, Guanqun
   Jian, Xing
   Yang, Cai-Guang
   Cui, Qiang
   He, Chuan
TI Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase
SO NATURE
LA English
DT Article
ID base-excision-repair; crystal-structures; alkb protein; fto gene; demethylation; 3-methylthymine; recognition; bacterial; lesions; damage
AB Mononuclear iron-containing oxygenases conduct a diverse variety of oxidationfunctions in biology(1,2), includingthe oxidative demethylation of methylated nucleic acids and histones(3,4). Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids(5,6), which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes(7-11). Here we present structural characterization of oxidation intermediates for these demethylases. Using a chemical cross-linking strategy(12,13), complexes of AlkB-double stranded DNA (dsDNA) containing 1,N-6-etheno adenine (epsilon A), N-3-methyl thymine (3-meT) and N-3-methyl cytosine (3-meC) are stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and alpha-ketoglutarate (alpha KG), to dioxygen initiates oxidation in crystallo. Glycol (from epsilon A) and hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the oxidative demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is oxidatively removed from different biological substrates.
C1 [Yi, Chengqi; Jia, Guifang; Zhang, Wen; Zheng, Guanqun; Jian, Xing; Yang, Cai-Guang; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Yi, Chengqi; Jia, Guifang; Zhang, Wen; Zheng, Guanqun; Jian, Xing; Yang, Cai-Guang; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
   [Hou, Guanhua; Cui, Qiang] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
   [Hou, Guanhua; Cui, Qiang] Univ Wisconsin, Inst Theoret Chem, Madison, WI 53706 USA.
   [Dai, Qing] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Yang, Cai-Guang] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China.
C3 University of Chicago; University of Chicago; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Chicago; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS
RP He, CA (corresponding author), Univ Chicago, Dept Chem, 929 E 57th St, Chicago, IL 60637 USA.
EM chuanhe@uchicago.edu
FU National Institutes of Health [GM071440, GM084028]; Advanced Photon Source at Argonne National Laboratory; United States Department of Energy; Division Of Chemistry; Direct For Mathematical & Physical Scien [0840494] Funding Source: National Science Foundation
NR 38
TC 127
Z9 156
U1 0
U2 93
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 330
EP U223
DI 10.1038/nature09497
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000056
PM 21068844
DA 2026-03-09
ER

PT J
AU Kang, K
   Pulver, SR
   Panzano, VC
   Chang, EC
   Griffith, LC
   Theobald, DL
   Garrity, PA
AF Kang, Kyeongjin
   Pulver, Stefan R.
   Panzano, Vincent C.
   Chang, Elaine C.
   Griffith, Leslie C.
   Theobald, Douglas L.
   Garrity, Paul A.
TI Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception
SO NATURE
LA English
DT Article
ID multiple sequence alignment; covalent modification; maximum-likelihood; channel trpa1; ion channels; painless; chemosensation; activation; expression; receptors
AB Chemical nociception, the detection of tissue-damaging chemicals, is important for animal survival and causes human pain and inflammation, but its evolutionary origins are largely unknown. Reactive electrophiles are a class of noxious compounds humans find pungent and irritating, such as allyl isothiocyanate (in wasabi) and acrolein ( in cigarette smoke)(1-3). Diverse animals, from insects to humans, find reactive electrophiles aversive(1-3), but whether this reflects conservation of an ancient sensory modality has been unclear. Here we identify the molecular basis of reactive electrophile detection in flies. We demonstrate that Drosophila TRPA1 (Transient receptor potential A1), the Drosophila melanogaster orthologue of the human irritant sensor, acts in gustatory chemosensors to inhibit reactive electrophile ingestion. We show that fly and mosquito TRPA1 orthologues are molecular sensors of electrophiles, using a mechanism conserved with vertebrate TRPA1s. Phylogenetic analyses indicate that invertebrate and vertebrate TRPA1s share a common ancestor that possessed critical characteristics required for electrophile detection. These findings support emergence of TRPA1-based electrophile detection in a common bilaterian ancestor, with widespread conservation throughout vertebrate and invertebrate evolution. Such conservation contrasts with the evolutionary divergence of canonical olfactory and gustatory receptors and may relate to electrophile toxicity. We propose that human pain perception relies on an ancient chemical sensor conserved across similar to 500 million years of animal evolution.
C1 [Kang, Kyeongjin; Pulver, Stefan R.; Panzano, Vincent C.; Chang, Elaine C.; Griffith, Leslie C.; Garrity, Paul A.] Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
   [Kang, Kyeongjin; Pulver, Stefan R.; Panzano, Vincent C.; Chang, Elaine C.; Griffith, Leslie C.; Garrity, Paul A.] Brandeis Univ, Volen Ctr Complex Syst, Dept Biol, Waltham, MA 02454 USA.
   [Theobald, Douglas L.] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA.
C3 Brandeis University; Brandeis University; Brandeis University
RP Garrity, PA (corresponding author), Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
EM pgarrity@brandeis.edu
FU NIMH [R21 MH080206, RO1 MH067284]; NINDS [PO1 NS044232]; Royal Society; National Institute of Mental Health [R01MH067284] Funding Source: NIH RePORTER
NR 38
TC 275
Z9 328
U1 2
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 597
EP U155
DI 10.1038/nature08848
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200049
PM 20237474
DA 2026-03-09
ER

PT J
AU Chapman, JA
   Kirkness, EF
   Simakov, O
   Hampson, SE
   Mitros, T
   Weinmaier, T
   Rattei, T
   Balasubramanian, PG
   Borman, J
   Busam, D
   Disbennett, K
   Pfannkoch, C
   Sumin, N
   Sutton, GG
   Viswanathan, LD
   Walenz, B
   Goodstein, DM
   Hellsten, U
   Kawashima, T
   Prochnik, SE
   Putnam, NH
   Shu, SQ
   Blumberg, B
   Dana, CE
   Gee, L
   Kibler, DF
   Law, L
   Lindgens, D
   Martinez, DE
   Peng, JS
   Wigge, PA
   Bertulat, B
   Guder, C
   Nakamura, Y
   Ozbek, S
   Watanabe, H
   Khalturin, K
   Hemmrich, G
   Franke, A
   Augustin, R
   Fraune, S
   Hayakawa, E
   Hayakawa, S
   Hirose, M
   Hwang, JS
   Ikeo, K
   Nishimiya-Fujisawa, C
   Ogura, A
   Takahashi, T
   Steinmetz, PRH
   Zhang, XM
   Aufschnaiter, R
   Eder, MK
   Gorny, AK
   Salvenmoser, W
   Heimberg, AM
   Wheeler, BM
   Peterson, KJ
   Boettger, A
   Tischler, P
   Wolf, A
   Gojobori, T
   Remington, KA
   Strausberg, RL
   Venter, JC
   Technau, U
   Hobmayer, B
   Bosch, TCG
   Holstein, TW
   Fujisawa, T
   Bode, HR
   David, CN
   Rokhsar, DS
   Steele, RE
AF Chapman, Jarrod A.
   Kirkness, Ewen F.
   Simakov, Oleg
   Hampson, Steven E.
   Mitros, Therese
   Weinmaier, Thomas
   Rattei, Thomas
   Balasubramanian, Prakash G.
   Borman, Jon
   Busam, Dana
   Disbennett, Kathryn
   Pfannkoch, Cynthia
   Sumin, Nadezhda
   Sutton, Granger G.
   Viswanathan, Lakshmi Devi
   Walenz, Brian
   Goodstein, David M.
   Hellsten, Uffe
   Kawashima, Takeshi
   Prochnik, Simon E.
   Putnam, Nicholas H.
   Shu, Shengquiang
   Blumberg, Bruce
   Dana, Catherine E.
   Gee, Lydia
   Kibler, Dennis F.
   Law, Lee
   Lindgens, Dirk
   Martinez, Daniel E.
   Peng, Jisong
   Wigge, Philip A.
   Bertulat, Bianca
   Guder, Corina
   Nakamura, Yukio
   Ozbek, Suat
   Watanabe, Hiroshi
   Khalturin, Konstantin
   Hemmrich, Georg
   Franke, Andre
   Augustin, Rene
   Fraune, Sebastian
   Hayakawa, Eisuke
   Hayakawa, Shiho
   Hirose, Mamiko
   Hwang, Jung Shan
   Ikeo, Kazuho
   Nishimiya-Fujisawa, Chiemi
   Ogura, Atshushi
   Takahashi, Toshio
   Steinmetz, Patrick R. H.
   Zhang, Xiaoming
   Aufschnaiter, Roland
   Eder, Marie-Kristin
   Gorny, Anne-Kathrin
   Salvenmoser, Willi
   Heimberg, Alysha M.
   Wheeler, Benjamin M.
   Peterson, Kevin J.
   Boettger, Angelika
   Tischler, Patrick
   Wolf, Alexander
   Gojobori, Takashi
   Remington, Karin A.
   Strausberg, Robert L.
   Venter, J. Craig
   Technau, Ulrich
   Hobmayer, Bert
   Bosch, Thomas C. G.
   Holstein, Thomas W.
   Fujisawa, Toshitaka
   Bode, Hans R.
   David, Charles N.
   Rokhsar, Daniel S.
   Steele, Robert E.
TI The dynamic genome of Hydra
SO NATURE
LA English
DT Article
ID tyrosine kinase; sea-anemone; stem-cells; gene; molecules; maintenance; expression; evolution; origins; cluster
AB The freshwater cnidarian Hydra was first described in 1702(1) and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals(2). Today, Hydra is an important model for studies of axial patterning(3), stem cell biology(4) and regeneration(5). Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis(6) and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.
C1 [Blumberg, Bruce; Dana, Catherine E.; Gee, Lydia; Law, Lee; Lindgens, Dirk; Peng, Jisong; Bode, Hans R.; Steele, Robert E.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA.
   [Chapman, Jarrod A.; Goodstein, David M.; Hellsten, Uffe; Prochnik, Simon E.; Putnam, Nicholas H.; Shu, Shengquiang] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Kirkness, Ewen F.; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G.; Viswanathan, Lakshmi Devi; Walenz, Brian; Remington, Karin A.; Strausberg, Robert L.; Venter, J. Craig] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Simakov, Oleg; Balasubramanian, Prakash G.; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Holstein, Thomas W.] Heidelberg Univ, Dept Mol Evolut & Genom, Inst Zool, D-69120 Heidelberg, Germany.
   [Simakov, Oleg; Mitros, Therese; Kawashima, Takeshi; Putnam, Nicholas H.; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Hampson, Steven E.; Kibler, Dennis F.] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA.
   [Weinmaier, Thomas; Rattei, Thomas; Tischler, Patrick] Tech Univ Munich, Dept Genome Oriented Bioinformat, D-85354 Freising Weihenstephan, Germany.
   [Blumberg, Bruce; Gee, Lydia; Law, Lee; Lindgens, Dirk; Peng, Jisong; Bode, Hans R.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
   [Dana, Catherine E.; Steele, Robert E.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA.
   [Martinez, Daniel E.] Pomona Coll, Dept Biol, Claremont, CA 91711 USA.
   [Wigge, Philip A.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Khalturin, Konstantin; Hemmrich, Georg; Franke, Andre; Augustin, Rene; Fraune, Sebastian; Bosch, Thomas C. G.] Univ Kiel, Inst Zool, D-24098 Kiel, Germany.
   [Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Gojobori, Takashi; Fujisawa, Toshitaka] Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
   [Takahashi, Toshio] Suntory Inst Bioorgan Res, Osaka 6188503, Japan.
   [Steinmetz, Patrick R. H.; Technau, Ulrich] Univ Vienna, Dept Mol Evolut & Dev, A-1090 Vienna, Austria.
   [Zhang, Xiaoming] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
   [Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Hobmayer, Bert] Univ Innsbruck, Inst Zool, A-6020 Innsbruck, Austria.
   [Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Hobmayer, Bert] Univ Innsbruck, Ctr Mol Biosci, A-6020 Innsbruck, Austria.
   [Heimberg, Alysha M.; Peterson, Kevin J.] Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA.
   [Wheeler, Benjamin M.] N Carolina State Univ, Dept Comp Sci, Raleigh, NC 27695 USA.
   [Boettger, Angelika; Wolf, Alexander; David, Charles N.] Univ Munich, Dept Biol 2, D-82152 Planegg Martinsried, Germany.
C3 University of California System; University of California Irvine; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; J. Craig Venter Institute; Ruprecht Karls University Heidelberg; University of California System; University of California Berkeley; University of California System; University of California Irvine; Technical University of Munich; University of California System; University of California Irvine; University of California System; University of California Irvine; Claremont Colleges; Pomona College; Salk Institute; University of Kiel; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Suntory Holdings Ltd; University of Vienna; University of Kansas; University of Kansas Medical Center; University of Innsbruck; University of Innsbruck; Dartmouth College; North Carolina State University; University of Munich
RP Steele, RE (corresponding author), Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA.
EM dsrokhsar@gmail.com; resteele@uci.edu
FU National Science Foundation [IBN-0120591]; NSF [DEB-0716960]; Austrian Science Fund; Norwegian Research Council; Austrian Science Fund [FWF P16685, FWF P20734]; R. Melmon and the Gordon and Betty Moore Foundation; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Deutsche Forschungsgemeinschaft [SFB617-A1, SFB488-A12]; TOYOBO Biotechnology Foundation; Alexander von Humboldt Foundation; Austrian Science Fund (FWF) [P 21108, P 20734] Funding Source: researchfish; Austrian Science Fund (FWF) [P20734] Funding Source: Austrian Science Fund (FWF)
NR 30
TC 629
Z9 736
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 592
EP 596
DI 10.1038/nature08830
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200048
PM 20228792
DA 2026-03-09
ER

PT J
AU Perets, HB
   Gal-Yam, A
   Mazzali, PA
   Arnett, D
   Kagan, D
   Filippenko, AV
   Li, W
   Arcavi, I
   Cenko, SB
   Fox, DB
   Leonard, DC
   Moon, DS
   Sand, DJ
   Soderberg, AM
   Anderson, JP
   James, PA
   Foley, RJ
   Ganeshalingam, M
   Ofek, EO
   Bildsten, L
   Nelemans, G
   Shen, KJ
   Weinberg, NN
   Metzger, BD
   Piro, AL
   Quataert, E
   Kiewe, M
   Poznanski, D
AF Perets, H. B.
   Gal-Yam, A.
   Mazzali, P. A.
   Arnett, D.
   Kagan, D.
   Filippenko, A. V.
   Li, W.
   Arcavi, I.
   Cenko, S. B.
   Fox, D. B.
   Leonard, D. C.
   Moon, D. -S.
   Sand, D. J.
   Soderberg, A. M.
   Anderson, J. P.
   James, P. A.
   Foley, R. J.
   Ganeshalingam, M.
   Ofek, E. O.
   Bildsten, L.
   Nelemans, G.
   Shen, K. J.
   Weinberg, N. N.
   Metzger, B. D.
   Piro, A. L.
   Quataert, E.
   Kiewe, M.
   Poznanski, D.
TI A faint type of supernova from a white dwarf with a helium-rich companion
SO NATURE
LA English
DT Article
ID core-collapse supernovae; ia supernova; galaxy; models; star; telescope
AB Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae(1,2). Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The 'old' environment near the supernova location, and the very low derived ejected mass (similar to 0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous(3,4) or a regular(1) type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive (44)Ti.
C1 [Perets, H. B.; Gal-Yam, A.; Arcavi, I.; Kiewe, M.] Weizmann Inst Sci, Dept Particle Phys & Astrophys, Fac Phys, IL-76100 Rehovot, Israel.
   [Perets, H. B.; Sand, D. J.; Soderberg, A. M.; Foley, R. J.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Mazzali, P. A.] Scuola Normale Super Pisa, I-56127 Pisa, Italy.
   [Mazzali, P. A.] Max Planck Inst Astrophys, D-85748 Garching, Germany.
   [Mazzali, P. A.] INAF Oss Astron Padova, I-35122 Padua, Italy.
   [Arnett, D.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Kagan, D.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Filippenko, A. V.; Li, W.; Cenko, S. B.; Ganeshalingam, M.; Weinberg, N. N.; Metzger, B. D.; Piro, A. L.; Quataert, E.; Poznanski, D.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Fox, D. B.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Leonard, D. C.] San Diego State Univ, Dept Astron, San Diego, CA 92182 USA.
   [Moon, D. -S.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Sand, D. J.] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Anderson, J. P.] Univ Chile, Dept Astron, Camino El Observ, Santiago, Chile.
   [Anderson, J. P.; James, P. A.] Liverpool John Moores Univ, Astrophys Res Inst, Birkenhead CH41 1LD, Merseyside, England.
   [Ofek, E. O.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Bildsten, L.; Shen, K. J.] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Bildsten, L.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Nelemans, G.] Radboud Univ Nijmegen, Dept Astrophys, NL-6500 GL Nijmegen, Netherlands.
   [Poznanski, D.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
C3 Weizmann Institute of Science; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Scuola Normale Superiore di Pisa; Max Planck Society; University of Padua; University of Arizona; University of Texas System; University of Texas Austin; University of California System; University of California Berkeley; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; California State University System; San Diego State University; University of Toronto; Universidad de Chile; Liverpool John Moores University; California Institute of Technology; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Radboud University Nijmegen; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Gal-Yam, A (corresponding author), Weizmann Inst Sci, Dept Particle Phys & Astrophys, Fac Phys, IL-76100 Rehovot, Israel.
EM hperets@cfa.harvard.edu; avishay.gal-yam@weizmann.ac.il
FU ISF/FIRST Fellowship; Ilan Ramon-Fulbright Fellowship; Weizmann-Minerva grant; Israeli Science Foundation; EU; Benoziyo Center for Astrophysics; Peter and Patricia Gruber Awards; US National Science Foundation; US Department of Energy; Richard and Rhoda Goldman Fund; Sylvia & Jim Katzman Foundation; TABASGO Foundation; STFC [PP/E001149/1, ST/H002391/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E001149/1, ST/H002391/1] Funding Source: researchfish
NR 28
TC 283
Z9 322
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 MAY 20
PY 2010
VL 465
IS 7296
BP 322
EP 325
DI 10.1038/nature09056
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200034
PM 20485429
DA 2026-03-09
ER

PT J
AU Mitsuhashi, R
   Suzuki, Y
   Yamanari, Y
   Mitamura, H
   Kambe, T
   Ikeda, N
   Okamoto, H
   Fujiwara, A
   Yamaji, M
   Kawasaki, N
   Maniwa, Y
   Kubozono, Y
AF Mitsuhashi, Ryoji
   Suzuki, Yuta
   Yamanari, Yusuke
   Mitamura, Hiroki
   Kambe, Takashi
   Ikeda, Naoshi
   Okamoto, Hideki
   Fujiwara, Akihiko
   Yamaji, Minoru
   Kawasaki, Naoko
   Maniwa, Yutaka
   Kubozono, Yoshihiro
TI Superconductivity in alkali-metal-doped picene
SO NATURE
LA English
DT Article
ID thin-films
AB Efforts to identify and develop new superconducting materials continue apace, motivated by both fundamental science and the prospects for application. For example, several new superconducting material systems have been developed in the recent past, including calcium-intercalated graphite compounds(1), boron-doped diamond(2) and-most prominently-iron arsenides such as LaO1-xFxFeAs (ref. 3). In the case of organic superconductors, however, no new material system with a high superconducting transition temperature (T-c) has been discovered in the past decade. Here we report that intercalating an alkali metal into picene, a wide-bandgap semiconducting solid hydrocarbon, produces metallic behaviour and superconductivity. Solid potassium-intercalated picene (K(x)picene) shows T-c values of 7K and 18 K, depending on the metal content. The drop of magnetization in Kxpicene solids at the transition temperature is sharp (<2 K), similar to the behaviour of Ca-intercalated graphite(1). The Tc of 18K is comparable to that of K-intercalated C-60 (ref. 4). This discovery of superconductivity in K(x)picene shows that organic hydrocarbons are promising candidates for improved T-c values.
C1 [Mitsuhashi, Ryoji; Mitamura, Hiroki; Kawasaki, Naoko; Kubozono, Yoshihiro] Okayama Univ, Surface Sci Res Lab, Okayama 7008530, Japan.
   [Suzuki, Yuta; Yamanari, Yusuke; Kambe, Takashi; Ikeda, Naoshi] Okayama Univ, Dept Phys, Okayama 7008530, Japan.
   [Okamoto, Hideki] Okayama Univ, Dept Chem, Okayama 7008530, Japan.
   [Okamoto, Hideki] Kyushu Univ, Inst Mat Chem & Engn, Fukuoka 8128581, Japan.
   [Fujiwara, Akihiko] Japan Adv Inst Sci & Technol, Kanazawa, Ishikawa 9231292, Japan.
   [Yamaji, Minoru] Gunma Univ, Dept Chem & Chem Biol, Kiryu, Gunma 3768515, Japan.
   [Maniwa, Yutaka] Tokyo Metropolitan Univ, Dept Phys, Hachioji, Tokyo 1920397, Japan.
C3 Okayama University; Okayama University; Okayama University; Kyushu University; Japan Advanced Institute of Science & Technology (JAIST); Gunma University; Tokyo Metropolitan University
RP Kubozono, Y (corresponding author), Okayama Univ, Surface Sci Res Lab, Okayama 7008530, Japan.
EM kubozono@cc.okayama-u.ac.jp
FU MEXT, Japan [20045012, 18340104]; Grants-in-Aid for Scientific Research [20045012, 18340104] Funding Source: KAKEN
NR 20
TC 444
Z9 475
U1 3
U2 342
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 76
EP 79
DI 10.1038/nature08859
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500036
PM 20203605
DA 2026-03-09
ER

PT J
AU Jung, M
   Reichstein, M
   Ciais, P
   Seneviratne, SI
   Sheffield, J
   Goulden, ML
   Bonan, G
   Cescatti, A
   Chen, JQ
   de Jeu, R
   Dolman, AJ
   Eugster, W
   Gerten, D
   Gianelle, D
   Gobron, N
   Heinke, J
   Kimball, J
   Law, BE
   Montagnani, L
   Mu, QZ
   Mueller, B
   Oleson, K
   Papale, D
   Richardson, AD
   Roupsard, O
   Running, S
   Tomelleri, E
   Viovy, N
   Weber, U
   Williams, C
   Wood, E
   Zaehle, S
   Zhang, K
AF Jung, Martin
   Reichstein, Markus
   Ciais, Philippe
   Seneviratne, Sonia I.
   Sheffield, Justin
   Goulden, Michael L.
   Bonan, Gordon
   Cescatti, Alessandro
   Chen, Jiquan
   de Jeu, Richard
   Dolman, A. Johannes
   Eugster, Werner
   Gerten, Dieter
   Gianelle, Damiano
   Gobron, Nadine
   Heinke, Jens
   Kimball, John
   Law, Beverly E.
   Montagnani, Leonardo
   Mu, Qiaozhen
   Mueller, Brigitte
   Oleson, Keith
   Papale, Dario
   Richardson, Andrew D.
   Roupsard, Olivier
   Running, Steve
   Tomelleri, Enrico
   Viovy, Nicolas
   Weber, Ulrich
   Williams, Christopher
   Wood, Eric
   Zaehle, Soenke
   Zhang, Ke
TI Recent decline in the global land evapotranspiration trend due to limited moisture supply
SO NATURE
LA English
DT Article
ID validation; biosphere; products; climate; impact; cycle
AB More than half of the solar energy absorbed by land surfaces is currently used to evaporate water(1). Climate change is expected to intensify the hydrological cycle(2) and to alter evapotranspiration, with implications for ecosystem services and feedback to regional and global climate. Evapotranspiration changes may already be under way, but direct observational constraints are lacking at the global scale. Until such evidence is available, changes in the water cycle on land-a key diagnostic criterion of the effects of climate change and variability-remain uncertain. Here we provide a data-driven estimate of global land evapotranspiration from 1982 to 2008, compiled using a global monitoring network(3), meteorological and remote-sensing observations, and a machine-learning algorithm(4). In addition, we have assessed evapotranspiration variations over the same time period using an ensemble of process-based land-surface-models. Our results suggest that global annual evapotranspiration increased on average by 7.1 +/- 1.0 millimetres per year per decade from 1982 to 1997. After that, coincident with the last major El Nino event in 1998, the global evapotranspiration increase seems to have ceased until 2008. This change was driven primarily by moisture limitation in the Southern Hemisphere, particularly Africa and Australia. In these regions, microwave satellite observations indicate that soil moisture decreased from 1998 to 2008. Hence, increasing soil-moisture limitations on evapotranspiration largely explain the recent decline of the global land-evapotranspiration trend. Whether the changing behaviour of evapotranspiration is representative of natural climate variability or reflects a more permanent reorganization of the land water cycle is a key question for earth system science.
C1 [Jung, Martin; Reichstein, Markus; Tomelleri, Enrico; Weber, Ulrich; Zaehle, Soenke] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Ciais, Philippe; Viovy, Nicolas] CNRS, CEA, LSCE, F-91191 Gif Sur Yvette, France.
   [Ciais, Philippe; Viovy, Nicolas] UVSQ, F-91191 Gif Sur Yvette, France.
   [Seneviratne, Sonia I.; Mueller, Brigitte] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Sheffield, Justin; Wood, Eric] Princeton Univ, Dept Civil & Environm Engn, Princeton, NJ 08544 USA.
   [Goulden, Michael L.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA 92697 USA.
   [Bonan, Gordon; Oleson, Keith] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Cescatti, Alessandro] Commiss European Communities, Directorate Gen Joint Res Ctr, Inst Environm & Sustainabil, Climate Change Unit, I-21027 Ispra, VA, Italy.
   [Chen, Jiquan] Univ Toledo, Dept Environm Sci, Toledo, OH 43606 USA.
   [de Jeu, Richard; Dolman, A. Johannes] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Hydrol & Geoenvironm Sci, NL-1081 HV Amsterdam, Netherlands.
   [Eugster, Werner] ETH, Inst Plant Sci, CH-8092 Zurich, Switzerland.
   [Gerten, Dieter; Heinke, Jens] Potsdam Inst Climate Impact Res, D-14473 Potsdam, Germany.
   [Gianelle, Damiano] Fdn Edmund Mach, Environm & Nat Resources Area, Ist Agr San Michele Adige, Res & Innovat Ctr, Trento, Italy.
   [Gobron, Nadine] Commiss European Communities, DG Joint Res Ctr, Inst Environm & Sustainabil, Global Environm Monitoring Unit, I-21027 Ispra, VA, Italy.
   [Kimball, John; Zhang, Ke] Univ Montana, Flathead Lake Biol Stn, Div Biol Sci, Polson, MT 59860 USA.
   [Law, Beverly E.] Oregon State Univ, Dept Forest Ecosyst & Soc, Corvallis, OR 97331 USA.
   [Montagnani, Leonardo] Forest Serv & Agcy Environm, I-39100 Bolzano, Italy.
   [Mu, Qiaozhen; Running, Steve] Univ Montana, Numer Terradynam Simulat Grp, Coll Forestry & Conservat, Missoula, MT 59812 USA.
   [Papale, Dario] Univ Tuscia, Dept Forest Environm & Resources, I-01100 Viterbo, Italy.
   [Richardson, Andrew D.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Roupsard, Olivier] Cirad Persyst, UPR Fonctionnement & Pilotage Ecosyst Plantat 80, F-34060 Montpellier, France.
   [Williams, Christopher] Clark Univ, Grad Sch Geog, Worcester, MA 01610 USA.
C3 Max Planck Society; CEA; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Swiss Federal Institutes of Technology Domain; ETH Zurich; Princeton University; University of California System; University of California Irvine; National Center Atmospheric Research (NCAR) - USA; European Commission Joint Research Centre; EC JRC ISPRA Site; University System of Ohio; University of Toledo; Vrije Universiteit Amsterdam; Swiss Federal Institutes of Technology Domain; ETH Zurich; Potsdam Institut fur Klimafolgenforschung; Fondazione Edmund Mach; European Commission Joint Research Centre; EC JRC ISPRA Site; University of Montana System; University of Montana; Oregon State University; University of Montana System; University of Montana; Tuscia University; Harvard University; CIRAD; Clark University
RP Jung, M (corresponding author), Max Planck Inst Biogeochem, D-07745 Jena, Germany.
EM mjung@bgc-jena.mpg.de; mreichstein@bgc-jena.mpg.de
FU Canadian Foundation for Climate and Atmospheric Sciences; Natural Sciences and Engineering Research Council of Canada; BIOCAP; Environment Canada and Natural Resources Canada; European Union [036946, 226520]; Max-Planck Society; US National Science Foundation [ATM-0910766]; Euro-Mediterranean Centre for Climate Change; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0910766] Funding Source: National Science Foundation
NR 30
TC 1842
Z9 2118
U1 28
U2 1534
PU NATURE PUBLISHING 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 21
PY 2010
VL 467
IS 7318
BP 951
EP 954
DI 10.1038/nature09396
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700035
PM 20935626
DA 2026-03-09
ER

PT J
AU Elliot, JL
   Person, MJ
   Zuluaga, CA
   Bosh, AS
   Adams, ER
   Brothers, TC
   Gulbis, AAS
   Levine, SE
   Lockhart, M
   Zangari, AM
   Babcock, BA
   DuPré, K
   Pasachoff, JM
   Souza, SP
   Rosing, W
   Secrest, N
   Bright, L
   Dunham, EW
   Sheppard, SS
   Kakkala, M
   Tilleman, T
   Berger, B
   Briggs, JW
   Jacobson, G
   Valleli, P
   Volz, B
   Rapoport, S
   Hart, R
   Brucker, M
   Michel, R
   Mattingly, A
   Zambrano-Marin, L
   Meyer, AW
   Wolf, J
   Ryan, EV
   Ryan, WH
   Morzinski, K
   Grigsby, B
   Brimacombe, J
   Ragozzine, D
   Montano, HG
   Gilmore, A
AF Elliot, J. L.
   Person, M. J.
   Zuluaga, C. A.
   Bosh, A. S.
   Adams, E. R.
   Brothers, T. C.
   Gulbis, A. A. S.
   Levine, S. E.
   Lockhart, M.
   Zangari, A. M.
   Babcock, B. A.
   DuPre, K.
   Pasachoff, J. M.
   Souza, S. P.
   Rosing, W.
   Secrest, N.
   Bright, L.
   Dunham, E. W.
   Sheppard, S. S.
   Kakkala, M.
   Tilleman, T.
   Berger, B.
   Briggs, J. W.
   Jacobson, G.
   Valleli, P.
   Volz, B.
   Rapoport, S.
   Hart, R.
   Brucker, M.
   Michel, R.
   Mattingly, A.
   Zambrano-Marin, L.
   Meyer, A. W.
   Wolf, J.
   Ryan, E. V.
   Ryan, W. H.
   Morzinski, K.
   Grigsby, B.
   Brimacombe, J.
   Ragozzine, D.
   Montano, H. G.
   Gilmore, A.
TI Size and albedo of Kuiper belt object 55636 from a stellar occultation
SO NATURE
LA English
DT Article
ID dwarf planet haumea; 2003 el61; collisional family; color diversity; satellites; members
AB The Kuiper belt is a collection of small bodies (Kuiper belt objects, KBOs) that lie beyond the orbit of Neptune and which are believed to have formed contemporaneously with the planets. Their small size and great distance make them difficult to study. KBO 55636 (2002 TX300) is a member of the water-ice-rich Haumea KBO collisional family(1). The Haumea family are among the most highly reflective objects in the Solar System. Dynamical calculations indicate that the collision that created KBO 55636 occurred at least 1 Gyr ago(2,3). Here we report observations of a multi-chord stellar occultation by KBO 55636, which occurred on 9 October 2009 UT. We find that it has a mean radius of 143 +/- 65 km (assuming a circular solution). Allowing for possible elliptical shapes, we find a geometric albedo of 0.88(0.06)(+0.15) in the V photometric band, which establishes that KBO 55636 is smaller than previously thought and that, like its parent body, it is highly reflective. The dynamical age implies either that KBO 55636 has an active resurfacing mechanism, or that fresh water-ice in the outer Solar System can persist for gigayear timescales.
C1 [Elliot, J. L.; Person, M. J.; Zuluaga, C. A.; Bosh, A. S.; Adams, E. R.; Brothers, T. C.; Gulbis, A. A. S.; Levine, S. E.; Lockhart, M.; Zangari, A. M.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Elliot, J. L.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Elliot, J. L.; Bright, L.; Dunham, E. W.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [Gulbis, A. A. S.] So Africa Large Telescope & S African Astron Obse, ZA-8935 Cape Town, South Africa.
   [Levine, S. E.; Tilleman, T.] USNO, Flagstaff, AZ 86001 USA.
   [Levine, S. E.] Amer Assoc Variable Star Observers, Cambridge, MA 02138 USA.
   [Babcock, B. A.] Williams Coll, Dept Phys, Williamstown, MA 01267 USA.
   [DuPre, K.; Pasachoff, J. M.; Souza, S. P.] Williams Coll, Dept Astron, Williamstown, MA 01267 USA.
   [Rosing, W.] Las Cumbres Observ Global Telescope Network, Santa Barbara, CA 93117 USA.
   [Secrest, N.] Univ Hawaii, Hilo, HI 96720 USA.
   [Sheppard, S. S.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
   [Kakkala, M.] Univ Hawaii, Dept Geol, Leeward Community Coll, Pearl City, HI 96782 USA.
   [Berger, B.; Briggs, J. W.; Jacobson, G.; Valleli, P.; Volz, B.] Amateur Telescope Makers Boston, Westford, MA 01886 USA.
   [Briggs, J. W.] Dexter Southfield Sch, Brookline, MA 02145 USA.
   [Rapoport, S.] Mt Stromlo & Siding Spring Observ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Hart, R.] Univ So Queensland, Mt Kent Observ, Toowoomba, Qld 4350, Australia.
   [Brucker, M.] Univ Nebraska, Dept Phys & Astron, Lincoln, NE 68588 USA.
   [Michel, R.] Univ Nacl Autonoma Mexico, Inst Astron, Ensenada 22800, Baja California, Mexico.
   [Mattingly, A.] IBM Corp, St Leonards, NSW 2065, Australia.
   [Zambrano-Marin, L.] Univ Texas Brownsville, Texas Southmost Coll, Nompuewenu Observ, Brownsville, TX 78520 USA.
   [Meyer, A. W.] NASA, Univ Space Res Assoc, SOFIA, Moffett Field, CA 94035 USA.
   [Wolf, J.] NASA, Deutsch SOFIA Inst, SOFIA, Moffett Field, CA 94035 USA.
   [Ryan, E. V.; Ryan, W. H.] Magdalena Ridge Observ, Socorro, NM 87801 USA.
   [Morzinski, K.; Grigsby, B.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Brimacombe, J.] James Cook Univ, Cairns, Qld 4870, Australia.
   [Ragozzine, D.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Montano, H. G.] Univ Nacl Autonoma Mexico, Astron Observ, Managua, Nicaragua.
   [Gilmore, A.] Mt John Univ Observ, Lake Tekapo 7945, New Zealand.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Williams College; Williams College; University of Hawaii System; University Hawaii Hilo; Carnegie Institution for Science; University of Hawaii System; Leeward Community College; Australian National University; University of Southern Queensland; University of Nebraska System; University of Nebraska Lincoln; Universidad Nacional Autonoma de Mexico; International Business Machines (IBM); IBM Australia; University of Texas System; University of Texas Rio Grande Valley; National Aeronautics & Space Administration (NASA); Universities Space Research Association (USRA); National Aeronautics & Space Administration (NASA); University of California System; University of California Santa Cruz; James Cook University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University; Universidad Nacional Autonoma de Mexico
RP Elliot, JL (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM jle@mit.edu
FU NASA; NSF
NR 30
TC 81
Z9 90
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 897
EP 900
DI 10.1038/nature09109
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500031
PM 20559381
DA 2026-03-09
ER

PT J
AU Morello, A
   Pla, JJ
   Zwanenburg, FA
   Chan, KW
   Tan, KY
   Huebl, H
   Mottonen, M
   Nugroho, CD
   Yang, CY
   van Donkelaar, JA
   Alves, ADC
   Jamieson, DN
   Escott, CC
   Hollenberg, LCL
   Clark, RG
   Dzurak, AS
AF Morello, Andrea
   Pla, Jarryd J.
   Zwanenburg, Floris A.
   Chan, Kok W.
   Tan, Kuan Y.
   Huebl, Hans
   Mottonen, Mikko
   Nugroho, Christopher D.
   Yang, Changyi
   van Donkelaar, Jessica A.
   Alves, Andrew D. C.
   Jamieson, David N.
   Escott, Christopher C.
   Hollenberg, Lloyd C. L.
   Clark, Robert G.
   Dzurak, Andrew S.
TI Single-shot readout of an electron spin in silicon
SO NATURE
LA English
DT Article
ID quantum dots; nuclear-spin; transistor; computation; relaxation; resonance; donors
AB The size of silicon transistors used in microelectronic devices is shrinking to the level at which quantum effects become important(1). Although this presents a significant challenge for the further scaling of microprocessors, it provides the potential for radical innovations in the form of spin-based quantum computers(2-4) and spintronic devices(5). An electron spin in silicon can represent a well-isolated quantum bit with long coherence times(6) because of the weak spin-orbit coupling(7) and the possibility of eliminating nuclear spins from the bulk crystal(8). However, the control of single electrons in silicon has proved challenging, and so far the observation and manipulation of a single spin has been impossible. Here we report the demonstration of single-shot, time-resolved readout of an electron spin in silicon. This has been performed in a device consisting of implanted phosphorus donors(9) coupled to a metaloxide-semiconductor single-electron transistor(10,11)-compatible with current microelectronic technology. We observed a spin lifetime of similar to 6 seconds at a magnetic field of 1.5 tesla, and achieved a spin readout fidelity better than 90 per cent. High-fidelity single-shot spin readout in silicon opens the way to the development of a new generation of quantum computing and spintronic devices, built using the most important material in the semiconductor industry.
C1 [Morello, Andrea; Pla, Jarryd J.; Zwanenburg, Floris A.; Chan, Kok W.; Tan, Kuan Y.; Huebl, Hans; Mottonen, Mikko; Nugroho, Christopher D.; Escott, Christopher C.; Clark, Robert G.; Dzurak, Andrew S.] Univ New S Wales, Sch Elect Engn & Telecommun, Australian Res Council Ctr Excellence Quantum Com, Sydney, NSW 2052, Australia.
   [Yang, Changyi; van Donkelaar, Jessica A.; Alves, Andrew D. C.; Jamieson, David N.; Hollenberg, Lloyd C. L.] Univ Melbourne, Sch Phys, Australian Res Council Ctr Excellence Quantum Com, Melbourne, Vic 3010, Australia.
   [Mottonen, Mikko] Aalto Univ, Dept Appl Phys COMP, Aalto 00076, Finland.
   [Mottonen, Mikko] Aalto Univ, Low Temp Lab, Aalto 00076, Finland.
C3 University of New South Wales Sydney; University of Melbourne; Aalto University; Aalto University
RP Morello, A (corresponding author), Univ New S Wales, Sch Elect Engn & Telecommun, Australian Res Council Ctr Excellence Quantum Com, Sydney, NSW 2052, Australia.
EM a.morello@unsw.edu.au
FU Australian Research Council; Australian Government; US National Security Agency; US Army Research Office [W911NF-08-1-0527]; Academy of Finland; Emil Aaltonen foundation
NR 30
TC 630
Z9 714
U1 3
U2 246
PU 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 7
PY 2010
VL 467
IS 7316
BP 687
EP 691
DI 10.1038/nature09392
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500033
PM 20877281
DA 2026-03-09
ER

PT J
AU Ravi, M
   Chan, SWL
AF Ravi, Maruthachalam
   Chan, Simon W. L.
TI Haploid plants produced by centromere-mediated genome elimination
SO NATURE
LA English
DT Article
ID chromosome elimination; maize; mutation; wheat; gene; inheritance; anthers; culture
AB Production of haploid plants that inherit chromosomes from only one parent can greatly accelerate plant breeding(1-3). Haploids generated from a heterozygous individual and converted to diploid create instant homozygous lines, bypassing generations of inbreeding. Two methods are generally used to produce haploids. First, cultured gametophyte cells may be regenerated into haploid plants(4), but many species and genotypes are recalcitrant to this process(2,5). Second, haploids can be induced from rare interspecific crosses, in which one parental genome is eliminated after fertilization(6-11). The molecular basis for genome elimination is not understood, but one theory posits that centromeres from the two parent species interact unequally with the mitotic spindle, causing selective chromosome loss(12-14). Here we show that haploid Arabidopsis thaliana plants can be easily generated through seeds by manipulating a single centromere protein, the centromere-specific histone CENH3 (called CENP-A in human). When cenh3 null mutants expressing altered CENH3 proteins are crossed to wild type, chromosomes from the mutant are eliminated, producing haploid progeny. Haploids are spontaneously converted into fertile diploids through meiotic non-reduction, allowing their genotype to be perpetuated. Maternal and paternal haploids can be generated through reciprocal crosses. We have also exploited centromere-mediated genome elimination to convert a natural tetraploid Arabidopsis into a diploid, reducing its ploidy to simplify breeding. As CENH3 is universal in eukaryotes, our method may be extended to produce haploids in any plant species.
C1 [Ravi, Maruthachalam; Chan, Simon W. L.] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Chan, SWL (corresponding author), Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA.
EM srchan@ucdavis.edu
FU Hellman Family Foundation; University of California, Davis
NR 36
TC 468
Z9 596
U1 19
U2 293
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 615
EP U180
DI 10.1038/nature08842
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200053
PM 20336146
DA 2026-03-09
ER

PT J
AU Huang, Z
   White, PS
   Brookhart, M
AF Huang, Zheng
   White, Peter S.
   Brookhart, Maurice
TI Ligand exchanges and selective catalytic hydrogenation in molecular single crystals
SO NATURE
LA English
DT Article
ID coordination polymer; transfer dehydrogenation; pincer complexes; iridium; transformation; elimination; conversion; framework; network; bonds
AB Chemical reactions inside single crystals are likely to be highly selective, but examples of single crystal to single crystal (SC-SC) transformations are uncommon, because crystallinity is difficult to retain following the rearrangement of atoms in the solid state(1-19). The most widely studied SC-SC transformations involve solvent exchange reactions in porous coordination polymers or metal-organic frameworks, which take advantage of the robust polymeric networks of the hosts(2,8,9-11). Examples of reactions occurring within molecular organic crystals generally involve photo-induced reactions, such as the coupling of alkenes or alkynes within the crystal(1,2,12-15). For nonporous molecular inorganic or organometallic crystals, single-crystal transformations involving the formation or cleavage of metal-ligand bonds are rare(17-21); known examples usually involve ligand loss from the single crystal and reversible religation, a process sometimes accompanied by decay of the single crystal to a microcrystalline powder(20,21). Here we report a series of SC-SC transformations that involve the interchange of multiple small gaseous ligands (N(2), CO, NH(3), C(2)H(4), H(2) and O(2)) at an iridium centre in molecular single crystals of a pincer Ir(I) complex. The single crystal remains intact during these ligand-exchange reactions, which occur within the crystal and do not require prior ligand extrusion. We reveal a selective catalytic transformation within a nonporous molecular crystal: pincer iridium single crystals ligated with nitrogen, ethylene or hydrogen show selective hydrogenation of ethylene relative to propylene (25:1) when surface sites are passified by CO.
C1 [Huang, Zheng; White, Peter S.; Brookhart, Maurice] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill
RP Brookhart, M (corresponding author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA.
EM mbrookhart@unc.edu
FU National Science Foundation under the auspices of the Centre for Enabling New Technologies through Catalysis (CENTC)
NR 30
TC 153
Z9 167
U1 2
U2 228
PU 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 3
PY 2010
VL 465
IS 7298
BP 598
EP 601
DI 10.1038/nature09085
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000037
PM 20520710
DA 2026-03-09
ER

PT J
AU Cameron, P
   Hiroi, M
   Ngai, J
   Scott, K
AF Cameron, Peter
   Hiroi, Makoto
   Ngai, John
   Scott, Kristin
TI The molecular basis for water taste in Drosophila
SO NATURE
LA English
DT Article
ID gustatory receptor neurons; pox-neuro; channels; behavior; protein; system; brain
AB The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis(1). Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources(2-4), but little is known about the underlying molecular mechanism for water taste detection. Here we identify a member of the degenerin/epithelial sodium channel family(5), PPK28, as an osmosensitive ion channel that mediates the cellular and behavioural response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons, and that loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypoosmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behaviour, providing the framework for examining the molecular basis for water detection in other animals.
C1 [Scott, Kristin] Univ Calif Berkeley, Dept Mol & Cell Biol, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Ngai, John] Univ Calif Berkeley, Funct Genom Lab, Berkeley, CA 94720 USA.
   [Scott, Kristin] 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; Howard Hughes Medical Institute; University of California System; University of California Berkeley
RP Scott, K (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Helen Wills Neurosci Inst, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM kscott@berkeley.edu
FU NIH (NIDCD); Burroughs-Wellcome CAREER Award; John Merck Award; NIH
NR 27
TC 213
Z9 276
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 MAY 6
PY 2010
VL 465
IS 7294
BP 91
EP U101
DI 10.1038/nature09011
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900037
PM 20364123
DA 2026-03-09
ER

PT J
AU Iwai, M
   Takizawa, K
   Tokutsu, R
   Okamuro, A
   Takahashi, Y
   Minagawa, J
AF Iwai, Masakazu
   Takizawa, Kenji
   Tokutsu, Ryutaro
   Okamuro, Akira
   Takahashi, Yuichiro
   Minagawa, Jun
TI Isolation of the elusive supercomplex that drives cyclic electron flow in photosynthesis
SO NATURE
LA English
DT Article
ID cytochrome b(6)f complex; chlamydomonas-reinhardtii; photosystem-i; state transitions; transport; arabidopsis; plants; photophosphorylation; plastocyanin; acclimation
AB Photosynthetic light reactions establish electron flow in the chloroplast's thylakoid membranes, leading to the production of the ATP and NADPH that participate in carbon fixation. Two modes of electron flow exist-linear electron flow (LEF) from water to NADP 1 via photosystem (PS) II and PSI in series(1) and cyclic electron flow (CEF) around PSI (ref. 2). Although CEF is essential for satisfying the varying demand for ATP, the exact molecule(s) and operational site are as yet unclear. In the green alga Chlamydomonas reinhardtii, the electron flow shifts from LEF to CEF on preferential excitation of PSII (ref. 3), which is brought about by an energy balancing mechanism between PSII and PSI (state transitions(4)). Here, we isolated a protein super-complex composed of PSI with its own light-harvesting complex (LHCI), the PSII light-harvesting complex (LHCII), the cytochrome b(6)f complex (Cyt bf), ferredoxin (Fd)-NADPH oxidoreductase (FNR), and the integral membrane protein PGRL1 (ref. 5) from C. reinhardtii cells under PSII-favouring conditions. Spectroscopic analyses indicated that on illumination, reducing equivalents from downstream of PSI were transferred to Cyt bf, whereas oxidised PSI was re-reduced by reducing equivalents from Cyt bf, indicating that this supercomplex is engaged in CEF (Supplementary Fig. 1). Thus, formation and dissociation of the PSI-LHCI-LHCII-FNR-Cyt bf-PGRL1 supercomplex not only controlled the energy balance of the two photosystems, but also switched the mode of photosynthetic electron flow.
C1 [Iwai, Masakazu; Takizawa, Kenji; Tokutsu, Ryutaro; Minagawa, Jun] Hokkaido Univ, Inst Low Temp Sci, Sapporo, Hokkaido 0600819, Japan.
   [Okamuro, Akira; Takahashi, Yuichiro] Okayama Univ, Fac Sci, Dept Biol, Okayama 7008530, Japan.
C3 Hokkaido University; Okayama University
RP Minagawa, J (corresponding author), Hokkaido Univ, Inst Low Temp Sci, Sapporo, Hokkaido 0600819, Japan.
EM minagawa@lowtem.hokudai.ac.jp
FU Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology [18GS0318, 2120006309, 2157003109]; Japan Science and Technology Agency; Natural Sciences by the Mitsubishi Foundation; Grants-in-Aid for Scientific Research [18GS0318] Funding Source: KAKEN
NR 32
TC 355
Z9 398
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 APR 22
PY 2010
VL 464
IS 7292
BP 1210
EP U134
DI 10.1038/nature08885
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100041
PM 20364124
DA 2026-03-09
ER

PT J
AU Joesch, M
   Schnell, B
   Raghu, SV
   Reiff, DF
   Borst, A
AF Joesch, Maximilian
   Schnell, Bettina
   Raghu, Shamprasad Varija
   Reiff, Dierk F.
   Borst, Alexander
TI ON and OFF pathways in Drosophila motion vision
SO NATURE
LA English
DT Article
ID optic lobe; visual interneurons; response property; wild-type; melanogaster; expression; medulla; channel; neurons; system
AB Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5(1). Here we examine how these pathways contribute to visual motion detection by combining genetic block and reconstitution of neural activity in different lamina cell types with whole-cell recordings from downstream motion-sensitive neurons(2,3). We find reduced responses to moving gratings if L1 or L2 is blocked; however, reconstitution of photoreceptor input to only L1 or L2 results in wild-type responses. Thus, the first experiment indicates the necessity of both pathways, whereas the second indicates sufficiency of each single pathway. This contradiction can be explained by electrical coupling between L1 and L2, allowing for activation of both pathways even when only one of them receives photoreceptor input. A fundamental difference between the L1 pathway and the L2 pathway is uncovered when blocking L1 or L2 output while presenting moving edges of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the response to moving ON edges, whereas blocking L2 eliminates the response to moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON and OFF bipolar cell pathways in the vertebrate retina(4), photoreceptor signals segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.
C1 [Joesch, Maximilian; Schnell, Bettina; Raghu, Shamprasad Varija; Reiff, Dierk F.; Borst, Alexander] MPI Neurobiol, Dept Syst & Computat Neurobiol, D-82152 Martinsried, Germany.
RP Borst, A (corresponding author), MPI Neurobiol, Dept Syst & Computat Neurobiol, Klopferspitz 18, D-82152 Martinsried, Germany.
EM borst@neuro.mpg.de
NR 30
TC 251
Z9 305
U1 2
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 300
EP U186
DI 10.1038/nature09545
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000050
PM 21068841
DA 2026-03-09
ER

PT J
AU Karunadasa, HI
   Chang, CJ
   Long, JR
AF Karunadasa, Hemamala I.
   Chang, Christopher J.
   Long, Jeffrey R.
TI A molecular molybdenum-oxo catalyst for generating hydrogen from water
SO NATURE
LA English
DT Article
ID transition-metal-complexes; active-site; oxidative addition; low overpotentials; evolution; chemistry; enzymes; models; h-2
AB A growing awareness of issues related to anthropogenic climate change and an increase in global energy demand have made the search for viable carbon-neutral sources of renewable energy one of the most important challenges in science today(1). The chemical community is therefore seeking efficient and inexpensive catalysts that can produce large quantities of hydrogen gas from water(1-7). Here we identify a molybdenum-oxo complex that can catalytically generate gaseous hydrogen either from water at neutral pH or from sea water. This work shows that high-valency metal-oxo species can be used to create reduction catalysts that are robust and functional in water, a concept that has broad implications for the design of 'green' and sustainable chemistry cycles.
C1 [Karunadasa, Hemamala I.; Chang, Christopher J.; Long, Jeffrey R.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Karunadasa, Hemamala I.; Chang, Christopher J.; Long, Jeffrey R.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA.
   [Chang, Christopher J.] 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; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Howard Hughes Medical Institute
RP Chang, CJ (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM chrischang@berkeley.edu; jrlong@berkeley.edu
FU NSF [CHE-0617063]; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; Tyco Electronics
NR 30
TC 636
Z9 714
U1 1
U2 355
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1329
EP 1333
DI 10.1038/nature08969
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000042
PM 20428167
DA 2026-03-09
ER

PT J
AU Kolokotrones, T
   Savage, V
   Deeds, EJ
   Fontana, W
AF Kolokotrones, Tom
   Savage, Van
   Deeds, Eric J.
   Fontana, Walter
TI Curvature in metabolic scaling
SO NATURE
LA English
DT Article
ID body-size; energy-metabolism; temperature; power
AB For more than three-quarters of a century it has been assumed(1) that basal metabolic rate increases as body mass raised to some power p. However, there is no broad consensus regarding the value of p: whereas many studies have asserted that p is 3/4 (refs 1-4; 'Kleiber's law'), some have argued that it is 2/3 (refs 5-7), and others have found that it varies depending on factors like environment and taxonomy(6,8-16). Here we show that the relationship between mass and metabolic rate has convex curvature on a logarithmic scale, and is therefore not a pure power law, even after accounting for body temperature. This finding has several consequences. First, it provides an explanation for the puzzling variability in estimates of p, settling a long-standing debate. Second, it constitutes a stringent test for theories of metabolic scaling. A widely debated model(17) based on vascular system architecture fails this test, and we suggest modifications that could bring it into compliance with the observed curvature. Third, it raises the intriguing question of whether the scaling relation limits body size.
C1 [Kolokotrones, Tom; Deeds, Eric J.; Fontana, Walter] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Savage, Van] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
C3 Harvard University; Harvard Medical School; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Fontana, W (corresponding author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM walter@hms.harvard.edu
FU NIA NIH HHS [R01 AG034994] Funding Source: Medline
NR 30
TC 280
Z9 305
U1 2
U2 124
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 753
EP 756
DI 10.1038/nature08920
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000044
PM 20360740
DA 2026-03-09
ER

PT J
AU Iwabu, M
   Yamauchi, T
   Okada-Iwabu, M
   Sato, K
   Nakagawa, T
   Funata, M
   Yamaguchi, M
   Namiki, S
   Nakayama, R
   Tabata, M
   Ogata, H
   Kubota, N
   Takamoto, I
   Hayashi, YK
   Yamauchi, N
   Waki, H
   Fukayama, M
   Nishino, I
   Tokuyama, K
   Ueki, K
   Oike, Y
   Ishii, S
   Hirose, K
   Shimizu, T
   Touhara, K
   Kadowaki, T
AF Iwabu, Masato
   Yamauchi, Toshimasa
   Okada-Iwabu, Miki
   Sato, Koji
   Nakagawa, Tatsuro
   Funata, Masaaki
   Yamaguchi, Mamiko
   Namiki, Shigeyuki
   Nakayama, Ryo
   Tabata, Mitsuhisa
   Ogata, Hitomi
   Kubota, Naoto
   Takamoto, Iseki
   Hayashi, Yukiko K.
   Yamauchi, Naoko
   Waki, Hironori
   Fukayama, Masashi
   Nishino, Ichizo
   Tokuyama, Kumpei
   Ueki, Kohjiro
   Oike, Yuichi
   Ishii, Satoshi
   Hirose, Kenzo
   Shimizu, Takao
   Touhara, Kazushige
   Kadowaki, Takashi
TI Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1
SO NATURE
LA English
DT Article
ID activated protein-kinase; fatty-acid oxidation; muscle fiber-type; skeletal-muscle; insulin-resistance; receptor activation; phosphorylation; cloning; disease; obesity
AB Adiponectin is an anti-diabetic adipokine. Its receptors possess a seven-transmembrane topology with the amino terminus located intracellularly, which is the opposite of G-protein-coupled receptors. Here we provide evidence that adiponectin induces extracellular Ca2+ influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKK beta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca2+ concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1 alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.
C1 [Iwabu, Masato; Yamauchi, Toshimasa; Okada-Iwabu, Miki; Funata, Masaaki; Yamaguchi, Mamiko; Nakayama, Ryo; Kubota, Naoto; Takamoto, Iseki; Waki, Hironori; Ueki, Kohjiro; Kadowaki, Takashi] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo 1130033, Japan.
   [Iwabu, Masato; Yamauchi, Toshimasa; Okada-Iwabu, Miki] Univ Tokyo, Dept Integrated Mol Sci Metab Dis, Century Med & Res Ctr 22, Tokyo 1130033, Japan.
   [Namiki, Shigeyuki; Hirose, Kenzo] Univ Tokyo, Grad Sch Med, Dept Neurobiol, Tokyo 1130033, Japan.
   [Yamauchi, Naoko; Fukayama, Masashi] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo 1130033, Japan.
   [Ishii, Satoshi; Shimizu, Takao] Univ Tokyo, Fac Med, Dept Biochem & Mol Biol, Tokyo 1130033, Japan.
   [Sato, Koji; Touhara, Kazushige] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
   [Nakagawa, Tatsuro; Touhara, Kazushige] Univ Tokyo, Dept Integrated Biosci, Chiba 2778562, Japan.
   [Tabata, Mitsuhisa] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Genet, Kumamoto 8600811, Japan.
   [Ogata, Hitomi; Tokuyama, Kumpei] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan.
   [Hayashi, Yukiko K.; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo 1878502, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; Kumamoto University; University of Tsukuba; National Center for Neurology & Psychiatry - Japan
RP Yamauchi, T (corresponding author), Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo 1130033, Japan.
EM tyamau-tky@umin.net; kadowaki-3im@h.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [20229008, 20390254]; Grants-in-Aid for Scientific Research [20390254, 19002011, 20229008, 21390278, 22790244, 21680035] Funding Source: KAKEN
NR 45
TC 846
Z9 956
U1 1
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 APR 29
PY 2010
VL 464
IS 7293
BP 1313
EP 1319
DI 10.1038/nature08991
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000038
PM 20357764
DA 2026-03-09
ER

PT J
AU Andersen, CBF
   Madsen, M
   Storm, T
   Moestrup, SK
   Andersen, GR
AF Andersen, Christian Brix Folsted
   Madsen, Mette
   Storm, Tina
   Moestrup, Soren K.
   Andersen, Gregers R.
TI Structural basis for receptor recognition of vitamin-B12-intrinsic factor complexes
SO NATURE
LA English
DT Article
ID factor-vitamin b-12; human intrinsic-factor; electron-density maps; mannan-binding lectin; x-ray-structure; ligand recognition; crystal-structure; cubilin; protein; identification
AB Cobalamin (Cbl, vitamin B-12) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin and the 45-kDa transmembrane protein amnionless(1,2). Loss of function of any of these proteins ultimately leads to Cbl deficiency in man(3,4). Here we present the crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB5-8)(5) determined at 3.3 angstrom resolution. The structure provides insight into how several CUB (for 'complement C1r/C1s, Uegf, Bmp1') domains collectively function as modular ligand-binding regions, and how two distant CUB domains embrace the Cbl molecule by binding the two IF domains in a Ca2+-dependent manner. This dual-point model provides a probable explanation of how Cbl indirectly induces ligand-receptor coupling. Finally, the comparison of Ca2+-binding CUB domains and the low-density lipoprotein (LDL) receptor-type A modules suggests that the electrostatic pairing of a basic ligand arginine/lysine residue with Ca2+-coordinating acidic aspartates/glutamates is a common theme of Ca2+-dependent ligand-receptor interactions.
C1 [Andersen, Christian Brix Folsted; Madsen, Mette; Storm, Tina; Moestrup, Soren K.] Aarhus Univ, Dept Med Biochem, DK-8000 Aarhus C, Denmark.
   [Andersen, Christian Brix Folsted; Andersen, Gregers R.] Aarhus Univ, Dept Mol Biol, DK-8000 Aarhus C, Denmark.
C3 Aarhus University; Aarhus University
RP Moestrup, SK (corresponding author), Aarhus Univ, Dept Med Biochem, DK-8000 Aarhus C, Denmark.
EM skm@biokemi.au.dk
FU Lundbeck foundation; Danish Science Research Council; Novo Nordisk Foundation; Lundbeck Foundation [R7-2006-752] Funding Source: researchfish
NR 34
TC 98
Z9 114
U1 1
U2 31
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 445
EP U147
DI 10.1038/nature08874
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100054
PM 20237569
DA 2026-03-09
ER

PT J
AU Ruschak, AM
   Religa, TL
   Breuer, S
   Witt, S
   Kay, LE
AF Ruschak, Amy M.
   Religa, Tomasz L.
   Breuer, Sarah
   Witt, Susanne
   Kay, Lewis E.
TI The proteasome antechamber maintains substrates in an unfolded state
SO NATURE
LA English
DT Article
ID side-chain dynamics; 20s proteasome; nmr-spectroscopy; folding pathway; methyl-groups; beta-sheet; ww domain; relaxation; protein; mechanism
AB Eukaryotes and archaea use a protease called the proteasome that has an integral role in maintaining cellular function through the selective degradation of proteins(1-4). Proteolysis occurs in a barrelshaped 20S core particle, which in Thermoplasma acidophilum is built from four stacked homoheptameric rings of subunits, alpha and beta, arranged alpha(7)beta(7)beta(7)alpha(7) (ref. 5). These rings form three interconnected cavities, including a pair of antechambers (formed by alpha(7)beta(7)) through which substrates are passed before degradation and a catalytic chamber (beta(7)beta(7)) where the peptide-bond hydrolysis reaction occurs(4,5). Although it is clear that substrates must be unfolded to enter through narrow, gated passageways (13 angstrom in diameter) located on the alpha-rings(1,6,7), the structural and dynamical properties of substrates inside the proteasome antechamber remain unclear. Confinement in the antechamber might be expected to promote folding and thus impede proteolysis. Here we investigate the folding, stability and dynamics of three small protein substrates in the antechamber by methyl transverse-relaxation-optimized NMR spectroscopy(8). We show that these substrates interact actively with the antechamber walls and have drastically altered kinetic and equilibrium properties that maintain them in unstructured states so as to be accessible for hydrolysis.
C1 [Ruschak, Amy M.; Religa, Tomasz L.; Kay, Lewis E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Ruschak, Amy M.; Religa, Tomasz L.; Kay, Lewis E.] Univ Toronto, Dept Biochem & Chem, Toronto, ON M5S 1A8, Canada.
   [Breuer, Sarah; Witt, Susanne] Max Planck Inst Biochem, Dept Biol Struct, D-82152 Martinsried, Germany.
C3 University of Toronto; University of Toronto; Max Planck Society
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 [ALTF 827-2006]; Canadian Institutes of Health Research (CIHR); Canada Research Chair in Biochemistry; Natural Sciences and Engineering Research Council of Canada
NR 34
TC 98
Z9 107
U1 1
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 868
EP U142
DI 10.1038/nature09444
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700072
PM 20944750
DA 2026-03-09
ER

PT J
AU Pravec, P
   Vokrouhlicky, D
   Polishook, D
   Scheeres, DJ
   Harris, AW
   Galád, A
   Vaduvescu, O
   Pozo, F
   Barr, A
   Longa, P
   Vachier, F
   Colas, F
   Pray, DP
   Pollock, J
   Reichart, D
   Ivarsen, K
   Haislip, J
   LaCluyze, A
   Kusnirák, P
   Henych, T
   Marchis, F
   Macomber, B
   Jacobson, SA
   Krugly, YN
   Sergeev, AV
   Leroy, A
AF Pravec, P.
   Vokrouhlicky, D.
   Polishook, D.
   Scheeres, D. J.
   Harris, A. W.
   Galad, A.
   Vaduvescu, O.
   Pozo, F.
   Barr, A.
   Longa, P.
   Vachier, F.
   Colas, F.
   Pray, D. P.
   Pollock, J.
   Reichart, D.
   Ivarsen, K.
   Haislip, J.
   LaCluyze, A.
   Kusnirak, P.
   Henych, T.
   Marchis, F.
   Macomber, B.
   Jacobson, S. A.
   Krugly, Yu. N.
   Sergeev, A. V.
   Leroy, A.
TI Formation of asteroid pairs by rotational fission
SO NATURE
LA English
DT Article
ID full 2-body problem; binary asteroids; stability; origin
AB Pairs of asteroids sharing similar heliocentric orbits, but not bound together, were found recently(1-3). Backward integrations of their orbits indicated that they separated gently with low relative velocities, but did not provide additional insight into their formation mechanism. A previously hypothesized rotational fission process 4 may explain their formation-critical predictions are that the mass ratios are less than about 0.2 and, as the mass ratio approaches this upper limit, the spin period of the larger body becomes long. Here we report photometric observations of a sample of asteroid pairs, revealing that the primaries of pairs with mass ratios much less than 0.2 rotate rapidly, near their critical fission frequency. As the mass ratio approaches 0.2, the primary period grows long. This occurs as the total energy of the system approaches zero, requiring the asteroid pair to extract an increasing fraction of energy from the primary's spin in order to escape. We do not find asteroid pairs with mass ratios larger than 0.2. Rotationally fissioned systems beyond this limit have insufficient energy to disrupt. We conclude that asteroid pairs are formed by the rotational fission of a parent asteroid into a proto-binary system, which subsequently disrupts under its own internal system dynamics soon after formation.
C1 [Pravec, P.; Galad, A.; Kusnirak, P.; Henych, T.] Astron Inst AS CR, CZ-25165 Ondrejov, Czech Republic.
   [Vokrouhlicky, D.] Charles Univ Prague, Inst Astron, CZ-18000 Prague, Czech Republic.
   [Polishook, D.] Tel Aviv Univ, Wise Observ, IL-69978 Tel Aviv, Israel.
   [Polishook, D.] Tel Aviv Univ, Dept Geophys & Planetary Phys, IL-69978 Tel Aviv, Israel.
   [Scheeres, D. J.] Univ Colorado, Dept Aerosp Engn Sci, Boulder, CO 80309 USA.
   [Harris, A. W.] Space Sci Inst, La Canada Flintridge, CA 91011 USA.
   [Galad, A.] Comenius Univ, Modra Observ, SK-84248 Bratislava, Slovakia.
   [Vaduvescu, O.; Pozo, F.; Barr, A.; Longa, P.] Univ Catolica Norte, Inst Astron, Antofagasta, Chile.
   [Vaduvescu, O.] Isaac Newton Grp Telescopes, E-38700 Santa Cruz De La Palma, Canary Isl, Spain.
   [Vachier, F.; Colas, F.] IMCCE CNRS Observ Paris, F-75014 Paris, France.
   [Pray, D. P.] Carbuncle Hill Observ, W Brookfield, MA 01585 USA.
   [Pollock, J.] Appalachian State Univ, Dept Phys & Astron, Boone, NC 28608 USA.
   [Reichart, D.; Ivarsen, K.; Haislip, J.; LaCluyze, A.] Univ N Carolina, Dept Phys & Astron, Chapel Hill, NC 27514 USA.
   [Marchis, F.; Macomber, B.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Marchis, F.; Macomber, B.] SETI Inst, Mountain View, CA 94043 USA.
   [Jacobson, S. A.] Univ Colorado, Dept Astrophys & Planetary Sci, Boulder, CO 80309 USA.
   [Krugly, Yu. N.; Sergeev, A. V.] Kharkov Natl Univ, Inst Astron, UA-61022 Kharkov, Ukraine.
   [Leroy, A.] Observ Midi Pyrenees & Assoc, Pic Du Midi, France.
C3 Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; Charles University Prague; Tel Aviv University; Tel Aviv University; University of Colorado System; University of Colorado Boulder; Comenius University Bratislava; Universidad Catolica del Norte; Isaac Newton Group of Telescopes; Universite PSL; Observatoire de Paris; University of North Carolina; Appalachian State University; University of North Carolina; University of North Carolina Chapel Hill; University of California System; University of California Berkeley; SETI Institute; University of Colorado System; University of Colorado Boulder; Ministry of Education & Science of Ukraine; VN Karazin Kharkiv National University
RP Pravec, P (corresponding author), Astron Inst AS CR, Fricova 1, CZ-25165 Ondrejov, Czech Republic.
EM ppravec@asu.cas.cz
FU Grant Agency of the Czech Republic; Czech Ministry of Education; Israeli Ministry of Science; NASA; NSF; Slovak Grant Agency for Science; CNRS; Planetary Society; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0807468] Funding Source: National Science Foundation
NR 14
TC 176
Z9 193
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1085
EP 1088
DI 10.1038/nature09315
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600035
PM 20740010
DA 2026-03-09
ER

PT J
AU Lyman, JM
   Good, SA
   Gouretski, VV
   Ishii, M
   Johnson, GC
   Palmer, MD
   Smith, DM
   Willis, JK
AF Lyman, John M.
   Good, Simon A.
   Gouretski, Viktor V.
   Ishii, Masayoshi
   Johnson, Gregory C.
   Palmer, Matthew D.
   Smith, Doug M.
   Willis, Josh K.
TI Robust warming of the global upper ocean
SO NATURE
LA English
DT Article
ID sea-level rise; heat-content; temperature; reevaluation; variability; profiles; quality; argo; xbt
AB A large (similar to 10(23) J) multi-decadal globally averaged warming signal in the upper 300 m of the world's oceans was reported roughly a decade ago(1) and is attributed to warming associated with anthropogenic greenhouse gases(2,3). The majority of the Earth's total energy uptake during recent decades has occurred in the upper ocean(3), but the underlying uncertainties in ocean warming are unclear, limiting our ability to assess closure of sea-level budgets(4-7), the global radiation imbalance(8) and climate models(5). For example, several teams have recently produced different multi-year estimates of the annually averaged global integral of upper-ocean heat content anomalies (hereafter OHCA curves) or, equivalently, the thermosteric sea-level rise(5,9-16). Patterns of inter-annual variability, in particular, differ among methods. Here we examine several sources of uncertainty that contribute to differences among OHCA curves from 1993 to 2008, focusing on the difficulties of correcting biases in expendable bathythermograph (XBT) data. XBT data constitute the majority of the in situ measurements of upper-ocean heat content from 1967 to 2002, and we find that the uncertainty due to choice of XBT bias correction dominates among-method variability in OHCA curves during our 1993-2008 study period. Accounting for multiple sources of uncertainty, a composite of several OHCA curves using different XBT bias corrections still yields a statistically significant linear warming trend for 1993-2008 of 0.64 W m(-2) (calculated for the Earth's entire surface area), with a 90-per-cent confidence interval of 0.53-0.75 W m(-2).
C1 [Lyman, John M.] Univ Hawaii Manoa, Joint Inst Marine & Atmospher Res, Honolulu, HI 96822 USA.
   [Lyman, John M.; Johnson, Gregory C.] NOAA, Pacific Marine Environm Lab, Seattle, WA 98115 USA.
   [Good, Simon A.; Palmer, Matthew D.; Smith, Doug M.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Gouretski, Viktor V.] Univ Hamburg, D-20144 Hamburg, Germany.
   [Ishii, Masayoshi] Meteorol Res Inst, Climate Res Dept, Tsukuba, Ibaraki 3050052, Japan.
   [Ishii, Masayoshi] Japan Agcy Marine Earth Sci & Technol, Kanazawa Ku, Yokohama, Kanagawa 2360001, Japan.
   [Willis, Josh K.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 University of Hawaii System; University of Hawaii Manoa; National Oceanic Atmospheric Admin (NOAA) - USA; Met Office - UK; Hadley Centre; University of Hamburg; Meteorological Research Institute - Japan; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP Lyman, JM (corresponding author), Univ Hawaii Manoa, Joint Inst Marine & Atmospher Res, Honolulu, HI 96822 USA.
EM john.lyman@noaa.gov
FU US National Oceanic and Atmospheric Administration (NOAA) Climate Program Office; NOAA; DECC/Defra [GA01101]
NR 30
TC 276
Z9 316
U1 1
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 MAY 20
PY 2010
VL 465
IS 7296
BP 334
EP 337
DI 10.1038/nature09043
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200037
PM 20485432
DA 2026-03-09
ER

PT J
AU Suenaga, K
   Koshino, M
AF Suenaga, Kazu
   Koshino, Masanori
TI Atom-by-atom spectroscopy at graphene edge
SO NATURE
LA English
DT Article
ID electron-microscopy; fine-structure; resolution; voltage
AB The properties of many nanoscale devices are sensitive to local atomic configurations, and so elemental identification and electronic state analysis at the scale of individual atoms is becoming increasingly important. For example, graphene is regarded as a promising candidate for future devices, and the electronic properties of nanodevices constructed from this material are in large part governed by the edge structures(1). The atomic configurations at graphene boundaries have been investigated by transmission electron microscopy and scanning tunnelling microscopy(2-4), but the electronic properties of these edge states have not yet been determined with atomic resolution. Whereas simple elemental analysis at the level of single atoms can now be achieved by means of annular dark field imaging(5) or electron energy-loss spectroscopy(6,7), obtaining fine-structure spectroscopic information about individual light atoms such as those of carbon has been hampered by a combination of extremely weak signals and specimen damage by the electron beam. Here we overcome these difficulties to demonstrate site-specific single-atom spectroscopy at a graphene boundary, enabling direct investigation of the electronic and bonding structures of the edge atoms-in particular, discrimination of single-, double- and triple-coordinated carbon atoms is achieved with atomic resolution. By demonstrating how rich chemical information can be obtained from single atoms through energy-loss near-edge fine-structure analysis(8), our results should open the way to exploring the local electronic structures of various nanodevices and individual molecules.
C1 [Suenaga, Kazu; Koshino, Masanori] Natl Inst Adv Ind Sci & Technol, Nanotube Res Ctr, Tsukuba, Ibaraki 3058565, Japan.
C3 National Institute of Advanced Industrial Science & Technology (AIST)
RP Suenaga, K (corresponding author), Natl Inst Adv Ind Sci & Technol, Nanotube Res Ctr, AIST Cent 5, Tsukuba, Ibaraki 3058565, Japan.
EM suenaga-kazu@aist.go.jp
FU JST
NR 21
TC 434
Z9 471
U1 1
U2 302
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1088
EP 1090
DI 10.1038/nature09664
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800055
PM 21160475
DA 2026-03-09
ER

PT J
AU Ammirante, M
   Luo, JL
   Grivennikov, S
   Nedospasov, S
   Karin, M
AF Ammirante, Massimo
   Luo, Jun-Li
   Grivennikov, Sergei
   Nedospasov, Sergei
   Karin, Michael
TI B-cell-derived lymphotoxin promotes castration-resistant prostate cancer
SO NATURE
LA English
DT Article
ID factor-kappa-b; ikk-alpha; chronic inflammation; t-cells; activation; interleukin-6; progression; metastasis; expression; release
AB Prostate cancer (CaP) progresses from prostatic intraepithelial neoplasia through locally invasive adenocarcinoma to castration-resistant metastatic carcinoma(1). Although radical prostatectomy, radiation and androgen ablation are effective therapies for androgen-dependent CaP, metastatic castration-resistant CaP is a major complication with high mortality(2). Androgens stimulate growth and survival of prostate epithelium and early CaP. Although most patients initially respond to androgen ablation, many develop castration-resistant CaP within 12-18 months(2). Despite extensive studies, the mechanisms underlying the emergence of castration-resistant CaP remain poorly understood and their elucidation is critical for developing improved therapies. Curiously, castration-resistant CaP remains androgen-receptor dependent, and potent androgen-receptor antagonists induce tumour regression in castrated mice(3). The role of inflammation in castration-resistant CaP has not been addressed, although it was reported that intrinsic NF-kappa B activation supports its growth(4). Inflammation is a localized protective reaction to injury or infection, but it also has a pathogenic role in many diseases, including cancer(5). Whereas acute inflammation is critical for host defence, chronic inflammation contributes to tumorigenesis and metastatic progression. The inflammation-responsive I kappa B kinase (IKK)-beta and its target NF-kB have important tumour-promoting functions within malignant cells and inflammatory cells(6). The latter, including macrophages and lymphocytes, are important elements of the tumour microenvironment(7-9), but the mechanisms underlying their recruitment remain obscure, although they are thought to depend on chemokine and cytokine production(10). We found that CaP progression is associated with inflammatory infiltration and activation of IKK-alpha, which stimulates metastasis by an NF-kappa B-independent, cell autonomous mechanism(11). Here we show that androgen ablation causes infiltration of regressing androgen-dependent tumours with leukocytes, including B cells, in which IKK-beta activation results in production of cytokines that activate IKK-alpha and STAT3 in CaP cells to enhance hormone-free survival.
C1 [Ammirante, Massimo; Grivennikov, Sergei; Karin, Michael] Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Ammirante, Massimo; Grivennikov, Sergei; Karin, Michael] Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA.
   [Luo, Jun-Li] Scripps Res Inst Florida, Dept Canc Biol, Jupiter, FL 33458 USA.
   [Nedospasov, Sergei] VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Russian Academy of Sciences; Engelhardt Institute of Molecular Biology, RAS
RP Karin, M (corresponding author), Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU Fondazione Italiana per la Ricerca sul Cancro; American-Italian Cancer Foundation; Life Science Research Fellowship; National Institutes of Health; US Army Medical Research and Material Command and Prostate Cancer Foundation; Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
NR 39
TC 507
Z9 592
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 MAR 11
PY 2010
VL 464
IS 7286
BP 302
EP U187
DI 10.1038/nature08782
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100052
PM 20220849
DA 2026-03-09
ER

PT J
AU Rouget, C
   Papin, C
   Boureux, A
   Meunier, AC
   Franco, B
   Robine, N
   Lai, EC
   Pelisson, A
   Simonelig, M
AF Rouget, Christel
   Papin, Catherine
   Boureux, Anthony
   Meunier, Anne-Cecile
   Franco, Benedicte
   Robine, Nicolas
   Lai, Eric C.
   Pelisson, Alain
   Simonelig, Martine
TI Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo
SO NATURE
LA English
DT Article
ID translational regulation; axis specification; binding-protein; germline; localization; nanos; piwi; melanogaster; activation; mutations
AB Piwi-associated RNAs (piRNAs), a specific class of 24- to 30-nucleotide-long RNAs produced by the Piwi-type of Argonaute proteins, have a specific germline function in repressing transposable elements. This repression is thought to involve heterochromatin formation and transcriptional and post-transcriptional silencing(1-6). The piRNA pathway has other essential functions in germline stem cell maintenance(7) and in maintaining germline DNA integrity(8-10). Here we uncover an unexpected function of the piRNA pathway in the decay of maternal messenger RNAs and in translational repression in the early embryo. A subset of maternal mRNAs is degraded in the embryo at the maternal-to-zygotic transition. In Drosophila, maternal mRNA degradation depends on the RNA-binding protein Smaug and the deadenylase CCR4(11-13), as well as the zygotic expression of a microRNA cluster(14). Using mRNA encoding the embryonic posterior morphogen Nanos (Nos) as a paradigm to study maternal mRNA decay, we found that CCR4-mediated deadenylation of nos depends on components of the piRNA pathway including piRNAs complementary to a specific region in the nos 3' untranslated region. Reduced deadenylation when piRNA-induced regulation is impaired correlates with nos mRNA stabilization and translational derepression in the embryo, resulting in head development defects. Aubergine, one of the Argonaute proteins in the piRNA pathway, is present in a complex with Smaug, CCR4, nos mRNA and piRNAs that target the nos 3' untranslated region, in the bulk of the embryo. We propose that piRNAs and their associated proteins act together with Smaug to recruit the CCR4 deadenylation complex to specific mRNAs, thus promoting their decay. Because the piRNAs involved in this regulation are produced from transposable elements, this identifies a direct developmental function for transposable elements in the regulation of gene expression.
C1 [Rouget, Christel; Papin, Catherine; Meunier, Anne-Cecile; Franco, Benedicte; Simonelig, Martine] CNRS, UPR1142, Inst Human Genet, mRNA Regulat & Dev, F-34396 Montpellier 5, France.
   [Boureux, Anthony] Univ Montpellier 2, CNRS, UMR5237, CRBM, F-34293 Montpellier, France.
   [Robine, Nicolas; Lai, Eric C.] Sloan Kettering Inst, Dept Dev Biol, Rockefeller Res Labs 1017, New York, NY 10065 USA.
   [Pelisson, Alain] CNRS, UPR1142, Inst Human Genet, RNA Silencing & Control Transposit, F-34396 Montpellier 5, France.
C3 Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Memorial Sloan Kettering Cancer Center; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS)
RP Simonelig, M (corresponding author), CNRS, UPR1142, Inst Human Genet, mRNA Regulat & Dev, 141 Rue Cardonille, F-34396 Montpellier 5, France.
EM Martine.Simonelig@igh.cnrs.fr
FU Centre National de la Recherche Scientifique [UPR1142]; Agence Nationale de la Recherche (ANR Blanche) [ANR-06-BLAN-0343]; Fondation pour la Recherche Medicale (FRM); Association pour la Recherche sur le Cancer (ARC); National Institutes of Health (NIH) [R01-GM083300]; Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0343] Funding Source: Agence Nationale de la Recherche (ANR); National Institute of General Medical Sciences [R01GM083300] Funding Source: NIH RePORTER
NR 40
TC 365
Z9 438
U1 3
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 28
PY 2010
VL 467
IS 7319
BP 1128
EP U144
DI 10.1038/nature09465
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600052
PM 20953170
DA 2026-03-09
ER

PT J
AU Sasaki, J
   Kofuji, S
   Itoh, R
   Momiyama, T
   Takayama, K
   Murakami, H
   Chida, S
   Tsuya, Y
   Takasuga, S
   Eguchi, S
   Asanuma, K
   Horie, Y
   Miura, K
   Davies, EM
   Mitchell, C
   Yamazaki, M
   Hirai, H
   Takenawa, T
   Suzuki, A
   Sasaki, T
AF Sasaki, Junko
   Kofuji, Satoshi
   Itoh, Reietsu
   Momiyama, Toshihiko
   Takayama, Kiyohiko
   Murakami, Haruka
   Chida, Shinsuke
   Tsuya, Yuko
   Takasuga, Shunsuke
   Eguchi, Satoshi
   Asanuma, Ken
   Horie, Yasuo
   Miura, Kouichi
   Davies, Elizabeth Michele
   Mitchell, Christina
   Yamazaki, Masakazu
   Hirai, Hirokazu
   Takenawa, Tadaomi
   Suzuki, Akira
   Sasaki, Takehiko
TI The PtdIns(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic neuronal death
SO NATURE
LA English
DT Article
ID inositol polyphosphate 4-phosphatase; huntingtons-disease; lentiviral vectors; nmda receptors; purkinje-cell; in-vivo; system; pten; mice; phosphoinositides
AB Phosphorylated derivatives of phosphatidylinositol, collectively referred to as phosphoinositides, occur in the cytoplasmic leaflet of cellular membranes and regulate activities such as vesicle transport, cytoskeletal reorganization and signal transduction(1,2). Recent studies have indicated an important role for phosphoinositide metabolism in the aetiology of diseases such as cancer, diabetes, myopathy and inflammation(3-5). Although the biological functions of the phosphatases that regulate phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P-3)have been well characterized, little is known about the functions of the phosphatases regulating the closely related molecule phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P-2). Here we show that inositol polyphosphate phosphatase 4A (INPP4A), a PtdIns(3,4)P2 phosphatase, is a suppressor of glutamate excitotoxicity in the central nervous system. Targeted disruption of the Inpp4a gene in mice leads to neurodegeneration in the striatum, the input nucleus of the basal ganglia that has a central role inmotor and cognitive behaviours. Notably, Inpp4a(-/-) mice show severe involuntary movement disorders. In vitro, Inpp4a gene silencing via short hairpin RNA renders cultured primary striatal neurons vulnerable to cell death mediated by N-methyl-D-aspartatetype glutamate receptors (NMDARs). Mechanistically, INPP4A is found at the postsynaptic density and regulates synaptic NMDAR localization and NMDAR-mediated excitatory postsynaptic current. Thus, INPP4A protects neurons from excitotoxic cell death and thereby maintains the functional integrity of the brain. Our study demonstrates that PtdIns(3,4)P-2, PtdIns(3,4,5)P-3 and the phosphatases acting on them can have distinct regulatory roles, and provides insight into the unique aspects and physiological significance of PtdIns(3,4)P-2 metabolism. INPP4A represents, to our knowledge, the first signalling protein with a function in neurons to suppress excitotoxic cell death. The discovery of a direct link between PtdIns(3,4)P-2 metabolism and the regulation of neurodegeneration and involuntary movements may aid the development of new approaches for the treatment of neurodegenerative disorders.
C1 [Sasaki, Junko; Kofuji, Satoshi; Itoh, Reietsu; Murakami, Haruka; Chida, Shinsuke; Tsuya, Yuko; Takasuga, Shunsuke; Eguchi, Satoshi; Asanuma, Ken; Sasaki, Takehiko] Akita Univ, Grad Sch Med, Dept Med Biol, Akita 0108543, Japan.
   [Sasaki, Junko; Kofuji, Satoshi; Itoh, Reietsu; Takayama, Kiyohiko; Murakami, Haruka; Chida, Shinsuke; Tsuya, Yuko; Takasuga, Shunsuke; Eguchi, Satoshi; Asanuma, Ken; Yamazaki, Masakazu; Hirai, Hirokazu; Suzuki, Akira; Sasaki, Takehiko] Gunma Univ, Global COE Program, Gunma 3718511, Japan.
   [Sasaki, Junko; Kofuji, Satoshi; Itoh, Reietsu; Takayama, Kiyohiko; Murakami, Haruka; Chida, Shinsuke; Tsuya, Yuko; Takasuga, Shunsuke; Eguchi, Satoshi; Asanuma, Ken; Yamazaki, Masakazu; Hirai, Hirokazu; Suzuki, Akira; Sasaki, Takehiko] Akita Univ, Gunma 3718511, Japan.
   [Momiyama, Toshihiko] Jikei Univ, Sch Med, Dept Pharmacol, Tokyo 1058461, Japan.
   [Takayama, Kiyohiko; Hirai, Hirokazu] Gunma Univ, Dept Neurophysiol, Grad Sch Med, Gunma 3718511, Japan.
   [Horie, Yasuo; Miura, Kouichi] Akita Univ, Grad Sch Med, Dept Gastroenterol & Neurol, Akita 0108543, Japan.
   [Davies, Elizabeth Michele; Mitchell, Christina] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Takenawa, Tadaomi] Kobe Univ, Grad Sch Med, Dept Biochem & Mol Biol, Div Lipid Biochem, Kobe, Hyogo 6500017, Japan.
   [Takenawa, Tadaomi] Kobe Univ, Grad Sch Med, Global COE Program, Kobe, Hyogo 6500017, Japan.
   [Suzuki, Akira] Kyushu Univ, Med Inst Bioregulat, Div Embryon & Genet Engn, Fukuoka 8128582, Japan.
C3 Akita University; Gunma University; Akita University; Jikei University; Gunma University; Akita University; Monash University; Kobe University; Kobe University; Kyushu University
RP Sasaki, J (corresponding author), Akita Univ, Grad Sch Med, Dept Med Biol, Akita 0108543, Japan.
EM sasakij@med.akita-u.ac.jp; tsasaki@med.akita-u.ac.jp
FU Ministry of Education, Culture, Sports and Technology of Japan (MEXT); Japan Society for the Promotion of Science (JSPS); Japan Science and Technology Corporation (JST); Naito Foundation; Toray Science Foundation; MEXT; Grants-in-Aid for Scientific Research [21200075, 21500374, 22790055] Funding Source: KAKEN
NR 40
TC 93
Z9 105
U1 0
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 MAY 27
PY 2010
VL 465
IS 7297
BP 497
EP U127
DI 10.1038/nature09023
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700039
PM 20463662
DA 2026-03-09
ER

PT J
AU Khajetoorians, AA
   Chilian, B
   Wiebe, J
   Schuwalow, S
   Lechermann, F
   Wiesendanger, R
AF Khajetoorians, Alexander A.
   Chilian, Bruno
   Wiebe, Jens
   Schuwalow, Sergej
   Lechermann, Frank
   Wiesendanger, Roland
TI Detecting excitation and magnetization of individual dopants in a semiconductor
SO NATURE
LA English
DT Article
ID quantum dots; spectroscopy; surface; spins; spintronics; microscopy; gaas; mn
AB An individual magnetic atom doped into a semiconductor is a promising building block for bottom-up spintronic devices and quantum-logic gates(1-3). Moreover, it provides a perfect model system for the atomic-scale investigation of fundamental effects such as magnetism in dilute magnetic semiconductors(4). However, dopants in semiconductors so far have not been studied by magnetically sensitive techniques with atomic resolution that correlate the atomic structure with the dopant's magnetism. Here we show electrical excitation and read-out of a spin associated with a single magnetic dopant in a semiconductor host. We use spin-resolved scanning tunnelling spectroscopy to measure the spin excitations and the magnetization curve of individual iron surface-dopants embedded within a two-dimensional electron gas confined to an indium antimonide (110) surface. The dopants act like isolated quantum spins the states of which are governed by a substantial magnetic anisotropy that forces the spin to lie in the surface plane. This result is corroborated by our first principles calculations. The demonstrated methodology opens new routes for the investigation of sample systems that are more widely studied in the field of spintronics-that is, Mn in GaAs (ref. 5), magnetic ions in semiconductor quantum dots(3), nitrogen-vacancy centres in diamond(6) and phosphorus spins in silicon(7).
C1 [Khajetoorians, Alexander A.; Chilian, Bruno; Wiebe, Jens; Wiesendanger, Roland] Univ Hamburg, Inst Appl Phys, D-20355 Hamburg, Germany.
   [Schuwalow, Sergej; Lechermann, Frank] Univ Hamburg, Inst Theoret Phys 1, D-20355 Hamburg, Germany.
C3 University of Hamburg; University of Hamburg
RP Wiebe, J (corresponding author), Univ Hamburg, Inst Appl Phys, Jungiusstr 11, D-20355 Hamburg, Germany.
EM jwiebe@physnet.uni-hamburg.de
FU ERC; Deutsche Forschungsgemeinschaft [SFB668]; Graduiertenkolleg [1286]; City of Hamburg via the cluster of excellence
NR 29
TC 90
Z9 97
U1 2
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1084
EP 1087
DI 10.1038/nature09519
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600042
PM 20981095
DA 2026-03-09
ER

PT J
AU Rubin, CJ
   Zody, MC
   Eriksson, J
   Meadows, JRS
   Sherwood, E
   Webster, MT
   Jiang, L
   Ingman, M
   Sharpe, T
   Ka, S
   Hallböök, F
   Besnier, F
   Carlborg, Ö
   Bed'hom, B
   Tixier-Boichard, M
   Jensen, P
   Siegel, P
   Lindblad-Toh, K
   Andersson, L
AF Rubin, Carl-Johan
   Zody, Michael C.
   Eriksson, Jonas
   Meadows, Jennifer R. S.
   Sherwood, Ellen
   Webster, Matthew T.
   Jiang, Lin
   Ingman, Max
   Sharpe, Ted
   Ka, Sojeong
   Hallbook, Finn
   Besnier, Francois
   Carlborg, Orjan
   Bed'hom, Bertrand
   Tixier-Boichard, Michele
   Jensen, Per
   Siegel, Paul
   Lindblad-Toh, Kerstin
   Andersson, Leif
TI Whole-genome resequencing reveals loci under selection during chicken domestication
SO NATURE
LA English
DT Article
ID quantitative trait loci; body-weight; genetic dissection; growth; hormone; difference; conversion; epistasis; mutation; strain
AB Domestic animals are excellent models for genetic studies of phenotypic evolution(1-3). They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor(4). We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.
C1 [Rubin, Carl-Johan; Zody, Michael C.; Eriksson, Jonas; Meadows, Jennifer R. S.; Webster, Matthew T.; Jiang, Lin; Lindblad-Toh, Kerstin; Andersson, Leif] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden.
   [Zody, Michael C.; Sharpe, Ted; Lindblad-Toh, Kerstin] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
   [Zody, Michael C.; Sharpe, Ted; Lindblad-Toh, Kerstin] MIT, Cambridge, MA 02142 USA.
   [Sherwood, Ellen] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
   [Ingman, Max] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden.
   [Ka, Sojeong; Hallbook, Finn] Uppsala Univ, Dept Neurosci, SE-75124 Uppsala, Sweden.
   [Besnier, Francois; Carlborg, Orjan; Andersson, Leif] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden.
   [Bed'hom, Bertrand; Tixier-Boichard, Michele] INRA, Anim Genet & Integrat Biol UMR1313, F-78350 Jouy En Josas, France.
   [Jensen, Per] Linkoping Univ, IFM Biol, SE-58183 Linkoping, Sweden.
   [Siegel, Paul] Virginia Polytech Inst & State Univ, Dept Anim & Poultry Sci, Blacksburg, VA 24061 USA.
C3 Uppsala University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Karolinska Institutet; Uppsala University; Uppsala University; Swedish University of Agricultural Sciences; Universite Paris Saclay; INRAE; AgroParisTech; Linkoping University; Virginia Polytechnic Institute & State University
RP Andersson, L (corresponding author), Uppsala Univ, Dept Med Biochem & Microbiol, Box 582, SE-75123 Uppsala, Sweden.
EM leif.andersson@imbim.uu.se
FU Swedish Foundation for Strategic Research; Knut and Alice Wallenberg Foundation; Swedish National Infrastructure for Computing; The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning; European Young Investigator awards
NR 41
TC 828
Z9 999
U1 7
U2 365
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 587
EP U145
DI 10.1038/nature08832
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200047
PM 20220755
DA 2026-03-09
ER

PT J
AU Kodera, N
   Yamamoto, D
   Ishikawa, R
   Ando, T
AF Kodera, Noriyuki
   Yamamoto, Daisuke
   Ishikawa, Ryoki
   Ando, Toshio
TI Video imaging of walking myosin V by high-speed atomic force microscopy
SO NATURE
LA English
DT Article
ID hand-over-hand; processive myosin; mechanism; adp; coordination; movement; dynamics; kinetics; binding; stroke
AB The dynamic behaviour of myosin V molecules translocating along actin filaments has been mainly studied by optical microscopy. The processive hand-over-hand movement coupled with hydrolysis of adenosine triphosphate was thereby demonstrated. However, the protein molecules themselves are invisible in the observations and have therefore been visualized by electron microscopy in the stationary states. The concomitant assessment of structure and dynamics has been unfeasible, a situation prevailing throughout biological research. Here we directly visualize myosin V molecules walking along actin tracks, using high-speed atomic force microscopy. The high-resolution movies not only provide corroborative 'visual evidence' for previously speculated or demonstrated molecular behaviours, including lever-arm swing, but also reveal more detailed behaviours of the molecules, leading to a comprehensive understanding of the motor mechanism. Our direct and dynamic high-resolution visualization is a powerful new approach to studying the structure and dynamics of biomolecules in action.
C1 [Kodera, Noriyuki; Yamamoto, Daisuke; Ando, Toshio] Kanazawa Univ, Dept Phys, Kanazawa, Ishikawa 9201192, Japan.
   [Kodera, Noriyuki; Yamamoto, Daisuke; Ando, Toshio] JST, CREST, Chiyoda Ku, Tokyo 1020075, Japan.
   [Ishikawa, Ryoki] Gunma Univ, Grad Sch Med, Dept Mol & Cellular Pharmacol, Maebashi, Gunma 3718511, Japan.
C3 Kanazawa University; Japan Science & Technology Agency (JST); Gunma University
RP Ando, T (corresponding author), Kanazawa Univ, Dept Phys, Kakuma Machi, Kanazawa, Ishikawa 9201192, Japan.
EM tando@kenroku.kanazawa-u.ac.jp
FU JST; JSPS; MEXT-Japan; Grants-in-Aid for Scientific Research [21113002, 20221006, 21590270] Funding Source: KAKEN
NR 35
TC 682
Z9 793
U1 6
U2 282
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 72
EP +
DI 10.1038/nature09450
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900037
PM 20935627
DA 2026-03-09
ER

PT J
AU Nielsen, LP
   Risgaard-Petersen, N
   Fossing, H
   Christensen, PB
   Sayama, M
AF Nielsen, Lars Peter
   Risgaard-Petersen, Nils
   Fossing, Henrik
   Christensen, Peter Bondo
   Sayama, Mikio
TI Electric currents couple spatially separated biogeochemical processes in marine sediment
SO NATURE
LA English
DT Article
ID porphyry sulfide mineralization; organic-carbon; water; model; electrochemistry; community; diffusion; reduction; transport
AB Some bacteria are capable of extracellular electron transfer, thereby enabling them to use electron acceptors and donors without direct cell contact(1-4). Beyond the micrometre scale, however, no firm evidence has previously existed that spatially segregated biogeochemical processes can be coupled by electric currents in nature. Here we provide evidence that electric currents running through defaunated sediment couple oxygen consumption at the sediment surface to oxidation of hydrogen sulphide and organic carbon deep within the sediment. Altering the oxygen concentration in the sea water overlying the sediment resulted in a rapid (<1-h) change in the hydrogen sulphide concentration within the sediment more than 12 mm below the oxic zone, a change explicable by transmission of electrons but not by diffusion of molecules. Mass balances indicated that more than 40% of total oxygen consumption in the sediment was driven by electrons conducted from the anoxic zone. A distinct pH peak in the oxic zone could be explained by electrochemical oxygen reduction, but not by any conventional sets of aerobic sediment processes. We suggest that the electric current was conducted by bacterial nanowires combined with pyrite, soluble electron shuttles and outer-membrane cytochromes. Electrical communication between distant chemical and biological processes in nature adds a new dimension to our understanding of biogeochemistry and microbial ecology.
C1 [Nielsen, Lars Peter] Aarhus Univ, Dept Biol Sci, DK-8000 Aarhus C, Denmark.
   [Risgaard-Petersen, Nils] Aarhus Univ, Ctr Geomicrobiol, DK-8000 Aarhus C, Denmark.
   [Fossing, Henrik; Christensen, Peter Bondo] Aarhus Univ, Natl Environm Res Inst, Dept Marine Ecol, DK-8600 Silkeborg, Denmark.
   [Sayama, Mikio] Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058569, Japan.
C3 Aarhus University; Aarhus University; Aarhus University; Danish National Environmental Research Institute; National Institute of Advanced Industrial Science & Technology (AIST)
RP Nielsen, LP (corresponding author), Aarhus Univ, Dept Biol Sci, Ny Munkegade 114, DK-8000 Aarhus C, Denmark.
EM biolpn@biology.au.dk
FU Aarhus University Research Foundation; Danish National Research Foundation; Max Planck Society; Japan Society for the Promotion of Science
NR 30
TC 434
Z9 510
U1 18
U2 474
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1071
EP 1074
DI 10.1038/nature08790
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400034
PM 20182510
DA 2026-03-09
ER

PT J
AU Hirschey, MD
   Shimazu, T
   Goetzman, E
   Jing, E
   Schwer, B
   Lombard, DB
   Grueter, CA
   Harris, C
   Biddinger, S
   Ilkayeva, OR
   Stevens, RD
   Li, Y
   Saha, AK
   Ruderman, NB
   Bain, JR
   Newgard, CB
   Farese, RV
   Alt, F
   Kahn, CR
   Verdin, E
AF Hirschey, Matthew D.
   Shimazu, Tadahiro
   Goetzman, Eric
   Jing, Enxuan
   Schwer, Bjoern
   Lombard, David B.
   Grueter, Carrie A.
   Harris, Charles
   Biddinger, Sudha
   Ilkayeva, Olga R.
   Stevens, Robert D.
   Li, Yu
   Saha, Asish K.
   Ruderman, Neil B.
   Bain, James R.
   Newgard, Christopher B.
   Farese, Robert V., Jr.
   Alt, FrederickW.
   Kahn, C. Ronald
   Verdin, Eric
TI SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
SO NATURE
LA English
DT Article
ID coa dehydrogenase-deficiency; gene-expression profiles; hepatic steatosis; liver-disease; acetylation; risk; sirtuins; roles; mice
AB Sirtuins are NAD(+)-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, including acetyl coenzyme A synthetase 2 (refs 1, 2). Mice lacking both Sirt3 alleles appear phenotypically normal under basal conditions, but show marked hyperacetylation of several mitochondrial proteins(3). Here we report that SIRT3 expression is upregulated during fasting in liver and brown adipose tissues. During fasting, livers from mice lacking SIRT3 had higher levels of fatty-acid oxidation intermediate products and triglycerides, associated with decreased levels of fatty-acid oxidation, compared to livers from wild-type mice. Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3. LCAD is deacetylated in wild-type mice under fasted conditions and by SIRT3 in vitro and in vivo; and hyperacetylation of LCAD reduces its enzymatic activity. Mice lacking SIRT3 exhibit hallmarks of fatty-acid oxidation disorders during fasting, including reduced ATP levels and intolerance to cold exposure. These findings identify acetylation as a novel regulatory mechanism for mitochondrial fatty-acid oxidation and demonstrate that SIRT3 modulates mitochondrial intermediary metabolism and fatty-acid use during fasting.
C1 [Hirschey, Matthew D.; Shimazu, Tadahiro; Schwer, Bjoern; Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
   [Hirschey, Matthew D.; Shimazu, Tadahiro; Schwer, Bjoern; Verdin, Eric] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Goetzman, Eric] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15201 USA.
   [Jing, Enxuan; Biddinger, Sudha; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
   [Schwer, Bjoern; Lombard, David B.; Alt, FrederickW.] Harvard Univ, Sch Med, Childrens Hosp,Immune Dis Inst,Dept Genet, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Grueter, Carrie A.; Harris, Charles; Farese, Robert V., Jr.] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Ilkayeva, Olga R.; Stevens, Robert D.; Bain, James R.; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA.
   [Li, Yu] Cell Signaling Technol, Danvers, MA 01923 USA.
   [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Med Ctr, Diabet Unit, Boston, MA 02118 USA.
   [Saha, Asish K.; Ruderman, Neil B.] Boston Univ, Med Ctr, Dept Physiol & Med Biophys, Boston, MA 02118 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; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); University of California System; University of California San Francisco; The J David Gladstone Institutes; Duke University; Cell Signaling Technology; Boston University; Boston University
RP Verdin, E (corresponding author), Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
EM everdin@gladstone.ucsf.edu
FU Elison Medical Foundation; National Institute on Aging; National Institutes of Health (NIH) [PO1 HL068758-06A1, DK019514-29, R01 DK067509-04]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK026743, U2CDK059637] Funding Source: NIH RePORTER
NR 43
TC 1407
Z9 1628
U1 4
U2 297
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 121
EP U137
DI 10.1038/nature08778
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500046
PM 20203611
DA 2026-03-09
ER

PT J
AU Greenland, PT
   Lynch, SA
   van der Meer, AFG
   Murdin, BN
   Pidgeon, CR
   Redlich, B
   Vinh, NQ
   Aeppli, G
AF Greenland, P. T.
   Lynch, S. A.
   van der Meer, A. F. G.
   Murdin, B. N.
   Pidgeon, C. R.
   Redlich, B.
   Vinh, N. Q.
   Aeppli, G.
TI Coherent control of Rydberg states in silicon
SO NATURE
LA English
DT Article
ID donors; excitation; blockade
AB Laser cooling and electromagnetic traps have led to a revolution in atomic physics, yielding dramatic discoveries ranging from Bose-Einstein condensation to the quantum control of single atoms(1). Of particular interest, because they can be used in the quantum control of one atom by another, are excited Rydberg states(2-4), where wavefunctions are expanded from their ground-state extents of less than 0.1 nm to several nanometres and even beyond; this allows atoms far enough apart to be non-interacting in their ground states to strongly interact in their excited states. For eventual application of such states(5), a solid-state implementation is very desirable. Here we demonstrate the coherent control of impurity wavefunctions in the most ubiquitous donor in a semiconductor, namely phosphorus-doped silicon. In our experiments, we use a free-electron laser to stimulate and observe photon echoes(6,7), the orbital analogue of the Hahn spin echo(8), and Rabi oscillations familiar from magnetic resonance spectroscopy. As well as extending atomic physicists' explorations(1-3,9) of quantum phenomena to the solid state, our work adds coherent terahertz radiation, as a particularly precise regulator of orbitals in solids, to the list of controls, such as pressure and chemical composition, already familiar to materials scientists(10).
C1 [Greenland, P. T.; Lynch, S. A.; Aeppli, G.] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Greenland, P. T.; Lynch, S. A.; Aeppli, G.] UCL, Dept Phys & Astron, London WC1H 0AH, England.
   [van der Meer, A. F. G.; Redlich, B.; Vinh, N. Q.] FOM Inst Plasma Phys Rijnhuizen, NL-3430 BE Nieuwegein, Netherlands.
   [Murdin, B. N.] Univ Surrey, Adv Technol Inst, Guildford GU2 7XH, Surrey, England.
   [Pidgeon, C. R.] Heriot Watt Univ, Dept Phys, Edinburgh EH14 4AS, Midlothian, Scotland.
C3 University of London; University College London; University of London; University College London; University of Surrey; Heriot Watt University
RP Greenland, PT (corresponding author), UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
EM ptg@globalnet.co.uk
FU Netherlands Organisation for Scientific Research; Engineering and Physical Sciences Research Council [EP/H026622/1, EP/E061265/1]; Engineering and Physical Sciences Research Council [EP/E061265/1, EP/H026622/1] Funding Source: researchfish; EPSRC [EP/H026622/1, EP/E061265/1] Funding Source: UKRI
NR 24
TC 114
Z9 122
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1057
EP U116
DI 10.1038/nature09112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900048
PM 20577211
DA 2026-03-09
ER

PT J
AU Binzel, RP
   Morbidelli, A
   Merouane, S
   DeMeo, FE
   Birlan, M
   Vernazza, P
   Thomas, CA
   Rivkin, AS
   Bus, SJ
   Tokunaga, AT
AF Binzel, Richard P.
   Morbidelli, Alessandro
   Merouane, Sihane
   DeMeo, Francesca E.
   Birlan, Mirel
   Vernazza, Pierre
   Thomas, Cristina A.
   Rivkin, Andrew S.
   Bus, Schelte J.
   Tokunaga, Alan T.
TI Earth encounters as the origin of fresh surfaces on near-Earth asteroids
SO NATURE
LA English
DT Article
ID spectroscopic survey; spectral property; population; eros
AB Telescopic measurements of asteroids' colours rarely match laboratory reflectance spectra of meteorites owing to a 'space weathering'(1,2) process that rapidly(3) reddens asteroid surfaces in less than 10(6) years. 'Unweathered' asteroids (those having spectra matching the most commonly falling ordinary chondrite meteorites), however, are seen among small bodies the orbits of which cross inside Mars and the Earth. Various explanations have been proposed for the origin of these fresh surface colours, ranging from collisions(4) to planetary encounters(5). Less reddened asteroids seem to cross most deeply into the terrestrial planet region, strengthening(6) the evidence for the planetary-encounter theory(5), but encounter details within 10(6) years remain to be shown. Here we report that asteroids displaying unweathered spectra (so-called 'Q-types'(7)) have experienced orbital intersections closer than the Earth-Moon distance within the past 5 x 10(5) years. These Q-type asteroids are not currently found among asteroids showing no evidence of recent close planetary encounters. Our results substantiate previous work(5): tidal stress(8), strong enough to disturb and expose unweathered surface grains, is the most likely dominant short-term asteroid resurfacing process. Although the seismology details are yet to be worked out, the identification of rapid physical processes that can produce both fresh and weathered asteroid surfaces resolves the decades-long(9) puzzle of the difference in colour of asteroids and meteorites.
C1 [Binzel, Richard P.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Binzel, Richard P.; Birlan, Mirel] Observ Paris, IMCCE, F-75014 Paris, France.
   [Morbidelli, Alessandro] Univ Nice Sophia Antipolis, CNRS, Dept Cassiopee, Observ Cote Azur, F-06304 Nice, France.
   [Merouane, Sihane; DeMeo, Francesca E.] Observ Paris, LESIA, F-92195 Meudon, France.
   [Vernazza, Pierre] ESA, ESTEC, NL-2200 AG Noordwijk, Netherlands.
   [Thomas, Cristina A.] No Arizona Univ, Dept Phys, Flagstaff, AZ 86011 USA.
   [Thomas, Cristina A.] No Arizona Univ, Dept Astron, Flagstaff, AZ 86011 USA.
   [Rivkin, Andrew S.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Bus, Schelte J.; Tokunaga, Alan T.] Univ Hawaii, Inst Astron, Hilo, HI 96720 USA.
C3 Massachusetts Institute of Technology (MIT); Sorbonne Universite; Universite PSL; Observatoire de Paris; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; European Space Agency; European Space Research & Technology Centre; Northern Arizona University; Northern Arizona University; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; University of Hawaii System; University Hawaii Hilo
RP Binzel, RP (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM rpb@mit.edu
FU National Science Foundation [0506716]; NASA [NAG5-12355]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0506716] Funding Source: National Science Foundation
NR 28
TC 162
Z9 175
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 331
EP 334
DI 10.1038/nature08709
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100038
PM 20090748
DA 2026-03-09
ER

PT J
AU Baranzini, SE
   Mudge, J
   van Velkinburgh, JC
   Khankhanian, P
   Khrebtukova, I
   Miller, NA
   Zhang, L
   Farmer, AD
   Bell, CJ
   Kim, RW
   May, GD
   Woodward, JE
   Caillier, SJ
   McElroy, JP
   Gomez, R
   Pando, MJ
   Clendenen, LE
   Ganusova, EE
   Schilkey, FD
   Ramaraj, T
   Khan, OA
   Huntley, JJ
   Luo, SJ
   Kwok, P
   Wu, TD
   Schroth, GP
   Oksenberg, JR
   Hauser, SL
   Kingsmore, SF
AF Baranzini, Sergio E.
   Mudge, Joann
   van Velkinburgh, Jennifer C.
   Khankhanian, Pouya
   Khrebtukova, Irina
   Miller, Neil A.
   Zhang, Lu
   Farmer, Andrew D.
   Bell, Callum J.
   Kim, Ryan W.
   May, Gregory D.
   Woodward, Jimmy E.
   Caillier, Stacy J.
   McElroy, Joseph P.
   Gomez, Refujia
   Pando, Marcelo J.
   Clendenen, Leonda E.
   Ganusova, Elena E.
   Schilkey, Faye D.
   Ramaraj, Thiruvarangan
   Khan, Omar A.
   Huntley, Jim J.
   Luo, Shujun
   Kwok, Pui-yan
   Wu, Thomas D.
   Schroth, Gary P.
   Oksenberg, Jorge R.
   Hauser, Stephen L.
   Kingsmore, Stephen F.
TI Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
SO NATURE
LA English
DT Article
ID dna methylation; concordance; cells; pathogenesis; profiles; rates; risk; maps
AB Monozygotic or 'identical' twins have been widely studied to dissect the relative contributions of genetics and environment in human diseases. In multiple sclerosis (MS), an autoimmune demyelinating disease and common cause of neurodegeneration and disability in young adults, disease discordance in monozygotic twins has been interpreted to indicate environmental importance in its pathogenesis(1-8). However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture(9-12). Here we report the genome sequences of one MS-discordant monozygotic twin pair, and messenger RNA transcriptome and epigenome sequences of CD4(+) lymphocytes from three MS-discordant, monozygotic twin pairs. No reproducible differences were detected between co-twins among similar to 3.6 million single nucleotide polymorphisms (SNPs) or similar to 0.2 million insertion-deletion polymorphisms. Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and insertion-deletion genotypes, or the expression of similar to 19,000 genes in CD4(+) T cells. Only 2 to 176 differences in the methylation of similar to 2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to similar to 800 methylation differences between T cells of unrelated individuals and several thousand differences between tissues or between normal and cancerous tissues. In the first systematic effort to estimate sequence variation among monozygotic co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first, to our knowledge, female, twin and autoimmune disease individual genome sequences reported.
C1 [Baranzini, Sergio E.; Khankhanian, Pouya; Caillier, Stacy J.; McElroy, Joseph P.; Gomez, Refujia; Oksenberg, Jorge R.; Hauser, Stephen L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Mudge, Joann; van Velkinburgh, Jennifer C.; Miller, Neil A.; Farmer, Andrew D.; Bell, Callum J.; Kim, Ryan W.; May, Gregory D.; Woodward, Jimmy E.; Clendenen, Leonda E.; Ganusova, Elena E.; Schilkey, Faye D.; Ramaraj, Thiruvarangan; Kingsmore, Stephen F.] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
   [Khrebtukova, Irina; Zhang, Lu; Huntley, Jim J.; Luo, Shujun; Schroth, Gary P.] Illumina Inc, Hayward, CA 94545 USA.
   [Pando, Marcelo J.] Stanford Med Sch, Ctr Blood, Palo Alto, CA 94303 USA.
   [Khan, Omar A.] Wayne State Med Sch, Dept Neurol, Detroit, MI 48201 USA.
   [Kwok, Pui-yan] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   [Kwok, Pui-yan; Oksenberg, Jorge R.; Hauser, Stephen L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Wu, Thomas D.] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
C3 University of California System; University of California San Francisco; National Center for Genome Resources (NCGR); Illumina; Stanford University; Wayne State University; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Roche Holding; Genentech; Roche Holding USA
RP Baranzini, SE (corresponding author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
EM sebaran@cgl.ucsf.edu; sfk@ncgr.org
FU Small Ventures USA Inc.; A. J. Brass Foundation; Nancy Davis Foundation; NIH [RR016480, RO1NS26799, RO1NS46297]; National MS Society (NMSS) [RG3060C8, RG2901D9]
NR 33
TC 372
Z9 422
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1351
EP U6
DI 10.1038/nature08990
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000047
PM 20428171
DA 2026-03-09
ER

PT J
AU Decin, L
   Agúndez, M
   Barlow, MJ
   Daniel, F
   Cernicharo, J
   Lombaert, R
   De Beck, E
   Royer, P
   Vandenbussche, B
   Wesson, R
   Polehampton, ET
   Blommaert, JADL
   De Meester, W
   Exter, K
   Feuchtgruber, H
   Gear, WK
   Gomez, HL
   Groenewegen, MAT
   Guélin, M
   Hargrave, PC
   Huygen, R
   Imhof, P
   Ivison, RJ
   Jean, C
   Kahane, C
   Kerschbaum, F
   Leeks, SJ
   Lim, T
   Matsuura, M
   Olofsson, G
   Posch, T
   Regibo, S
   Savini, G
   Sibthorpe, B
   Swinyard, BM
   Yates, JA
   Waelkens, C
AF Decin, L.
   Agundez, M.
   Barlow, M. J.
   Daniel, F.
   Cernicharo, J.
   Lombaert, R.
   De Beck, E.
   Royer, P.
   Vandenbussche, B.
   Wesson, R.
   Polehampton, E. T.
   Blommaert, J. A. D. L.
   De Meester, W.
   Exter, K.
   Feuchtgruber, H.
   Gear, W. K.
   Gomez, H. L.
   Groenewegen, M. A. T.
   Guelin, M.
   Hargrave, P. C.
   Huygen, R.
   Imhof, P.
   Ivison, R. J.
   Jean, C.
   Kahane, C.
   Kerschbaum, F.
   Leeks, S. J.
   Lim, T.
   Matsuura, M.
   Olofsson, G.
   Posch, T.
   Regibo, S.
   Savini, G.
   Sibthorpe, B.
   Swinyard, B. M.
   Yates, J. A.
   Waelkens, C.
TI Warm water vapour in the sooty outflow from a luminous carbon star
SO NATURE
LA English
DT Article
ID circumstellar envelope; model atmospheres; inner wind; rich; irc+10216; chemistry; emission; ammonia; silicon
AB The detection(1) of circumstellar water vapour around the ageing carbon star IRC + 10216 challenged the current understanding of chemistry in old stars, because water was predicted(2) to be almost absent in carbon-rich stars. Several explanations for the water were postulated, including the vaporization of icy bodies (comets or dwarf planets) in orbit around the star(1), grain surface reactions(3), and photochemistry in the outer circumstellar envelope(4). With a single water line detected so far from this one carbon-rich evolved star, it is difficult to discriminate between the different mechanisms proposed. Here we report the detection of dozens of water vapour lines in the far-infrared and sub-millimetre spectrum of IRC + 10216 using the Herschel satellite(5). This includes some high-excitation lines with energies corresponding to similar to 1,000 K, which can be explained only if water is present in the warm inner sooty region of the envelope. A plausible explanation for the warm water appears to be the penetration of ultraviolet photons deep into a clumpy circumstellar envelope. This mechanism also triggers the formation of other molecules, such as ammonia, whose observed abundances(6) are much higher than hitherto predicted(7).
C1 [Decin, L.; Lombaert, R.; De Beck, E.; Royer, P.; Vandenbussche, B.; Blommaert, J. A. D. L.; De Meester, W.; Exter, K.; Huygen, R.; Jean, C.; Regibo, S.; Waelkens, C.] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Decin, L.] Univ Amsterdam, Sterrenkundig Inst Anton Pannekoek, NL-1098 Amsterdam, Netherlands.
   [Agundez, M.; Daniel, F.; Cernicharo, J.] INTA CSIC, CAB, Dept Astrophys, Lab Mol Astrophys, Madrid 28850, Spain.
   [Barlow, M. J.; Wesson, R.; Matsuura, M.; Savini, G.; Yates, J. A.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Polehampton, E. T.; Leeks, S. J.; Lim, T.; Swinyard, B. M.] Rutherford Appleton Lab, Space Sci & Technol Dept, Didcot OX11 0QX, Oxon, England.
   [Polehampton, E. T.] Univ Lethbridge, Inst Space Imaging Sci, Lethbridge, AB T1J 1B1, Canada.
   [Agundez, M.] Observ Paris, LUTH, F-92190 Meudon, France.
   [Feuchtgruber, H.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Gear, W. K.; Gomez, H. L.; Hargrave, P. C.] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, S Glam, Wales.
   [Groenewegen, M. A. T.] Royal Observ Belgium, B-1180 Brussels, Belgium.
   [Imhof, P.] Blue Sky Spect, Lethbridge, AB T1J 0N9, Canada.
   [Ivison, R. J.; Sibthorpe, B.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Olofsson, G.] Stockholm Univ, AlbaNova Univ Ctr, Dept Astron, S-10691 Stockholm, Sweden.
   [Kerschbaum, F.; Posch, T.] Univ Vienna, Dept Astron, A-1180 Vienna, Austria.
   [Matsuura, M.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Guelin, M.] Inst Radioastron Millimetr, F-38406 St Martin Dheres, France.
   [Kahane, C.] Observ Grenoble, Astrophys Lab, F-38041 Grenoble 9, France.
C3 KU Leuven; University of Amsterdam; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); University of London; University College London; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of Lethbridge; Universite Paris Cite; Universite PSL; Observatoire de Paris; Max Planck Society; Cardiff University; University of Edinburgh; Stockholm University; University of Vienna; University of London; University College London; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Decin, L (corresponding author), Katholieke Univ Leuven, Inst Sterrenkunde, Celestijnenlaan 200D, B-3001 Louvain, Belgium.
EM Leen.Decin@ster.kuleuven.be
FU BMVIT (Austria); ESA-PRODEX (Belgium); CEA/CNES (France); DLR (Germany); ASI (Italy); CICT/MCT (Spain); CSA (Canada); NAOC (China); CEA, CNES, CNRS (France); MCINN (Spain); SNSB (Sweden); STFC (UK); NASA (USA); INSU/CNRS (France); MPG (Germany); IGN (Spain); STFC [ST/H008543/1, ST/G002827/1] Funding Source: UKRI; Science and Technology Facilities Council [PP/E001181/1, ST/H008543/1, ST/G002827/1] Funding Source: researchfish
NR 30
TC 85
Z9 92
U1 0
U2 21
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 64
EP 67
DI 10.1038/nature09344
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200035
PM 20811453
DA 2026-03-09
ER

PT J
AU Hiraga, T
   Miyazaki, T
   Tasaka, M
   Yoshida, H
AF Hiraga, Takehiko
   Miyazaki, Tomonori
   Tasaka, Miki
   Yoshida, Hidehiro
TI Mantle superplasticity and its self-made demise
SO NATURE
LA English
DT Article
ID earths lower mantle; grain-growth; mgsio3 perovskite; transition-zone; deformation; diffusion; flow; constraints; forsterite; feldspar
AB The unusual capability of solid crystalline materials to deform plastically, known as superplasticity, has been found in metals and even in ceramics(1). Such superplastic behaviour has been speculated for decades to take place in geological materials, ranging from surface ice sheets to the Earth's lowermantle(2-8). In materials science, superplasticity is confirmed when the material deforms with large tensile strain without failure; however, no experimental studies have yet shown this characteristic in geomaterials. Here we show that polycrystalline forsterite + periclase (9:1) and forsterite 1 enstatite + diopside (7:2.5:0.5), which are good analogues for Earth's mantle, undergo homogeneous elongation of up to 500 per cent under subsolidus conditions. Such superplastic deformation is accompanied by strain hardening, which is well explained by the grain size sensitivity of superplasticity and grain growth under grain switching conditions (that is, grain boundary sliding); grain boundary sliding is the main deformation mechanism for superplasticity. We apply the observed strain-grain size-viscosity relationship to portions of the mantle where superplasticity has been presumed to take place, such as localized shear zones in the upper mantle and within subducting slabs penetrating into the transition zone and lower mantle after a phase transformation. Calculations show that superplastic flow in the mantle is inevitably accompanied by significant grain growth that can bring fine grained (<= 1 mu m) rocks to coarse-grained (1-10 mm) aggregates, resulting in increasing mantle viscosity and finally termination of superplastic flow.
C1 [Hiraga, Takehiko; Miyazaki, Tomonori; Tasaka, Miki] Univ Tokyo, Earthquake Res Inst, Bunkyo Ku, Tokyo 1130032, Japan.
   [Yoshida, Hidehiro] Natl Inst Mat Sci, Nano Ceram Ctr, Tsukuba, Ibaraki 3050047, Japan.
C3 University of Tokyo; National Institute for Materials Science
RP Hiraga, T (corresponding author), Univ Tokyo, Earthquake Res Inst, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan.
EM hiraga@eri.u-tokyo.ac.jp
FU JSPS [A 20684024]; Earthquake Research Institute;  [A 19686042];  [B 21360328];  [474-19053008]; Grants-in-Aid for Scientific Research [20684024] Funding Source: KAKEN
NR 28
TC 72
Z9 79
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 23
PY 2010
VL 468
IS 7327
BP 1091
EP U490
DI 10.1038/nature09685
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800056
PM 21179165
DA 2026-03-09
ER

PT J
AU Wang, Q
   Mynar, JL
   Yoshida, M
   Lee, E
   Lee, M
   Okuro, K
   Kinbara, K
   Aida, T
AF Wang, Qigang
   Mynar, Justin L.
   Yoshida, Masaru
   Lee, Eunji
   Lee, Myongsoo
   Okuro, Kou
   Kinbara, Kazushi
   Aida, Takuzo
TI High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder
SO NATURE
LA English
DT Article
ID nanocomposite hydrogels; medicine; polymer
AB With the world's focus on reducing our dependency on fossil-fuel energy, the scientific community can investigate new plastic materials that are much less dependent on petroleum than are conventional plastics. Given increasing environmental issues, the idea of replacing plastics with water-based gels, so-called hydrogels, seems reasonable. Here we report that water and clay (2-3 per cent by mass), when mixed with a very small proportion (<0.4 per cent by mass) of organic components, quickly form a transparent hydrogel. This material can be moulded into shape-persistent, free-standing objects owing to its exceptionally great mechanical strength, and rapidly and completely self-heals when damaged. Furthermore, it preserves biologically active proteins for catalysis. So far(1) no other hydrogels, including conventional ones formed by mixing polymeric cations and anions(2,3) or polysaccharides and borax(4), have been reported to possess all these features. Notably, this material is formed only by non-covalent forces resulting from the specific design of a telechelic dendritic macromolecule with multiple adhesive termini for binding to clay.
C1 [Wang, Qigang; Mynar, Justin L.; Okuro, Kou; Kinbara, Kazushi; Aida, Takuzo] Univ Tokyo, Sch Engn, Dept Chem & Biotechnol, Bunkyo Ku, Tokyo 1138656, Japan.
   [Mynar, Justin L.; Aida, Takuzo] Natl Museum Emerging Sci & Innovat, Japan Sci & Technol Agcy, ERATO SORST Nanospace Project, Koto Ku, Tokyo 1350064, Japan.
   [Yoshida, Masaru] Natl Inst Adv Ind Sci & Technol, Nanotechnol Res Inst, Tsukuba, Ibaraki 3058565, Japan.
   [Lee, Eunji; Lee, Myongsoo] Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea.
   [Lee, Eunji; Lee, Myongsoo] Seoul Natl Univ, Ctr Supramol Nanoassembly, Seoul 151747, South Korea.
C3 University of Tokyo; Japan Science & Technology Agency (JST); National Institute of Advanced Industrial Science & Technology (AIST); Seoul National University (SNU); Seoul National University (SNU)
RP Aida, T (corresponding author), Univ Tokyo, Sch Engn, Dept Chem & Biotechnol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
EM jmynar@berkeley.edu; aida@macro.t.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science
NR 30
TC 1435
Z9 1585
U1 12
U2 2119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 339
EP 343
DI 10.1038/nature08693
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100040
PM 20090750
DA 2026-03-09
ER

PT J
AU Lay, T
   Ammon, CJ
   Kanamori, H
   Rivera, L
   Koper, KD
   Hutko, AR
AF Lay, Thorne
   Ammon, Charles J.
   Kanamori, Hiroo
   Rivera, Luis
   Koper, Keith D.
   Hutko, Alexander R.
TI The 2009 Samoa-Tonga great earthquake triggered doublet
SO NATURE
LA English
DT Article
ID coupled subduction zones; stress transfer; seismicity; inversion; cycle; times
AB Great earthquakes (having seismic magnitudes of at least 8) usually involve abrupt sliding of rock masses at a boundary between tectonic plates. Such interplate ruptures produce dynamic and static stress changes that can activate nearby intraplate aftershocks, as is commonly observed in the trench-slope region seaward of a great subduction zone thrust event(1-4). The earthquake sequence addressed here involves a rare instance in which a great trench-slope intraplate earthquake triggered extensive interplate faulting, reversing the typical pattern and broadly expanding the seismic and tsunami hazard. On 29 September 2009, within two minutes of the initiation of a normal faulting event with moment magnitude 8.1 in the outer trench-slope at the northern end of the Tonga subduction zone, two major interplate underthrusting subevents (both with moment magnitude 7.8), with total moment equal to a second great earthquake of moment magnitude 8.0, ruptured the nearby subduction zone megathrust. The collective faulting produced tsunami waves with localized regions of about 12 metres run-up that claimed 192 lives in Samoa, American Samoa and Tonga. Overlap of the seismic signals obscured the fact that distinct faults separated by more than 50km had ruptured with different geometries, with the triggered thrust faulting only being revealed by detailed seismic wave analyses. Extensive interplate and intraplate aftershock activity was activated over a large region of the northern Tonga subduction zone.
C1 [Lay, Thorne] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Ammon, Charles J.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Kanamori, Hiroo] CALTECH, Seismol Lab, Pasadena, CA 91125 USA.
   [Rivera, Luis] Univ Strasbourg, CNRS, UMR7516, Inst Phys Globe Strasbourg, Strasbourg, France.
   [Koper, Keith D.] St Louis Univ, Dept Earth & Atmospher Sci, St Louis, MO 63108 USA.
   [Hutko, Alexander R.] US Geol Survey, NEIC, Denver, CO 80225 USA.
C3 University of California System; University of California Santa Cruz; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; California Institute of Technology; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Saint Louis University; United States Department of the Interior; United States Geological Survey
RP Lay, T (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
EM tlay@ucsc.edu
FU NSF [EAR0635570]; USGS [05HQGR0174]
NR 33
TC 166
Z9 187
U1 2
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 AUG 19
PY 2010
VL 466
IS 7309
BP 964
EP U85
DI 10.1038/nature09214
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300032
PM 20725038
DA 2026-03-09
ER

PT J
AU Choi, JH
   Banks, AS
   Estall, JL
   Kajimura, S
   Boström, P
   Laznik, D
   Ruas, JL
   Chalmers, MJ
   Kamenecka, TM
   Blüher, M
   Griffin, PR
   Spiegelman, BM
AF Choi, Jang Hyun
   Banks, Alexander S.
   Estall, Jennifer L.
   Kajimura, Shingo
   Bostroem, Pontus
   Laznik, Dina
   Ruas, Jorge L.
   Chalmers, Michael J.
   Kamenecka, Theodore M.
   Blueher, Matthias
   Griffin, Patrick R.
   Spiegelman, Bruce M.
TI Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγ by Cdk5
SO NATURE
LA English
DT Article
ID activated-receptor-gamma; insulin-resistance; ligand-binding; adipose-tissue; oligonucleotide arrays; expression; adipogenesis; hormone; thiazolidinediones; stimulation
AB Obesity induced in mice by high-fat feeding activates the protein kinase Cdk5 (cyclin-dependent kinase 5) in adipose tissues. This results in phosphorylation of the nuclear receptor PPAR gamma (peroxisome proliferator-activated receptor c), a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. This modification of PPAR gamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin. The phosphorylation of PPAR gamma by Cdk5 is blocked by anti-diabetic PPAR gamma ligands, such as rosiglitazone and MRL24. This inhibition works both in vivo and in vitro, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPAR gamma phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. All these findings strongly suggest that Cdk5-mediated phosphorylation of PPAR gamma may be involved in the pathogenesis of insulin-resistance, and present an opportunity for development of an improved generation of anti-diabetic drugs through PPAR gamma.
C1 [Choi, Jang Hyun; Banks, Alexander S.; Estall, Jennifer L.; Kajimura, Shingo; Bostroem, Pontus; Laznik, Dina; Ruas, Jorge L.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Choi, Jang Hyun; Banks, Alexander S.; Estall, Jennifer L.; Kajimura, Shingo; Bostroem, Pontus; Laznik, Dina; Ruas, Jorge L.; 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.; Estall, Jennifer L.; Kajimura, Shingo; Bostroem, Pontus; Laznik, Dina; Ruas, Jorge L.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Chalmers, Michael J.; Kamenecka, Theodore M.; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
   [Blueher, Matthias] Univ Leipzig, Dept Med, Leipzig, Germany.
C3 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; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Leipzig University
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
FU NIH [DK31405, DK087853]; Deutsche Forschungsgemeinschaft (DFG); N National Institute of Mental Health [U54-MH084512]; NIH National Institute of General Medical Sciences [R01-GM084041]; Clinical Research group [KFO 152, BL 833/1-1]
NR 46
TC 751
Z9 864
U1 2
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 451
EP U1
DI 10.1038/nature09291
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200027
PM 20651683
DA 2026-03-09
ER

PT J
AU Ito, S
   D'Alessio, AC
   Taranova, OV
   Hong, K
   Sowers, LC
   Zhang, Y
AF Ito, Shinsuke
   D'Alessio, Ana C.
   Taranova, Olena V.
   Hong, Kwonho
   Sowers, Lawrence C.
   Zhang, Yi
TI Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification
SO NATURE
LA English
DT Article
ID zygotic paternal genome; embryonic stem-cells; dna methylation; demethylation; 5-hydroxymethylcytosine; pluripotency; patterns; gene
AB DNA methylation is one of the best-characterized epigenetic modifications(1-4). Although the enzymes that catalyse DNA methylation have been characterized, enzymes responsible for demethylation have been elusive(5). A recent study indicates that the human TET1 protein could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process(6). Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction. Tet1 has an important role in mouse embryonic stem (ES) cell maintenance through maintaining the expression of Nanog in ES cells. Downregulation of Nanog via Tet1 knockdown correlates with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification.
C1 [Ito, Shinsuke; D'Alessio, Ana C.; Taranova, Olena V.; Hong, Kwonho; Zhang, Yi] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
   [Ito, Shinsuke; D'Alessio, Ana C.; Taranova, Olena V.; Hong, Kwonho; Zhang, Yi] Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Sowers, Lawrence C.] Loma Linda Univ, Sch Med, Dept Basic Sci, Loma Linda, CA 92350 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; Howard Hughes Medical Institute; University of North Carolina; University of North Carolina Chapel Hill; Loma Linda University
RP Zhang, Y (corresponding author), Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
EM yi_zhang@med.unc.edu
FU NIH [GM68804, CA084487]
NR 19
TC 2083
Z9 2517
U1 2
U2 315
PU 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 26
PY 2010
VL 466
IS 7310
BP 1129
EP U151
DI 10.1038/nature09303
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600045
PM 20639862
DA 2026-03-09
ER

PT J
AU Dang, SY
   Sun, LF
   Huang, YJ
   Lu, FR
   Liu, YF
   Gong, HP
   Wang, JW
   Yan, NE
AF Dang, Shangyu
   Sun, Linfeng
   Huang, Yongjian
   Lu, Feiran
   Liu, Yufeng
   Gong, Haipeng
   Wang, Jiawei
   Yan, Nieng
TI Structure of a fucose transporter in an outward-open conformation
SO NATURE
LA English
DT Article
ID h+ symport protein; lactose permease; mechanism; binding; identification; fucp; site
AB The major facilitator superfamily (MFS) transporters are an ancient and widespread family of secondary active transporters(1). In Escherichia coli, the uptake of L-fucose, a source of carbon for microorganisms, is mediated by an MFS proton symporter, FucP(2,3). Despite intensive study of the MFS transporters, atomic structure information is only available on three proteins and the outward-open conformation has yet to be captured(4-6). Here we report the crystal structure of FucP at 3.1 angstrom resolution, which shows that it contains an outward-open, amphipathic cavity. The similarly folded amino and carboxyl domains of FucP have contrasting surface features along the transport path, with negative electrostatic potential on the N domain and hydrophobic surface on the C domain. FucP only contains two acidic residues along the transport path, Asp 46 and Glu 135, which can undergo cycles of protonation and deprotonation. Their essential role in active transport is supported by both in vivo and in vitro experiments. Structure-based biochemical analyses provide insights into energy coupling, substrate recognition and the transport mechanism of FucP.
C1 [Wang, Jiawei] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   Tsinghua Univ, Sch Med, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University
RP Wang, JW (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM jwwang@tsinghua.edu.cn; nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918802]; Tsinghua University [985]; Yuyuan Foundation; Li Foundation
NR 33
TC 228
Z9 270
U1 1
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 7
PY 2010
VL 467
IS 7316
BP 734
EP U130
DI 10.1038/nature09406
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500044
PM 20877283
DA 2026-03-09
ER

PT J
AU Komiyama, T
   Sato, TR
   O'Connor, DH
   Zhang, YX
   Huber, D
   Hooks, BM
   Gabitto, M
   Svoboda, K
AF Komiyama, Takaki
   Sato, Takashi R.
   O'Connor, Daniel H.
   Zhang, Ying-Xin
   Huber, Daniel
   Hooks, Bryan M.
   Gabitto, Mariano
   Svoboda, Karel
TI Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice
SO NATURE
LA English
DT Article
ID in-vivo; cellular resolution; prefrontal cortex; cross-correlation; transgenic mice; rat; organization; neurons; networks; channelrhodopsin-2
AB Cortical neurons form specific circuits(1), but the functional structure of this microarchitecture and its relation to behaviour are poorly understood. Two-photon calcium imaging can monitor activity of spatially defined neuronal ensembles in the mammalian cortex(2-5). Here we applied this technique to the motor cortex of mice performing a choice behaviour. Head-fixed mice were trained to lick in response to one of two odours, and to withhold licking for the other odour(6,7). Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation(8,9) and trans-synaptic tracing(10,11) identified two non-overlapping candidate tongue motor cortical areas. Inactivating either area impaired voluntary licking. Imaging in layer 2/3 showed neurons with diverse response types in both areas. Activity in approximately half of the imaged neurons distinguished trial types associated with different actions. Many neurons showed modulation coinciding with or preceding the action, consistent with their involvement in motor control. Neurons with different response types were spatially intermingled. Nearby neurons (within similar to 150 mm) showed pronounced coincident activity. These temporal correlations increased with learning within and across behavioural sessions, specifically for neuron pairs with similar response types. We propose that correlated activity in specific ensembles of functionally related neurons is a signature of learning-related circuit plasticity. Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour.
C1 [Komiyama, Takaki; Sato, Takashi R.; O'Connor, Daniel H.; Zhang, Ying-Xin; Huber, Daniel; Hooks, Bryan M.; Svoboda, Karel] HHMI, Ashburn, VA 20147 USA.
   [Gabitto, Mariano] Univ Calif San Diego, HHMI, La Jolla, CA 92093 USA.
   [Gabitto, Mariano] Univ Calif San Diego, Dept Neurobiol, La Jolla, CA 92093 USA.
   [Gabitto, Mariano] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 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; University of California System; University of California San Diego
RP Komiyama, T (corresponding author), HHMI, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM komiyamat@janelia.hhmi.org
FU Howard Hughes Medical Institute
NR 38
TC 359
Z9 444
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 APR 22
PY 2010
VL 464
IS 7292
BP 1182
EP U99
DI 10.1038/nature08897
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100035
PM 20376005
DA 2026-03-09
ER

PT J
AU Mücke, M
   Figueroa, E
   Bochmann, J
   Hahn, C
   Murr, K
   Ritter, S
   Villas-Boas, CJ
   Rempe, G
AF Muecke, Martin
   Figueroa, Eden
   Bochmann, Joerg
   Hahn, Carolin
   Murr, Karim
   Ritter, Stephan
   Villas-Boas, Celso J.
   Rempe, Gerhard
TI Electromagnetically induced transparency with single atoms in a cavity
SO NATURE
LA English
DT Article
ID strongly interacting photons; generation
AB Optical nonlinearities offer unique possibilities for the control of light with light. A prominent example is electromagnetically induced transparency (EIT), where the transmission of a probe beam through an optically dense medium is manipulated by means of a control beam(1-3). Scaling such experiments into the quantum domain with one (or just a few) particles of light and matter will allow for the implementation of quantum computing protocols with atoms and photons(4-7), or the realization of strongly interacting photon gases exhibiting quantum phase transitions of light(8,9). Reaching these aims is challenging and requires an enhanced matter-light interaction, as provided by cavity quantum electrodynamics(10-12). Here we demonstrate EIT with a single atom quasi-permanently trapped inside a high-finesse optical cavity. The atom acts as a quantum-optical transistor with the ability to coherently control(13) the transmission of light through the cavity. We investigate the scaling of EIT when the atom number is increased one-by-one. The measured spectra are in excellent agreement with a theoretical model. Merging EIT with cavity quantum electrodynamics and single quanta of matter is likely to become the cornerstone for novel applications, such as dynamic control of the photon statistics of propagating light fields(14) or the engineering of Fock state superpositions of flying light pulses(15)
C1 [Muecke, Martin; Figueroa, Eden; Bochmann, Joerg; Hahn, Carolin; Murr, Karim; Ritter, Stephan; Villas-Boas, Celso J.; Rempe, Gerhard] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Villas-Boas, Celso J.] Univ Fed Sao Carlos, Dept Fis, BR-13565905 Sao Paulo, Brazil.
C3 Max Planck Society; Universidade Federal de Sao Carlos
RP Figueroa, E (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM eden.figueroa@mpq.mpg.de
FU Deutsche Forschungsgemeinschaft (Research Unit) [635]; European Union (IST); Alexander von Humboldt Foundation; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; Brazilian National Institute for Science and Technology of Quantum Information (INCT-IQ)
NR 33
TC 270
Z9 294
U1 3
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 755
EP 758
DI 10.1038/nature09093
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800039
PM 20463661
DA 2026-03-09
ER

PT J
AU Ohiorhenuan, IE
   Mechler, F
   Purpura, KP
   Schmid, AM
   Hu, Q
   Victor, JD
AF Ohiorhenuan, Ifije E.
   Mechler, Ferenc
   Purpura, Keith P.
   Schmid, Anita M.
   Hu, Qin
   Victor, Jonathan D.
TI Sparse coding and high-order correlations in fine-scale cortical networks
SO NATURE
LA English
DT Article
ID primary visual-cortex; neurons; connectivity; information; population; responses; retina
AB Connectivity in the cortex is organized at multiple scales(1-5), suggesting that scale-dependent correlated activity is particularly important for understanding the behaviour of sensory cortices and their function in stimulus encoding. We analysed the scale-dependent structure of cortical interactions by using maximum entropy models(6-9) to characterize multiple-tetrode recordings from primary visual cortex of anaesthetized macaque monkeys (Macaca mulatta). We compared the properties of firing patterns among local clusters of neurons (<300 mm apart) with those of neurons separated by larger distances (600-2,500 mu m). Here we report that local firing patterns are distinctive: whereas multi-neuronal firing patterns at larger distances can be predicted by pairwise interactions, patterns within local clusters often show evidence of high-order correlations. Surprisingly, these local correlations are flexible and rapidly reorganized by visual input. Although they modestly reduce the amount of information that a cluster conveys, they also modify the format of this information, creating sparser codes by increasing the periods of total quiescence, and concentrating information into briefer periods of common activity. These results imply a hierarchical organization of neuronal correlations: simple pairwise correlations link neurons over scales of tens to hundreds of minicolumns, but on the scale of a few minicolumns, ensembles of neurons form complex subnetworks whose moment-to-moment effective connectivity is dynamically reorganized by the stimulus.
C1 [Ohiorhenuan, Ifije E.; Mechler, Ferenc; Purpura, Keith P.; Schmid, Anita M.; Hu, Qin; Victor, Jonathan D.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
C3 Cornell University; Weill Cornell Medicine
RP Ohiorhenuan, IE (corresponding author), Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
EM ifo2001@med.cornell.edu
FU National Institutes of Health [EY19454, GM07739, EY09314]; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
NR 30
TC 244
Z9 279
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 JUL 29
PY 2010
VL 466
IS 7306
BP 617
EP U4
DI 10.1038/nature09178
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100052
PM 20601940
DA 2026-03-09
ER

PT J
AU Ali, JR
   Huber, M
AF Ali, Jason R.
   Huber, Matthew
TI Mammalian biodiversity on Madagascar controlled by ocean currents
SO NATURE
LA English
DT Article
ID mozambique channel; colonization; origins; dispersal; primates; climate; nuclear; africa
AB Madagascar hosts one of the world's most unusual, endemic, diverse and threatened concentrations of fauna(1). To explain its unique, imbalanced biological diversity, G. G. Simpson proposed the 'sweepstakes hypothesis', according to which the ancestors of Madagascar's present-day mammal stock rafted there from Africa(2). This is an important hypothesis in biogeography and evolutionary theory for how animals colonize new frontiers(1,3-5), but its validity is questioned(5-9). Studies suggest that currents were inconsistent with rafting to Madagascar(9) and that land bridges provided the migrants' passage(5-8). Here we show that currents could have transported the animals to the island and highlight evidence inconsistent with the land-bridge hypothesis. Using palaeogeographic reconstructions and palaeo-oceanographic modelling, we find that strong surface currents flowed from northeast Mozambique and Tanzania eastward towards Madagascar during the Palaeogene period, exactly as required by the 'sweepstakes process'. Subsequently, Madagascar advanced north towards the equatorial gyre and the regional current system evolved into its modern configuration with flows westward(10) from Madagascar to Africa. This may explain why no fully non-aquatic land mammals have colonized Madagascar since the arrival of the rodents and carnivorans during the early-Miocene epoch. One implication is that rafting may be the dominant means of overseas dispersal in the Cenozoic era when palaeocurrent directions are properly considered.
C1 [Huber, Matthew] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
   [Huber, Matthew] Purdue Univ, Purdue Climate Change Res Ctr, W Lafayette, IN 47907 USA.
   [Ali, Jason R.] Univ Hong Kong, Dept Earth Sci, Hong Kong, Hong Kong, Peoples R China.
C3 Purdue University System; Purdue University; Purdue University System; Purdue University; University of Hong Kong
RP Huber, M (corresponding author), Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
EM huberm@purdue.edu
FU US National Science Foundation (NSF) [0927946-ATM]
NR 33
TC 235
Z9 268
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 FEB 4
PY 2010
VL 463
IS 7281
BP 653
EP U80
DI 10.1038/nature08706
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900034
PM 20090678
DA 2026-03-09
ER

PT J
AU van Dokkum, PG
   Conroy, C
AF van Dokkum, Pieter G.
   Conroy, Charlie
TI A substantial population of low-mass stars in luminous elliptical galaxies
SO NATURE
LA English
DT Article
ID m-dwarf; stellar; evolution; fragmentation; constraints; spectra; growth
AB The stellar initial mass function (IMF) describes the mass distribution of stars at the time of their formation and is of fundamental importance for many areas of astrophysics. The IMF is reasonably well constrained in the disk of the Milky Way(1) but we have very little direct information on the form of the IMF in other galaxies and at earlier cosmic epochs. Here we report observations of the Na I doublet(2,3) and the Wing-Ford molecular FeH band(4,5) in the spectra of elliptical galaxies. These lines are strong in stars with masses less than 0.3 M-circle dot (where M-circle dot is the mass of the Sun) and are weak or absent in all other types of stars(5-7). We unambiguously detect both signatures, consistent with previous studies(8) that were based on data of lower signal-to-noise ratio. The direct detection of the light of low-mass stars implies that they are very abundant in elliptical galaxies, making up over 80% of the total number of stars and contributing more than 60% of the total stellar mass. We infer that the IMF in massive star-forming galaxies in the early Universe produced many more low-mass stars than the IMF in the Milky Way disk, and was probably slightly steeper than the Salpeter form(9) in the mass range 0.1 M-circle dot to 1 M-circle dot.
C1 [van Dokkum, Pieter G.] Yale Univ, Dept Astron, New Haven, CT 06511 USA.
   [Conroy, Charlie] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Conroy, Charlie] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 Yale University; Princeton University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University
RP van Dokkum, PG (corresponding author), Yale Univ, Dept Astron, New Haven, CT 06511 USA.
EM pieter.vandokkum@yale.edu
FU Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908368] Funding Source: National Science Foundation
NR 30
TC 427
Z9 455
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 DEC 16
PY 2010
VL 468
IS 7326
BP 940
EP 942
DI 10.1038/nature09578
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600041
PM 21124316
DA 2026-03-09
ER

PT J
AU Chao, HT
   Chen, HM
   Samaco, RC
   Xue, MS
   Chahrour, M
   Yoo, J
   Neul, JL
   Gong, SC
   Lu, HC
   Heintz, N
   Ekker, M
   Rubenstein, JLR
   Noebels, JL
   Rosenmund, C
   Zoghbi, HY
AF Chao, Hsiao-Tuan
   Chen, Hongmei
   Samaco, Rodney C.
   Xue, Mingshan
   Chahrour, Maria
   Yoo, Jong
   Neul, Jeffrey L.
   Gong, Shiaoching
   Lu, Hui-Chen
   Heintz, Nathaniel
   Ekker, Marc
   Rubenstein, John L. R.
   Noebels, Jeffrey L.
   Rosenmund, Christian
   Zoghbi, Huda Y.
TI Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes
SO NATURE
LA English
DT Article
ID glutamic-acid decarboxylase; cpg-binding protein-2; mouse model; neuronal mecp2; young girls; 67 kda; mice; gene; schizophrenia; mutation
AB Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (c-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.
C1 [Chao, Hsiao-Tuan; Xue, Mingshan; Noebels, Jeffrey L.; Rosenmund, Christian; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
   [Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C.; Chahrour, Maria; Noebels, Jeffrey L.; Rosenmund, Christian; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Yoo, Jong; Noebels, Jeffrey L.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
   [Neul, Jeffrey L.; Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Neul, Jeffrey L.; Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
   [Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
   [Gong, Shiaoching; Heintz, Nathaniel] Rockefeller Univ, New York, NY 10021 USA.
   [Gong, Shiaoching; Heintz, Nathaniel] Howard Hughes Med Inst, New York, NY 10021 USA.
   [Ekker, Marc] Univ Ottawa, Dept Biol, Ctr Adv Res Environm Genom, Ottawa, ON K1N 6N5, Canada.
   [Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Howard Hughes Medical Institute; Baylor College of Medicine; Rockefeller University; Howard Hughes Medical Institute; University of Ottawa; University of California System; University of California San Francisco
RP Rosenmund, C (corresponding author), Charite, Neurosci Res Ctr, D-10117 Berlin, Germany.
EM christian.rosenmund@charite.de; hzoghbi@bcm.edu
FU Howard Hughes Medical Institute; National Institute of Neurological Disorders and Stroke (NINDS) [HD053862, 29709]; Simons Foundation; Rett Syndrome Research Trust; Intellectual and Developmental Disability Research Centers [HD024064]; International Rett Syndrome Foundation; Autism Speaks; National Institute of Mental Health [F31MH078678]; Baylor Research Advocates for Student Scientists; McNair Fellowships; National Institute of Neurological Disorders and Stroke [T32NS043124, R01NS057819] Funding Source: NIH RePORTER
NR 50
TC 923
Z9 1103
U1 4
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 263
EP 269
DI 10.1038/nature09582
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000043
PM 21068835
DA 2026-03-09
ER

PT J
AU Di-Poï, N
   Montoya-Burgos, JI
   Miller, H
   Pourquié, O
   Milinkovitch, MC
   Duboule, D
AF Di-Poi, Nicolas
   Montoya-Burgos, Juan I.
   Miller, Hilary
   Pourquie, Olivier
   Milinkovitch, Michel C.
   Duboule, Denis
TI Changes in Hox genes' structure and function during the evolution of the squamate body plan
SO NATURE
LA English
DT Article
ID phylogenetic analysis; clusters; snakes; embryos; complex; growth; mouse; code
AB Hox genes are central to the specification of structures along the anterior-posterior body axis(1,2), and modifications in their expression have paralleled the emergence of diversity in vertebrate body plans(3,4). Here we describe the genomic organization of Hox clusters in different reptiles and show that squamates have accumulated unusually large numbers of transposable elements at these loci(5), reflecting extensive genomic rearrangements of coding and non-coding regulatory regions. Comparative expression analyses between two species showing different axial skeletons, the corn snake and the whiptail lizard, revealed major alterations in Hox13 and Hox10 expression features during snake somitogenesis, in line with the expansion of both caudal and thoracic regions. Variations in both protein sequences and regulatory modalities of posterior Hox genes suggest how this genetic system has dealt with its intrinsic collinear constraint to accompany the substantial morphological radiation observed in this group.
C1 [Di-Poi, Nicolas; Montoya-Burgos, Juan I.; Milinkovitch, Michel C.; Duboule, Denis] Univ Geneva, Dept Zool & Anim Biol, Natl Res Ctr Frontiers Genet, CH-1211 Geneva 4, Switzerland.
   [Miller, Hilary] Victoria Univ Wellington, Sch Biol Sci, Wellington 6140, New Zealand.
   [Pourquie, Olivier] Howard Hughes Med Inst, Kansas City, MO 64110 USA.
   [Pourquie, Olivier] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Duboule, Denis] Fed Inst Technol EPFL, Sch Life Sci, CH-1015 Lausanne, Switzerland.
C3 University of Geneva; Victoria University Wellington; Howard Hughes Medical Institute; Stowers Institute for Medical Research; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+)
RP Duboule, D (corresponding author), Univ Geneva, Dept Zool & Anim Biol, Natl Res Ctr Frontiers Genet, Sci 3, CH-1211 Geneva 4, Switzerland.
EM denis.duboule@unige.ch
FU University of Geneva; Federal Institute of Technology in Lausanne; Swiss National Research Fund; National Research Center (NCCR); EU; ERC
NR 30
TC 134
Z9 152
U1 2
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 99
EP 103
DI 10.1038/nature08789
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500041
PM 20203609
DA 2026-03-09
ER

PT J
AU Pasini, D
   Cloos, PAC
   Walfridsson, J
   Olsson, L
   Bukowski, JP
   Johansen, JV
   Bak, M
   Tommerup, N
   Rappsilber, J
   Helin, K
AF Pasini, Diego
   Cloos, Paul A. C.
   Walfridsson, Julian
   Olsson, Linda
   Bukowski, John-Paul
   Johansen, Jens V.
   Bak, Mads
   Tommerup, Niels
   Rappsilber, Juri
   Helin, Kristian
TI JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells
SO NATURE
LA English
DT Article
ID histone methyltransferase activity; developmental regulators; cardiac development; jumonji; ezh2; differentiation; gastrulation; methylation; proteins; enhancer
AB The Polycomb group (PcG) proteins have an important role in controlling the expression of genes essential for development, differentiation and maintenance of cell fates(1,2). The Polycomb repressive complex 2 (PRC2) is believed to regulate transcriptional repression by catalysing the di- and tri-methylation of lysine 27 on histone H3 (H3K27me2/3)(2). At present, it is unknown how the PcG proteins are recruited to their target promoters in mammalian cells(3). Here we show that PRC2 forms a stable complex with the Jumonji- and ARID-domain-containing protein, JARID2 (ref. 4). Using genome-wide location analysis, we show that JARID2 binds to more than 90% of previously mapped PcG target genes. Notably, we show that JARID2 is sufficient to recruit PcG proteins to a heterologous promoter, and that inhibition of JARID2 expression leads to a major loss of PcG binding and to a reduction of H3K27me3 levels on target genes. Consistent with an essential role for PcG proteins in early development(5-8), we demonstrate that JARID2 is required for the differentiation of mouse embryonic stem cells. Thus, these results demonstrate that JARID2 is essential for the binding of PcG proteins to target genes and, consistent with this, for the proper differentiation of embryonic stem cells and normal development.
C1 [Pasini, Diego; Cloos, Paul A. C.; Walfridsson, Julian; Olsson, Linda; Bukowski, John-Paul; Johansen, Jens V.; Helin, Kristian] Univ Copenhagen, BRIC, DK-2200 Copenhagen N, Denmark.
   [Pasini, Diego; Cloos, Paul A. C.; Walfridsson, Julian; Olsson, Linda; Bukowski, John-Paul; Helin, Kristian] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen N, Denmark.
   [Bak, Mads; Tommerup, Niels] Univ Copenhagen, Dept Cellular & Mol Med, Wilhelm Johannsen Ctr Funct Genome Res, DK-2200 Copenhagen N, 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 N, Denmark.
EM kristian.helin@bric.ku.dk
FU Danish Medical Research Council; Benzon Foundation; NordForsk (Nordic Union); Danish National Research Foundation; Lundbeck Foundation; Danish Cancer Society; Novo Nordisk Foundation; Danish Natural Science Research Council; Lundbeck Foundation [R67-2010-6206, R13-2007-1172] Funding Source: researchfish
NR 33
TC 456
Z9 551
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 MAR 11
PY 2010
VL 464
IS 7286
BP 306
EP U193
DI 10.1038/nature08788
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100053
PM 20075857
DA 2026-03-09
ER

PT J
AU Ruta, V
   Datta, SR
   Vasconcelos, ML
   Freeland, J
   Looger, LL
   Axel, R
AF Ruta, Vanessa
   Datta, Sandeep Robert
   Vasconcelos, Maria Luisa
   Freeland, Jessica
   Looger, Loren L.
   Axel, Richard
TI A dimorphic pheromone circuit in Drosophila from sensory input to descending output
SO NATURE
LA English
DT Article
ID green fluorescent protein; male courtship behavior; receptor neurons; neural circuitry; fruitless gene; melanogaster; representation; aggression; organization; brain
AB Drosophila show innate olfactory-driven behaviours that are observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically programmed. Despite the numerical simplicity of the fly nervous system, features of the anatomical organization of the fly brain often confound the delineation of these circuits. Here we identify a neural circuit responsive to cVA, a pheromone that elicits sexually dimorphic behaviours(1-4). We have combined neural tracing using an improved photoactivatable green fluorescent protein (PA-GFP) with electrophysiology, optical imaging and laser-mediated microlesioning to map this circuit from the activation of sensory neurons in the antennae to the excitation of descending neurons in the ventral nerve cord. This circuit is concise and minimally comprises four neurons, connected by three synapses. Three of these neurons are overtly dimorphic and identify a male-specific neuropil that integrates inputs from multiple sensory systems and sends outputs to the ventral nerve cord. This neural pathway suggests a means by which a single pheromone can elicit different behaviours in the two sexes.
C1 [Ruta, Vanessa; Datta, Sandeep Robert; Vasconcelos, Maria Luisa; Freeland, Jessica; Axel, Richard] Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Ruta, Vanessa; Datta, Sandeep Robert; Vasconcelos, Maria Luisa; Freeland, Jessica; Axel, Richard] Columbia Univ Coll Phys & Surg, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University; Howard Hughes Medical Institute
RP Axel, R (corresponding author), Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
EM ra27@columbia.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative; Helen Hay Whitney Foundation; Burroughs Welcome Fund; Howard Hughes Medical Institute
NR 33
TC 270
Z9 328
U1 4
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 686
EP U106
DI 10.1038/nature09554
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700039
PM 21124455
DA 2026-03-09
ER

PT J
AU Yu, Q
   Shan, ZW
   Li, J
   Huang, XX
   Xiao, L
   Sun, J
   Ma, E
AF Yu, Qian
   Shan, Zhi-Wei
   Li, Ju
   Huang, Xiaoxu
   Xiao, Lin
   Sun, Jun
   Ma, Evan
TI Strong crystal size effect on deformation twinning
SO NATURE
LA English
DT Article
ID materials science; titanium; strength; behavior; nucleation; dependence; maximum; growth; twins; ti
AB Deformation twinning(1-6) in crystals is a highly coherent inelastic shearing process that controls the mechanical behaviour of many materials, but its origin and spatio-temporal features are shrouded in mystery. Using micro-compression and in situ nano-compression experiments, here we find that the stress required for deformation twinning increases drastically with decreasing sample size of a titanium alloy single crystal(7,8), until the sample size is reduced to one micrometre, below which the deformation twinning is entirely replaced by less correlated, ordinary dislocation plasticity. Accompanying the transition in deformation mechanism, the maximum flow stress of the submicrometre-sized pillars was observed to saturate at a value close to titanium's ideal strength(9,10). We develop a 'stimulated slip' model to explain the strong size dependence of deformation twinning. The sample size in transition is relatively large and easily accessible in experiments, making our understanding of size dependence(11-17) relevant for applications.
C1 [Yu, Qian; Shan, Zhi-Wei; Xiao, Lin; Sun, Jun; Ma, Evan] Xi An Jiao Tong Univ, CAMP Nano, State Key Lab Mech Behav Mat, Xian 710049, Peoples R China.
   [Shan, Zhi-Wei] Hysitron Inc, Minneapolis, MN 55344 USA.
   [Li, Ju] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
   [Huang, Xiaoxu] Tech Univ Denmark, Riso Natl Lab Sustainable Energy, Mat Res Div, Danish Chinese Ctr Nanomet, DK-4000 Roskilde, Denmark.
   [Ma, Evan] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21218 USA.
C3 Xi'an Jiaotong University; Hysitron, Inc.; University of Pennsylvania; Technical University of Denmark; Johns Hopkins University
RP Sun, J (corresponding author), Xi An Jiao Tong Univ, CAMP Nano, State Key Lab Mech Behav Mat, Xian 710049, Peoples R China.
EM liju@seas.upenn.edu; junsun@mail.xjtu.edu.cn
FU NSFC [50671077, 50720145101, 50831004, 50925104]; 973 Program of China [2004CB619303, 2007CB613804, 2010CB613003]; 111 Project of China [B06025]; ONR [N00014-05-1-0504]; NSF [CMMI-0728069]; MRSEC [DMR-0520020]; AFOSR [FA9550-08-1-0325]; Danish National Research Foundation; US Department of Energy [DE-AC02-05CH11231]; Div Of Civil, Mechanical, & Manufact Inn; Directorate For Engineering [0728069] Funding Source: National Science Foundation
NR 30
TC 614
Z9 683
U1 26
U2 1017
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 335
EP 338
DI 10.1038/nature08692
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100039
PM 20090749
DA 2026-03-09
ER

PT J
AU Uemura, S
   Aitken, CE
   Korlach, J
   Flusberg, BA
   Turner, SW
   Puglisi, JD
AF Uemura, Sotaro
   Aitken, Colin Echeverria
   Korlach, Jonas
   Flusberg, Benjamin A.
   Turner, Stephen W.
   Puglisi, Joseph D.
TI Real-time tRNA transit on single translating ribosomes at codon resolution
SO NATURE
LA English
DT Article
ID allosteric 3-site model; elongation-factor g; l1 stalk; polymerase molecules; antibiotics; mechanisms; selection; movement; dynamics; guides
AB Translation by the ribosome occurs by a complex mechanism involving the coordinated interaction of multiple nucleic acid and protein ligands. Here we use zero-mode waveguides (ZMWs) and sophisticated detection instrumentation to allow real-time observation of translation at physiologically relevant micromolar ligand concentrations. Translation at each codon is monitored by stable binding of transfer RNAs (tRNAs)-labelled with distinct fluorophores-to translating ribosomes, which allows direct detection of the identity of tRNA molecules bound to the ribosome and therefore the underlying messenger RNA (mRNA) sequence. We observe the transit of tRNAs on single translating ribosomes and determine the number of tRNA molecules simultaneously bound to the ribosome, at each codon of an mRNA molecule. Our results show that ribosomes are only briefly occupied by two tRNA molecules and that release of deacylated tRNA from the exit (E) site is uncoupled from binding of aminoacyl-tRNA site (A-site) tRNA and occurs rapidly after translocation. The methods outlined here have broad application to the study of mRNA sequences, and the mechanism and regulation of translation.
C1 [Uemura, Sotaro; Aitken, Colin Echeverria; Puglisi, Joseph D.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Uemura, Sotaro] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
   [Aitken, Colin Echeverria; Puglisi, Joseph D.] Stanford Univ, Sch Med, Biophys Program, Stanford, CA 94305 USA.
   [Korlach, Jonas; Flusberg, Benjamin A.; Turner, Stephen W.] Pacific Biosci Inc, Menlo Pk, CA 94025 USA.
C3 Stanford University; Japan Science & Technology Agency (JST); Stanford University
RP Puglisi, JD (corresponding author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
EM puglisi@stanford.edu
FU National Institutes of Health [GM51266]; National Institute of General Medical Sciences [R01GM051266] Funding Source: NIH RePORTER
NR 28
TC 288
Z9 363
U1 0
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1012
EP U73
DI 10.1038/nature08925
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000032
PM 20393556
DA 2026-03-09
ER

PT J
AU Choi, KS
   Goban, A
   Papp, SB
   van Enk, SJ
   Kimble, HJ
AF Choi, K. S.
   Goban, A.
   Papp, S. B.
   van Enk, S. J.
   Kimble, H. J.
TI Entanglement of spin waves among four quantum memories
SO NATURE
LA English
DT Article
ID schrodinger cat state; atomic ensembles; networks; differentiate; distance; systems
AB Quantum networks are composed of quantum nodes that interact coherently through quantum channels, and open a broad frontier of scientific opportunities(1). For example, a quantum network can serve as a 'web' for connecting quantum processors for computation(2,3) and communication(4), or as a 'simulator' allowing investigations of quantum critical phenomena arising from interactions among the nodes mediated by the channels(5,6). The physical realization of quantum networks generically requires dynamical systems capable of generating and storing entangled states among multiple quantum memories, and efficiently transferring stored entanglement into quantum channels for distribution across the network. Although such capabilities have been demonstrated for diverse bipartite systems(7-12), entangled states have not been achieved for interconnects capable of 'mapping' multipartite entanglement stored in quantum memories to quantum channels. Here we demonstrate measurement-induced entanglement stored in four atomic memories; user-controlled, coherent transfer of the atomic entanglement to four photonic channels; and characterization of the full quadripartite entanglement using quantum uncertainty relations(13-16). Our work therefore constitutes an advance in the distribution of multipartite entanglement across quantum networks. We also show that our entanglement verification method is suitable for studying the entanglement order of condensed-matter systems in thermal equilibrium(17,18).
C1 [Choi, K. S.; Goban, A.; Papp, S. B.; Kimble, H. J.] CALTECH, Norman Bridge Lab Phys 12 33, Pasadena, CA 91125 USA.
   [van Enk, S. J.] Univ Oregon, Dept Phys, Eugene, OR 97403 USA.
C3 California Institute of Technology; University of Oregon
RP Kimble, HJ (corresponding author), CALTECH, Norman Bridge Lab Phys 12 33, Pasadena, CA 91125 USA.
EM hjkimble@caltech.edu
FU National Science Foundation; DOD; Northrop Grumman Corporation; Intelligence Advanced Research Projects Activity; Nakajima Foundation; Center for Physics of Information at Caltech; Direct For Mathematical & Physical Scien; Division Of Physics [0803371] Funding Source: National Science Foundation
NR 47
TC 120
Z9 135
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 412
EP U235
DI 10.1038/nature09568
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100037
PM 21085175
DA 2026-03-09
ER

PT J
AU Chen, XJ
   Struzhkin, VV
   Yu, Y
   Goncharov, AF
   Lin, CT
   Mao, HK
   Hemley, RJ
AF Chen, Xiao-Jia
   Struzhkin, Viktor V.
   Yu, Yong
   Goncharov, Alexander F.
   Lin, Cheng-Tian
   Mao, Ho-kwang
   Hemley, Russell J.
TI Enhancement of superconductivity by pressure-driven competition in electronic order
SO NATURE
LA English
DT Article
ID transition-temperature; single-crystals; raman-scattering; dependence; cuprate; copper; planes; nmr; gpa; tc
AB Finding ways to achieve higher values of the transition temperature, T-c, in superconductors remains a great challenge. The superconducting phase is often one of several competing types of electronic order, including antiferromagnetism and charge density waves(1-5). An emerging trend documented in heavy-fermion(1) and organic(2) conductors is that the maximum T-c for superconductivity occurs under external conditions that cause the critical temperature for a competing order to go to zero. Recently, such competition has been found in multilayer copper oxide high-temperature superconductors (HTSCs3-5) that possess two crystallographically inequivalent CuO2 planes in the unit cell. However, whether the competing electronic state can be suppressed to enhance T-c in HTSCs remains an open question. Here we show that pressure-driven phase competition leads to an unusual two-step enhancement of T-c in optimally doped trilayer Bi2Sr2Ca2Cu3O10+delta (Bi2223). We find that T-c first increases with pressure and then decreases after passing through a maximum. Unexpectedly, T-c increases again when the pressure is further raised above a critical value of around 24 GPa, surpassing the first maximum. The presence of this critical pressure is a manifestation of the crossover from the competing order to superconductivity in the inner of the three CuO2 planes. We suggest that the increase at higher pressures occurs as a result of competition between pairing and phase ordering in different CuO2 planes.
C1 [Chen, Xiao-Jia; Struzhkin, Viktor V.; Yu, Yong; Goncharov, Alexander F.; Mao, Ho-kwang; Hemley, Russell J.] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Chen, Xiao-Jia] S China Univ Technol, Dept Phys, Guangzhou 510640, Peoples R China.
   [Lin, Cheng-Tian] Max Planck Inst Festkorperforsch, D-70569 Stuttgart, Germany.
C3 Carnegie Institution for Science; South China University of Technology; Max Planck Society
RP Chen, XJ (corresponding author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA.
EM xjchen@ciw.edu; hmao@gl.ciw.edu; rhemley@gl.ciw.edu
FU DOE [DE-SC0001057, DE-FG02-02ER45955, DEFC03-03NA00144]; Carnegie Canada; NSFC [10874046]; U.S. Department of Energy (DOE) [DE-FG02-02ER45955, DE-SC0001057] Funding Source: U.S. Department of Energy (DOE)
NR 29
TC 111
Z9 124
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 AUG 19
PY 2010
VL 466
IS 7309
BP 950
EP 953
DI 10.1038/nature09293
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300029
PM 20725035
DA 2026-03-09
ER

PT J
AU Vogel, JP
   Garvin, DF
   Mockler, TC
   Schmutz, J
   Rokhsar, D
   Bevan, MW
   Barry, K
   Lucas, S
   Harmon-Smith, M
   Lail, K
   Tice, H
   Grimwood, J
   McKenzie, N
   Huo, NX
   Gu, YQ
   Lazo, GR
   Anderson, OD
   You, FM
   Luo, MC
   Dvorak, J
   Wright, J
   Febrer, M
   Idziak, D
   Hasterok, R
   Lindquist, E
   Wang, M
   Fox, SE
   Priest, HD
   Filichkin, SA
   Givan, SA
   Bryant, DW
   Chang, JH
   Wu, HY
   Wu, W
   Hsia, AP
   Schnable, PS
   Kalyanaraman, A
   Barbazuk, B
   Michael, TP
   Hazen, SP
   Bragg, JN
   Laudencia-Chingcuanco, D
   Weng, YQ
   Haberer, G
   Spannagl, M
   Mayer, K
   Rattei, T
   Mitros, T
   Lee, SJ
   Rose, JKC
   Mueller, LA
   York, TL
   Wicker, T
   Buchmann, JP
   Tanskanen, J
   Schulman, AH
   Gundlach, H
   de Oliveira, AC
   Maia, LD
   Belknap, W
   Jiang, N
   Lai, JS
   Zhu, LC
   Ma, JX
   Sun, C
   Pritham, E
   Salse, J
   Murat, F
   Abrouk, M
   Bruggmann, R
   Messing, J
   Fahlgren, N
   Sullivan, CM
   Carrington, JC
   Chapman, EJ
   May, GD
   Zhai, JX
   Ganssmann, M
   Gurazada, SGR
   German, M
   Meyers, BC
   Green, PJ
   Tyler, L
   Wu, JJ
   Thomson, J
   Chen, S
   Scheller, HV
   Harholt, J
   Ulvskov, P
   Kimbrel, JA
   Bartley, LE
   Cao, PJ
   Jung, KH
   Sharma, MK
   Vega-Sanchez, M
   Ronald, P
   Dardick, CD
   De Bodt, S
   Verelst, W
   Inze, D
   Heese, M
   Schnittger, A
   Yang, XH
   Kalluri, UC
   Tuskan, GA
   Hua, ZH
   Vierstra, RD
   Cui, Y
   Ouyang, SH
   Sun, QX
   Liu, ZY
   Yilmaz, A
   Grotewold, E
   Sibout, R
   Hematy, K
   Mouille, G
   Höfte, H
   Pelloux, J
   O'Connor, D
   Schnable, J
   Rowe, S
   Harmon, F
   Cass, CL
   Sedbrook, JC
   Byrne, ME
   Walsh, S
   Higgins, J
   Li, PH
   Brutnell, T
   Unver, T
   Budak, H
   Belcram, H
   Charles, M
   Chalhoub, B
   Baxter, I
AF Vogel, John P.
   Garvin, David F.
   Mockler, Todd C.
   Schmutz, Jeremy
   Rokhsar, Dan
   Bevan, Michael W.
   Barry, Kerrie
   Lucas, Susan
   Harmon-Smoth, Miranda
   Lail, Kathleen
   Tice, Hope
   Grimwood, Jane
   McKenzie, Neil
   Huo, Naxin
   Gu, Yong Q
   Lazo, Gerard R.
   Anderson, Olin D.
   You, Frank M.
   Luo, Ming-Cheng
   Dvorak, Jan
   Wright, Jan
   Febrer, Melanie
   Idziak, Dominika
   Hasterok, Robert
   Lindquist, Erika
   Wang, Mei
   Fox, Samuel E.
   Priest, Henry D.
   Filichkin, Sergei A.
   Givan, Scott A.
   Bryant, Douglas W.
   Chang, Jeff H.
   Wu, Haiyan
   Wu, Wei
   Hsia, An-Ping
   Schnable, Patrick S.
   Kalyanaraman, Anantharaman
   Baarbazuk, Brad
   Michael, Todd P.
   Hazen, Samuel P.
   Bragg, Jennifer N.
   Laudencia-Chingcuanco, Debbie
   Weng, Yiqun
   Haberer, Georg
   Spannagl, Mianuel
   Mayer, Klaus
   Rattei, Thomas
   Mitros, Therese
   Lee, Sang-Jik
   Rose, Jocelyn K. C.
   Mueller, Lukas A.
   York, Thomas L.
   Wicker, Thomas
   Buchmann, Jan P.
   Tanskanen, Jaakko
   Schulman, Alan H.
   Gundlach, Heidrun
   de Oliveira, Antonio Costa
   Maia, Luciano da C.
   Belknap, William
   Jiang, Ning
   Lai, Jinsheng
   Zhu, Liucun
   Ma, Jianxin
   Sun, Cheng
   Pritham, Ellen
   Salse, Jerome
   Murat, Florent
   Abrouk, Michael
   Bruggmann, Remy
   Messing, Joachim
   Fahlgren, Noah
   Sullivan, Christopher M.
   Carrington, James C.
   Chapman, Elisabeth J.
   May, Greg D.
   Zhai, Jixian
   Ganssmann, Matthias
   Gurazada, Sai Guna Ranjan
   German, Marcelo
   Meyers, Blake C.
   Green, Pamela J.
   Tyler, Ludmila
   Wu, Jiajie
   Thomson, James
   Chen, Shan
   Scheller, Henrik V.
   Harholt, Jesper
   Ulvskov, Peter
   Kimbrel, Jeffrey A.
   Bartley, Laura E.
   Cao, Peijian
   Jung, Ki-Hong
   Sharma, Manoj K.
   Vega-Sanchez, Miguel
   Ronald, Pamela
   Dardick, Christopher D.
   De Bodt, Stefanie
   Verelst, Wim
   Inze, Dirk
   Heese, Maren
   Schnittger, Arp
   Yang, Xiaohan
   Kalluri, Udaya C.
   Tuskan, Gerald A.
   Hua, Zhihua
   Vierstra, Richard D.
   Cui, Yu
   Ouyang, Shuhong
   Sun, Qixin
   Liu, Zhiyong
   Yilmaz, Alper
   Grotewold, Erich
   Sibout, Richard
   Hematy, Kian
   Mouille, Gregory
   Hoefte, Herman
   Pelloux, Jerome
   O'Connor, Devin
   Schbnable, James
   Rowe, Scott
   Harmon, Frank
   Cass, Cynthia L.
   Sedbrook, John C.
   Byrne, Mary E.
   Walsh, Sean
   Higgins, Janet
   Li, Pinghua
   Brutnell, Thomas
   Unver, Turgay
   Budak, Hikmet
   Belcram, Harry
   Charles, Mathieu
   Chalhoub, Boulos
   Baxter, Ivan
TI Genome sequencing and analysis of the model grass Brachypodium distachyon
SO NATURE
LA English
DT Article
ID agrobacterium-mediated transformation; intraspecies diversity; rice; evolution; divergence; wheat; map; identification; triticeae; dynamics
AB Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops.
C1 [Vogel, John P.; Huo, Naxin; Gu, Yong Q; Lazo, Gerard R.; Anderson, Olin D.; Bragg, Jennifer N.; Laudencia-Chingcuanco, Debbie; Belknap, William; Tyler, Ludmila; Wu, Jiajie; Thomson, James] USDA ARS, Western Reg Res Ctr, Albany, CA 94710 USA.
   [Garvin, David F.] USDA ARS, Plant Sci Res Unit, St Paul, MN 55108 USA.
   [Garvin, David F.] Univ Minnesota, St Paul, MN 55108 USA.
   [Mockler, Todd C.; Fox, Samuel E.; Priest, Henry D.; Filichkin, Sergei A.; Givan, Scott A.; Bryant, Douglas W.; Chang, Jeff H.; Fahlgren, Noah; Sullivan, Christopher M.; Carrington, James C.; Chapman, Elisabeth J.; Kimbrel, Jeffrey A.] Oregon State Univ, Corvallis, OR 97331 USA.
   [Schmutz, Jeremy; Grimwood, Jane] HudsonAlpha Inst, Huntsville, AL 35806 USA.
   [Rokhsar, Dan; Barry, Kerrie; Lucas, Susan; Harmon-Smoth, Miranda; Lail, Kathleen; Tice, Hope; Febrer, Melanie; Lindquist, Erika; Wang, Mei] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Rokhsar, Dan; Mitros, Therese; Tyler, Ludmila] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Bevan, Michael W.; McKenzie, Neil; Wright, Jan; Byrne, Mary E.; Walsh, Sean; Higgins, Janet] John Innes Ctr, Norwich NR4 7UJ, Norfolk, England.
   [You, Frank M.; Luo, Ming-Cheng; Dvorak, Jan; Wu, Jiajie; Bartley, Laura E.; Cao, Peijian; Jung, Ki-Hong; Sharma, Manoj K.; Vega-Sanchez, Miguel; Ronald, Pamela] Univ Calif Davis, Davis, CA 95616 USA.
   [Idziak, Dominika; Hasterok, Robert] Univ Silesia, Katowice, Poland.
   [Wu, Haiyan; Wu, Wei; Hsia, An-Ping; Schnable, Patrick S.] Iowa State Univ, Ames, IA 50011 USA.
   [Kalyanaraman, Anantharaman] Washington State Univ, Pullman, WA 99163 USA.
   [Baarbazuk, Brad] Univ Florida, Gainesville, FL 32611 USA.
   [Michael, Todd P.; Bruggmann, Remy; Messing, Joachim] Rutgers State Univ, Piscataway, NJ 08855 USA.
   [Hazen, Samuel P.; Chen, Shan] Univ Massachusetts, Amherst, MA 01003 USA.
   [Weng, Yiqun] Univ Wisconsin, USDA ARS, Vegetable Crops Res Unit, Dept Hort, Madison, WI 53706 USA.
   [Haberer, Georg; Spannagl, Mianuel; Mayer, Klaus; Gundlach, Heidrun] Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany.
   [Rattei, Thomas] Tech Univ Munich, D-80333 Munich, Germany.
   [Lee, Sang-Jik; Rose, Jocelyn K. C.] Cornell Univ, Ithaca, NY 14853 USA.
   [Mueller, Lukas A.; York, Thomas L.; Li, Pinghua; Brutnell, Thomas] Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA.
   [Wicker, Thomas; Buchmann, Jan P.] Univ Zurich, CH-8008 Zurich, Switzerland.
   [Tanskanen, Jaakko; Schulman, Alan H.] MTT Agrifood Res, FIN-00014 Helsinki, Finland.
   [Tanskanen, Jaakko; Schulman, Alan H.] Univ Helsinki, FIN-00014 Helsinki, Finland.
   [de Oliveira, Antonio Costa; Maia, Luciano da C.] Univ Fed Pelotas, BR-96001970 Pelotas, RS, Brazil.
   [Jiang, Ning] Michigan State Univ, E Lansing, MI 48824 USA.
   [Wu, Haiyan; Schnable, Patrick S.; Lai, Jinsheng; Cui, Yu; Ouyang, Shuhong; Sun, Qixin; Liu, Zhiyong] China Agr Univ, Beijing 10094, Peoples R China.
   [Zhu, Liucun; Ma, Jianxin] Purdue Univ, W Lafayette, IN 47907 USA.
   [Sun, Cheng; Pritham, Ellen] Univ Texas, Arlington, TX 76019 USA.
   [Salse, Jerome; Murat, Florent; Abrouk, Michael] INRA, UMR 1095, F-63100 Clermont Ferrand, France.
   [Chapman, Elisabeth J.] Univ Calif San Diego, La Jolla, CA 92093 USA.
   [May, Greg D.] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
   [Zhai, Jixian; Ganssmann, Matthias; Gurazada, Sai Guna Ranjan; German, Marcelo; Meyers, Blake C.; Green, Pamela J.] Univ Delaware, Newark, DE 19716 USA.
   [Scheller, Henrik V.; Bartley, Laura E.; Cao, Peijian; Jung, Ki-Hong; Sharma, Manoj K.; Vega-Sanchez, Miguel; Ronald, Pamela] Joint Bioenergy Inst, Emeryville, CA 94720 USA.
   [Harholt, Jesper; Ulvskov, Peter] Univ Copenhagen, DK-1871 Frederiksberg, Denmark.
   [Dardick, Christopher D.] USDA ARS, Appalachian Fruit Res Stn, Kearneysville, WV 25430 USA.
   [De Bodt, Stefanie; Verelst, Wim; Inze, Dirk] VIB, VIB Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [De Bodt, Stefanie; Verelst, Wim; Inze, Dirk] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium.
   [Heese, Maren; Schnittger, Arp] CNRS, Inst Biol Mol Plantes, F-67084 Strasbourg, France.
   [Yang, Xiaohan; Kalluri, Udaya C.; Tuskan, Gerald A.] BioEnergy Sci Ctr, Oak Ridge, TN 37831 USA.
   [Yang, Xiaohan; Kalluri, Udaya C.; Tuskan, Gerald A.] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA.
   [Hua, Zhihua; Vierstra, Richard D.] Univ Wisconsin, Madison, WI 53706 USA.
   [Yilmaz, Alper; Grotewold, Erich] Ohio State Univ, Columbus, OH 43210 USA.
   [Sibout, Richard; Hematy, Kian; Mouille, Gregory; Hoefte, Herman] INRA, Inst Jean Pierre Bourgin, UMR1318, F-78026 Versailles, France.
   [Pelloux, Jerome] Univ Picardie, F-80039 Amiens, France.
   [O'Connor, Devin; Schbnable, James; Rowe, Scott; Harmon, Frank] Univ Calif Berkeley, Plant Gene Express Ctr, Albany, CA 94710 USA.
   [Cass, Cynthia L.; Sedbrook, John C.] Illinois State Univ, Normal, IL 61790 USA.
   [Cass, Cynthia L.; Sedbrook, John C.] DOE, Great Lakes Bioenergy Res Ctr, Normal, IL 61790 USA.
   [Unver, Turgay; Budak, Hikmet] Sabanci Univ, T-34956 Istanbul, Turkey.
   [Belcram, Harry; Charles, Mathieu; Chalhoub, Boulos] INRA CNRS UEVE, Unite Rech Genomique Vegetale, F-91057 Evry, France.
   [Baxter, Ivan] USDA ARS, Donald Danforth Plant Sci Ctr, St Louis, MO 63130 USA.
C3 United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); University of Minnesota System; University of Minnesota Twin Cities; Oregon State University; HudsonAlpha Institute for Biotechnology; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; University of California System; University of California Berkeley; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; University of California System; University of California Davis; University of Silesia in Katowice; Iowa State University; Washington State University; State University System of Florida; University of Florida; Rutgers University System; Rutgers University New Brunswick; University of Massachusetts System; University of Massachusetts Amherst; University of Wisconsin System; University of Wisconsin Madison; United States Department of Agriculture (USDA); Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; Cornell University; Cornell University; Boyce Thompson Institute for Plant Research; University of Zurich; Natural Resources Institute Finland (Luke); University of Helsinki; Universidade Federal de Pelotas; Michigan State University; China Agricultural University; Purdue University System; Purdue University; University of Texas System; University of Texas Arlington; INRAE; University of California System; University of California San Diego; National Center for Genome Resources (NCGR); University of Delaware; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; University of Copenhagen; United States Department of Agriculture (USDA); Flanders Institute for Biotechnology (VIB); Ghent University; Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; United States Department of Energy (DOE); Oak Ridge National Laboratory; BioEnergy Science Center (BESC); United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Wisconsin System; University of Wisconsin Madison; University System of Ohio; Ohio State University; Universite Paris Saclay; INRAE; Universite de Picardie Jules Verne (UPJV); University of California System; University of California Berkeley; Illinois State University; United States Department of Energy (DOE); Sabanci University; INRAE; Donald Danforth Plant Science Center; United States Department of Agriculture (USDA)
RP Vogel, JP (corresponding author), USDA ARS, Western Reg Res Ctr, Albany, CA 94710 USA.
FU US Department of Energy Joint Genome Institute; BBSRC; EU; GABI Barlex; Oregon State Agricultural Research Foundation; BBSRC [BB/E004725/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E004725/1] Funding Source: researchfish
NR 46
TC 1447
Z9 1649
U1 5
U2 435
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 763
EP 768
DI 10.1038/nature08747
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300030
PM 20148030
DA 2026-03-09
ER

PT J
AU Daneman, R
   Zhou, L
   Kebede, AA
   Barres, BA
AF Daneman, Richard
   Zhou, Lu
   Kebede, Amanuel A.
   Barres, Ben A.
TI Pericytes are required for blood-brain barrier integrity during embryogenesis
SO NATURE
LA English
DT Article
ID central-nervous-system; endothelial-cells; in-vitro; up-regulation; astrocytes; occludin; rats; cns; oligodendrocytes; morphogenesis
AB Vascular endothelial cells in the central nervous system (CNS) forma barrier that restricts the movement of molecules and ions between the blood and the brain. This blood-brain barrier (BBB) is crucial to ensure proper neuronal function and protect the CNS from injury and disease(1). Transplantation studies have demonstrated that the BBB is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells(2). Owing to the close spatial relationship between astrocytes and endothelial cells, it has been hypothesized that astrocytes induce this critical barrier postnatally(3), but the timing of BBB formation has been controversial(4-9). Here we demonstrate that the barrier is formed during embryogenesis as endothelial cells invade the CNS and pericytes are recruited to the nascent vessels, over a week before astrocyte generation. Analysing mice with null and hypomorphic alleles of Pdgfrb, which have defects in pericyte generation, we demonstrate that pericytes are necessary for the formation of the BBB, and that absolute pericyte coverage determines relative vascular permeability. We demonstrate that pericytes regulate functional aspects of the BBB, including the formation of tight junctions and vesicle trafficking in CNS endothelial cells. Pericytes do not induce BBB-specific gene expression in CNS endothelial cells, but inhibit the expression of molecules that increase vascular permeability and CNS immune cell infiltration. These data indicate that pericyte-endothelial cell interactions are critical to regulate the BBB during development, and disruption of these interactions may lead to BBB dysfunction and neuroinflammation during CNS injury and disease.
C1 [Daneman, Richard; Kebede, Amanuel A.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   [Zhou, Lu; Barres, Ben A.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
C3 University of California System; University of California San Francisco; Stanford University
RP Daneman, R (corresponding author), Univ Calif San Francisco, Dept Anat, 513 Parnassus Ave,HSW1301, San Francisco, CA 94143 USA.
EM Richard.daneman@ucsf.edu
FU NINDS [R01-NS045621]; Myelin Repair Foundation; NMSS [RG3936A7]; UCSF; AHA
NR 33
TC 1639
Z9 1959
U1 6
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 NOV 25
PY 2010
VL 468
IS 7323
BP 562
EP U238
DI 10.1038/nature09513
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200042
PM 20944625
DA 2026-03-09
ER

PT J
AU Tripp, HJ
   Bench, SR
   Turk, KA
   Foster, RA
   Desany, BA
   Niazi, F
   Affourtit, JP
   Zehr, JP
AF Tripp, H. James
   Bench, Shellie R.
   Turk, Kendra A.
   Foster, Rachel A.
   Desany, Brian A.
   Niazi, Faheem
   Affourtit, Jason P.
   Zehr, Jonathan P.
TI Metabolic streamlining in an open-ocean nitrogen-fixing cyanobacterium
SO NATURE
LA English
DT Article
ID subtropical north pacific; blue-green-algae; unicellular cyanobacteria; n-2-fixing cyanobacteria; diversity; fixation; dna; expression; genm; system
AB Nitrogen (N-2)-fixing marine cyanobacteria are an important source of fixed inorganic nitrogen that supports oceanic primary productivity and carbon dioxide removal from the atmosphere(1). A globally distributed(2,3), periodically abundant(4) N-2-fixing(5) marine cyanobacterium, UCYN-A, was recently found to lack the oxygen-producing photosystem II complex(6) of the photosynthetic apparatus, indicating a novel metabolism, but remains uncultivated. Here we show, from metabolic reconstructions inferred from the assembly of the complete UCYN-A genome using massively parallel pyro-sequencing of paired-end reads, that UCYN-A has a photofermentative metabolism and is dependent on other organisms for essential compounds. We found that UCYN-A lacks a number of major metabolic pathways including the tricarboxylic acid cycle, but retains sufficient electron transport capacity to generate energy and reducing power from light. Unexpectedly, UCYN-A has a reduced genome (1.44 megabases) that is structurally similar to many chloroplasts and some bacteria, in that it contains inverted repeats of ribosomal RNA operons(7). The lack of biosynthetic pathways for several amino acids and purines suggests that this organism depends on other organisms, either in close association or in symbiosis, for critical nutrients. However, size fractionation experiments using natural populations have so far not provided evidence of a symbiotic association with another microorganism. The UCYN-A cyanobacterium is a paradox in evolution and adaptation to the marine environment, and is an example of the tight metabolic coupling between microorganisms in oligotrophic oceanic microbial communities.
C1 [Tripp, H. James; Bench, Shellie R.; Turk, Kendra A.; Foster, Rachel A.; Zehr, Jonathan P.] Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
   [Desany, Brian A.; Niazi, Faheem; Affourtit, Jason P.] Roche Co, Branford, CT 06405 USA.
C3 University of California System; University of California Santa Cruz; Roche Holding; Roche Holding USA
RP Zehr, JP (corresponding author), Univ Calif Santa Cruz, Ocean Sci Dept, 1156 High St, Santa Cruz, CA 95064 USA.
EM zehrj@ucsc.edu
FU Gordon and Betty Moore Foundation; US National Science Foundation (NSF); NSF Center for Microbial Oceanography: Research and Education
NR 30
TC 256
Z9 300
U1 5
U2 158
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 90
EP 94
DI 10.1038/nature08786
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500039
PM 20173737
DA 2026-03-09
ER

PT J
AU Meer, MV
   Kondrashov, AS
   Artzy-Randrup, Y
   Kondrashov, FA
AF Meer, Margarita V.
   Kondrashov, Alexey S.
   Artzy-Randrup, Yael
   Kondrashov, Fyodor A.
TI Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness
SO NATURE
LA English
DT Article
ID molecular phylogeny; secondary structures; population-genetics; protein evolution; missing data; mutations; selection; divergence; drosophila; whales
AB A long-standing controversy in evolutionary biology is whether or not evolving lineages can cross valleys on the fitness landscape that correspond to low-fitness genotypes, which can eventually enable them to reach isolated fitness peaks(1-9). Here we study the fitness landscapes traversed by switches between different AU and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles corresponding to GU and AC non-Watson-Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles. Substitutions leading to a Watson Crick switch are strongly correlated, especially in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial genome. Using these data we estimate that a typical Watson-Crick switch involves crossing a fitness valley of a depth of about 10(-3) or even about 10(-2), with AC intermediates being slightly more deleterious than GU intermediates. This compensatory evolution must proceed through rare intermediate variants that never reach fixation(2). The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules(10,11) implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.
C1 [Meer, Margarita V.; Kondrashov, Fyodor A.] Ctr Genom Regulat, Bioinformat & Genom Programme, Barcelona 08003, Spain.
   [Kondrashov, Alexey S.; Artzy-Randrup, Yael] Univ Michigan, Inst Life Sci, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
   [Artzy-Randrup, Yael] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 49109 USA.
   [Artzy-Randrup, Yael] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 49109 USA.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Kondrashov, FA (corresponding author), Ctr Genom Regulat, Bioinformat & Genom Programme, C Dr Aiguader 88,Barcelona Biomed Res Pk Bldg, Barcelona 08003, Spain.
EM fyodor.kondrashov@crg.es
NR 48
TC 69
Z9 80
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 MAR 11
PY 2010
VL 464
IS 7286
BP 279
EP U159
DI 10.1038/nature08691
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100047
PM 20182427
DA 2026-03-09
ER

PT J
AU Cornwallis, CK
   West, SA
   Davis, KE
   Griffin, AS
AF Cornwallis, Charlie K.
   West, Stuart A.
   Davis, Katie E.
   Griffin, Ashleigh S.
TI Promiscuity and the evolutionary transition to complex societies
SO NATURE
LA English
DT Article
ID kin selection; birds; paternity; constraints; monogamy; behavior; helpers; models; spite
AB Theory predicts that the evolution of cooperative behaviour is favoured by low levels of promiscuity leading to high within-group relatedness(1-5). However, in vertebrates, cooperation often occurs between non-relatives and promiscuity rates are among the highest recorded. Here we resolve this apparent inconsistency with a phylogenetic analysis of 267 bird species, demonstrating that cooperative breeding is associated with low promiscuity; that in cooperative species, helping is more common when promiscuity is low; and that intermediate levels of promiscuity favour kin discrimination. Overall, these results suggest that promiscuity is a unifying feature across taxa in explaining transitions to and from cooperative societies.
C1 [Cornwallis, Charlie K.; Griffin, Ashleigh S.] Univ Oxford, Dept Zool, Edward Grey Inst, Oxford OX1 3PS, England.
   [West, Stuart A.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Davis, Katie E.] Nat Hist Museum, Dept Entomol, London SW7 5BD, England.
C3 University of Oxford; University of Oxford; Natural History Museum London
RP Griffin, AS (corresponding author), Univ Oxford, Dept Zool, Edward Grey Inst, S Parks Rd, Oxford OX1 3PS, England.
EM ashleigh.griffin@zoo.ox.ac.uk
FU ERC; Royal Society
NR 42
TC 272
Z9 289
U1 1
U2 367
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 969
EP U91
DI 10.1038/nature09335
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300033
PM 20725039
DA 2026-03-09
ER

PT J
AU Blake, RE
   Chang, SJ
   Lepland, A
AF Blake, Ruth E.
   Chang, Sae Jung
   Lepland, Aivo
TI Phosphate oxygen isotopic evidence for a temperate and biologically active Archaean ocean
SO NATURE
LA English
DT Article
ID barberton greenstone-belt; swaziland supergroup; biogenic apatites; mountain land; early-life; phosphorus; iron; cherts; water; adsorption
AB Oxygen and silicon isotope compositions of cherts(1-3) and studies of protein evolution(4) have been interpreted to reflect ocean temperatures of 55-85 degrees C during the early Palaeoarchaean era (similar to 3.5 billion years ago). A recent study combining oxygen and hydrogen isotope compositions of cherts, however, makes a case for Archaean ocean temperatures being no greater than 40 degrees C (ref. 5). Ocean temperature can also be assessed using the oxygen isotope composition of phosphate. Recent studies show that O-18:O-16 ratios of dissolved inorganic phosphate (delta O-18(P)) reflect ambient seawater temperature as well as biological processing that dominates marine phosphorus cycling at low temperature(6,7). All forms of life require and concentrate phosphorus, and as a result of biological processing, modern marine phosphates have delta O-18(P) values typically between 19-26 parts per thousand (VSMOW)(7,8), highly evolved from presumed source values of similar to 6-8 parts per thousand that are characteristic of apatite in igneous rocks(9,10) and meteorites(11). Here we report oxygen isotope compositions of phosphates in sediments from the 3.2-3.5-billion-year-old Barberton Greenstone Belt in South Africa. We find that delta O-18(P) values range from 9.3 parts per thousand to 19.9 parts per thousand and include the highest values reported for Archaean rocks. The temperatures calculated from our highest delta O-18(P) values and assuming equilibrium with sea water with delta O-18=0% (ref. 12) range from 26 degrees C to 35 degrees C. The higher delta O-18(P) values are similar to those of modern marine phosphate and suggest a well-developed phosphorus cycle and evolved biologic activity on the Archaean Earth.
C1 [Blake, Ruth E.; Chang, Sae Jung] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Lepland, Aivo] Geol Survey Norway, N-7491 Trondheim, Norway.
   [Lepland, Aivo] Tallinn Univ Technol, Inst Geol, EE-19086 Tallinn, Estonia.
C3 Yale University; Geological Survey of Norway; Tallinn University of Technology
RP Blake, RE (corresponding author), Yale Univ, Dept Geol & Geophys, POB 6666, New Haven, CT 06520 USA.
EM ruth.blake@yale.edu
FU Directorate For Geosciences; Division Of Ocean Sciences [0928247] Funding Source: National Science Foundation
NR 37
TC 174
Z9 207
U1 6
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 APR 15
PY 2010
VL 464
IS 7291
BP 1029
EP U89
DI 10.1038/nature08952
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000036
PM 20393560
DA 2026-03-09
ER

PT J
AU Dousse, A
   Suffczynski, J
   Beveratos, A
   Krebs, O
   Lemaître, A
   Sagnes, I
   Bloch, J
   Voisin, P
   Senellart, P
AF Dousse, Adrien
   Suffczynski, Jan
   Beveratos, Alexios
   Krebs, Olivier
   Lemaitre, Aristide
   Sagnes, Isabelle
   Bloch, Jacqueline
   Voisin, Paul
   Senellart, Pascale
TI Ultrabright source of entangled photon pairs
SO NATURE
LA English
DT Article
ID single quantum-dot; 2 qubits; state; microcavity; teleportation; fidelity
AB A source of triggered entangled photon pairs is a key component in quantum information science(1); it is needed to implement functions such as linear quantum computation(2), entanglement swapping(3) and quantum teleportation(4). Generation of polarization entangled photon pairs can be obtained through parametric conversion in nonlinear optical media(5-7) or by making use of the radiative decay of two electron-hole pairs trapped in a semiconductor quantum dot(8-11). Today, these sources operate at a very low rate, below 0.01 photon pairs per excitation pulse, which strongly limits their applications. For systems based on parametric conversion, this low rate is intrinsically due to the Poissonian statistics of the source(12). Conversely, a quantum dot can emit a single pair of entangled photons with a probability near unity but suffers from a naturally very low extraction efficiency. Here we show that this drawback can be overcome by coupling an optical cavity in the formof a 'photonic molecule'(13) to a single quantum dot. Two coupled identical pillars-the photonic molecule-were etched in a semiconductor planar microcavity, using an optical lithography method(14) that ensures a deterministic coupling to the biexciton and exciton energy states of a pre-selected quantum dot. The Purcell effect ensures that most entangled photon pairs are emitted into two cavity modes, while improving the indistinguishability of the two optical recombination paths(15,16). A polarization entangled photon pair rate of 0.12 per excitation pulse (with a concurrence of 0.34) is collected in the first lens. Our results open the way towards the fabrication of solid state triggered sources of entangled photon pairs, with an overall (creation and collection) efficiency of 80%.
C1 [Dousse, Adrien; Suffczynski, Jan; Beveratos, Alexios; Krebs, Olivier; Lemaitre, Aristide; Sagnes, Isabelle; Bloch, Jacqueline; Voisin, Paul; Senellart, Pascale] CNRS, Lab Photon & Nanostruct, F-91460 Marcoussis, France.
C3 Centre National de la Recherche Scientifique (CNRS)
RP Senellart, P (corresponding author), CNRS, Lab Photon & Nanostruct, Route Nozay, F-91460 Marcoussis, France.
EM Pascale.Senellart@lpn.cnrs.fr
FU European Project NanoEPR; French ANR [P3N]
NR 30
TC 528
Z9 573
U1 0
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 217
EP 220
DI 10.1038/nature09148
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800032
PM 20613838
DA 2026-03-09
ER

PT J
AU Russo, I
   Babbitt, S
   Muralidharan, V
   Butler, T
   Oksman, A
   Goldberg, DE
AF Russo, Ilaria
   Babbitt, Shalon
   Muralidharan, Vasant
   Butler, Tamira
   Oksman, Anna
   Goldberg, Daniel E.
TI Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; parasite proteins; food vacuole; falciparum; trafficking; virulence; calpain; reveals
AB During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development.
C1 [Goldberg, Daniel E.] Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Microbiol, St Louis, MO 63110 USA.
   Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Howard Hughes Medical Institute; Washington University (WUSTL)
RP Goldberg, DE (corresponding author), Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Microbiol, St Louis, MO 63110 USA.
EM Goldberg@borcim.wustl.edu
FU NIH [AI-047798]
NR 23
TC 247
Z9 301
U1 1
U2 33
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 632
EP 636
DI 10.1038/nature08726
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900029
PM 20130644
DA 2026-03-09
ER

PT J
AU Daou, R
   Chang, J
   LeBoeuf, D
   Cyr-Choinière, O
   Laliberté, F
   Doiron-Leyraud, N
   Ramshaw, BJ
   Liang, RX
   Bonn, DA
   Hardy, WN
   Taillefer, L
AF Daou, R.
   Chang, J.
   LeBoeuf, David
   Cyr-Choiniere, Olivier
   Laliberte, Francis
   Doiron-Leyraud, Nicolas
   Ramshaw, B. J.
   Liang, Ruixing
   Bonn, D. A.
   Hardy, W. N.
   Taillefer, Louis
TI Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor
SO NATURE
LA English
DT Article
ID high-temperature superconductors; cuprate superconductors; magnetic order; mott insulator; fermi-surface; stripes; state
AB The nature of the pseudogap phase is a central problem in the effort to understand the high-transition-temperature (high-T-c) copper oxide superconductors(1). A fundamental question is what symmetries are broken when the pseudogap phase sets in, which occurs when the temperature decreases below a value T*. There is evidence from measurements of both polarized neutron diffraction(2,3) and the polar Kerr effect(4) that time-reversal symmetry is broken, but at temperatures that differ significantly from one another. Broken rotational symmetry was detected from both resistivity measurements(5) and inelastic neutron scattering(6-8) at low doping, and from scanning tunnelling spectroscopy(9,10) at low temperature, but showed no clear relation to T*. Here we report the observation of a large in-plane anisotropy of the Nernst effect in YBa2Cu3Oy that sets in precisely at T* throughout the doping phase diagram. We show that the CuO chains of the orthorhombic lattice are not responsible for this anisotropy, which is therefore an intrinsic property of the CuO2 planes. We conclude that the pseudogap phase is an electronic state that strongly breaks four-fold rotational symmetry. This narrows the range of possible states considerably, pointing to stripe or nematic order(11,12).
C1 [Daou, R.; Chang, J.; LeBoeuf, David; Cyr-Choiniere, Olivier; Laliberte, Francis; Doiron-Leyraud, Nicolas; Taillefer, Louis] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
   [Daou, R.; Chang, J.; LeBoeuf, David; Cyr-Choiniere, Olivier; Laliberte, Francis; Doiron-Leyraud, Nicolas; Taillefer, Louis] Univ Sherbrooke, RQMP, Sherbrooke, PQ J1K 2R1, Canada.
   [Ramshaw, B. J.; Liang, Ruixing; Bonn, D. A.; Hardy, W. N.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Liang, Ruixing; Bonn, D. A.; Hardy, W. N.; Taillefer, Louis] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
C3 University of Sherbrooke; University of Sherbrooke; University of British Columbia; Canadian Institute for Advanced Research (CIFAR)
RP Taillefer, L (corresponding author), Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
EM louis.taillefer@physique.usherbrooke.ca
FU Swiss National Science Foundation; Fonds quebecois de la recherche sur la nature et les technologies (FQRNT); Canadian Institute for Advanced Research; Canadian Natural Sciences and Engineering Research Council; FQRNT; the Canada Foundation for Innovation; Canada Research Chair
NR 30
TC 486
Z9 541
U1 6
U2 263
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 519
EP 522
DI 10.1038/nature08716
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100046
PM 20110997
DA 2026-03-09
ER

PT J
AU Thompson, DWJ
   Wallace, JM
   Kennedy, JJ
   Jones, PD
AF Thompson, David W. J.
   Wallace, John M.
   Kennedy, John J.
   Jones, Phil D.
TI An abrupt drop in Northern Hemisphere sea surface temperature around 1970
SO NATURE
LA English
DT Article
ID climate; variability; oscillation; icoads
AB The twentieth-century trend in global-mean surface temperature was not monotonic: temperatures rose from the start of the century to the 1940s, fell slightly during the middle part of the century, and rose rapidly from the mid-1970s onwards(1). The warming-cooling-warming pattern of twentieth-century temperatures is typically interpreted as the superposition of long-term warming due to increasing greenhouse gases and either cooling due to a mid-twentieth century increase of sulphate aerosols in the troposphere(2-4), or changes in the climate of the world's oceans that evolve over decades (oscillatory multidecadal variability)(2,5). Loadings of sulphate aerosol in the troposphere are thought to have had a particularly important role in the differences in temperature trends between the Northern and Southern hemispheres during the decades following the Second World War(2-4). Here we show that the hemispheric differences in temperature trends in the middle of the twentieth century stem largely from a rapid drop in Northern Hemisphere sea surface temperatures of about 0.3 degrees C between about 1968 and 1972. The timescale of the drop is shorter than that associated with either tropospheric aerosol loadings or previous characterizations of oscillatory multidecadal variability. The drop is evident in all available historical sea surface temperature data sets, is not traceable to changes in the attendant metadata, and is not linked to any known biases in surface temperature measurements. The drop is not concentrated in any discrete region of the Northern Hemisphere oceans, but its amplitude is largest over the northern North Atlantic.
C1 [Thompson, David W. J.] Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
   [Wallace, John M.] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Kennedy, John J.] Met Off, Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Jones, Phil D.] Univ E Anglia, Climat Res Unit, Norwich NR4 7TJ, Norfolk, England.
C3 Colorado State University System; Colorado State University Fort Collins; University of Washington; University of Washington Seattle; Met Office - UK; Hadley Centre; University of East Anglia
RP Thompson, DWJ (corresponding author), Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
EM davet@atmos.colostate.edu
FU National Science Foundation [ATM-0132190, ATM-0613082, ATM-0812802]; Department of Energy and Climate Change and Defra (DECC/Defra) [GA01101]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0936255] Funding Source: National Science Foundation; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0812802] Funding Source: National Science Foundation
NR 26
TC 105
Z9 117
U1 1
U2 48
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 444
EP 447
DI 10.1038/nature09394
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200039
PM 20864999
DA 2026-03-09
ER

PT J
AU Vierbuchen, T
   Ostermeier, A
   Pang, ZP
   Kokubu, Y
   Südhof, TC
   Wernig, M
AF Vierbuchen, Thomas
   Ostermeier, Austin
   Pang, Zhiping P.
   Kokubu, Yuko
   Suedhof, Thomas C.
   Wernig, Marius
TI Direct conversion of fibroblasts to functional neurons by defined factors
SO NATURE
LA English
DT Article
ID embryonic stem-cells; somatic-cells; mature b; nuclear transfer; pluripotency; expression; proteins; transplantation; progenitors; generation
AB Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 ( also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.
C1 [Vierbuchen, Thomas; Ostermeier, Austin; Kokubu, Yuko; Wernig, Marius] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, Palo Alto, CA 94304 USA.
   [Vierbuchen, Thomas; Ostermeier, Austin; Wernig, Marius] Stanford Univ, Sch Med, Program Canc Biol, Palo Alto, CA 94304 USA.
   [Pang, Zhiping P.; Suedhof, Thomas C.] Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Palo Alto, CA 94304 USA.
   [Suedhof, Thomas C.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Palo Alto, CA 94304 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute
RP Wernig, M (corresponding author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Pathol, 1050 Arastradero Rd, Palo Alto, CA 94304 USA.
EM wernig@stanford.edu
FU Institute for Stem Cell Biology and Regenerative Medicine at Stanford; Donald E. and Delia B. Baxter Foundation; William Stinehart Jr and the Reed Foundation; National Institute of Health [1018438-142-PABCA]; Ruth and Robert Halperin Stanford Graduate Fellowship; NARSAD; NIH/NINDS [5T32NS007280]; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER
NR 37
TC 2351
Z9 2993
U1 4
U2 443
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1035
EP U50
DI 10.1038/nature08797
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400027
PM 20107439
DA 2026-03-09
ER

PT J
AU Tung, CC
   Lobo, PA
   Kimlicka, L
   Van Petegem, F
AF Tung, Ching-Chieh
   Lobo, Paolo A.
   Kimlicka, Lynn
   Van Petegem, Filip
TI The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule
SO NATURE
LA English
DT Article
ID inositol 1,4,5-trisphosphate receptor; calcium-release channel; mutation hot-spot; s-nitrosylation; ca2+ release; macromolecular structures; crystal-structure; atomic models; muscle; domain
AB Many physiological events require transient increases in cytosolic Ca2+ concentrations. Ryanodine receptors (RyRs) are ion channels that govern the release of Ca2+ from the endoplasmic and sarcoplasmic reticulum(1). Mutations in RyRs can lead to severe genetic conditions that affect both cardiac and skeletal muscle, but locating the mutated residues in the full-length channel structure has been difficult(2,3). Here we show the 2.5 angstrom resolution crystal structure of a region spanning three domains of RyR type 1 (RyR1), encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps(4,5) unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kDa cytoplasmic vestibule around the four-fold symmetry axis. We pinpoint the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2. The mutations can be classified into three groups: those that destabilize the interfaces between the three amino-terminal domains, disturb the folding of individual domains or affect one of six interfaces with other parts of the receptor. We propose a model whereby the opening of a RyR coincides with allosterically coupled motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. The crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and will be useful for developing new strategies to modulate RyR function in disease states.
C1 [Tung, Ching-Chieh; Lobo, Paolo A.; Kimlicka, Lynn; Van Petegem, Filip] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
C3 University of British Columbia
RP Van Petegem, F (corresponding author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
EM filip.vanpetegem@gmail.com
FU Canadian Institutes of Health Research (CIHR); Heart and Stroke Foundation of Canada
NR 37
TC 168
Z9 184
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 NOV 25
PY 2010
VL 468
IS 7323
BP 585
EP U267
DI 10.1038/nature09471
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200047
PM 21048710
DA 2026-03-09
ER

PT J
AU Rocheleau, T
   Ndukum, T
   Macklin, C
   Hertzberg, JB
   Clerk, AA
   Schwab, KC
AF Rocheleau, T.
   Ndukum, T.
   Macklin, C.
   Hertzberg, J. B.
   Clerk, A. A.
   Schwab, K. C.
TI Preparation and detection of a mechanical resonator near the ground state of motion
SO NATURE
LA English
DT Article
ID resolved-side-band; parametric transducer; oscillator; cavity
AB Cold, macroscopic mechanical systems are expected to behave contrary to our usual classical understanding of reality; the most striking and counterintuitive predictions involve the existence of states in which the mechanical system is located in two places simultaneously. Various schemes have been proposed to generate and detect such states(1,2), and all require starting from mechanical states that are close to the lowest energy eigenstate, the mechanical ground state. Here we report the cooling of the motion of a radio-frequency nanomechanical resonator by parametric coupling to a driven, microwave-frequency superconducting resonator. Starting from a thermal occupation of 480 quanta, we have observed occupation factors as low as 3.8 +/- 1.3 and expect the mechanical resonator to be found with probability 0.21 in the quantum ground state of motion. Further cooling is limited by random excitation of the microwave resonator and heating of the dissipative mechanical bath. This level of cooling is expected to make possible a series of fundamental quantum mechanical observations including direct measurement of the Heisenberg uncertainty principle and quantum entanglement with qubits.
C1 [Schwab, K. C.] CALTECH, Pasadena, CA 91125 USA.
   [Clerk, A. A.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Hertzberg, J. B.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Rocheleau, T.; Ndukum, T.; Macklin, C.] Cornell Univ, Dept Phys, Ithaca, NY 14853 USA.
C3 California Institute of Technology; McGill University; University System of Maryland; University of Maryland College Park; Cornell University
RP Schwab, KC (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM schwab@caltech.edu
FU Fundamental Questions Institute [RFP2-08-27]; US National Science Foundation (NSF) [DMR-0804567, ECS-0335765]
NR 30
TC 428
Z9 484
U1 2
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 72
EP 75
DI 10.1038/nature08681
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900032
PM 20010604
DA 2026-03-09
ER

PT J
AU Theobald, DL
AF Theobald, Douglas L.
TI A formal test of the theory of universal common ancestry
SO NATURE
LA English
DT Article
ID genetic code; evolution; hypotheses; likelihood; selection; proteins; homology; origin; life
AB Universal common ancestry (UCA) is a central pillar of modern evolutionary theory(1). As first suggested by Darwin(2), the theory of UCA posits that all extant terrestrial organisms share a common genetic heritage, each being the genealogical descendant of a single species from the distant past(3-6). The classic evidence for UCA, although massive, is largely restricted to 'local' common ancestry-for example, of specific phyla rather than the entirety of life-and has yet to fully integrate the recent advances from modern phylogenetics and probability theory. Although UCA is widely assumed, it has rarely been subjected to formal quantitative testing(7-10), and this has led to critical commentary emphasizing the intrinsic technical difficulties in empirically evaluating a theory of such broad scope(1,5,8,9,11-15). Furthermore, several researchers have proposed that early life was characterized by rampant horizontal gene transfer, leading some to question the monophyly of life(11,14,15). Here I provide the first, to my knowledge, formal, fundamental test of UCA, without assuming that sequence similarity implies genetic kinship. I test UCA by applying model selection theory(5,16,17) to molecular phylogenies, focusing on a set of ubiquitously conserved proteins that are proposed to be orthologous. Among a wide range of biological models involving the independent ancestry of major taxonomic groups, the model selection tests are found to overwhelmingly support UCA irrespective of the presence of horizontal gene transfer and symbiotic fusion events. These results provide powerful statistical evidence corroborating the monophyly of all known life.
C1 Brandeis Univ, Dept Biochem, Waltham, MA 01778 USA.
C3 Brandeis University
RP Theobald, DL (corresponding author), Brandeis Univ, Dept Biochem, Waltham, MA 01778 USA.
EM dtheobald@brandeis.edu
NR 36
TC 147
Z9 184
U1 1
U2 132
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 219
EP U104
DI 10.1038/nature09014
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500035
PM 20463738
DA 2026-03-09
ER

PT J
AU Parfitt, SA
   Ashton, NM
   Lewis, SG
   Abel, RL
   Coope, GR
   Field, MH
   Gale, R
   Hoare, PG
   Larkin, NR
   Lewis, MD
   Karloukovski, V
   Maher, BA
   Peglar, SM
   Preece, RC
   Whittaker, JE
   Stringer, CB
AF Parfitt, Simon A.
   Ashton, Nick M.
   Lewis, Simon G.
   Abel, Richard L.
   Coope, G. Russell
   Field, Mike H.
   Gale, Rowena
   Hoare, Peter G.
   Larkin, Nigel R.
   Lewis, Mark D.
   Karloukovski, Vassil
   Maher, Barbara A.
   Peglar, Sylvia M.
   Preece, Richard C.
   Whittaker, John E.
   Stringer, Chris B.
TI Early Pleistocene human occupation at the edge of the boreal zone in northwest Europe
SO NATURE
LA English
DT Article
ID colonization; temperatures; mechanisms; dispersal; sediments; record
AB The dispersal of early humans from Africa by 1.75 Myr ago led to a marked expansion of their range, from the island of Flores in the east to the Iberian peninsula in the west(1-5). This range encompassed tropical forest, savannah and Mediterranean habitats, but has hitherto not been demonstrated beyond 45 degrees N. Until recently, early colonization in Europe was thought to be confined to the area south of the Pyrenees and Alps. However, evidence from Pakefield (Suffolk, UK) at similar to 0.7 Myrindicated that humans occupied northern European latitudes when a Mediterranean-type climate prevailed(6). This provided the basis for an 'ebb and flow' model, where human populations were thought to survive in southern refugia during cold stages, only expanding northwards during fully temperate climates(5). Here we present new evidence from Happisburgh (Norfolk, UK) demonstrating that Early Pleistocene hominins were present in northern Europe >0.78 Myr ago when they were able to survive at the southern edge of the boreal zone. This has significant implications for our understanding of early human behaviour, adaptation and survival, as well as the tempo and mode of colonization after their first dispersal out of Africa.
C1 [Ashton, Nick M.] British Museum, Dept Prehistory & Europe, London N1 5QJ, England.
   [Parfitt, Simon A.] UCL, Inst Archaeol, London WC1H 0PY, England.
   [Parfitt, Simon A.; Lewis, Mark D.; Peglar, Sylvia M.; Whittaker, John E.; Stringer, Chris B.] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England.
   [Lewis, Simon G.] Queen Mary Univ London, Dept Geog, London E1 4NS, England.
   [Abel, Richard L.] Nat Hist Museum, Dept Mineral, London SW7 5BD, England.
   [Field, Mike H.] Leiden Univ, Dept Archaeol, NL-2300 RA Leiden, Netherlands.
   [Coope, G. Russell] Univ Birmingham, Sch Earth Sci, Birmingham B15 2TT, W Midlands, England.
   [Gale, Rowena] Royal Bot Gardens, Jodrell Lab, Richmond TW9 3AB, Surrey, England.
   [Hoare, Peter G.] Univ Sydney, Sch Geosci, Sydney, NSW 2006, Australia.
   [Larkin, Nigel R.] Norfolk Museums & Archaeol Serv, Norwich NR1 3JQ, Norfolk, England.
   [Karloukovski, Vassil; Maher, Barbara A.] Univ Lancaster, Ctr Environm Magnetism & Palaeomagnetism, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Preece, Richard C.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
C3 University of London; University College London; Natural History Museum London; University of London; Queen Mary University London; Natural History Museum London; Leiden University - Excl LUMC; Leiden University; University of Birmingham; Royal Botanic Gardens, Kew; University of Sydney; Lancaster University; University of Cambridge
RP Ashton, NM (corresponding author), British Museum, Dept Prehistory & Europe, Franks House,38-56 Orsman Rd, London N1 5QJ, England.
EM nashton@thebritishmuseum.ac.uk
FU British Museum; Ancient Human Occupation of Britain (AHOB)
NR 30
TC 291
Z9 308
U1 3
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 8
PY 2010
VL 466
IS 7303
BP 229
EP 233
DI 10.1038/nature09117
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800035
PM 20613840
DA 2026-03-09
ER

PT J
AU Srivastava, M
   Simakov, O
   Chapman, J
   Fahey, B
   Gauthier, MEA
   Mitros, T
   Richards, GS
   Conaco, C
   Dacre, M
   Hellsten, U
   Larroux, C
   Putnam, NH
   Stanke, M
   Adamska, M
   Darling, A
   Degnan, SM
   Oakley, TH
   Plachetzki, DC
   Zhai, YF
   Adamski, M
   Calcino, A
   Cummins, SF
   Goodstein, DM
   Harris, C
   Jackson, DJ
   Leys, SP
   Shu, SQ
   Woodcroft, BJ
   Vervoort, M
   Kosik, KS
   Manning, G
   Degnan, BM
   Rokhsar, DS
AF Srivastava, Mansi
   Simakov, Oleg
   Chapman, Jarrod
   Fahey, Bryony
   Gauthier, Marie E. A.
   Mitros, Therese
   Richards, Gemma S.
   Conaco, Cecilia
   Dacre, Michael
   Hellsten, Uffe
   Larroux, Claire
   Putnam, Nicholas H.
   Stanke, Mario
   Adamska, Maja
   Darling, Aaron
   Degnan, Sandie M.
   Oakley, Todd H.
   Plachetzki, David C.
   Zhai, Yufeng
   Adamski, Marcin
   Calcino, Andrew
   Cummins, Scott F.
   Goodstein, David M.
   Harris, Christina
   Jackson, Daniel J.
   Leys, Sally P.
   Shu, Shengqiang
   Woodcroft, Ben J.
   Vervoort, Michel
   Kosik, Kenneth S.
   Manning, Gerard
   Degnan, Bernard M.
   Rokhsar, Daniel S.
TI The Amphimedon queenslandica genome and the evolution of animal complexity
SO NATURE
LA English
DT Article
ID sea-anemone; monosiga-brevicollis; tyrosine kinases; gene repertoire; origin; sponge; protein; expression; inference; adhesion
AB Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse 'toolkit' of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic-and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.
C1 [Srivastava, Mansi; Mitros, Therese; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Srivastava, Mansi; Mitros, Therese; Rokhsar, Daniel S.] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Simakov, Oleg] Heidelberg Univ, D-69117 Heidelberg, Germany.
   [Chapman, Jarrod; Hellsten, Uffe; Goodstein, David M.; Shu, Shengqiang; Rokhsar, Daniel S.] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
   [Fahey, Bryony; Gauthier, Marie E. A.; Richards, Gemma S.; Larroux, Claire; Adamska, Maja; Degnan, Sandie M.; Adamski, Marcin; Calcino, Andrew; Cummins, Scott F.; Harris, Christina; Jackson, Daniel J.; Woodcroft, Ben J.; Degnan, Bernard M.] Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
   [Conaco, Cecilia; Kosik, Kenneth S.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
   [Dacre, Michael; Zhai, Yufeng; Manning, Gerard] Salk Inst Biol Studies, Razavi Newman Ctr Bioinformat, La Jolla, CA 92037 USA.
   [Putnam, Nicholas H.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA.
   [Stanke, Mario] Abt Bioinformat, Inst Mikrobiol & Genet, D-37077 Gottingen, Germany.
   [Darling, Aaron] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA.
   [Oakley, Todd H.; Plachetzki, David C.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Leys, Sally P.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
   [Vervoort, Michel] Univ Paris 07, CNRS, UMR 7592, Dev & Neurobiol Program,Inst Jacques Monod, F-75205 Paris 13, France.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; Ruprecht Karls University Heidelberg; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; University of Queensland; University of California System; University of California Santa Barbara; Salk Institute; Rice University; University of California System; University of California Davis; University of California System; University of California Santa Barbara; University of Alberta; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
RP Srivastava, M (corresponding author), Whitehead Inst Biomed Res, Cambridge, MA 02138 USA.
EM mansi@wi.mit.edu; b.degnan@uq.edu.au; dsrokhsar@gmail.com
FU Australian Research Council; US Department of Energy Joint Genome Institute; NSF; NIH/NHGRI; University of Queensland; Sars International Centre for Marine Molecular Biology; DFG; ANR; CNRS; Gordon and Betty Moore Foundation; Office of Science of the US Department of Energy [DE-AC02-05CH11231]
NR 65
TC 806
Z9 936
U1 2
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 AUG 5
PY 2010
VL 466
IS 7307
BP 720
EP U3
DI 10.1038/nature09201
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500031
PM 20686567
DA 2026-03-09
ER

PT J
AU Chia, NY
   Chan, YS
   Feng, B
   Lu, XY
   Orlov, YL
   Moreau, D
   Kumar, P
   Yang, L
   Jiang, JM
   Lau, MS
   Huss, M
   Soh, BS
   Kraus, P
   Li, P
   Lufkin, T
   Lim, B
   Clarke, ND
   Bard, F
   Ng, HH
AF Chia, Na-Yu
   Chan, Yun-Shen
   Feng, Bo
   Lu, Xinyi
   Orlov, Yuriy L.
   Moreau, Dimitri
   Kumar, Pankaj
   Yang, Lin
   Jiang, Jianming
   Lau, Mei-Sheng
   Huss, Mikael
   Soh, Boon-Seng
   Kraus, Petra
   Li, Pin
   Lufkin, Thomas
   Lim, Bing
   Clarke, Neil D.
   Bard, Frederic
   Ng, Huck-Hui
TI A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
SO NATURE
LA English
DT Article
ID defined factors; mouse embryos; self-renewal; lines; establishment; transcription; expression; regulator; proteins; complex
AB The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology(1). The full potential of hESCs in research and clinical applications requires a detailed understanding of the genetic network that governs the unique properties of hESCs. Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs. Interestingly, functionally distinct complexes involved in transcriptional regulation and chromatin remodelling are among the factors identified in the screen. To understand the roles of these potential regulators of hESCs, we studied transcription factor PRDM14 to gain new insights into its functional roles in the regulation of pluripotency. We showed that PRDM14 regulates directly the expression of key pluripotency gene POU5F1 through its proximal enhancer. Genome-wide location profiling experiments revealed that PRDM14 colocalized extensively with other key transcription factors such as OCT4, NANOG and SOX2, indicating that PRDM14 is integrated into the core transcriptional regulatory network. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Altogether, our study uncovers a wealth of novel hESC regulators wherein PRDM14 exemplifies a key transcription factor required for the maintenance of hESC identity and the reacquisition of pluripotency in human somatic cells.
C1 [Chia, Na-Yu; Chan, Yun-Shen; Feng, Bo; Lu, Xinyi; Yang, Lin; Jiang, Jianming; Lau, Mei-Sheng; Ng, Huck-Hui] Genome Inst Singapore, Gene Regulat Lab, Singapore 138672, Singapore.
   [Chia, Na-Yu; Ng, Huck-Hui] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore.
   [Chan, Yun-Shen; Ng, Huck-Hui] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117456, Singapore.
   [Lu, Xinyi; Ng, Huck-Hui] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
   [Orlov, Yuriy L.; Huss, Mikael; Clarke, Neil D.] Genome Inst Singapore, Computat & Syst Biol Grp, Singapore 138672, Singapore.
   [Moreau, Dimitri; Kumar, Pankaj; Bard, Frederic] Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Lim, Bing] Harvard Univ, Sch Med, Ctr Life Sci, Boston, MA 02115 USA.
   [Clarke, Neil D.; Bard, Frederic; Ng, Huck-Hui] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Nanyang Technological University; National University of Singapore; National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Harvard University; Harvard Medical School; National University of Singapore
RP Ng, HH (corresponding author), Genome Inst Singapore, Gene Regulat Lab, 60 Biopolis St, Singapore 138672, Singapore.
EM fbard@imcb.a-star.edu.sg; nghh@gis.a-star.edu.sg
FU Biomedical Research Council (BMRC); Agency for Science, Technology and Research (A*STAR); Singapore Stem Cell Consortium
NR 30
TC 376
Z9 468
U1 0
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 316
EP U207
DI 10.1038/nature09531
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000053
PM 20953172
DA 2026-03-09
ER

PT J
AU Ribet, D
   Hamon, M
   Gouin, E
   Nahori, MA
   Impens, F
   Neyret-Kahn, H
   Gevaert, K
   Vandekerckhove, J
   Dejean, A
   Cossart, P
AF Ribet, David
   Hamon, Melanie
   Gouin, Edith
   Nahori, Marie-Anne
   Impens, Francis
   Neyret-Kahn, Helene
   Gevaert, Kris
   Vandekerckhove, Joel
   Dejean, Anne
   Cossart, Pascale
TI Listeria monocytogenes impairs SUMOylation for efficient infection
SO NATURE
LA English
DT Article
ID growth-factor-beta; histone modifications; sumo pathway; protein; cells; host; proteomics; family; entry; mice
AB During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation and escape from host immune responses. Post-translational modifications are unique mechanisms that allow cells to rapidly, locally and specifically modify activity or interactions of key proteins. Some of these modifications, including phosphorylation and ubiquitylation(1,2), can be induced by pathogens. However, the effects of pathogenic bacteria on SUMOylation, an essential post-translational modification in eukaryotic cells(3), remain largely unknown. Here we show that infection with Listeria monocytogenes leads to a decrease in the levels of cellular SUMO-conjugated proteins. This event is triggered by the bacterial virulence factor listeriolysin O (LLO), which induces a proteasome-independent degradation of Ubc9, an essential enzyme of the SUMOylation machinery, and a proteasome-dependent degradation of some SUMOylated proteins. The effect of LLO on Ubc9 is dependent on the pore-forming capacity of the toxin and is shared by other bacterial pore-forming toxins like perfringolysin O(PFO) and pneumolysin (PLY). Ubc9 degradation was also observed in vivo in infected mice. Furthermore, we show that SUMO overexpression impairs bacterial infection. Together, our results reveal that Listeria, and probably other pathogens, dampen the host response by decreasing the SUMOylation level of proteins critical for infection.
C1 [Ribet, David; Hamon, Melanie; Gouin, Edith; Nahori, Marie-Anne; Cossart, Pascale] Inst Pasteur, Dept Biol Cellulaire & Infect, Unite Interact Bacteries Cellules, F-75015 Paris, France.
   [Ribet, David; Hamon, Melanie; Gouin, Edith; Nahori, Marie-Anne; Cossart, Pascale] INRA, USC2020, F-75015 Paris, France.
   [Ribet, David; Hamon, Melanie; Gouin, Edith; Nahori, Marie-Anne; Cossart, Pascale] INSERM, U604, F-75015 Paris, France.
   [Impens, Francis; Gevaert, Kris; Vandekerckhove, Joel] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Impens, Francis; Gevaert, Kris; Vandekerckhove, Joel] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Neyret-Kahn, Helene; Dejean, Anne] Inst Pasteur, Dept Biol Cellulaire & Infect, Unite Org Nucl & Oncogenese, F-75015 Paris, France.
   [Neyret-Kahn, Helene; Dejean, Anne] INSERM, U579, F-75015 Paris, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; INRAE; Institut National de la Sante et de la Recherche Medicale (Inserm); Flanders Institute for Biotechnology (VIB); Ghent University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Cossart, P (corresponding author), Inst Pasteur, Dept Biol Cellulaire & Infect, Unite Interact Bacteries Cellules, F-75015 Paris, France.
EM pascale.cossart@pasteur.fr
FU Institut Pasteur; INSERM; INRA; European Research Council (ERC) [233348]; Fund for Scientific Research Flanders (Belgium) [G.0042.07]; Concerted Research Actions [BOF07/GOA/012]; Ghent University; Inter University Attraction Poles [IUAP06]; Association pour la Recherche sur le Cancer; Research Assistant of the Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek - Vlaanderen)
NR 32
TC 167
Z9 198
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1192
EP U111
DI 10.1038/nature08963
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100037
PM 20414307
DA 2026-03-09
ER

PT J
AU Zhang, JT
   Tang, Y
   Lee, K
   Ouyang, M
AF Zhang, Jiatao
   Tang, Yun
   Lee, Kwan
   Ouyang, Min
TI Tailoring light-matter-spin interactions in colloidal hetero-nanostructures
SO NATURE
LA English
DT Article
ID quantum-dot; electron-spin; dynamics; manipulation; plasmonics; energy
AB The interplay between light and matter is the basis of many fundamental processes and various applications(1). Harnessing light-matter interactions in principle allows operation of solid state devices under new physical principles: for example, the a. c. optical Stark effect (OSE) has enabled coherent quantum control schemes of spins in semiconductors, with the potential for realizing quantum devices based on spin qubits(2-5). However, as the dimension of semiconductors is reduced, light-matter coupling is typically weakened, thus limiting applications at the nanoscale. Recent experiments have demonstrated significant enhancement of nanoscale light-matter interactions, albeit with the need for a high-finesse cavity(6,7), ultimately preventing device down-scaling and integration. Here we report that a sizable OSE can be achieved at substantial energy detuning in a cavity-free colloidal metal-semiconductor core-shell hetero-nanostructure, in which the metal surface plasmon is tuned to resonate spectrally with a semiconductor exciton transition. We further demonstrate that this resonantly enhanced OSE exhibits polarization dependence and provides a viable mechanism for coherent ultrafast spin manipulation within colloidal nanostructures. The plasmon-exciton resonant nature further enables tailoring of both OSE and spin manipulation by tuning plasmon resonance intensity and frequency. These results open a pathway for tailoring light-matter-spin interactions through plasmon-exciton resonant coupling in a judiciously engineered nanostructure, and offer a basis for future applications in quantum information processing at the nanoscale. More generally, integrated nanostructures with resonantly enhanced light-matter interactions should serve as a test bed for other emerging fields, including nano-biophotonics and nano-energy(8,9).
C1 [Zhang, Jiatao; Tang, Yun; Lee, Kwan; Ouyang, Min] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Zhang, Jiatao; Tang, Yun; Lee, Kwan; Ouyang, Min] Univ Maryland, Ctr Nanophys & Adv Mat, 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 Ouyang, M (corresponding author), Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
EM mouyang@umd.edu
FU ONR [N000140710787]; NSF [DMR-0547194]; Beckman YIP grant [0609259093]
NR 29
TC 241
Z9 270
U1 1
U2 368
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 1
PY 2010
VL 466
IS 7302
BP 91
EP 95
DI 10.1038/nature09150
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800040
PM 20596017
DA 2026-03-09
ER

PT J
AU Bond-Lamberty, B
   Thomson, A
AF Bond-Lamberty, Ben
   Thomson, Allison
TI Temperature-associated increases in the global soil respiration record
SO NATURE
LA English
DT Article
ID interannual variability; terrestrial ecosystems; carbon; climate; sensitivity; boreal; co2; decomposition; constraints; vegetation
AB Soil respiration, R-S, the flux of microbially and plant-respired carbon dioxide (CO2) from the soil surface to the atmosphere, is the second-largest terrestrial carbon flux(1-3). However, the dynamics of R-S are not well understood and the global flux remains poorly constrained(4,5). Ecosystem warming experiments(6,7), modelling analyses(8,9) and fundamental biokinetics(10) all suggest that R-S should change with climate. This has been difficult to confirm observationally because of the high spatial variability of R-S, inaccessibility of the soil medium and the inability of remote-sensing instruments to measure R-S on large scales. Despite these constraints, it may be possible to discern climate-driven changes in regional or global R-S values in the extant four-decade record of R-S chamber measurements. Here we construct a database of worldwide R-S observations matched with high-resolution historical climate data and find a previously unknown temporal trend in the R-S record after accounting for mean annual climate, leaf area, nitrogen deposition and changes in CO2 measurement technique. We find that the air temperature anomaly (the deviation from the 1961-1990 mean) is significantly and positively correlated with changes in R-S. We estimate that the global R-S in 2008 (that is, the flux integrated over the Earth's land surface over 2008) was 98 +/- 12 Pg C and that it increased by 0.1 Pg C yr(-1) between 1989 and 2008, implying a global R-S response to air temperature (Q(10)) of 1.5. An increasing global R-S value does not necessarily constitute a positive feedback to the atmosphere, as it could be driven by higher carbon inputs to soil rather than by mobilization of stored older carbon. The available data are, however, consistent with an acceleration of the terrestrial carbon cycle in response to global climate change.
C1 [Bond-Lamberty, Ben; Thomson, Allison] Univ Maryland, Pacific NW Natl Lab, Joint Global Change Res Inst, College Pk, MD 20740 USA.
C3 United States Department of Energy (DOE); Pacific Northwest National Laboratory; University System of Maryland; University of Maryland College Park
RP Bond-Lamberty, B (corresponding author), Univ Maryland, Pacific NW Natl Lab, Joint Global Change Res Inst, 5825 Univ Res Court,Suite 3500, College Pk, MD 20740 USA.
EM bondlamberty@pnl.gov
FU US Department of Energy Office of Science; Pacific Northwest National Laboratory
NR 30
TC 1288
Z9 1625
U1 33
U2 1234
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 579
EP U132
DI 10.1038/nature08930
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200045
PM 20336143
DA 2026-03-09
ER

PT J
AU Veselka, N
   McErlain, DD
   Holdsworth, DW
   Eger, JL
   Chhem, RK
   Mason, MJ
   Brain, KL
   Faure, PA
   Fenton, MB
AF Veselka, Nina
   McErlain, David D.
   Holdsworth, David W.
   Eger, Judith L.
   Chhem, Rethy K.
   Mason, Matthew J.
   Brain, Kirsty L.
   Faure, Paul A.
   Fenton, M. Brock
TI A bony connection signals laryngeal echolocation in bats
SO NATURE
LA English
DT Article
ID computed-tomography; middle-ear; evolution; mammals; apparatus; region; flight
AB Echolocation is an active form of orientation in which animals emit sounds and then listen to reflected echoes of those sounds to form images of their surroundings in their brains(1). Although echolocation is usually associated with bats, it is not characteristic of all bats(2,3). Most echolocating bats produce signals in the larynx, but within one family of mainly non-echolocating species (Pteropodidae), a few species use echolocation sounds produced by tongue clicks(4,5). Here we demonstrate, using data obtained from micro-computed tomography scans of 26 species (n = 35 fluid-preserved bats), that proximal articulation of the stylohyal bone (part of the mammalian hyoid apparatus) with the tympanic bone always distinguishes laryngeally echolocating bats from all other bats (that is, non-echolocating pteropodids and those that echo-locate with tongue clicks). In laryngeally echolocating bats, the proximal end of the stylohyal bone directly articulates with the tympanic bone and is often fused with it. Previous research on the morphology of the stylohyal bone in the oldest known fossil bat (Onychonycteris finneyi) suggested that it did not echolocate(6), but our findings suggest that O. finneyi may have used laryngeal echolocation because its stylohyal bones may have articulated with its tympanic bones. The present findings reopen basic questions about the timing and the origin of flight and echolocation in the early evolution of bats. Our data also provide an independent anatomical character by which to distinguish laryngeally echolocating bats from other bats.
C1 [Veselka, Nina; Fenton, M. Brock] Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada.
   [McErlain, David D.; Holdsworth, David W.] Univ Western Ontario, Robarts Res Inst, Imaging Res Labs, London, ON N6A 5B7, Canada.
   [McErlain, David D.] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5B7, Canada.
   [Holdsworth, David W.] Univ Western Ontario, Schulich Sch Med & Dent, Dept Surg, London, ON N6A 5K8, Canada.
   [Eger, Judith L.] Royal Ontario Museum, Dept Nat Hist, Toronto, ON M5S 2C6, Canada.
   [Chhem, Rethy K.] Med Univ Vienna, Div Human Hlth, Dept Radiol, A-1090 Vienna, Austria.
   [Chhem, Rethy K.] IAEA, Div Human Hlth, A-1400 Vienna, Austria.
   [Mason, Matthew J.; Brain, Kirsty L.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
   [Faure, Paul A.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada.
C3 Western University (University of Western Ontario); Western University (University of Western Ontario); University Western Ontario Hospital; Western University (University of Western Ontario); Western University (University of Western Ontario); Royal Ontario Museum; Medical University of Vienna; International Atomic Energy Agency; University of Cambridge; McMaster University
RP Fenton, MB (corresponding author), Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada.
EM bfenton@uwo.ca
FU Canadian Institutes of Health Research [CIHR MOP-89852]; Natural Sciences and Engineering Research Council of Canada; Canada Foundation for Innovation; Ontario Innovation Trust
NR 30
TC 103
Z9 122
U1 1
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 939
EP 942
DI 10.1038/nature08737
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700044
PM 20098413
DA 2026-03-09
ER

PT J
AU Gao, M
   Nettles, RE
   Belema, M
   Snyder, LB
   Nguyen, VN
   Fridell, RA
   Serrano-Wu, MH
   Langley, DR
   Sun, JH
   O'Boyle, DR
   Lemm, JA
   Wang, CF
   Knipe, JO
   Chien, C
   Colonno, RJ
   Grasela, DM
   Meanwell, NA
   Hamann, LG
AF Gao, Min
   Nettles, Richard E.
   Belema, Makonen
   Snyder, Lawrence B.
   Nguyen, Van N.
   Fridell, Robert A.
   Serrano-Wu, Michael H.
   Langley, David R.
   Sun, Jin-Hua
   O'Boyle, Donald R.
   Lemm, Julie A.
   Wang, Chunfu
   Knipe, Jay O.
   Chien, Caly
   Colonno, Richard J.
   Grasela, Dennis M.
   Meanwell, Nicholas A.
   Hamann, Lawrence G.
TI Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
SO NATURE
LA English
DT Article
ID hepatitis-c virus; nonstructural proteins; domain; rna
AB The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people(1). Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus(2,3). The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent-RNA polymerase NS5B(4). Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC50) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.
C1 [Belema, Makonen; Snyder, Lawrence B.; Nguyen, Van N.; Serrano-Wu, Michael H.; Meanwell, Nicholas A.; Hamann, Lawrence G.] Bristol Myers Squibb Co, Res & Dev, Dept Discovery Chem, Wallingford, CT 06492 USA.
   [Nettles, Richard E.; Chien, Caly; Grasela, Dennis M.] Bristol Myers Squibb Co, Res & Dev, Dept Discovery Med & Clin Pharmacol, Princeton, NJ 08543 USA.
   [Langley, David R.] Bristol Myers Squibb Co, Res & Dev, Dept Comp Aided Drug Design, Wallingford, CT 06492 USA.
   [Knipe, Jay O.] Bristol Myers Squibb Co, Res & Dev, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA.
   [Gao, Min; Fridell, Robert A.; Sun, Jin-Hua; O'Boyle, Donald R.; Lemm, Julie A.; Wang, Chunfu; Colonno, Richard J.] Bristol Myers Squibb Co, Res & Dev, Dept Virol, Wallingford, CT 06492 USA.
C3 Bristol-Myers Squibb; Bristol-Myers Squibb; Bristol-Myers Squibb; Bristol-Myers Squibb; Bristol-Myers Squibb
RP Meanwell, NA (corresponding author), Bristol Myers Squibb Co, Res & Dev, Dept Discovery Chem, 5 Res Pkwy, Wallingford, CT 06492 USA.
EM Nicholas.Meanwell@bms.com
NR 23
TC 805
Z9 916
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 96
EP U108
DI 10.1038/nature08960
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900038
PM 20410884
DA 2026-03-09
ER

PT J
AU Hassan, F
   Kamruzzaman, M
   Mekalanos, JJ
   Faruque, SM
AF Hassan, Faizule
   Kamruzzaman, M.
   Mekalanos, John J.
   Faruque, Shah M.
TI Satellite phage TLCφ enables toxigenic conversion by CTX phage through dif site alteration
SO NATURE
LA English
DT Article
ID vibrio-cholerae o139; filamentous phage; integration; genome; toxin; form; recombinases; replication; genes; xerd
AB Bacterial chromosomes often carry integrated genetic elements (for example plasmids, transposons, prophages and islands) whose precise function and contribution to the evolutionary fitness of the host bacterium are unknown. The CTX phi prophage, which encodes cholera toxin in Vibrio cholerae(1), is known to be adjacent to a chromosomally integrated element of unknown function termed the toxin-linked cryptic (TLC)(2). Here we report the characterization of a TLC-related element that corresponds to the genome of a satellite filamentous phage (TLC-Kn phi 1), which uses the morphogenesis genes of another filamentous phage (fs2 phi) to form infectious TLC-Kn phi 1 phage particles. The TLC-Kn phi 1 phage genome carries a sequence similar to the dif recombination sequence, which functions in chromosome dimer resolution using XerC and XerD recombinases(3). The dif sequence is also exploited by lysogenic filamentous phages (for example CTX phi) for chromosomal integration of their genomes. Bacterial cells defective in the dimer resolution often show an aberrant filamentous cell morphology(3,4). We found that acquisition and chromosomal integration of the TLC-Kn phi 1 genome restored a perfect dif site and normal morphology to V. cholerae wild-type and mutant strains with dif(-) filamentation phenotypes. Furthermore, lysogeny of a dif(-) non-toxigenic V. cholerae with TLC-Kn phi 1 promoted its subsequent toxigenic conversion through integration of CTX phi into the restored dif site. These results reveal a remarkable level of cooperative interactions between multiple filamentous phages in the emergence of the bacterial pathogen that causes cholera.
C1 [Hassan, Faizule; Kamruzzaman, M.; Faruque, Shah M.] Int Ctr Diarrhoeal Dis Res, Mol Genet Lab, Dhaka 1212, Bangladesh.
   [Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
C3 International Centre for Diarrhoeal Disease Research (ICDDR); Harvard University; Harvard Medical School
RP Faruque, SM (corresponding author), Int Ctr Diarrhoeal Dis Res, Mol Genet Lab, Dhaka 1212, Bangladesh.
EM faruque@icddrb.org
FU National Institutes of Health under Harvard Medical School and the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) [RO1-GM068851, RO1-AI070963]
NR 21
TC 80
Z9 98
U1 1
U2 18
PU 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 21
PY 2010
VL 467
IS 7318
BP 982
EP 985
DI 10.1038/nature09469
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700042
PM 20944629
DA 2026-03-09
ER

PT J
AU Pastor, F
   Kolonias, D
   Giangrande, PH
   Gilboa, E
AF Pastor, Fernando
   Kolonias, Despina
   Giangrande, Paloma H.
   Gilboa, Eli
TI Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay
SO NATURE
LA English
DT Article
ID combination immunotherapy; t-cells; expression; recognition; rejection; aptamers
AB The main reason why tumours are not controlled by the immune system is that, unlike pathogens, they do not express potent tumour rejection antigens (TRAs). Tumour vaccination aims at stimulating a systemic immune response targeted to, mostly weak, antigens expressed in the disseminated tumour lesions. Main challenges in developing effective vaccination protocols are the identification of potent and broadly expressed TRAs1-3 and effective adjuvants to stimulate a robust and durable immune response(4-6). Here we describe an alternative approach in which the expression of new, and thereby potent, antigens are induced in tumour cells by inhibiting nonsense-mediated messenger RNA decay (NMD)(7-10). Small interfering RNA (siRNA)-mediated inhibition of NMD in tumour cells led to the expression of new antigenic determinants and their immune-mediated rejection. In subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to significant inhibition of tumour growth that was superior to that of vaccination with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing irradiated tumour cells(11), and could be further enhanced by co-stimulation. Tumour-targeted NMD inhibition forms the basis of a simple, broadly useful, and clinically feasible approach to enhance the antigenicity of disseminated tumours leading to their immune recognition and rejection. The cell-free chemically synthesized oligonucleotide backbone of aptamer-siRNAs reduces the risk of immunogenicity and enhances the feasibility of generating reagents suitable for clinical use.
C1 [Pastor, Fernando; Kolonias, Despina; Gilboa, Eli] Univ Miami, Miller Sch Med Miami, Dodson Interdisciplinary Immunotherapy Inst, Dept Microbiol & Immunol, Miami, FL 33134 USA.
   [Giangrande, Paloma H.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
   [Giangrande, Paloma H.] Univ Iowa, Dept Radiat Oncol, Mol & Cellular Biol Program, Iowa City, IA 52242 USA.
C3 University of Miami; University of Iowa; University of Iowa
RP Gilboa, E (corresponding author), Univ Miami, Miller Sch Med Miami, Dodson Interdisciplinary Immunotherapy Inst, Dept Microbiol & Immunol, Miami, FL 33134 USA.
EM egilboa@med.miami.edu
FU Dodson foundation; Sylvester Comprehensive Cancer Center (Medical School, University of Miami)
NR 30
TC 232
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 MAY 13
PY 2010
VL 465
IS 7295
BP 227
EP U114
DI 10.1038/nature08999
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500037
PM 20463739
DA 2026-03-09
ER

PT J
AU Schuster, SC
   Miller, W
   Ratan, A
   Tomsho, LP
   Giardine, B
   Kasson, LR
   Harris, RS
   Petersen, DC
   Zhao, FQ
   Qi, J
   Alkan, C
   Kidd, JM
   Sun, YZ
   Drautz, DI
   Bouffard, P
   Muzny, DM
   Reid, JG
   Nazareth, LV
   Wang, QY
   Burhans, R
   Riemer, C
   Wittekindt, NE
   Moorjani, P
   Tindall, EA
   Danko, CG
   Teo, WS
   Buboltz, AM
   Zhang, ZH
   Ma, QY
   Oosthuysen, A
   Steenkamp, AW
   Oostuisen, H
   Venter, P
   Gajewski, J
   Zhang, Y
   Pugh, BF
   Makova, KD
   Nekrutenko, A
   Mardis, ER
   Patterson, N
   Pringle, TH
   Chiaromonte, F
   Mullikin, JC
   Eichler, EE
   Hardison, RC
   Gibbs, RA
   Harkins, TT
   Hayes, VM
AF Schuster, Stephan C.
   Miller, Webb
   Ratan, Aakrosh
   Tomsho, Lynn P.
   Giardine, Belinda
   Kasson, Lindsay R.
   Harris, Robert S.
   Petersen, Desiree C.
   Zhao, Fangqing
   Qi, Ji
   Alkan, Can
   Kidd, Jeffrey M.
   Sun, Yazhou
   Drautz, Daniela I.
   Bouffard, Pascal
   Muzny, Donna M.
   Reid, Jeffrey G.
   Nazareth, Lynne V.
   Wang, Qingyu
   Burhans, Richard
   Riemer, Cathy
   Wittekindt, Nicola E.
   Moorjani, Priya
   Tindall, Elizabeth A.
   Danko, Charles G.
   Teo, Wee Siang
   Buboltz, Anne M.
   Zhang, Zhenhai
   Ma, Qianyi
   Oosthuysen, Arno
   Steenkamp, Abraham W.
   Oostuisen, Hermann
   Venter, Philippus
   Gajewski, John
   Zhang, Yu
   Pugh, B. Franklin
   Makova, Kateryna D.
   Nekrutenko, Anton
   Mardis, Elaine R.
   Patterson, Nick
   Pringle, Tom H.
   Chiaromonte, Francesca
   Mullikin, James C.
   Eichler, Evan E.
   Hardison, Ross C.
   Gibbs, Richard A.
   Harkins, Timothy T.
   Hayes, Vanessa M.
TI Complete Khoisan and Bantu genomes from southern Africa
SO NATURE
LA English
DT Article
ID copy number; sequence; inversion; mtdna; gene
AB The genetic structure of the indigenous hunter-gatherer peoples of southern Africa, the oldest known lineage of modern human, is important for understanding human diversity. Studies based on mitochondrial(1) and small sets of nuclear markers(2) have shown that these hunter-gatherers, known as Khoisan, San, or Bushmen, are genetically divergent from other humans(1,3). However, until now, fully sequenced human genomes have been limited to recently diverged populations(4-8). Here we present the complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and a Bantu from southern Africa, as well as protein-coding regions from an additional three hunter-gatherers from disparate regions of the Kalahari. We characterize the extent of whole-genome and exome diversity among the five men, reporting 1.3 million novel DNA differences genome-wide, including 13,146 novel amino acid variants. In terms of nucleotide substitutions, the Bushmen seem to be, on average, more different from each other than, for example, a European and an Asian. Observed genomic differences between the hunter-gatherers and others may help to pinpoint genetic adaptations to an agricultural lifestyle. Adding the described variants to current databases will facilitate inclusion of southern Africans in medical research efforts, particularly when family and medical histories can be correlated with genome-wide data.
C1 [Schuster, Stephan C.; Miller, Webb; Ratan, Aakrosh; Tomsho, Lynn P.; Giardine, Belinda; Kasson, Lindsay R.; Harris, Robert S.; Zhao, Fangqing; Qi, Ji; Sun, Yazhou; Drautz, Daniela I.; Wang, Qingyu; Burhans, Richard; Riemer, Cathy; Wittekindt, Nicola E.; Buboltz, Anne M.; Zhang, Zhenhai; Ma, Qianyi; Gajewski, John; Zhang, Yu; Pugh, B. Franklin; Makova, Kateryna D.; Nekrutenko, Anton; Chiaromonte, Francesca; Hardison, Ross C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, Wartik Lab 310, University Pk, PA 16802 USA.
   [Petersen, Desiree C.; Tindall, Elizabeth A.; Teo, Wee Siang; Hayes, Vanessa M.] Univ New S Wales, Lowy Canc Res Ctr C25, Childrens Canc Inst Australia Med Res, Canc Genet Grp, Randwick, NSW 2031, Australia.
   [Alkan, Can; Kidd, Jeffrey M.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Alkan, Can; Kidd, Jeffrey M.; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Bouffard, Pascal; Harkins, Timothy T.] Roche Diagnostics Corp, Indianapolis, IN 46250 USA.
   [Muzny, Donna M.; Reid, Jeffrey G.; Nazareth, Lynne V.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Moorjani, Priya] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Danko, Charles G.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [Venter, Philippus] Univ Limpopo, ZA-0727 Sovenga, South Africa.
   [Mardis, Elaine R.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [Patterson, Nick] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Patterson, Nick] Harvard Univ, Cambridge Ctr, Cambridge, MA 02142 USA.
   [Pringle, Tom H.] Sperling Fdn, Eugene, OR 97405 USA.
   [Mullikin, James C.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Children's Cancer Institute; University of New South Wales Sydney; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Roche Holding; Roche Holding USA; Baylor College of Medicine; Harvard University; Harvard Medical School; Cornell University; University of Limpopo; Washington University (WUSTL); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Schuster, SC (corresponding author), Penn State Univ, Ctr Comparat Genom & Bioinformat, Wartik Lab 310, University Pk, PA 16802 USA.
EM scs@bx.psu.edu; vhayes@ccia.unsw.edu.au
FU Pennsylvania State University; National Human Genome Research Institute, National Institutes of Health; NSF [DEB-0733029]; NIH [R01GM087472]; Gordon and Betty Moore Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0850103] Funding Source: National Science Foundation; Office of Advanced Cyberinfrastructure (OAC); Direct For Computer & Info Scie & Enginr [0821527] Funding Source: National Science Foundation; National Human Genome Research Institute [ZIBHG000196, ZIAHG200330, R01HG004160] Funding Source: NIH RePORTER
NR 30
TC 310
Z9 380
U1 2
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 943
EP 947
DI 10.1038/nature08795
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700045
PM 20164927
DA 2026-03-09
ER

PT J
AU Johannessen, CM
   Boehm, JS
   Kim, SY
   Thomas, SR
   Wardwell, L
   Johnson, LA
   Emery, CM
   Stransky, N
   Cogdill, AP
   Barretina, J
   Caponigro, G
   Hieronymus, H
   Murray, RR
   Salehi-Ashtiani, K
   Hill, DE
   Vidal, M
   Zhao, JJ
   Yang, XP
   Alkan, O
   Kim, S
   Harris, JL
   Wilson, CJ
   Myer, VE
   Finan, PM
   Root, DE
   Roberts, TM
   Golub, T
   Flaherty, KT
   Dummer, R
   Weber, BL
   Sellers, WR
   Schlegel, R
   Wargo, JA
   Hahn, WC
   Garraway, LA
AF Johannessen, Cory M.
   Boehm, Jesse S.
   Kim, So Young
   Thomas, Sapana R.
   Wardwell, Leslie
   Johnson, Laura A.
   Emery, Caroline M.
   Stransky, Nicolas
   Cogdill, Alexandria P.
   Barretina, Jordi
   Caponigro, Giordano
   Hieronymus, Haley
   Murray, Ryan R.
   Salehi-Ashtiani, Kourosh
   Hill, David E.
   Vidal, Marc
   Zhao, Jean J.
   Yang, Xiaoping
   Alkan, Ozan
   Kim, Sungjoon
   Harris, Jennifer L.
   Wilson, Christopher J.
   Myer, Vic E.
   Finan, Peter M.
   Root, David E.
   Roberts, Thomas M.
   Golub, Todd
   Flaherty, Keith T.
   Dummer, Reinhard
   Weber, Barbara L.
   Sellers, William R.
   Schlegel, Robert
   Wargo, Jennifer A.
   Hahn, William C.
   Garraway, Levi A.
TI COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
SO NATURE
LA English
DT Article
ID tumor progression; signaling pathway; braf; mutations; cancer; cells; gene; transformation; sensitivity; activation
AB Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas(1). Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma(2-6)-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials(7-9). However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance(10-12). Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies(13). Here we expressed similar to 600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.
C1 [Johannessen, Cory M.; Boehm, Jesse S.; Kim, So Young; Thomas, Sapana R.; Johnson, Laura A.; Stransky, Nicolas; Barretina, Jordi; Hieronymus, Haley; Yang, Xiaoping; Alkan, Ozan; Root, David E.; Golub, Todd; Hahn, William C.; Garraway, Levi A.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Johannessen, Cory M.; Kim, So Young; Thomas, Sapana R.; Wardwell, Leslie; Johnson, Laura A.; Emery, Caroline M.; Barretina, Jordi; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Kim, So Young; Murray, Ryan R.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc; Hahn, William C.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
   [Cogdill, Alexandria P.; Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol Med Oncol & Dermatol, Boston, MA 02114 USA.
   [Barretina, Jordi; Golub, Todd; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Caponigro, Giordano; Wilson, Christopher J.; Myer, Vic E.; Finan, Peter M.; Weber, Barbara L.; Sellers, William R.; Schlegel, Robert] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Hieronymus, Haley; Golub, Todd] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Murray, Ryan R.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc; Zhao, Jean J.; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Murray, Ryan R.; Salehi-Ashtiani, Kourosh; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Zhao, Jean J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Kim, Sungjoon; Harris, Jennifer L.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
   [Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard 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 Medical School; Novartis; Novartis USA; Harvard University; Harvard Medical School; 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; Novartis; Novartis USA; University of Zurich; University Zurich Hospital
RP Garraway, LA (corresponding author), Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM Levi_Garraway@dfci.harvard.edu
FU NIH [CA134502]; Novartis Institutes for Biomedical Research; Melanoma Research Alliance; Starr Cancer Consortium; US National Cancer Institute [R33 CA128625, RC2 CA148268]; Swiss National Foundation [310040-103671]; Gottfried and Julia Bangerter Rhyner Stiftung; Ellison Foundation; DFCI Strategic Initiative
NR 29
TC 1186
Z9 1427
U1 0
U2 115
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 968
EP U370
DI 10.1038/nature09627
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600048
PM 21107320
DA 2026-03-09
ER

PT J
AU Gonzalez-Suarez, E
   Jacob, AP
   Jones, J
   Miller, R
   Roudier-Meyer, MP
   Erwert, R
   Pinkas, J
   Branstetter, D
   Dougall, WC
AF Gonzalez-Suarez, Eva
   Jacob, Allison P.
   Jones, Jon
   Miller, Robert
   Roudier-Meyer, Martine P.
   Erwert, Ryan
   Pinkas, Jan
   Branstetter, Dan
   Dougall, William C.
TI RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis
SO NATURE
LA English
DT Article
ID hormone replacement therapy; human breast-tumors; gland development; transgenic mice; medroxyprogesterone acetate; osteoclast differentiation; osteoprotegerin-ligand; cell function; receptor; expression
AB RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK(1,2). Mammary glands of RANK-and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium(3). It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis(4), and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed(5,6). However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone-and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone-and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.
C1 [Gonzalez-Suarez, Eva; Jacob, Allison P.; Jones, Jon; Miller, Robert; Erwert, Ryan; Dougall, William C.] Amgen Inc, Dept Hematol Oncol Res, Seattle, WA 98119 USA.
   [Roudier-Meyer, Martine P.; Branstetter, Dan] Amgen Inc, Dept Pathol, Seattle, WA 98119 USA.
   [Pinkas, Jan] Amgen Inc, Dept Hematol Oncol Res, Cambridge, MA 02139 USA.
C3 Amgen; Amgen; Amgen
RP Dougall, WC (corresponding author), Amgen Inc, Dept Hematol Oncol Res, Seattle, WA 98119 USA.
EM dougallw@amgen.com
NR 28
TC 473
Z9 523
U1 3
U2 49
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 103
EP +
DI 10.1038/nature09495
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900044
PM 20881963
DA 2026-03-09
ER

PT J
AU Regier, JC
   Shultz, JW
   Zwick, A
   Hussey, A
   Ball, B
   Wetzer, R
   Martin, JW
   Cunningham, CW
AF Regier, Jerome C.
   Shultz, Jeffrey W.
   Zwick, Andreas
   Hussey, April
   Ball, Bernard
   Wetzer, Regina
   Martin, Joel W.
   Cunningham, Clifford W.
TI Arthropod relationships revealed by phylogenomic analysis of nuclear protein-coding sequences
SO NATURE
LA English
DT Article
ID bayesian-inference; complete 28s; mitochondrial; gene; hypothesis; crustacea; myriapods; ecdysozoa; evolution; hexapoda
AB The remarkable antiquity, diversity and ecological significance of arthropods have inspired numerous attempts to resolve their deep phylogenetic history, but the results of two decades of intensive molecular phylogenetics have been mixed(1-7). The discovery that terrestrial insects (Hexapoda) are more closely related to aquatic Crustacea than to the terrestrial centipedes and millipedes(2,8) (Myriapoda) was an early, if exceptional, success. More typically, analyses based on limited samples of taxa and genes have generated results that are inconsistent, weakly supported and highly sensitive to analytical conditions(7,9,10). Here we present strongly supported results from likelihood, Bayesian and parsimony analyses of over 41 kilobases of aligned DNA sequence from 62 single-copy nuclear protein-coding genes from 75 arthropod species. These species represent every major arthropod lineage, plus five species of tardigrades and onychophorans as outgroups. Our results strongly support Pancrustacea (Hexapoda plus Crustacea) but also strongly favour the traditional morphology-based Mandibulata(11) (Myriapoda plus Pancrustacea) over the molecule-based Paradoxopoda (Myriapoda plus Chelicerata)(2,5,12). In addition to Hexapoda, Pancrustacea includes three major extant lineages of 'crustaceans', each spanning a significant range of morphological disparity. These are Oligostraca (ostracods, mystacocarids, branchiurans and pentastomids), Vericrustacea (malacostracans, thecostracans, copepods and branchiopods) and Xenocarida (cephalocarids and remipedes). Finally, within Pancrustacea we identify Xenocarida as the long-sought sister group to the Hexapoda, a result confirming that 'crustaceans' are not monophyletic. These results provide a statistically well-supported phylogenetic framework for the largest animal phylum and represent a step towards ending the often-heated, century-long debate on arthropod relationships.
C1 [Ball, Bernard; Cunningham, Clifford W.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Regier, Jerome C.; Shultz, Jeffrey W.; Zwick, Andreas; Hussey, April] Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA.
   [Shultz, Jeffrey W.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
   [Shultz, Jeffrey W.] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA.
   [Wetzer, Regina; Martin, Joel W.] Nat Hist Museum Los Angeles Cty, Los Angeles, CA 90007 USA.
C3 Duke University; University System of Maryland; University of Maryland Baltimore; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park
RP Cunningham, CW (corresponding author), Duke Univ, Dept Biol, Durham, NC 27708 USA.
EM cliff@duke.edu
FU Maryland Agricultural Experiment Station; Whiteley Center; US National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1042845] Funding Source: National Science Foundation
NR 43
TC 780
Z9 873
U1 3
U2 424
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1079
EP U98
DI 10.1038/nature08742
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400036
PM 20147900
DA 2026-03-09
ER

PT J
AU Adesnik, H
   Scanziani, M
AF Adesnik, Hillel
   Scanziani, Massimo
TI Lateral competition for cortical space by layer-specific horizontal circuits
SO NATURE
LA English
DT Article
ID primary visual-cortex; somatosensory barrel cortex; action-potential initiation; pyramidal neurons; in-vivo; orientation selectivity; gabaergic interneurons; synaptic connections; sensory responses; striate cortex
AB The cerebral cortex constructs a coherent representation of the world by integrating distinct features of the sensory environment. Although these features are processed vertically across cortical layers, horizontal projections interconnecting neighbouring cortical domains allow these features to be processed in a context-dependent manner. Despite the wealth of physiological and psychophysical studies addressing the function of horizontal projections, how they coordinate activity among cortical domains remains poorly understood. We addressed this question by selectively activating horizontal projection neurons in mouse somatosensory cortex, and determined how the resulting spatial pattern of excitation and inhibition affects cortical activity. We found that horizontal projections suppress superficial layers while simultaneously activating deeper cortical output layers. This layer-specific modulation does not result from a spatial separation of excitation and inhibition, but from a layer-specific ratio between these two opposing conductances. Through this mechanism, cortical domains exploit horizontal projections to compete for cortical space.
C1 [Adesnik, Hillel; Scanziani, Massimo] Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Adesnik, Hillel; Scanziani, Massimo] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Scanziani, M (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
EM massimo@ucsd.edu
FU National Institute for Mental Health [R01 MH70058]; Helen Hay Whitney Foundation
NR 47
TC 275
Z9 342
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 APR 22
PY 2010
VL 464
IS 7292
BP 1155
EP U71
DI 10.1038/nature08935
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100029
PM 20414303
DA 2026-03-09
ER

PT J
AU Beroukhim, R
   Mermel, CH
   Porter, D
   Wei, G
   Raychaudhuri, S
   Donovan, J
   Barretina, J
   Boehm, JS
   Dobson, J
   Urashima, M
   Mc Henry, KT
   Pinchback, RM
   Ligon, AH
   Cho, YJ
   Haery, L
   Greulich, H
   Reich, M
   Winckler, W
   Lawrence, MS
   Weir, BA
   Tanaka, KE
   Chiang, DY
   Bass, AJ
   Loo, A
   Hoffman, C
   Prensner, J
   Liefeld, T
   Gao, Q
   Yecies, D
   Signoretti, S
   Maher, E
   Kaye, FJ
   Sasaki, H
   Tepper, JE
   Fletcher, JA
   Tabernero, J
   Baselga, J
   Tsao, MS
   Demichelis, F
   Rubin, MA
   Janne, PA
   Daly, MJ
   Nucera, C
   Levine, RL
   Ebert, BL
   Gabriel, S
   Rustgi, AK
   Antonescu, CR
   Ladanyi, M
   Letai, A
   Garraway, LA
   Loda, M
   Beer, DG
   True, LD
   Okamoto, A
   Pomeroy, SL
   Singer, S
   Golub, TR
   Lander, ES
   Getz, G
   Sellers, WR
   Meyerson, M
AF Beroukhim, Rameen
   Mermel, Craig H.
   Porter, Dale
   Wei, Guo
   Raychaudhuri, Soumya
   Donovan, Jerry
   Barretina, Jordi
   Boehm, Jesse S.
   Dobson, Jennifer
   Urashima, Mitsuyoshi
   Mc Henry, Kevin T.
   Pinchback, Reid M.
   Ligon, Azra H.
   Cho, Yoon-Jae
   Haery, Leila
   Greulich, Heidi
   Reich, Michael
   Winckler, Wendy
   Lawrence, Michael S.
   Weir, Barbara A.
   Tanaka, Kumiko E.
   Chiang, Derek Y.
   Bass, Adam J.
   Loo, Alice
   Hoffman, Carter
   Prensner, John
   Liefeld, Ted
   Gao, Qing
   Yecies, Derek
   Signoretti, Sabina
   Maher, Elizabeth
   Kaye, Frederic J.
   Sasaki, Hidefumi
   Tepper, Joel E.
   Fletcher, Jonathan A.
   Tabernero, Josep
   Baselga, Jose
   Tsao, Ming-Sound
   Demichelis, Francesca
   Rubin, Mark A.
   Janne, Pasi A.
   Daly, Mark J.
   Nucera, Carmelo
   Levine, Ross L.
   Ebert, Benjamin L.
   Gabriel, Stacey
   Rustgi, Anil K.
   Antonescu, Cristina R.
   Ladanyi, Marc
   Letai, Anthony
   Garraway, Levi A.
   Loda, Massimo
   Beer, David G.
   True, Lawrence D.
   Okamoto, Aikou
   Pomeroy, Scott L.
   Singer, Samuel
   Golub, Todd R.
   Lander, Eric S.
   Getz, Gad
   Sellers, William R.
   Meyerson, Matthew
TI The landscape of somatic copy-number alteration across human cancers
SO NATURE
LA English
DT Article
ID acute lymphoblastic-leukemia; embryonic stem-cells; lung-cancer; chromosomal breakpoint; malignant-melanoma; adapter proteins; array cgh; genes; genome; amplification
AB A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappa B pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.
C1 [Beroukhim, Rameen; Mermel, Craig H.; Wei, Guo; Raychaudhuri, Soumya; Barretina, Jordi; Boehm, Jesse S.; Dobson, Jennifer; Pinchback, Reid M.; Haery, Leila; Greulich, Heidi; Reich, Michael; Winckler, Wendy; Lawrence, Michael S.; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Liefeld, Ted; Gao, Qing; Daly, Mark J.; Ebert, Benjamin L.; Gabriel, Stacey; Garraway, Levi A.; Golub, Todd R.; Lander, Eric S.; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Canc Program, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Beroukhim, Rameen; Mermel, Craig H.; Wei, Guo; Raychaudhuri, Soumya; Barretina, Jordi; Boehm, Jesse S.; Dobson, Jennifer; Pinchback, Reid M.; Haery, Leila; Greulich, Heidi; Reich, Michael; Winckler, Wendy; Lawrence, Michael S.; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Liefeld, Ted; Gao, Qing; Daly, Mark J.; Ebert, Benjamin L.; Gabriel, Stacey; Garraway, Levi A.; Golub, Todd R.; Lander, Eric S.; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Med & Populat Genet Grp, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
   [Beroukhim, Rameen; Mermel, Craig H.; Barretina, Jordi; Dobson, Jennifer; Haery, Leila; Greulich, Heidi; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Yecies, Derek; Signoretti, Sabina; Janne, Pasi A.; Letai, Anthony; Garraway, Levi A.; Loda, Massimo; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Mermel, Craig H.; Barretina, Jordi; Dobson, Jennifer; Haery, Leila; Greulich, Heidi; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Yecies, Derek; Signoretti, Sabina; Janne, Pasi A.; Letai, Anthony; Garraway, Levi A.; Loda, Massimo; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Mermel, Craig H.; Barretina, Jordi; Dobson, Jennifer; Haery, Leila; Greulich, Heidi; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Yecies, Derek; Signoretti, Sabina; Janne, Pasi A.; Letai, Anthony; Garraway, Levi A.; Loda, Massimo; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Mermel, Craig H.; Barretina, Jordi; Dobson, Jennifer; Haery, Leila; Greulich, Heidi; Weir, Barbara A.; Tanaka, Kumiko E.; Chiang, Derek Y.; Bass, Adam J.; Hoffman, Carter; Prensner, John; Yecies, Derek; Signoretti, Sabina; Janne, Pasi A.; Letai, Anthony; Garraway, Levi A.; Loda, Massimo; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Raychaudhuri, Soumya; Ligon, Azra H.; Greulich, Heidi; Bass, Adam J.; Signoretti, Sabina; Fletcher, Jonathan A.; Janne, Pasi A.; Ebert, Benjamin L.; Loda, Massimo] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Raychaudhuri, Soumya; Ligon, Azra H.; Greulich, Heidi; Bass, Adam J.; Signoretti, Sabina; Fletcher, Jonathan A.; Janne, Pasi A.; Ebert, Benjamin L.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Greulich, Heidi; Ebert, Benjamin L.; Lander, Eric S.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Greulich, Heidi; Ebert, Benjamin L.; Lander, Eric S.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Greulich, Heidi; Ebert, Benjamin L.; Lander, Eric S.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Greulich, Heidi; Ebert, Benjamin L.; Lander, Eric S.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Cho, Yoon-Jae; Pomeroy, Scott L.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
   [Nucera, Carmelo] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
   [Porter, Dale; Donovan, Jerry; Mc Henry, Kevin T.; Loo, Alice; Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA.
   [Urashima, Mitsuyoshi] Jikei Univ, Sch Med, Div Mol Epidemiol, Minato Ku, Tokyo 1058461, Japan.
   [Maher, Elizabeth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Kaye, Frederic J.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA.
   [Kaye, Frederic J.] Natl Naval Med Ctr, Bethesda, MD 20889 USA.
   [Sasaki, Hidefumi] Nagoya City Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 4678601, Japan.
   [Chiang, Derek Y.; Tepper, Joel E.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet & Radiat Oncol, Chapel Hill, NC 27599 USA.
   [Tabernero, Josep; Baselga, Jose] Vall Hebron Univ Hosp, Res Inst, Vall Hebron Inst Oncol, Med Oncol Program, Barcelona 08035, Spain.
   [Tabernero, Josep; Baselga, Jose] Autonomous Univ Barcelona, E-08035 Barcelona, Spain.
   [Tsao, Ming-Sound] Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2M9, Canada.
   [Tsao, Ming-Sound] Princess Margaret Hosp, Univ Hlth Network, Div Appl Mol Oncol, Toronto, ON M5G 2M9, Canada.
   [Tsao, Ming-Sound] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Demichelis, Francesca; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
   [Daly, Mark J.] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Levine, Ross L.; Antonescu, Cristina R.; Ladanyi, Marc; Singer, Samuel] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Levine, Ross L.; Antonescu, Cristina R.; Ladanyi, Marc; Singer, Samuel] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Rustgi, Anil K.] Univ Penn, Dept Med, GI Div, Philadelphia, PA 19104 USA.
   [Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
   [Beer, David G.] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA.
   [True, Lawrence D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
   [Okamoto, Aikou] Jikei Univ, Sch Med, Dept Obstet & Gynecol, Minato Ku, Tokyo 1058461, Japan.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; 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; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Novartis; Novartis USA; Jikei University; University of Texas System; University of Texas Southwestern Medical Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Walter Reed National Military Medical Center; Nagoya City University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Vall d'Hebron Institut d'Oncologia (VHIO); Autonomous University of Barcelona; Hospital Universitari Vall d'Hebron; Vall d'Hebron Institut de Recerca (VHIR); Autonomous University of Barcelona; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University Health Network Toronto; Cornell University; Weill Cornell Medicine; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Michigan System; University of Michigan; University of Washington; University of Washington Seattle; Jikei University; Howard Hughes Medical Institute
RP Lander, ES (corresponding author), Broad Inst MIT & Harvard, Canc Program, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM lander@broadinstitute.org; gadgetz@broadinstitute.org; william.sellers@novartis.com; matthew_meyerson@dfci.harvard.edu
FU National Institutes of Health (NIH) [P50CA90578, R01CA109038, R01CA109467, P01CA085859, P01CA 098101, K08CA122833]; Doris Duke Charitable Foundation; Sarah Thomas Monopoli Lung Cancer Research Fund; Seaman Corporation Fund for Lung Cancer Research; Lucas Foundation; National Cancer Institute [P01CA098101] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 49
TC 3142
Z9 3774
U1 0
U2 287
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 899
EP 905
DI 10.1038/nature08822
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700036
PM 20164920
DA 2026-03-09
ER

PT J
AU Roberts, SA
   Strande, N
   Burkhalter, MD
   Strom, C
   Havener, JM
   Hasty, P
   Ramsden, DA
AF Roberts, Steven A.
   Strande, Natasha
   Burkhalter, Martin D.
   Strom, Christina
   Havener, Jody M.
   Hasty, Paul
   Ramsden, Dale A.
TI Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends
SO NATURE
LA English
DT Article
ID double-strand breaks; dna-polymerase-beta; repair in-vitro; phosphate lyase; uracil excision; protein-kinase; cells; identification; dependence; roles
AB Mammalian cells require non-homologous end joining (NHEJ) for the efficient repair of chromosomal DNA double-strand breaks(1). A key feature of biological sources of strand breaks is associated nucleotide damage, including base loss (abasic or apurinic/apyrimidinic (AP) sites)(2). At single-strand breaks, 5'-terminal abasic sites are excised by the 5'-deoxyribose-5-phosphate (5'-dRP) lyase activity of DNA polymerase beta (pol beta)(3-6): here we show, in vitro and in cells, that accurate and efficient repair by NHEJ of double-strand breaks with such damage similarly requires 5'-dRP/AP lyase activity. Classically defined NHEJ is moreover uniquely effective at coupling this end-cleaning step to joining in cells, helping to distinguish this pathway from otherwise robust alternative NHEJ pathways. The NHEJ factor Ku can be identified as an effective 5'-dRP/AP lyase. In a similar manner to other lyases(7), Ku nicks DNA 3' of an abasic site by a mechanism involving a Schiff-base covalent intermediate with the abasic site. We show by using cell extracts that Ku is essential for the efficient removal of AP sites near double-strand breaks and, consistent with this result, that joining of such breaks is specifically decreased in cells complemented with a lyase-attenuated Ku mutant. Ku had previously been presumed only to recognize ends and recruit other factors that process ends; our data support an unexpected direct role for Ku in end-processing steps as well.
C1 [Roberts, Steven A.; Strande, Natasha; Burkhalter, Martin D.; Strom, Christina; Havener, Jody M.; Ramsden, Dale A.] Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Roberts, Steven A.; Strande, Natasha; Burkhalter, Martin D.; Strom, Christina; Havener, Jody M.; Ramsden, Dale A.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
   [Hasty, Paul] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, San Antonio, TX 78245 USA.
   [Hasty, Paul] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio
RP Ramsden, DA (corresponding author), Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM dale_ramsden@med.unc.edu
FU Public Health Service (PHS) [CA 84442, R01 CA76317-05A1, P01 AG17242]; Leukemia and Lymphoma Society; National Institute on Aging [P01AG017242] Funding Source: NIH RePORTER
NR 31
TC 154
Z9 193
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 APR 22
PY 2010
VL 464
IS 7292
BP 1214
EP U139
DI 10.1038/nature08926
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100042
PM 20383123
DA 2026-03-09
ER

PT J
AU Gao, ZH
   Liu, HL
   Daxinger, L
   Pontes, O
   He, XJ
   Qian, WQ
   Lin, HX
   Xie, MT
   Lorkovic, ZJ
   Zhang, SD
   Miki, D
   Zhan, XQ
   Pontier, D
   Lagrange, T
   Jin, HL
   Matzke, AJM
   Matzke, M
   Pikaard, CS
   Zhu, JK
AF Gao, Zhihuan
   Liu, Hai-Liang
   Daxinger, Lucia
   Pontes, Olga
   He, Xinjian
   Qian, Weiqiang
   Lin, Huixin
   Xie, Mingtang
   Lorkovic, Zdravko J.
   Zhang, Shoudong
   Miki, Daisuke
   Zhan, Xiangqiang
   Pontier, Dominique
   Lagrange, Thierry
   Jin, Hailing
   Matzke, Antonius J. M.
   Matzke, Marjori
   Pikaard, Craig S.
   Zhu, Jian-Kang
TI An RNA polymerase II- and AGO4-associated protein acts in RNA-directed DNA methylation
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; processing center; binding protein; argonaute4; glycosylase/lyase; transcription; resolution; pathways; patterns; body
AB DNA methylation is an important epigenetic mark in many eukaryotes(1-5). In plants, 24-nucleotide small interfering RNAs (siRNAs) bound to the effector protein, Argonaute 4 (AGO4), can direct de novo DNA methylation by the methyltransferase DRM2 (refs 2, 4-6). Here we report a new regulator of RNA-directed DNA methylation (RdDM) in Arabidopsis: RDM1. Loss-of-function mutations in the RDM1 gene impair the accumulation of 24-nucleotide siRNAs, reduce DNA methylation, and release transcriptional gene silencing at RdDM target loci. RDM1 encodes a small protein that seems to bind single-stranded methyl DNA, and associates and co-localizes with RNA polymerase II (Pol II, also known as NRPB), AGO4 and DRM2 in the nucleus. Our results indicate that RDM1 is a component of the RdDM effector complex and may have a role in linking siRNA production with pre-existing or de novo cytosine methylation. Our results also indicate that, although RDM1 and Pol V (also known as NRPE) may function together at some RdDM target sites in the peri-nucleolar siRNA processing centre, Pol II rather than Pol Vis associated with the RdDM effector complex at target sites in the nucleoplasm.
C1 [Gao, Zhihuan; Liu, Hai-Liang; He, Xinjian; Qian, Weiqiang; Lin, Huixin; Xie, Mingtang; Zhang, Shoudong; Miki, Daisuke; Zhan, Xiangqiang; Jin, Hailing; Zhu, Jian-Kang] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA.
   [Gao, Zhihuan; Liu, Hai-Liang; He, Xinjian; Qian, Weiqiang; Lin, Huixin; Xie, Mingtang; Zhang, Shoudong; Miki, Daisuke; Zhan, Xiangqiang; Zhu, Jian-Kang] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Liu, Hai-Liang] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
   [Daxinger, Lucia; Matzke, Antonius J. M.; Matzke, Marjori] Austrian Acad Sci, Gregor Mendel Inst Mol Plant Biol, A-1030 Vienna, Austria.
   [Pontes, Olga] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
   [He, Xinjian; Zhang, Shoudong; Zhan, Xiangqiang; Zhu, Jian-Kang] 4700 King Abdullah Univ Sci & Technol, Ctr Plant Stress Genom & Technol, Thuwal 239556900, Saudi Arabia.
   [Lorkovic, Zdravko J.] Med Univ Vienna, Max F Perutz Lab, A-1030 Vienna, Austria.
   [Pontier, Dominique; Lagrange, Thierry] Univ Perpignan, CNRS, IRD, LGDP,UMR 5096, F-66806 Perpignan, France.
   [Jin, Hailing] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA.
   [Pikaard, Craig S.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Pikaard, Craig S.] Indiana Univ, Dept Mol & Cellular Biochem, Bloomington, IN 47405 USA.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside; Tongji University; Austrian Academy of Sciences; Vienna Biocenter (VBC); Gregor Mendel Institute of Molecular Plant Biology (GMI); Washington University (WUSTL); King Abdullah University of Science & Technology; Medical University of Vienna; Universite Perpignan Via Domitia; Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); University of California System; University of California Riverside; Indiana University System; Indiana University Bloomington; Indiana University System; Indiana University Bloomington
RP Zhu, JK (corresponding author), Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA.
EM jian-kang.zhu@ucr.edu
FU National Institutes of Health; Austrian Fonds zur Forderung der wissenschaftlichen Forschung; National Science Foundation Career Award; Edward Mallinckrodt Foundation Award; Agence Nationale de la Recherche
NR 30
TC 213
Z9 260
U1 6
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 6
PY 2010
VL 465
IS 7294
BP 106
EP U118
DI 10.1038/nature09025
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900040
PM 20410883
DA 2026-03-09
ER

PT J
AU Nikoletopoulou, V
   Lickert, H
   Frade, JM
   Rencurel, C
   Giallonardo, P
   Zhang, LX
   Bibel, M
   Barde, YA
AF Nikoletopoulou, Vassiliki
   Lickert, Heiko
   Frade, Jose Maria
   Rencurel, Chantal
   Giallonardo, Patrizia
   Zhang, Lixin
   Bibel, Miriam
   Barde, Yves-Alain
TI Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not
SO NATURE
LA English
DT Article
ID nerve growth-factor; embryonic stem-cells; sympathetic neurons; genetic-evidence; messenger-rna; p75; expression; dependence; ganglia; mice
AB Neurons of the peripheral nervous system have long been known to require survival factors to prevent their death during development. But why they selectively become dependent on secretory molecules has remained a mystery, as is the observation that in the central nervous system, most neurons do not show this dependency. Using engineered embryonic stem cells, we show here that the neurotrophin receptors TrkA and TrkC (tropomyosin receptor kinase A and C, also known as Ntrk1 and Ntrk3, respectively) instruct developing neurons to die, both in vitro and in vivo. By contrast, TrkB (also known as Ntrk2), a closely related receptor primarily expressed in the central nervous system, does not. These results indicate that TrkA and TrkC behave as dependence receptors, explaining why developing sympathetic and sensory neurons become trophic-factor-dependent for survival. We suggest that the expansion of the Trk gene family that accompanied the segregation of the peripheral from the central nervous system generated a novel mechanism of cell number control.
C1 [Nikoletopoulou, Vassiliki; Rencurel, Chantal; Zhang, Lixin; Barde, Yves-Alain] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
   [Lickert, Heiko; Giallonardo, Patrizia] Helmholtz Zentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
   [Frade, Jose Maria] CSIC, Inst Cajal, E-28002 Madrid, Spain.
   [Bibel, Miriam] Novartis Inst BioMed Res, Neurodegenerat Dept, CH-4002 Basel, Switzerland.
C3 University of Basel; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Cajal (IC); Novartis
RP Nikoletopoulou, V (corresponding author), Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
EM n.vassiliki@unibas.ch; yves.barde@unibas.ch
FU DFG; consortium EuTRACC; Swiss National Foundation
NR 48
TC 167
Z9 202
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 59
EP U87
DI 10.1038/nature09336
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200034
PM 20811452
DA 2026-03-09
ER

PT J
AU Pinto, D
   Pagnamenta, AT
   Klei, L
   Anney, R
   Merico, D
   Regan, R
   Conroy, J
   Magalhaes, TR
   Correia, C
   Abrahams, BS
   Almeida, J
   Bacchelli, E
   Bader, GD
   Bailey, AJ
   Baird, G
   Battaglia, A
   Berney, T
   Bolshakova, N
   Bölte, S
   Bolton, PF
   Bourgeron, T
   Brennan, S
   Brian, J
   Bryson, SE
   Carson, AR
   Casallo, G
   Casey, J
   Chung, BHY
   Cochrane, L
   Corsello, C
   Crawford, EL
   Crossett, A
   Cytrynbaum, C
   Dawson, G
   de Jonge, M
   Delorme, R
   Drmic, I
   Duketis, E
   Duque, F
   Estes, A
   Farrar, P
   Fernandez, BA
   Folstein, SE
   Fombonne, E
   Freitag, CM
   Gilbert, J
   Gillberg, C
   Glessner, JT
   Goldberg, J
   Green, A
   Green, J
   Guter, SJ
   Hakonarson, H
   Heron, EA
   Hill, M
   Holt, R
   Howe, JL
   Hughes, G
   Hus, V
   Igliozzi, R
   Kim, C
   Klauck, SM
   Kolevzon, A
   Korvatska, O
   Kustanovich, V
   Lajonchere, CM
   Lamb, JA
   Laskawiec, M
   Leboyer, M
   Le Couteur, A
   Leventhal, BL
   Lionel, AC
   Liu, XQ
   Lord, C
   Lotspeich, L
   Lund, SC
   Maestrini, E
   Mahoney, W
   Mantoulan, C
   Marshall, CR
   McConachie, H
   McDougle, CJ
   McGrath, J
   McMahon, WM
   Merikangas, A
   Migita, O
   Minshew, NJ
   Mirza, GK
   Munson, J
   Nelson, SF
   Noakes, C
   Noor, A
   Nygren, G
   Oliveira, G
   Papanikolaou, K
   Parr, JR
   Parrini, B
   Paton, T
   Pickles, A
   Pilorge, M
   Piven, J
   Ponting, CP
   Posey, DJ
   Poustka, A
   Poustka, F
   Prasad, A
   Ragoussis, J
   Renshaw, K
   Rickaby, J
   Roberts, W
   Roeder, K
   Roge, B
   Rutter, ML
   Bierut, LJ
   Rice, JP
   Salt, J
   Sansom, K
   Sato, D
   Segurado, R
   Sequeira, AF
   Senman, L
   Shah, N
   Sheffield, VC
   Soorya, L
   Sousa, I
   Stein, O
   Sykes, N
   Stoppioni, V
   Strawbridge, C
   Tancredi, R
   Tansey, K
   Thiruvahindrapduram, B
   Thompson, AP
   Thomson, S
   Tryfon, A
   Tsiantis, J
   Van Engeland, H
   Vincent, JB
   Volkmar, F
   Wallace, S
   Wang, K
   Wang, ZZ
   Wassink, TH
   Webber, C
   Weksberg, R
   Wing, K
   Wittemeyer, K
   Wood, S
   Wu, J
   Yaspan, BL
   Zurawiecki, D
   Zwaigenbaum, L
   Buxbaum, JD
   Cantor, RM
   Cook, EH
   Coon, H
   Cuccaro, ML
   Devlin, B
   Ennis, S
   Gallagher, L
   Geschwind, DH
   Gill, M
   Haines, JL
   Hallmayer, J
   Miller, J
   Monaco, AP
   Nurnberger, JI
   Paterson, AD
   Pericak-Vance, MA
   Schellenberg, GD
   Szatmari, P
   Vicente, AM
   Vieland, VJ
   Wijsman, EM
   Scherer, SW
   Sutcliffe, JS
   Betancur, C
AF Pinto, Dalila
   Pagnamenta, Alistair T.
   Klei, Lambertus
   Anney, Richard
   Merico, Daniele
   Regan, Regina
   Conroy, Judith
   Magalhaes, Tiago R.
   Correia, Catarina
   Abrahams, Brett S.
   Almeida, Joana
   Bacchelli, Elena
   Bader, Gary D.
   Bailey, Anthony J.
   Baird, Gillian
   Battaglia, Agatino
   Berney, Tom
   Bolshakova, Nadia
   Boelte, Sven
   Bolton, Patrick F.
   Bourgeron, Thomas
   Brennan, Sean
   Brian, Jessica
   Bryson, Susan E.
   Carson, Andrew R.
   Casallo, Guillermo
   Casey, Jillian
   Chung, Brian H. Y.
   Cochrane, Lynne
   Corsello, Christina
   Crawford, Emily L.
   Crossett, Andrew
   Cytrynbaum, Cheryl
   Dawson, Geraldine
   de Jonge, Maretha
   Delorme, Richard
   Drmic, Irene
   Duketis, Eftichia
   Duque, Frederico
   Estes, Annette
   Farrar, Penny
   Fernandez, Bridget A.
   Folstein, Susan E.
   Fombonne, Eric
   Freitag, Christine M.
   Gilbert, John
   Gillberg, Christopher
   Glessner, Joseph T.
   Goldberg, Jeremy
   Green, Andrew
   Green, Jonathan
   Guter, Stephen J.
   Hakonarson, Hakon
   Heron, Elizabeth A.
   Hill, Matthew
   Holt, Richard
   Howe, Jennifer L.
   Hughes, Gillian
   Hus, Vanessa
   Igliozzi, Roberta
   Kim, Cecilia
   Klauck, Sabine M.
   Kolevzon, Alexander
   Korvatska, Olena
   Kustanovich, Vlad
   Lajonchere, Clara M.
   Lamb, Janine A.
   Laskawiec, Magdalena
   Leboyer, Marion
   Le Couteur, Ann
   Leventhal, Bennett L.
   Lionel, Anath C.
   Liu, Xiao-Qing
   Lord, Catherine
   Lotspeich, Linda
   Lund, Sabata C.
   Maestrini, Elena
   Mahoney, William
   Mantoulan, Carine
   Marshall, Christian R.
   McConachie, Helen
   McDougle, Christopher J.
   McGrath, Jane
   McMahon, William M.
   Merikangas, Alison
   Migita, Ohsuke
   Minshew, Nancy J.
   Mirza, Ghazala K.
   Munson, Jeff
   Nelson, Stanley F.
   Noakes, Carolyn
   Noor, Abdul
   Nygren, Gudrun
   Oliveira, Guiomar
   Papanikolaou, Katerina
   Parr, Jeremy R.
   Parrini, Barbara
   Paton, Tara
   Pickles, Andrew
   Pilorge, Marion
   Piven, Joseph
   Ponting, Chris P.
   Posey, David J.
   Poustka, Annemarie
   Poustka, Fritz
   Prasad, Aparna
   Ragoussis, Jiannis
   Renshaw, Katy
   Rickaby, Jessica
   Roberts, Wendy
   Roeder, Kathryn
   Roge, Bernadette
   Rutter, Michael L.
   Bierut, Laura J.
   Rice, John P.
   Salt, Jeff
   Sansom, Katherine
   Sato, Daisuke
   Segurado, Ricardo
   Sequeira, Ana F.
   Senman, Lili
   Shah, Naisha
   Sheffield, Val C.
   Soorya, Latha
   Sousa, Ines
   Stein, Olaf
   Sykes, Nuala
   Stoppioni, Vera
   Strawbridge, Christina
   Tancredi, Raffaella
   Tansey, Katherine
   Thiruvahindrapduram, Bhooma
   Thompson, Ann P.
   Thomson, Susanne
   Tryfon, Ana
   Tsiantis, John
   Van Engeland, Herman
   Vincent, John B.
   Volkmar, Fred
   Wallace, Simon
   Wang, Kai
   Wang, Zhouzhi
   Wassink, Thomas H.
   Webber, Caleb
   Weksberg, Rosanna
   Wing, Kirsty
   Wittemeyer, Kerstin
   Wood, Shawn
   Wu, Jing
   Yaspan, Brian L.
   Zurawiecki, Danielle
   Zwaigenbaum, Lonnie
   Buxbaum, Joseph D.
   Cantor, Rita M.
   Cook, Edwin H.
   Coon, Hilary
   Cuccaro, Michael L.
   Devlin, Bernie
   Ennis, Sean
   Gallagher, Louise
   Geschwind, Daniel H.
   Gill, Michael
   Haines, Jonathan L.
   Hallmayer, Joachim
   Miller, Judith
   Monaco, Anthony P.
   Nurnberger, John I., Jr.
   Paterson, Andrew D.
   Pericak-Vance, Margaret A.
   Schellenberg, Gerard D.
   Szatmari, Peter
   Vicente, Astrid M.
   Vieland, Veronica J.
   Wijsman, Ellen M.
   Scherer, Stephen W.
   Sutcliffe, James S.
   Betancur, Catalina
TI Functional impact of global rare copy number variation in autism spectrum disorders
SO NATURE
LA English
DT Article
ID hidden-markov model; snp genotyping data; genetic disorder; association; mutations; linkage; loci; ancestry; reveals; complex
AB The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours(1). Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability(2). Although ASDs are known to be highly heritable (similar to 90%)(3), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P=0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P=3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
C1 [Pinto, Dalila; Carson, Andrew R.; Casallo, Guillermo; Chung, Brian H. Y.; Cytrynbaum, Cheryl; Howe, Jennifer L.; Lionel, Anath C.; Liu, Xiao-Qing; Marshall, Christian R.; Migita, Ohsuke; Paton, Tara; Prasad, Aparna; Rickaby, Jessica; Sansom, Katherine; Sato, Daisuke; Thiruvahindrapduram, Bhooma; Wang, Zhouzhi; Weksberg, Rosanna; Paterson, Andrew D.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada.
   [Pinto, Dalila; Carson, Andrew R.; Casallo, Guillermo; Chung, Brian H. Y.; Cytrynbaum, Cheryl; Howe, Jennifer L.; Lionel, Anath C.; Liu, Xiao-Qing; Marshall, Christian R.; Migita, Ohsuke; Paton, Tara; Prasad, Aparna; Rickaby, Jessica; Sansom, Katherine; Sato, Daisuke; Thiruvahindrapduram, Bhooma; Wang, Zhouzhi; Weksberg, Rosanna; Paterson, Andrew D.; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1L7, Canada.
   [Pagnamenta, Alistair T.; Farrar, Penny; Holt, Richard; Mirza, Ghazala K.; Ragoussis, Jiannis; Sousa, Ines; Sykes, Nuala; Wing, Kirsty; Monaco, Anthony P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Klei, Lambertus; Wood, Shawn; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
   [Anney, Richard; Bolshakova, Nadia; Brennan, Sean; Cochrane, Lynne; Heron, Elizabeth A.; Hill, Matthew; Hughes, Gillian; McGrath, Jane; Merikangas, Alison; Segurado, Ricardo; Tansey, Katherine; Gallagher, Louise; Gill, Michael] Trinity Coll Dublin, Sch Med, Dept Psychiat, Autism Genet Grp, Dublin 8, Ireland.
   [Merico, Daniele; Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
   [Regan, Regina; Conroy, Judith; Casey, Jillian; Green, Andrew; Shah, Naisha; Ennis, Sean] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland.
   [Magalhaes, Tiago R.; Correia, Catarina; Sequeira, Ana F.; Vicente, Astrid M.] Inst Nacl Saude Dr Ricardo Jorge, P-1649016 Lisbon, Portugal.
   [Magalhaes, Tiago R.; Correia, Catarina; Sequeira, Ana F.; Vicente, Astrid M.] Gulbenkian Inst Sci, P-2780156 Oeiras, Portugal.
   [Magalhaes, Tiago R.; Correia, Catarina; Sequeira, Ana F.; Vicente, Astrid M.] BioFIG Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal.
   [Abrahams, Brett S.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA.
   [Abrahams, Brett S.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst, Los Angeles, CA 90095 USA.
   [Almeida, Joana; Duque, Frederico; Oliveira, Guiomar] Hosp Pediat Coimbra, P-3000076 Coimbra, Portugal.
   [Bacchelli, Elena; Maestrini, Elena] Univ Bologna, Dept Biol, I-40126 Bologna, Italy.
   [Bailey, Anthony J.; Laskawiec, Magdalena; Renshaw, Katy; Wallace, Simon] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England.
   [Baird, Gillian] Guys Hosp, Newcomen Ctr, London SE1 9RT, England.
   [Battaglia, Agatino; Igliozzi, Roberta; Parrini, Barbara; Tancredi, Raffaella] Stella Maris Inst Child & Adolescent Neuropsychia, I-56128 Pisa, Italy.
   [Berney, Tom; Le Couteur, Ann; McConachie, Helen] Univ Newcastle, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Boelte, Sven; Duketis, Eftichia; Freitag, Christine M.; Poustka, Fritz] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, D-60528 Frankfurt, Germany.
   [Bolton, Patrick F.] Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England.
   [Bourgeron, Thomas] Univ Paris 07, CNRS, URA 2182, Inst Pasteur, F-75015 Paris, France.
   [Brian, Jessica; Drmic, Irene; Noakes, Carolyn; Roberts, Wendy; Senman, Lili] Univ Toronto, Hosp Sick Children & Bloorview Kids Rehab, Autism Res Unit, Toronto, ON M5G 1X8, Canada.
   [Bryson, Susan E.] Dalhousie Univ, Dept Pediat & Psychol, Halifax, NS B3K 6R8, Canada.
   [Corsello, Christina; Hus, Vanessa; Lord, Catherine] Univ Michigan, Autism & Communicat Disorders Ctr, Ann Arbor, MI 48109 USA.
   [Crawford, Emily L.; Lund, Sabata C.; Thomson, Susanne; Yaspan, Brian L.; Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA.
   [Crawford, Emily L.; Lund, Sabata C.; Thomson, Susanne; Yaspan, Brian L.; Sutcliffe, James S.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Crawford, Emily L.; Lund, Sabata C.; Thomson, Susanne; Yaspan, Brian L.; Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37232 USA.
   [Crossett, Andrew; Roeder, Kathryn; Wu, Jing] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
   [Dawson, Geraldine] Autism Speaks, New York, NY 10016 USA.
   [Dawson, Geraldine] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [de Jonge, Maretha; Van Engeland, Herman] Univ Med Ctr, Dept Child Psychiat, NL-3508 GA Utrecht, Netherlands.
   [Delorme, Richard] Hop Robert Debre, AP HP, Fdn FondaMental, INSERM,U955, F-75019 Paris, France.
   [Estes, Annette] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA.
   [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada.
   [Fernandez, Bridget A.] Mem Univ Newfoundland, Discipline Med, St John, NF A1B 3V6, Canada.
   [Folstein, Susan E.; Gilbert, John; Cuccaro, Michael L.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33101 USA.
   [Fombonne, Eric] McGill Univ, Div Psychiat, Montreal, PQ H3A 1A1, Canada.
   [Gillberg, Christopher; Nygren, Gudrun] Univ Gothenburg, Dept Child & Adolescent Psychiat, S-41345 Gothenburg, Sweden.
   [Glessner, Joseph T.; Hakonarson, Hakon; Kim, Cecilia; Wang, Kai] Childrens Hosp Philadelphia, Ctr Appl Genom, Div Human Genet, Philadelphia, PA 19104 USA.
   [Goldberg, Jeremy; Strawbridge, Christina; Thompson, Ann P.; Szatmari, Peter] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada.
   [Green, Jonathan] Booth Hall Childrens Hosp, Acad Dept Child Psychiat, Manchester M9 7AA, Lancs, England.
   [Guter, Stephen J.; Salt, Jeff; Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
   [Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Klauck, Sabine M.; Poustka, Annemarie] German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany.
   [Kolevzon, Alexander; Soorya, Latha; Tryfon, Ana; Zurawiecki, Danielle; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
   [Korvatska, Olena] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Kustanovich, Vlad; Lajonchere, Clara M.] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA 90036 USA.
   [Lamb, Janine A.] Univ Manchester, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England.
   [Leboyer, Marion] Univ Paris 12, AP HP, Grp Hosp Henri Mondor Albert Chenevier, INSERM,U995,Dept Psychiat,Fdn FondaMental, F-94000 Creteil, France.
   [Leventhal, Bennett L.] Nathan S Kline Inst Psychiat Res NKI, Orangeburg, NY 10962 USA.
   [Leventhal, Bennett L.] NYU, Dept Child & Adolescent Psychiat, New York, NY 10016 USA.
   [Leventhal, Bennett L.] NYU, Ctr Child Study, New York, NY 10016 USA.
   [Lotspeich, Linda; Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Div Child & Adolescent Psychiat & Child Dev, Palo Alto, CA 94304 USA.
   [Mahoney, William] McMaster Univ, Dept Pediat, Hamilton, ON L8N 3Z5, Canada.
   [Mantoulan, Carine; Roge, Bernadette; Wittemeyer, Kerstin] Univ Toulouse Le Mirail, Ctr Eudes & Rech Psychopathol, F-31200 Toulouse, France.
   [McDougle, Christopher J.; Posey, David J.; Nurnberger, John I., Jr.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
   [McMahon, William M.; Coon, Hilary; Miller, Judith] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84108 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
   [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA.
   [Munson, Jeff] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Nelson, Stanley F.; Cantor, Rita M.] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Noor, Abdul; Vincent, John B.] Univ Toronto, Ctr Addict & Mental Hlth, Clarke Inst, Toronto, ON M5G 1X8, Canada.
   [Noor, Abdul; Vincent, John B.] Univ Toronto, Dept Psychiat, Toronto, ON M5G 1X8, Canada.
   [Papanikolaou, Katerina; Tsiantis, John] Univ Athens, Sch Med, Agia Sophia Childrens Hosp, Univ Dept Child Psychiat, GR-11527 Athens, Greece.
   [Berney, Tom; Le Couteur, Ann; McConachie, Helen; Parr, Jeremy R.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Berney, Tom; Le Couteur, Ann; McConachie, Helen; Parr, Jeremy R.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Pickles, Andrew] Univ Manchester, Sch Epidemiol & Hlth Sci, Dept Med, Manchester M13 9PT, Lancs, England.
   [Pilorge, Marion; Betancur, Catalina] INSERM, U952, F-75005 Paris, France.
   [Pilorge, Marion; Betancur, Catalina] CNRS, UMR 7224, F-75005 Paris, France.
   [Pilorge, Marion; Betancur, Catalina] UPMC, F-75005 Paris, France.
   [Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA.
   [Ponting, Chris P.; Webber, Caleb] Univ Oxford, MRC Funct Genom Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Rutter, Michael L.] Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.
   [Bierut, Laura J.; Rice, John P.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA.
   [Sheffield, Val C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
   [Sheffield, Val C.] Univ Iowa, Howard Hughes Med Inst, Carver Coll Med, Iowa City, IA 52242 USA.
   [Stein, Olaf; Vieland, Veronica J.] Nationwide Childrens Hosp, Res Inst, Battelle Ctr Math Med, Columbus, OH 43205 USA.
   [Stein, Olaf; Vieland, Veronica J.] Ohio State Univ, Columbus, OH 43205 USA.
   [Stoppioni, Vera] Osped Santa Croce, I-61032 Fano, Italy.
   [Volkmar, Fred] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
   [Wassink, Thomas H.] Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA.
   [Zwaigenbaum, Lonnie] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2J3, Canada.
   [Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Schellenberg, Gerard D.] Univ Penn, Philadelphia, PA 19104 USA.
   [Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Wijsman, Ellen M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Bader, Gary D.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Oxford; Wellcome Centre for Human Genetics; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Trinity College Dublin; University of Toronto; University College Dublin; Instituto Nacional de Saude Dr. Ricardo Jorge; Universidade de Lisboa; 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; Universidade de Coimbra; Centro Hospitalar e Universitario de Coimbra (CHUC); University of Bologna; University of Oxford; Guy's & St Thomas' NHS Foundation Trust; IRCCS Fondazione Stella Maris; Newcastle University - UK; Goethe University Frankfurt; University of London; King's College London; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Institut Pasteur Paris; University of Toronto; Holland Bloorview Kids Rehabilitation Hospital; Hospital for Sick Children (SickKids); Dalhousie University; University of Michigan System; University of Michigan; Vanderbilt University; Vanderbilt University; Vanderbilt University; Carnegie Mellon University; University of North Carolina; University of North Carolina Chapel Hill; Utrecht University; Utrecht University Medical Center; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Robert-Debre - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris-Est-Creteil-Val-de-Marne (UPEC); University of Washington; University of Washington Seattle; Memorial University Newfoundland; Memorial University Newfoundland; University of Miami; McGill University; University of Gothenburg; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; McMaster University; Manchester University NHS Foundation Trust; Royal Manchester Children's Hospital; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Helmholtz Association; German Cancer Research Center (DKFZ); Icahn School of Medicine at Mount Sinai; University of Washington; University of Washington Seattle; University of Manchester; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Henri-Mondor - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Nathan Kline Institute for Psychiatric Research; New York University; New York University; Stanford University; McMaster University; Universite de Toulouse; Universite de Toulouse - Jean Jaures; Indiana University System; Indiana University Indianapolis; Utah System of Higher Education; University of Utah; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Washington; University of Washington Seattle; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of Toronto; Centre for Addiction & Mental Health - Canada; University of Toronto; National & Kapodistrian University of Athens; The Aghia Sophia Children's Hospital; Newcastle University - UK; Newcastle University - UK; University of Manchester; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; University of North Carolina; University of North Carolina Chapel Hill; University of Oxford; University of London; King's College London; Washington University (WUSTL); University of Iowa; Howard Hughes Medical Institute; University of Iowa; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; University System of Ohio; Ohio State University; Yale University; University of Alberta; Vanderbilt University; University of Pennsylvania; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Toronto
RP Scherer, SW (corresponding author), Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada.
EM stephen.scherer@sickkids.ca
FU Autism Genome Project Consortium (AGP): Autism Speaks (USA); Health Research Board (HRB; Ireland); Medical Research Council (MRC; UK); Genome Canada/Ontario Genomics Institute; Hilibrand Foundation (USA); US National Institutes of Health (NIH) [HD055751, HD055782, HD055784, HD35465, MH52708, MH55284, MH57881, MH061009, MH06359, MH066673, MH080647, MH081754, MH66766, NS026630, NS042165, NS049261]; Canadian Institute for Advanced Research (CIFAR); Canadian Institutes for Health Research (CIHR); Assistance Publique-Hopitaux de Paris (France); Autistica; Canada Foundation for Innovation/Ontario Innovation Trust; Deutsche Forschungsgemeinschaft (Germany) [Po 255/17-4]; EC; Fundacao Calouste Gulbenkian (Portugal); Fondation de France; Fondation FondaMental (France); Fondation Orange (France); Fondation pour la Recherche Medicale (France); Fundacao para a Ciencia e Tecnologia (Portugal); Hospital for Sick Children Foundation; University of Toronto (Canada); INSERM (France); Institut Pasteur (France); Italian Ministry of Health [181]; John P Hussman Foundation (USA); McLaughlin Centre (Canada); Ontario Ministry of Research and Innovation (Canada); Seaver Foundation (USA); Swedish Science Council; Centre for Applied Genomics (Canada); Utah Autism Foundation (USA); Wellcome Trust (UK) [075491/Z/04]; Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801]; Netherlands Organization for Scientific Research [825.06.031]; GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto; Hospital for Sick Children (Canada); Medical Research Council [G9817803B, MC_U137761446, G0601030] Funding Source: researchfish; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P50HD055784] Funding Source: NIH RePORTER; National Institute of Mental Health [R37MH057881, T32MH065215] Funding Source: NIH RePORTER; National Institute on Deafness and Other Communication Disorders; National Institute of Neurological Disorders and Stroke [P50HD055784] Funding Source: NIH RePORTER; MRC [MC_U137761446, G0601030] Funding Source: UKRI
NR 30
TC 1563
Z9 1858
U1 2
U2 368
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 368
EP 372
DI 10.1038/nature09146
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100049
PM 20531469
DA 2026-03-09
ER

PT J
AU Povolotskaya, IS
   Kondrashov, FA
AF Povolotskaya, Inna S.
   Kondrashov, Fyodor A.
TI Sequence space and the ongoing expansion of the protein universe
SO NATURE
LA English
DT Article
ID amino-acid gain; common ancestor; maximum-likelihood; genome evolution; selection; perspective; prokaryotes; tolerance; epistasis; alignment
AB The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions(1-4). However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: similar to 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, similar to 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.
C1 [Povolotskaya, Inna S.; Kondrashov, Fyodor A.] Ctr Genom Regulat, Bioinformat & Genom Programme, Barcelona 08003, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG)
RP Kondrashov, FA (corresponding author), Ctr Genom Regulat, Bioinformat & Genom Programme, Calle Dr Aiguader 88,Barcelona Biomed Res Pk Bldg, Barcelona 08003, Spain.
EM fyodor.kondrashov@crg.es
NR 36
TC 156
Z9 188
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 JUN 17
PY 2010
VL 465
IS 7300
BP 922
EP U7
DI 10.1038/nature09105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500037
PM 20485343
DA 2026-03-09
ER

PT J
AU Okamoto, K
   Iwai, Y
   Oh-hora, M
   Yamamoto, M
   Morio, T
   Aoki, K
   Ohya, K
   Jetten, AM
   Akira, S
   Muta, T
   Takayanagi, H
AF Okamoto, Kazuo
   Iwai, Yoshiko
   Oh-hora, Masatsugu
   Yamamoto, Masahiro
   Morio, Tomohiro
   Aoki, Kazuhiro
   Ohya, Keiichi
   Jetten, Anton M.
   Akira, Shizuo
   Muta, Tatsushi
   Takayanagi, Hiroshi
TI IκBζ regulates TH17 development by cooperating with ROR nuclear receptors
SO NATURE
LA English
DT Article
ID targeted disruption; gamma-t; differentiation; transcription; induction; protein; cells; expression; apoptosis; roles
AB Interleukin (IL)-17-producing helper T (T(H)17) cells are a distinct T-cell subset characterized by its pathological role in autoimmune diseases(1-3). IL-6 and transforming growth factor-beta (TGF-beta) induce TH17 development, in which the orphan nuclear receptors, ROR gamma t and ROR alpha, have an indispensable role(4-6). However, in the absence of IL-6 and TGF-beta, the ectopic expression of ROR gamma t or ROR alpha leads to only a modest IL-17 production(5,7,8). Here we identify a nuclear I kappa B family member, I kappa B zeta (encoded by the Nfkbiz gene), as a transcription factor required for TH17 development in mice. The ectopic expression of I kappa B zeta in naive CD4(+) T cells together with ROR gamma t or ROR alpha potently induces T(H)17 development, even in the absence of IL-6 and TGF-beta. Notably, Nfkbiz(-/-) mice have a defect in T(H)17 development and a resistance to experimental autoimmune encephalomyelitis (EAE). The T-cell-intrinsic function of I kappa B zeta was clearly demonstrated by the resistance to EAE of the Rag2(-/-) mice into which Nfkbiz(-/-) CD4(+) T cells were transferred. In cooperation with ROR gamma t and RORa, I kappa B zeta enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. This study provides evidence for the transcriptional mechanisms underlying T(H)17 development and points to a molecular basis for a novel therapeutic strategy against autoimmune disease.
C1 [Okamoto, Kazuo; Oh-hora, Masatsugu; Takayanagi, Hiroshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Tokyo 1138549, Japan.
   [Okamoto, Kazuo; Oh-hora, Masatsugu; Takayanagi, Hiroshi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence Program, Bunkyo Ku, Tokyo 1138549, Japan.
   [Okamoto, Kazuo; Takayanagi, Hiroshi] Japan Sci & Technol Agcy, ERATO, Takayanagi Osteonetwork Project, Bunkyo Ku, Tokyo 1138549, Japan.
   [Iwai, Yoshiko] Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Bunkyo Ku, Tokyo 1138510, Japan.
   [Yamamoto, Masahiro] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Immune Regulat, Suita, Osaka 5650871, Japan.
   [Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan.
   [Morio, Tomohiro] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138519, Japan.
   [Aoki, Kazuhiro; Ohya, Keiichi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Hard Tissue Engn Pharmacol, Bunkyo Ku, Tokyo 1138549, Japan.
   [Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
   [Muta, Tatsushi] Tohoku Univ, Grad Sch Life Sci, Lab Cell Recognit & Response, Aoba Ku, Sendai, Miyagi 9808578, Japan.
C3 Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Japan Science & Technology Agency (JST); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); University of Osaka; University of Osaka; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); Tohoku University
RP Takayanagi, H (corresponding author), Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Yushima 1-5-45, Tokyo 1138549, Japan.
EM taka.csi@tmd.ac.jp
FU Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); ERATO; JST; NIEHS [Z01-ES-101586]; Takeda Life Science Foundation; Yokoyama Foundation; Ichiro Kanehara; National Institute of Environmental Health Sciences [ZIAES101586] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [21390088] Funding Source: KAKEN
NR 35
TC 226
Z9 258
U1 1
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1381
EP U13
DI 10.1038/nature08922
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000053
PM 20383124
DA 2026-03-09
ER

PT J
AU Yan, JS
   Aldrich, RW
AF Yan, Jiusheng
   Aldrich, Richard W.
TI LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium
SO NATURE
LA English
DT Article
ID leucine-rich repeat; potassium channels; beta-subunits; cloning; sensor; cells; expression; hkcnmb3; family; cancer
AB Large-conductance, voltage-and calcium-activated potassium (BK, or K(Ca)1.1) channels are ubiquitously expressed in electrically excitable and non-excitable cells(1,2), either as alpha-subunit (BK alpha) tetramers or together with tissue specific auxiliary beta-subunits (beta 1-beta 4)(3-5). Activation of BK channels typically requires coincident membrane depolarization and elevation in free cytosolic Ca2+ concentration ([Ca2+](i))(6,7), which are not physiological conditions for most non-excitable cells. Here we present evidence that in non-excitable LNCaP prostate cancer cells, BK channels can be activated at negative voltages without rises in [Ca2+](i) through their complex with an auxiliary protein, leucine-rich repeat (LRR)-containing protein 26 (LRRC26). LRRC26 modulates the gating of a BK channel by enhancing the allosteric coupling between voltage-sensor activation and the channel's closed-open transition. This finding reveals a novel auxiliary protein of a voltage- gated ion channel that gives an unprecedentedly large negative shift (similar to-140 mV) in voltage dependence and provides a molecular basis for activation of BK channels at physiological voltages and calcium levels in non-excitable cells.
C1 [Yan, Jiusheng; Aldrich, Richard W.] Univ Texas Austin, Ctr Learning & Memory, Neurobiol Sect, Austin, TX 78712 USA.
C3 University of Texas System; University of Texas Austin
RP Aldrich, RW (corresponding author), Univ Texas Austin, Ctr Learning & Memory, Neurobiol Sect, Austin, TX 78712 USA.
EM raldrich@mail.utexas.edu
FU American Heart Association
NR 28
TC 192
Z9 223
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 JUL 22
PY 2010
VL 466
IS 7305
BP 513
EP U15
DI 10.1038/nature09162
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200041
PM 20613726
DA 2026-03-09
ER

PT J
AU Assefa, S
   Xia, FNA
   Vlasov, YA
AF Assefa, Solomon
   Xia, Fengnian
   Vlasov, Yurii A.
TI Reinventing germanium avalanche photodetector for nanophotonic on-chip optical interconnects
SO NATURE
LA English
DT Article
ID insulator; gain; ge; photodiodes; noise
AB Integration of optical communication circuits directly into high-performance microprocessor chips can enable extremely powerful computer systems(1). A germanium photodetector that can be monolithically integrated with silicon transistor technology(2-8) is viewed as a key element in connecting chip components with infrared optical signals. Such a device should have the capability to detect very-low-power optical signals at very high speed. Although germanium avalanche photodetectors(9,10) (APD) using charge amplification close to avalanche breakdown can achieve high gain and thus detect low-power optical signals, they are universally considered to suffer from an intolerably high amplification noise characteristic of germanium(11). High gain with low excess noise has been demonstrated using a germanium layer only for detection of light signals, with amplification taking place in a separate silicon layer(12). However, the relatively thick semiconductor layers that are required in such structures limit APD speeds to about 10GHz, and require excessively high bias voltages of around 25V (ref. 12). Here we show how nanophotonic and nanoelectronic engineering aimed at shaping optical and electrical fields on the nanometre scale within a germanium amplification layer can overcome the otherwise intrinsically poor noise characteristics, achieving a dramatic reduction of amplification noise by over 70 per cent. By generating strongly non-uniform electric fields, the region of impact ionization in germanium is reduced to just 30nm, allowing the device to benefit from the noise reduction effects(13-15) that arise at these small distances. Furthermore, the smallness of the APDs means that a bias voltage of only 1.5V is required to achieve an avalanche gain of over 10dB with operational speeds exceeding 30GHz. Monolithic integration of such a device into computer chips might enable applications beyond computer optical interconnects(1)-in telecommunications(16), secure quantum key distribution(17), and subthreshold ultralow-power transistors(18).
C1 [Assefa, Solomon; Xia, Fengnian; Vlasov, Yurii A.] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA.
C3 International Business Machines (IBM); IBM USA
RP Assefa, S (corresponding author), IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA.
EM sassefa@us.ibm.com
NR 30
TC 511
Z9 607
U1 7
U2 396
PU NATURE PUBLISHING 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 4
PY 2010
VL 464
IS 7285
BP 80
EP U91
DI 10.1038/nature08813
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500037
PM 20203606
DA 2026-03-09
ER

PT J
AU Marinoni, C
   Buzzi, A
AF Marinoni, Christian
   Buzzi, Adeline
TI A geometric measure of dark energy with pairs of galaxies
SO NATURE
LA English
DT Article
ID cosmological constant; data release; real-space; universe; voids
AB Observations(1,2) indicate that the expansion of the Universe is accelerating, which is attributed to a 'dark energy' component that opposes gravity(3,4). There is a purely geometric test of the expansion of the Universe (the Alcock-Paczynski test), which would provide an independent way of investigating the abundance (Omega(X)) and equation of state (w(X)) of dark energy(5). It is based on an analysis of the geometrical distortions expected from comparing the real-space and redshift-space shape of distant cosmic structures, but it has proved difficult to implement(6-18). Here we report an analysis of the symmetry properties of distant pairs of galaxies from archival data(19,20). This allows us to determine that the Universe is flat. By alternately fixing its spatial geometry at Omega(k) equivalent to 0, and the dark energy equation-of-state parameter at w(X) equivalent to -1, and using the results of baryon acoustic oscillations, we can establish at the 68.3% confidence level that -0.85 > w(X) > - 1.12 and 0.60 < Omega(X) < 0.80.
C1 [Marinoni, Christian; Buzzi, Adeline] Univ Aix Marseille 1, CNRS, UMR 6207, Ctr Phys Theor, F-13288 Marseille 9, France.
   [Marinoni, Christian] Inst Univ France, F-75005 Paris, France.
C3 Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut Universitaire de France
RP Marinoni, C (corresponding author), Univ Aix Marseille 1, CNRS, UMR 6207, Ctr Phys Theor, Campus Luminy,Case 907, F-13288 Marseille 9, France.
EM marinoni@cpt.univ-mrs.fr
FU CNRS; Institut Universitaire de France
NR 29
TC 49
Z9 54
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 NOV 25
PY 2010
VL 468
IS 7323
BP 539
EP 541
DI 10.1038/nature09577
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200036
PM 21107424
DA 2026-03-09
ER

PT J
AU Marraffini, LA
   Sontheimer, EJ
AF Marraffini, Luciano A.
   Sontheimer, Erik J.
TI Self versus non-self discrimination during CRISPR RNA-directed immunity
SO NATURE
LA English
DT Article
ID resistant staphylococcus-aureus; provides acquired-resistance; identification; prokaryotes; repeats; system; plasmid; defense; gene; dna
AB All immune systems must distinguish self from non-self to repel invaders without inducing autoimmunity. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci protect bacteria and archaea from invasion by phage and plasmid DNA through a genetic interference pathway(1-9). CRISPR loci are present in similar to 40% and similar to 90% of sequenced bacterial and archaeal genomes, respectively(10), and evolve rapidly, acquiring new spacer sequences to adapt to highly dynamic viral populations(1,11-13). Immunity requires a sequence match between the invasive DNA and the spacers that lie between CRISPR repeats(1-9). Each cluster is genetically linked to a subset of the cas (CRISPR-associated) genes(14-16) that collectively encode >40 families of proteins involved in adaptation and interference. CRISPR loci encode small CRISPR RNAs (crRNAs) that contain a full spacer flanked by partial repeat sequences(2,17-19). CrRNA spacers are thought to identify targets by direct Watson-Crick pairing with invasive 'protospacer' DNA(2,3), but how they avoid targeting the spacer DNA within the encoding CRISPR locus itself is unknown. Here we have defined the mechanism of CRISPR self/non-self discrimination. In Staphylococcus epidermidis, target/crRNA mismatches at specific positions outside of the spacer sequence license foreign DNA for interference, whereas extended pairing between crRNA and CRISPR DNA repeats prevents autoimmunity. Hence, this CRISPR system uses the base-pairing potential of crRNAs not only to specify a target, but also to spare the bacterial chromosome from interference. Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways.
C1 [Marraffini, Luciano A.; Sontheimer, Erik J.] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
C3 Northwestern University
RP Marraffini, LA (corresponding author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2205 Tech Dr, Evanston, IL 60208 USA.
EM l-marraffini@northwestern.edu; erik@northwestern.edu
FU National Institutes of Health, USA
NR 34
TC 497
Z9 721
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 JAN 28
PY 2010
VL 463
IS 7280
BP 568
EP U194
DI 10.1038/nature08703
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100057
PM 20072129
DA 2026-03-09
ER

PT J
AU Horie, M
   Honda, T
   Suzuki, Y
   Kobayashi, Y
   Daito, T
   Oshida, T
   Ikuta, K
   Jern, P
   Gojobori, T
   Coffin, JM
   Tomonaga, K
AF Horie, Masayuki
   Honda, Tomoyuki
   Suzuki, Yoshiyuki
   Kobayashi, Yuki
   Daito, Takuji
   Oshida, Tatsuo
   Ikuta, Kazuyoshi
   Jern, Patric
   Gojobori, Takashi
   Coffin, John M.
   Tomonaga, Keizo
TI Endogenous non-retroviral RNA virus elements in mammalian genomes
SO NATURE
LA English
DT Article
ID borna-disease virus; dna; protein; sequences; biology; cdna
AB Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and approximately 8% of the human genome is made up of these elements(1,2). Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication(3-5), none has been found as DNA in the germline of animals. Bornaviruses, a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus(6-8). Here we show that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Borna-like N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, whereas those in primates must have been formed more than 40 million years ago. We also show that the N mRNA of a current mammalian bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give novel insights not only into generation of endogenous elements, but also into a role of bornavirus as a source of genetic novelty in its host.
C1 [Horie, Masayuki; Honda, Tomoyuki; Daito, Takuji; Ikuta, Kazuyoshi; Tomonaga, Keizo] Osaka Univ, Dept Virol, Res Inst Microbial Dis BIKEN, Suita, Osaka 5650871, Japan.
   [Honda, Tomoyuki] Japan Soc Promot Sci, Chiyoda Ku, Tokyo 1028472, Japan.
   [Suzuki, Yoshiyuki; Kobayashi, Yuki; Gojobori, Takashi] Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan.
   [Suzuki, Yoshiyuki; Kobayashi, Yuki; Gojobori, Takashi] Natl Inst Genet, DNA Data Bank Japan, Mishima, Shizuoka 4118540, Japan.
   [Oshida, Tatsuo] Obihiro Univ Agr & Vet Med, Dept Life Sci & Agr, Obihiro, Hokkaido 0808555, Japan.
   [Jern, Patric; Coffin, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
   [Tomonaga, Keizo] Japan Sci & Technol Agcy, PRESTO, Chiyoda Ku, Tokyo 1020075, Japan.
C3 University of Osaka; Japan Society for the Promotion of Science; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Obihiro University of Agriculture & Veterinary Medicine; Tufts University; Japan Science & Technology Agency (JST)
RP Tomonaga, K (corresponding author), Osaka Univ, Dept Virol, Res Inst Microbial Dis BIKEN, Suita, Osaka 5650871, Japan.
EM tomonaga@biken.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); Japan Science and Technology Agency; Ministry of Health, Labor and Welfare of Japan; National Cancer Institute [R37 CA 089441]; Wenner-Gren Foundation; George Kirby Foundation
NR 29
TC 353
Z9 415
U1 1
U2 82
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 84
EP U90
DI 10.1038/nature08695
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900035
PM 20054395
DA 2026-03-09
ER

PT J
AU Toms, DJ
AF Toms, David J.
TI Quantum gravitational contributions to quantum electrodynamics
SO NATURE
LA English
DT Article
ID one-loop divergences; field-theory; gauge-theory; renormalization; nonrenormalizability; invariance; scale
AB Quantum electrodynamics describes the interactions of electrons and photons. Electric charge (the gauge coupling constant) is energy dependent, and there is a previous claim that charge is affected by gravity (described by general relativity) with the implication that the charge is reduced at high energies. However, that claim has been very controversial and the matter has not been settled. Here I report an analysis (free from the earlier controversies) demonstrating that quantum gravity corrections to quantum electrodynamics have a quadratic energy dependence that result in the electric charge vanishing at high energies, a result known as asymptotic freedom.
C1 Newcastle Univ, Sch Math & Stat, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
C3 Newcastle University - UK
RP Toms, DJ (corresponding author), Newcastle Univ, Sch Math & Stat, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
EM d.j.toms@newcastle.ac.uk
NR 43
TC 72
Z9 74
U1 0
U2 17
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 56
EP 59
DI 10.1038/nature09506
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900034
PM 21048760
DA 2026-03-09
ER

PT J
AU Mulder, DW
   Boyd, ES
   Sarma, R
   Lange, RK
   Endrizzi, JA
   Broderick, JB
   Peters, JW
AF Mulder, David W.
   Boyd, Eric S.
   Sarma, Ranjana
   Lange, Rachel K.
   Endrizzi, James A.
   Broderick, Joan B.
   Peters, John W.
TI Stepwise [FeFe]-hydrogenase H-cluster assembly revealed in the structure of HydAΔEFG
SO NATURE
LA English
DT Article
ID hydrogenase; protein; maturation; biosynthesis; evolution; inference; cofactors; enzymes; mrbayes; ligand
AB Complex enzymes containing Fe-S clusters are ubiquitous in nature, where they are involved in a number of fundamental processes including carbon dioxide fixation, nitrogen fixation and hydrogen metabolism(1,2). Hydrogen metabolism is facilitated by the activity of three evolutionarily and structurally unrelated enzymes: the [NiFe]-hydrogenases, [FeFe]-hydrogenases and [Fe]-hydrogenases(3,4) (Hmd). The catalytic core of the [FeFe]-hydrogenase (HydA), termed the H-cluster, exists as a [4Fe-4S] subcluster linked by a cysteine thiolate to a modified 2Fe subcluster with unique non-protein ligands(5,6). The 2Fe subcluster and non-protein ligands are synthesized by the hydrogenase maturation enzymes HydE, HydF and HydG; however, the mechanism, synthesis and means of insertion of H-cluster components remain unclear(7-10). Here we show the structure of HydA(Delta EFG) (HydA expressed in a genetic background devoid of the active site H-cluster biosynthetic genes hydE, hydF and hydG) revealing the presence of a [4Fe-4S] cluster and an open pocket for the 2Fe subcluster. The structure indicates that H-cluster synthesis occurs in a stepwise manner, first with synthesis and insertion of the [4Fe-4S] subcluster by generalized host-cell machinery(11,12) and then with synthesis and insertion of the 2Fe subcluster by specialized hydE-, hydF- and hydG-encoded maturation machinery(7-10). Insertion of the 2Fe subcluster presumably occurs through a cationically charged channel that collapses following incorporation, as a result of conformational changes in two conserved loop regions. The structure, together with phylogenetic analysis, indicates that HydA emerged within bacteria most likely from a Nar1-like ancestor lacking the 2Fe subcluster, and that this was followed by acquisition in several unicellular eukaryotes.
C1 [Mulder, David W.; Boyd, Eric S.; Sarma, Ranjana; Lange, Rachel K.; Endrizzi, James A.; Broderick, Joan B.; Peters, John W.] Montana State Univ, Astrobiol Biogeocatalysis Res Ctr, Bozeman, MT 59717 USA.
   [Mulder, David W.; Boyd, Eric S.; Sarma, Ranjana; Lange, Rachel K.; Endrizzi, James A.; Broderick, Joan B.; Peters, John W.] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA.
C3 Montana State University System; Montana State University Bozeman; Montana State University System; Montana State University Bozeman
RP Peters, JW (corresponding author), Montana State Univ, Astrobiol Biogeocatalysis Res Ctr, Bozeman, MT 59717 USA.
EM john.peters@chemistry.montana.edu
FU US Air Force Office of Scientific Research Multidisciplinary University Research Initiative [FA9550-05-01-0365]; NASA Astrobiology Institute (NAI) [NNA08C-N85A]; NAI; US Department of Energy, Office of Biological and Environmental Research; US National Institutes of Health, National Center for Research Resources; US National Institute of General Medical Sciences
NR 45
TC 259
Z9 301
U1 1
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 248
EP U143
DI 10.1038/nature08993
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500042
PM 20418861
DA 2026-03-09
ER

PT J
AU Kapoor, A
   Goldberg, MS
   Cumberland, LK
   Ratnakumar, K
   Segura, MF
   Emanuel, PO
   Menendez, S
   Vardabasso, C
   LeRoy, G
   Vidal, CI
   Polsky, D
   Osman, I
   Garcia, BA
   Hernando, E
   Bernstein, E
AF Kapoor, Avnish
   Goldberg, Matthew S.
   Cumberland, Lara K.
   Ratnakumar, Kajan
   Segura, Miguel F.
   Emanuel, Patrick O.
   Menendez, Silvia
   Vardabasso, Chiara
   LeRoy, Gary
   Vidal, Claudia I.
   Polsky, David
   Osman, Iman
   Garcia, Benjamin A.
   Hernando, Eva
   Bernstein, Emily
TI The histone variant macroH2A suppresses melanoma progression through regulation of CDK8
SO NATURE
LA English
DT Article
ID inactive x-chromosome; core histone; cancer; metastasis; expression; gene; transcription; stage; lines
AB Cancer is a disease consisting of both genetic and epigenetic changes. Although increasing evidence demonstrates that tumour progression entails chromatin-mediated changes such as DNA methylation, the role of histone variants in cancer initiation and progression currently remains unclear. Histone variants replace conventional histones within the nucleosome and confer unique biological functions to chromatin(1-3). Here we report that the histone variant macroH2A (mH2A) suppresses tumour progression of malignant melanoma. Loss of mH2A isoforms, histone variants generally associated with condensed chromatin and fine-tuning of developmental gene expression programs(1,4-6), is positively correlated with increasing malignant phenotype of melanoma cells in culture and human tissue samples. Knockdown of mH2A isoforms in melanoma cells of low malignancy results in significantly increased proliferation and migration in vitro and growth and metastasis in vivo. Restored expression of mH2A isoforms rescues these malignant phenotypes in vitro and in vivo. We demonstrate that the tumour-promoting function of mH2A loss is mediated, at least in part, through direct transcriptional upregulation of CDK8. Suppression of CDK8, a colorectal cancer oncogene(7,8), inhibits proliferation of melanoma cells, and knockdown of CDK8 in cells depleted of mH2A suppresses the proliferative advantage induced by mH2A loss. Moreover, a significant inverse correlation between mH2A and CDK8 expression levels exists in melanoma patient samples. Taken together, our results demonstrate that mH2A is a critical component of chromatin that suppresses the development of malignant melanoma, a highly intractable cutaneous neoplasm.
C1 [Kapoor, Avnish; Goldberg, Matthew S.; Cumberland, Lara K.; Ratnakumar, Kajan; Vardabasso, Chiara; Bernstein, Emily] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
   [Kapoor, Avnish; Goldberg, Matthew S.; Cumberland, Lara K.; Ratnakumar, Kajan; Emanuel, Patrick O.; Vardabasso, Chiara; Vidal, Claudia I.; Bernstein, Emily] Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA.
   [Emanuel, Patrick O.; Vidal, Claudia I.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA.
   [Segura, Miguel F.; Menendez, Silvia; Polsky, David; Hernando, Eva] NYU, Dept Pathol, Langone Med Ctr, New York, NY 10016 USA.
   [Polsky, David; Osman, Iman] NYU, Dept Dermatol, Langone Med Ctr, New York, NY 10016 USA.
   [Segura, Miguel F.; Menendez, Silvia; Polsky, David; Osman, Iman; Hernando, Eva] NYU, Interdisciplinary Melanoma Cooperat Grp, Langone Med Ctr, New York, NY 10016 USA.
   [LeRoy, Gary; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; NYU Langone Medical Center; New York University; NYU Langone Medical Center; New York University; NYU Langone Medical Center; New York University; Princeton University
RP Bernstein, E (corresponding author), Mt Sinai Sch Med, Dept Oncol Sci, 1425 Madison Ave, New York, NY 10029 USA.
EM emily.bernstein@mssm.edu
FU American Skin Association; American Society for Mass Spectrometry; New Jersey Commission on Cancer Research; National Science Foundation [CBET-0941143]; National Institutes of Health [CA109388]; Sergei S. Zlinkoff Fund for Medical Education; New York University Cancer Institute Cancer Center [5P30CA016087-27]; Marc Jacobs Campaign; NYSTEM IDEA [C024291]; Harry L. Lloyd Charitable Trust; Ellison Medical Foundation; Tisch Cancer Institute; NCI [R21CA150117]; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 30
TC 337
Z9 420
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 DEC 23
PY 2010
VL 468
IS 7327
BP 1105
EP U509
DI 10.1038/nature09590
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800059
PM 21179167
DA 2026-03-09
ER

PT J
AU Bergeal, N
   Schackert, F
   Metcalfe, M
   Vijay, R
   Manucharyan, VE
   Frunzio, L
   Prober, DE
   Schoelkopf, RJ
   Girvin, SM
   Devoret, MH
AF Bergeal, N.
   Schackert, F.
   Metcalfe, M.
   Vijay, R.
   Manucharyan, V. E.
   Frunzio, L.
   Prober, D. E.
   Schoelkopf, R. J.
   Girvin, S. M.
   Devoret, M. H.
TI Phase-preserving amplification near the quantum limit with a Josephson ring modulator
SO NATURE
LA English
DT Article
ID parametric-amplifier; linear-amplifiers; shot-noise; fluctuations
AB Recent progress in solid-state quantum information processing(1) has stimulated the search for amplifiers and frequency converters with quantum-limited performance in the microwave range. Depending on the gain applied to the quadratures of a single spatial and temporal mode of the electromagnetic field, linear amplifiers can be classified into two categories ( phase sensitive and phase preserving) with fundamentally different noise properties(2). Phase-sensitive amplifiers use squeezing to reduce the quantum noise, but are useful only in cases in which a reference phase is attached to the signal, such as in homodyne detection. A phase-preserving amplifier would be preferable in many applications, but such devices have not been available until now. Here we experimentally realize a proposal(3) for an intrinsically phase-preserving, superconducting parametric amplifier of non-degenerate type. It is based on a Josephson ring modulator, which consists of four Josephson junctions in a Wheatstone bridge configuration. The device symmetry greatly enhances the purity of the amplification process and simplifies both its operation and its analysis. The measured characteristics of the amplifier in terms of gain and bandwidth are in good agreement with analytical predictions. Using a newly developed noise source, we show that the upper bound on the total system noise of our device under real operating conditions is three times the quantum limit. We foresee applications in the area of quantum analog signal processing, such as quantum non-demolition single-shot readout of qubits(4), quantum feedback(5) and the production of entangled microwave signal pairs(6).
C1 [Bergeal, N.; Schackert, F.; Metcalfe, M.; Vijay, R.; Manucharyan, V. E.; Frunzio, L.; Prober, D. E.; Schoelkopf, R. J.; Girvin, S. M.; Devoret, M. H.] Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
   [Bergeal, N.] ESPCI ParisTech, CNRS, LPEM UPR5, F-75005 Paris, France.
   [Metcalfe, M.] Univ Maryland, Joint Quantum Inst, College Pk, MD 20742 USA.
   [Vijay, R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
C3 Yale University; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); University System of Maryland; University of Maryland College Park; University of California System; University of California Berkeley
RP Bergeal, N (corresponding author), Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
EM nicolas.bergeal@espci.fr; michel.devoret@yale.edu
FU US National Security Agency through the US Army Research Office [W911NF-05-01-0365]; W. M. Keck Foundation; US National Science Foundation [DMR-032-5580]; College de France; French Agence Nationale de la Recherche
NR 30
TC 383
Z9 489
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 64
EP U70
DI 10.1038/nature09035
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900031
PM 20445625
DA 2026-03-09
ER

PT J
AU He, G
   Luo, WJ
   Li, P
   Remmers, C
   Netzer, WJ
   Hendrick, J
   Bettayeb, K
   Flajolet, M
   Gorelick, F
   Wennogle, LP
   Greengard, P
AF He, Gen
   Luo, Wenjie
   Li, Peng
   Remmers, Christine
   Netzer, William J.
   Hendrick, Joseph
   Bettayeb, Karima
   Flajolet, Marc
   Gorelick, Fred
   Wennogle, Lawrence P.
   Greengard, Paul
TI Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease
SO NATURE
LA English
DT Article
ID amyloid precursor protein; terminal fragment; epsilon; notch; differentiation; proteolysis; generation; mutations; cleavage; genes
AB Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer's disease(1). Formation of amyloid-beta is catalysed by gamma-secretase, a protease with numerous substrates(2,3). Little is known about the molecular mechanisms that confer substrate specificity on this potentially promiscuous enzyme. Knowledge of the mechanisms underlying its selectivity is critical for the development of clinically effective gamma-secretase inhibitors that can reduce amyloid-beta formation without impairing cleavage of other gamma-secretase substrates, especially Notch, which is essential for normal biological functions(3,4). Here we report the discovery of a novel gamma-secretase activating protein (GSAP) that drastically and selectively increases amyloid-beta production through a mechanism involving its interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF). GSAP does not interact with Notch, nor does it affect its cleavage. Recombinant GSAP stimulates amyloid-beta production in vitro. Reducing GSAP concentrations in cell lines decreases amyloid-beta concentrations. Knockdown of GSAP in a mouse model of Alzheimer's disease reduces levels of amyloid-beta and plaque development. GSAP represents a type of gamma-secretase regulator that directs enzyme specificity by interacting with a specific substrate. We demonstrate that imatinib, an anticancer drug previously found to inhibit amyloid-beta formation without affecting Notch cleavage 5, achieves its amyloid-beta-lowering effect by preventing GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase.
C1 [He, Gen; Luo, Wenjie; Remmers, Christine; Netzer, William J.; Bettayeb, Karima; Flajolet, Marc; Greengard, Paul] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA.
   [Li, Peng; Hendrick, Joseph; Wennogle, Lawrence P.] Intra Cellular Therapies Inc, New York, NY 10032 USA.
   [Gorelick, Fred] Yale Univ, Sch Med, Dept Internal Med & Cell Biol, New Haven, CT 06520 USA.
   [Gorelick, Fred] VA Connecticut Healthcare, New Haven, CT 06520 USA.
C3 Rockefeller University; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Connecticut Healthcare System
RP Greengard, P (corresponding author), Rockefeller Univ, Mol & Cellular Neurosci Lab, 1230 York Ave, New York, NY 10065 USA.
EM greengard@rockefeller.edu
FU NIH [AG09464]; DOD [W81XWH-09-1-0402]; Fisher Center for Alzheimer's Research Foundation; F. M. Kirby Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007017] Funding Source: NIH RePORTER
NR 26
TC 278
Z9 342
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 95
EP U129
DI 10.1038/nature09325
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200042
PM 20811458
DA 2026-03-09
ER

PT J
AU Wang, R
   Chadalavada, K
   Wilshire, J
   Kowalik, U
   Hovinga, KE
   Geber, A
   Fligelman, B
   Leversha, M
   Brennan, C
   Tabar, V
AF Wang, Rong
   Chadalavada, Kalyani
   Wilshire, Jennifer
   Kowalik, Urszula
   Hovinga, Koos E.
   Geber, Adam
   Fligelman, Boris
   Leversha, Margaret
   Brennan, Cameron
   Tabar, Viviane
TI Glioblastoma stem-like cells give rise to tumour endothelium
SO NATURE
LA English
DT Article
ID nervous-system; recurrent glioblastoma; in-vivo; angiogenesis; egfr; identification; recruitment; inhibition; pathways; marker
AB Glioblastoma (GBM) is among the most aggressive of human cancers(1). A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia(2). Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poorly defined(3-5). Here we demonstrate that a subpopulation of endothelial cells within glioblastomas harbour the same somatic mutations identified within tumour cells, such as amplification of EGFR and chromosome 7. We additionally demonstrate that the stem-cell-like CD133(+) fraction includes a subset of vascular endothelial-cadherin (CD144)-expressing cells that show characteristics of endothelial progenitors capable of maturation into endothelial cells. Extensive in vitro and in vivo lineage analyses, including single cell clonal studies, further show that a subpopulation of the CD133(+) stem-like cell fraction is multipotent and capable of differentiation along tumour and endothelial lineages, possibly via an intermediate CD133(+)/CD144(+) progenitor cell. The findings are supported by genetic studies of specific exons selected from The Cancer Genome Atlas(6), quantitative FISH and comparative genomic hybridization data that demonstrate identical genomic profiles in the CD133(+) tumour cells, their endothelial progenitor derivatives and mature endothelium. Exposure to the clinical anti-angiogenesis agent bevacizumab(7) or to a gamma-secretase inhibitor(8) as well as knockdown shRNA studies demonstrate that blocking VEGF or silencing VEGFR2 inhibits the maturation of tumour endothelial progenitors into endothelium but not the differentiation of CD133(+) cells into endothelial progenitors, whereas c-secretase inhibition or NOTCH1 silencing blocks the transition into endothelial progenitors. These data may provide new perspectives on the mechanisms of failure of anti-angiogenesis inhibitors currently in use. The lineage plasticity and capacity to generate tumour vasculature of the putative cancer stem cells within glioblastoma are novel findings that provide new insight into the biology of gliomas and the definition of cancer stemness, as well as the mechanisms of tumour neo-angiogenesis.
C1 [Wang, Rong; Kowalik, Urszula; Hovinga, Koos E.; Geber, Adam; Fligelman, Boris; Brennan, Cameron; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [Wang, Rong; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, New York, NY 10065 USA.
   [Wang, Rong; Brennan, Cameron; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10065 USA.
   [Hovinga, Koos E.] Univ Amsterdam, Acad Med Ctr, Neurosurg Ctr Amsterdam, NL-1105 AZ Amsterdam, Netherlands.
   [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Amsterdam; Academic Medical Center Amsterdam; Memorial Sloan Kettering Cancer Center
RP Tabar, V (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
EM tabarv@mskcc.org
FU New York State Stem Cell Science Fund (NYSTEM); National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 31
TC 973
Z9 1148
U1 1
U2 182
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 829
EP U128
DI 10.1038/nature09624
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700047
PM 21102433
DA 2026-03-09
ER

PT J
AU Piscitelli, CL
   Krishnamurthy, H
   Gouaux, E
AF Piscitelli, Chayne L.
   Krishnamurthy, Harini
   Gouaux, Eric
TI Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site
SO NATURE
LA English
DT Article
ID bacterial homolog; crystal-structure; acid transporter; binding-site; mechanism; reveals; proteins; na+
AB Neurotransmitter/sodium symporters (NSSs) couple the uptake of neurotransmitter with one or more sodium ions(1-3), removing neurotransmitter from the synaptic cleft. NSSs are essential to the function of chemical synapses, are associated with multiple neurological diseases and disorders(4), and are the targets of therapeutic and illicit drugs(5). LeuT, a prokaryotic orthologue of the NSS family, is a model transporter for understanding the relationships between molecular mechanism and atomic structure in a broad range of sodium-dependent and sodium-independent secondary transporters(6-13). At present there is a controversy over whether there are one or two high-affinity substrate binding sites in LeuT. The first-reported crystal structure of LeuT, together with subsequent functional and structural studies, provided direct evidence for a single, high-affinity, centrally located substrate-binding site, defined as the S1 site(14,15). Recent binding, flux and molecular simulation studies, however, have been interpreted in terms of a model where there are two high-affinity binding sites: the central, S1, site and a second, the S2 site, located within the extracellular vestibule(16). Furthermore, it was proposed that the S1 and S2 sites are allosterically coupled such that occupancy of the S2 site is required for the cytoplasmic release of substrate from the S1 site(16). Here we address this controversy by performing direct measurement of substrate binding to wild-type LeuT and to S2 site mutants using isothermal titration calorimetry, equilibrium dialysis and scintillation proximity assays. In addition, we perform uptake experiments to determine whether the proposed allosteric coupling between the putative S2 site and the S1 site manifests itself in the kinetics of substrate flux. We conclude that LeuT harbours a single, centrally located, high-affinity substrate-binding site and that transport is well described by a simple, single-substrate kinetic mechanism.
C1 [Piscitelli, Chayne L.; Krishnamurthy, Harini; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Piscitelli, Chayne L.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, 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; Oregon Health & Science University
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 ARCS foundation; NIH [T32 DK007680]
NR 25
TC 107
Z9 133
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1129
EP U538
DI 10.1038/nature09581
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800064
PM 21179170
DA 2026-03-09
ER

PT J
AU Boddey, JA
   Hodder, AN
   Günther, S
   Gilson, PR
   Patsiouras, H
   Kapp, EA
   Pearce, JA
   de Koning-Ward, TF
   Simpson, RJ
   Crabb, BS
   Cowman, AF
AF Boddey, Justin A.
   Hodder, Anthony N.
   Guenther, Svenja
   Gilson, Paul R.
   Patsiouras, Heather
   Kapp, Eugene A.
   Pearce, J. Andrew
   de Koning-Ward, Tania F.
   Simpson, Richard J.
   Crabb, Brendan S.
   Cowman, Alan F.
TI An aspartyl protease directs malaria effector proteins to the host cell
SO NATURE
LA English
DT Article
ID falciparum-infected erythrocytes; plasmodium export element; endoplasmic-reticulum; parasite proteins; hiv-1 protease; trafficking; expression; virulence; cytoadherence; invasion
AB Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.
C1 [Boddey, Justin A.; Hodder, Anthony N.; Guenther, Svenja; Pearce, J. Andrew; Simpson, Richard J.; Cowman, Alan F.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia.
   [Gilson, Paul R.; Crabb, Brendan S.] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3004, Australia.
   [Patsiouras, Heather; Kapp, Eugene A.; Simpson, Richard J.] Ludwig Inst Canc Res, Joint Prote Facil, Melbourne, Vic 3050, Australia.
   [de Koning-Ward, Tania F.] Deakin Univ, Waurn Ponds 3217, Australia.
C3 Walter & Eliza Hall Institute; Burnet Institute; Ludwig Institute for Cancer Research; Deakin University
RP Cowman, AF (corresponding author), Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia.
EM cowman@wehi.edu.au
FU National Health and Medical Research Council; National Institutes of Health [RO1 AI44008]
NR 34
TC 260
Z9 306
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 FEB 4
PY 2010
VL 463
IS 7281
BP 627
EP U52
DI 10.1038/nature08728
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900028
PM 20130643
DA 2026-03-09
ER

PT J
AU He, YP
   Wu, J
   Dressman, DC
   Iacobuzio-Donahue, C
   Markowitz, SD
   Velculescu, VE
   Diaz, LA
   Kinzler, KW
   Vogelstein, B
   Papadopoulos, N
AF He, Yiping
   Wu, Jian
   Dressman, Devin C.
   Iacobuzio-Donahue, Christine
   Markowitz, Sanford D.
   Velculescu, Victor E.
   Diaz, Luis A., Jr.
   Kinzler, Kenneth W.
   Vogelstein, Bert
   Papadopoulos, Nickolas
TI Heteroplasmic mitochondrial DNA mutations in normal and tumour cells
SO NATURE
LA English
DT Article
ID point mutations; control region; stem-cells; mtdna; individuals; cancer; replication; frequency; dynamics; genetics
AB The presence of hundreds of copies of mitochondrial DNA (mtDNA) in each human cell poses a challenge for the complete characterization of mtDNA genomes by conventional sequencing technologies(1). Here we describe digital sequencing of mtDNA genomes with the use of massively parallel sequencing-by-synthesis approaches. Although the mtDNA of human cells is considered to be homogeneous, we found widespread heterogeneity (heteroplasmy) in the mtDNA of normal human cells. Moreover, the frequency of heteroplasmic variants varied considerably between different tissues in the same individual. In addition to the variants identified in normal tissues, cancer cells harboured further homoplasmic and heteroplasmic mutations that could also be detected in patient plasma. These studies provide insights into the nature and variability of mtDNA sequences and have implications for mitochondrial processes during embryogenesis, cancer biomarker development and forensic analysis. In particular, they demonstrate that individual humans are characterized by a complex mixture of related mitochondrial genotypes rather than a single genotype.
C1 [He, Yiping; Wu, Jian; Dressman, Devin C.; Velculescu, Victor E.; Diaz, Luis A., Jr.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
   [He, Yiping; Wu, Jian; Dressman, Devin C.; Velculescu, Victor E.; Diaz, Luis A., Jr.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA.
   [Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA.
   [Markowitz, Sanford D.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
   [Markowitz, Sanford D.] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA.
   [Markowitz, Sanford D.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA.
   [Markowitz, Sanford D.] Howard Hughes Med Inst, Cleveland, OH 44106 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins Medicine; University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University Hospitals of Cleveland; University System of Ohio; Case Western Reserve University; Howard Hughes Medical Institute
RP Vogelstein, B (corresponding author), Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
EM vogelbe@jhmi.edu; npapado1@jhmi.edu
FU The Virginia and D. K. Ludwig Fund for Cancer Research; National Institutes of Health [CA57345, CA 43460, CA 62924, CA121113]; National Cancer Institute [P50CA062924, R01CA121113] Funding Source: NIH RePORTER
NR 30
TC 416
Z9 479
U1 0
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 610
EP U175
DI 10.1038/nature08802
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200052
PM 20200521
DA 2026-03-09
ER

PT J
AU vonHoldt, BM
   Pollinger, JP
   Lohmueller, KE
   Han, EJ
   Parker, HG
   Quignon, P
   Degenhardt, JD
   Boyko, AR
   Earl, DA
   Auton, A
   Reynolds, A
   Bryc, K
   Brisbin, A
   Knowles, JC
   Mosher, DS
   Spady, TC
   Elkahloun, A
   Geffen, E
   Pilot, M
   Jedrzejewski, W
   Greco, C
   Randi, E
   Bannasch, D
   Wilton, A
   Shearman, J
   Musiani, M
   Cargill, M
   Jones, PG
   Qian, ZW
   Huang, W
   Ding, ZL
   Zhang, YP
   Bustamante, CD
   Ostrander, EA
   Novembre, J
   Wayne, RK
AF vonHoldt, Bridgett M.
   Pollinger, John P.
   Lohmueller, Kirk E.
   Han, Eunjung
   Parker, Heidi G.
   Quignon, Pascale
   Degenhardt, Jeremiah D.
   Boyko, Adam R.
   Earl, Dent A.
   Auton, Adam
   Reynolds, Andy
   Bryc, Kasia
   Brisbin, Abra
   Knowles, James C.
   Mosher, Dana S.
   Spady, Tyrone C.
   Elkahloun, Abdel
   Geffen, Eli
   Pilot, Malgorzata
   Jedrzejewski, Wlodzimierz
   Greco, Claudia
   Randi, Ettore
   Bannasch, Danika
   Wilton, Alan
   Shearman, Jeremy
   Musiani, Marco
   Cargill, Michelle
   Jones, Paul G.
   Qian, Zuwei
   Huang, Wei
   Ding, Zhao-Li
   Zhang, Ya-Ping
   Bustamante, Carlos D.
   Ostrander, Elaine A.
   Novembre, John
   Wayne, Robert K.
TI Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication
SO NATURE
LA English
DT Article
ID linkage disequilibrium; population-structure; ancient dna; origin; wild; selection; genotype; deletion
AB Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication(1,2). To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data(3). Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.
C1 [vonHoldt, Bridgett M.; Pollinger, John P.; Knowles, James C.; Novembre, John; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Lohmueller, Kirk E.; Degenhardt, Jeremiah D.; Boyko, Adam R.; Auton, Adam; Reynolds, Andy; Bryc, Kasia; Brisbin, Abra; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [Han, Eunjung] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 14853 USA.
   [Parker, Heidi G.; Quignon, Pascale; Mosher, Dana S.; Spady, Tyrone C.; Elkahloun, Abdel; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Earl, Dent A.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Geffen, Eli] Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel.
   [Pilot, Malgorzata] Polish Acad Sci, Museum Zool, PL-00679 Warsaw, Poland.
   [Pilot, Malgorzata] Polish Acad Sci, Inst Zool, PL-00679 Warsaw, Poland.
   [Jedrzejewski, Wlodzimierz] Polish Acad Sci, Mammal Res Inst, PL-17230 Bialowieza, Poland.
   [Greco, Claudia; Randi, Ettore] ISPRA, I-40064 Ozzano Emilia B, Italy.
   [Bannasch, Danika] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
   [Wilton, Alan; Shearman, Jeremy] Univ New S Wales, Clive & Vera Ramaciotti Ctr Gene Funct Anal, Sydney, NSW 2052, Australia.
   [Wilton, Alan; Shearman, Jeremy] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia.
   [Musiani, Marco] Univ Calgary, Fac Environm Design, Calgary, AB T2N 1N4, Canada.
   [Cargill, Michelle] Affymetrix Corp, Santa Clara, CA 95051 USA.
   [Jones, Paul G.] WALTHAM Ctr Pet Nutr, Waltham On The Worlds LE14 4RT, Leics, England.
   [Qian, Zuwei; Huang, Wei] AZIA Ctr, Affymetrix Asia Pacific Sci Affairs & Collaborat, Shanghai 200120, Peoples R China.
   [Ding, Zhao-Li] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Kunming 650091, Peoples R China.
   [Zhang, Ya-Ping] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China.
   [Novembre, John] Univ Calif Los Angeles, Interdepartmental Program Bioinformat, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; Cornell University; University of California System; University of California Los Angeles; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of California System; University of California Santa Cruz; Tel Aviv University; Polish Academy of Sciences; Polish Academy of Sciences; Polish Academy of Sciences; Mammal Research Institute of the Polish Academy of Sciences; Italian Institute for Environmental Protection & Research (ISPRA); University of California System; University of California Davis; University of New South Wales Sydney; University of New South Wales Sydney; University of Calgary; Affymetrix; Mars; WALTHAM Petcare Science Institute; Yunnan University; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; University of California System; University of California Los Angeles
RP Wayne, RK (corresponding author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, 621 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM rwayne@ucla.edu
FU NSF; NIH; Polish Ministry of Science and Higher Education; European Nature Heritage Fund EURONATUR; National Basic Research Program of China; Chinese Academy of Sciences; Searle Scholars Program; National Human Genome Research Institute; Foundation for Polish Science; National Human Genome Research Institute [T32HG002536, ZICHG200365] Funding Source: NIH RePORTER
NR 37
TC 595
Z9 711
U1 2
U2 550
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 898
EP U109
DI 10.1038/nature08837
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300039
PM 20237475
DA 2026-03-09
ER

PT J
AU Llopis, PM
   Jackson, AF
   Sliusarenko, O
   Surovtsev, I
   Heinritz, J
   Emonet, T
   Jacobs-Wagner, C
AF Llopis, Paula Montero
   Jackson, Audrey F.
   Sliusarenko, Oleksii
   Surovtsev, Ivan
   Heinritz, Jennifer
   Emonet, Thierry
   Jacobs-Wagner, Christine
TI Spatial organization of the flow of genetic information in bacteria
SO NATURE
LA English
DT Article
ID cell-cycle progression; messenger-rna decay; escherichia-coli; caulobacter-crescentus; transcription; translation; expression; dna; visualization; localization
AB Eukaryotic cells spatially organize mRNA processes such as translation and mRNA decay. Much less is clear in bacterial cells where the spatial distribution of mature mRNA remains ambiguous. Using a sensitive method based on quantitative fluorescence in situ hybridization, we show here that in Caulobacter crescentus and Escherichia coli, chromosomally expressed mRNAs largely display limited dispersion from their site of transcription during their lifetime. We estimate apparent diffusion coefficients at least two orders of magnitude lower than expected for freely diffusing mRNA, and provide evidence in C. crescentus that this mRNA localization restricts ribosomal mobility. Furthermore, C. crescentus RNase E appears associated with the DNA independently of its mRNA substrates. Collectively, our findings show that bacteria can spatially organize translation and, potentially, mRNA decay by using the chromosome layout as a template. This chromosome-centric organization has important implications for cellular physiology and for our understanding of gene expression in bacteria.
C1 [Llopis, Paula Montero; Jackson, Audrey F.; Sliusarenko, Oleksii; Emonet, Thierry; Jacobs-Wagner, Christine] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Sliusarenko, Oleksii; Surovtsev, Ivan; Heinritz, Jennifer; Jacobs-Wagner, Christine] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Emonet, Thierry] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Jacobs-Wagner, Christine] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06510 USA.
C3 Yale University; Yale University; Howard Hughes Medical Institute; Yale University; Yale University
RP Jacobs-Wagner, C (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM christine.jacobs-wagner@yale.edu
FU Howard Hughes Medical Institute; National Institutes of Health [GM065835]
NR 38
TC 300
Z9 357
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 JUL 1
PY 2010
VL 466
IS 7302
BP 77
EP U90
DI 10.1038/nature09152
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800037
PM 20562858
DA 2026-03-09
ER

PT J
AU Chi, P
   Chen, Y
   Zhang, L
   Guo, XY
   Wongvipat, J
   Shamu, T
   Fletcher, JA
   Dewell, S
   Maki, RG
   Zheng, DY
   Antonescu, CR
   Allis, CD
   Sawyers, CL
AF Chi, Ping
   Chen, Yu
   Zhang, Lei
   Guo, Xingyi
   Wongvipat, John
   Shamu, Tambudzai
   Fletcher, Jonathan A.
   Dewell, Scott
   Maki, Robert G.
   Zheng, Deyou
   Antonescu, Cristina R.
   Allis, C. David
   Sawyers, Charles L.
TI ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours
SO NATURE
LA English
DT Article
ID interstitial-cells; gene-expression; mouse model; mutations; cajal; inhibition; gist
AB Gastrointestinal stromal tumour (GIST) is the most common human sarcoma and is primarily defined by activating mutations in the KIT or PDGFRA receptor tyrosine kinases(1,2). KIT is highly expressed in interstitial cells of Cajal (ICCs)-the presumed cell of origin for GIST-as well as in haematopoietic stem cells, melanocytes, mast cells and germ cells(2,3). Yet, families harbouring germline activating KIT mutations and mice with knock-in Kit mutations almost exclusively develop ICC hyperplasia and GIST(4-7), suggesting that the cellular context is important for KIT to mediate oncogenesis. Here we show that the ETS family member ETV1 is highly expressed in the subtypes of ICCs sensitive to oncogenic KIT mediated transformation(8), and is required for their development. In addition, ETV1 is universally highly expressed in GISTs and is required for growth of imatinib-sensitive and resistant GIST cell lines. Transcriptome profiling and global analyses of ETV1-binding sites suggest that ETV1 is a master regulator of an ICC-GIST-specific transcription network mainly through enhancer binding. The ETV1 transcriptional program is further regulated by activated KIT, which prolongs ETV1 protein stability and cooperates with ETV1 to promote tumorigenesis. We propose that GIST arises from ICCs with high levels of endogenous ETV1 expression that, when coupled with an activating KIT mutation, drives an oncogenic ETS transcriptional program. This differs from other ETS-dependent tumours such as prostate cancer, melanoma and Ewing sarcoma where genomic translocation or amplification drives aberrant ETS expression(9-11). It also represents a novel mechanism of oncogenic transcription factor activation.
C1 [Chi, Ping; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
   [Chi, Ping; Chen, Yu; Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Chen, Yu; Wongvipat, John; Shamu, Tambudzai; Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Zhang, Lei; Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Guo, Xingyi; Zheng, Deyou] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA.
   [Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Dewell, Scott] Rockefeller Univ, Genom Resource Ctr, New York, NY USA.
   [Zheng, Deyou] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.
   [Zheng, Deyou] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA.
   [Sawyers, Charles L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Rockefeller University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Rockefeller University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Howard Hughes Medical Institute
RP Sawyers, CL (corresponding author), Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
EM alliscd@rockefeller.edu; sawyersc@mskcc.org
FU National Cancer Institute [K08CA140946, 5F32CA130372, CA47179, CA148260]; US National Institute of Mental Health [R21MH087840]; National Cancer Institute-American Society of Clinical Oncology Cancer Foundation Clinical Investigator Team; American Society of Clinical Oncology; Doris Duke; Charles H Revson; Charles A. Dana foundations; Rockefeller University; American Cancer Society [CCE-106841, P01CA47179]; Life Raft Group; GIST; Shuman Family Fund for GIST Research; Cycle for Survival; Albert Einstein College of Medicine; National Institutes of Health [GM40922]; Starr Cancer Consortium; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM040922] Funding Source: NIH RePORTER
NR 33
TC 257
Z9 311
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 14
PY 2010
VL 467
IS 7317
BP 849
EP U117
DI 10.1038/nature09409
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700068
PM 20927104
DA 2026-03-09
ER

PT J
AU Blanche, PA
   Bablumian, A
   Voorakaranam, R
   Christenson, C
   Lin, W
   Gu, T
   Flores, D
   Wang, P
   Hsieh, WY
   Kathaperumal, M
   Rachwal, B
   Siddiqui, O
   Thomas, J
   Norwood, RA
   Yamamoto, M
   Peyghambarian, N
AF Blanche, P-A
   Bablumian, A.
   Voorakaranam, R.
   Christenson, C.
   Lin, W.
   Gu, T.
   Flores, D.
   Wang, P.
   Hsieh, W-Y
   Kathaperumal, M.
   Rachwal, B.
   Siddiqui, O.
   Thomas, J.
   Norwood, R. A.
   Yamamoto, M.
   Peyghambarian, N.
TI Holographic three-dimensional telepresence using large-area photorefractive polymer
SO NATURE
LA English
DT Article
ID computer-generated holography; display
AB Holography is a technique that is used to display objects or scenes in three dimensions. Such three-dimensional (3D) images, or holograms, can be seen with the unassisted eye and are very similar to how humans see the actual environment surrounding them. The concept of 3D telepresence, a real-time dynamic hologram depicting a scene occurring in a different location, has attracted considerable public interest since it was depicted in the original Star Wars film in 1977. However, the lack of sufficient computational power to produce realistic computer-generated holograms(1) and the absence of large-area and dynamically updatable holographic recording media(2) have prevented realization of the concept. Here we use a holographic stereographic technique(3) and a photorefractive polymer material as the recording medium(4) to demonstrate a holographic display that can refresh images every two seconds. A 50 Hz nanosecond pulsed laser is used to write the holographic pixels(5). Multicoloured holographic 3D images are produced by using angular multiplexing, and the full parallax display employs spatial multiplexing. 3D telepresence is demonstrated by taking multiple images from one location and transmitting the information via Ethernet to another location where the hologram is printed with the quasi-real-time dynamic 3D display. Further improvements could bring applications in telemedicine, prototyping, advertising, updatable 3D maps and entertainment.
C1 [Blanche, P-A; Bablumian, A.; Voorakaranam, R.; Christenson, C.; Thomas, J.; Norwood, R. A.; Peyghambarian, N.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
   [Lin, W.; Gu, T.; Flores, D.; Wang, P.; Hsieh, W-Y; Kathaperumal, M.; Rachwal, B.; Siddiqui, O.; Yamamoto, M.] Nitto Denko Tech Corp, Oceanside, CA 92054 USA.
C3 University of Arizona; Nitto Denko Corporation
RP Peyghambarian, N (corresponding author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA.
EM nnp@u.arizona.edu
FU AFOSR; DARPA; NSF ERC Center on Integrated Access Networks (CIAN)
NR 23
TC 470
Z9 567
U1 9
U2 585
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 80
EP 83
DI 10.1038/nature09521
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900039
PM 21048763
DA 2026-03-09
ER

PT J
AU Murton, JB
   Bateman, MD
   Dallimore, SR
   Teller, JT
   Yang, ZR
AF Murton, Julian B.
   Bateman, Mark D.
   Dallimore, Scott R.
   Teller, James T.
   Yang, Zhirong
TI Identification of Younger Dryas outburst flood path from Lake Agassiz to the Arctic Ocean
SO NATURE
LA English
DT Article
ID laurentide ice-sheet; tuktoyaktuk coastlands; climate-change; paleotopography; stratigraphy; meltwater; overflow; history; valley; margin
AB The melting Laurentide Ice Sheet discharged thousands of cubic kilometres of freshwater each year into surrounding oceans, at times suppressing the Atlantic meridional overturning circulation and triggering abrupt climate change(1-4). Understanding the physical mechanisms leading to events such as the Younger Dryas cold interval requires identification of the paths and timing of the freshwater discharges. Although Broecker et al. hypothesized in 1989 that an outburst from glacial Lake Agassiz triggered the Younger Dryas(1), specific evidence has so far proved elusive, leading Broecker to conclude in 2006 that "our inability to identify the path taken by the flood is disconcerting''(2). Here we identify the missing flood path-evident from gravels and a regional erosion surface-running through the Mackenzie River system in the Canadian Arctic Coastal Plain. Our modelling of the isostatically adjusted surface in the upstream Fort McMurray region, and a slight revision of the ice margin at this time, allows Lake Agassiz to spill into the Mackenzie drainage basin. From optically stimulated luminescence dating we have determined the approximate age of this Mackenzie River flood into the Arctic Ocean to be shortly after 13,000 years ago, near the start of the Younger Dryas. We attribute to this flood a boulder terrace near Fort McMurray with calibrated radiocarbon dates of over 11,500 years ago. A large flood into the Arctic Ocean at the start of the Younger Dryas leads us to reject the widespread view that Agassiz overflow at this time was solely eastward into the North Atlantic Ocean.
C1 [Murton, Julian B.] Univ Sussex, Dept Geog, Permafrost Lab, Brighton BN1 9QJ, E Sussex, England.
   [Bateman, Mark D.] Univ Sheffield, Dept Geog, Sheffield Ctr Int Drylands Res, Sheffield S10 2TN, S Yorkshire, England.
   [Dallimore, Scott R.] Geol Survey Canada, Sidney, BC V8L 4B2, Canada.
   [Teller, James T.; Yang, Zhirong] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
C3 University of Sussex; University of Sheffield; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; University of Manitoba
RP Murton, JB (corresponding author), Univ Sussex, Dept Geog, Permafrost Lab, Brighton BN1 9QJ, E Sussex, England.
EM j.b.murton@sussex.ac.uk
FU Royal Society; Quaternary Research Association; British Society for Geomorphology; Geological Survey of Canada; Natural Sciences and Engineering Research Council of Canada
NR 29
TC 220
Z9 252
U1 2
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 740
EP 743
DI 10.1038/nature08954
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000041
PM 20360738
DA 2026-03-09
ER

PT J
AU Huang, J
   Zarnitsyna, VI
   Liu, BY
   Edwards, LJ
   Jiang, N
   Evavold, BD
   Zhu, C
AF Huang, Jun
   Zarnitsyna, Veronika I.
   Liu, Baoyu
   Edwards, Lindsay J.
   Jiang, Ning
   Evavold, Brian D.
   Zhu, Cheng
TI The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness
SO NATURE
LA English
DT Article
ID ligand binding-kinetics; p-selectin; receptor microclusters; impact; affinity; microtopology; recognition; activation; threshold; surfaces
AB The T-cell receptor (TCR) interacts with peptide-major histocompatibility complexes (pMHC) to discriminate pathogens from self-antigens and trigger adaptive immune responses. Direct physical contact is required between the T cell and the antigen-presenting cell for cross-junctional binding where the TCR and pMHC are anchored on two-dimensional (2D) membranes of the apposing cells(1). Despite their 2D nature, TCR-pMHC binding kinetics have only been analysed three-dimensionally (3D) with a varying degree of correlation with the T-cell responsiveness(2-4). Here we use two mechanical assays(5,6) to show high 2D affinities between a TCR and its antigenic pMHC driven by rapid on-rates. Compared to their 3D counterparts, 2D affinities and on-rates of the TCR for a panel of pMHC ligands possess far broader dynamic ranges that match that of their corresponding T-cell responses. The best 3D predictor of response is the off-rate, with agonist pMHC dissociating the slowest(2-4). In contrast, 2D off-rates are up to 8,300-fold faster, with the agonist pMHC dissociating the fastest. Our 2D data suggest rapid antigen sampling by T cells and serial engagement of a few agonist pMHCs by TCRs in a large self pMHC background. Thus, the cellular environment amplifies the intrinsic TCR-pMHC binding to generate broad affinities and rapid kinetics that determine T-cell responsiveness.
C1 [Huang, Jun; Zarnitsyna, Veronika I.; Liu, Baoyu; Jiang, Ning; Zhu, Cheng] Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Edwards, Lindsay J.; Evavold, Brian D.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
C3 University System of Georgia; Georgia Institute of Technology; Emory University
RP Zhu, C (corresponding author), Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
EM bevavol@emory.edu; cheng.zhu@bme.gatech.edu
FU NIH [AI38282, AI060799]; National Multiple Sclerosis Society [RG4047-A-3];  [NS062358]; National Institute of Neurological Disorders and Stroke [R01NS071518] Funding Source: NIH RePORTER
NR 39
TC 408
Z9 510
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 8
PY 2010
VL 464
IS 7290
BP 932
EP U156
DI 10.1038/nature08944
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300046
PM 20357766
DA 2026-03-09
ER

PT J
AU DiCarlo, L
   Reed, MD
   Sun, L
   Johnson, BR
   Chow, JM
   Gambetta, JM
   Frunzio, L
   Girvin, SM
   Devoret, MH
   Schoelkopf, RJ
AF DiCarlo, L.
   Reed, M. D.
   Sun, L.
   Johnson, B. R.
   Chow, J. M.
   Gambetta, J. M.
   Frunzio, L.
   Girvin, S. M.
   Devoret, M. H.
   Schoelkopf, R. J.
TI Preparation and measurement of three-qubit entanglement in a superconducting circuit
SO NATURE
LA English
DT Article
ID horne-zeilinger entanglement; qubits; inequality; violation; photon; states
AB Traditionally, quantum entanglement has been central to foundational discussions of quantum mechanics. The measurement of correlations between entangled particles can have results at odds with classical behaviour. These discrepancies grow exponentially with the number of entangled particles(1). With the ample experimental(2-4) confirmation of quantum mechanical predictions, entanglement has evolved from a philosophical conundrum into a key resource for technologies such as quantum communication and computation(5). Although entanglement in superconducting circuits has been limited so far to two qubits(6-9), the extension of entanglement to three, eight and ten qubits has been achieved among spins(10), ions(11) and photons(12), respectively. A key question for solid-state quantum information processing is whether an engineered system could display the multi-qubit entanglement necessary for quantum error correction, which starts with tripartite entanglement. Here, using a circuit quantum electrodynamics architecture(13,14), we demonstrate deterministic production of three-qubit Greenberger-Horne-Zeilinger (GHZ) states(15) with fidelity of 88 per cent, measured with quantum state tomography. Several entanglement witnesses detect genuine three-qubit entanglement by violating biseparable bounds by 830 +/- 80 per cent. We demonstrate the first step of basic quantum error correction, namely the encoding of a logical qubit into a manifold of GHZ-like states using a repetition code. The integration of this encoding with decoding and error-correcting steps in a feedback loop will be the next step for quantum computing with integrated circuits.
C1 [DiCarlo, L.; Reed, M. D.; Sun, L.; Johnson, B. R.; Chow, J. M.; Frunzio, L.; Girvin, S. M.; Devoret, M. H.; Schoelkopf, R. J.] Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06511 USA.
   [Gambetta, J. M.] Univ Waterloo, Dept Phys & Astron, Waterloo, ON N2L 3G1, Canada.
   [Gambetta, J. M.] Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
C3 Yale University; University of Waterloo; University of Waterloo
RP DiCarlo, L (corresponding author), Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06511 USA.
EM leonardo.dicarlo@yale.edu; robert.schoelkopf@yale.edu
FU LPS/NSA [W911NF-05-1-0365]; IARPA [W911NF-09-1-0369]; NSF [DMR-0653377, DMR-0603369]; CNR-Istituto di Cibernetica, Pozzuoli, Italy; CIFAR; MITACS; MRI; NSERC
NR 29
TC 490
Z9 553
U1 1
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 574
EP 578
DI 10.1038/nature09416
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100035
PM 20882013
DA 2026-03-09
ER

PT J
AU Virgin, HW
   Walker, BD
AF Virgin, Herbert W.
   Walker, Bruce D.
TI Immunology and the elusive AIDS vaccine
SO NATURE
LA English
DT Article
ID simian immunodeficiency virus; t-cell responses; hiv-1 infection; neutralizing antibody; lymphocyte escape; immune control; macaque model; b-cells; replication; protection
AB Developing a human immunodeficiency virus (HIV) vaccine is critical to end the global acquired immunodeficiency syndrome (AIDS) epidemic, but many question whether this goal is achievable. Natural immunity is not protective, and despite immunogenicity of HIV vaccine candidates, human trials have exclusively yielded disappointing results. Nevertheless, there is an indication that success may be possible, but this will be dependent on understanding the antiviral immune response in unprecedented depth to identify and engineer the types of immunity required. Here we outline fundamental immunological questions that need to be answered to develop a protective HIV vaccine, and the immediate need to harness a much broader scientific community to achieve this goal.
C1 [Virgin, Herbert W.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
   [Virgin, Herbert W.] Washington Univ, Midwest Reg Ctr Excellence Biodef & Emerging Infe, St Louis, MO 63110 USA.
   [Walker, Bruce D.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA.
   [Walker, Bruce D.] Harvard Univ, Howard Hughes Med Inst, Charlestown, MA 02129 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Harvard University
RP Virgin, HW (corresponding author), Washington Univ, Sch Med, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA.
EM virgin@wustl.edu; bwalker@partners.org
FU National Institutes of Health; Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation
NR 101
TC 136
Z9 157
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 MAR 11
PY 2010
VL 464
IS 7286
BP 224
EP 231
DI 10.1038/nature08898
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100036
PM 20220841
DA 2026-03-09
ER

PT J
AU Cooper, OR
   Parrish, DD
   Stohl, A
   Trainer, M
   Nédélec, P
   Thouret, V
   Cammas, JP
   Oltmans, SJ
   Johnson, BJ
   Tarasick, D
   Leblanc, T
   McDermid, IS
   Jaffe, D
   Gao, R
   Stith, J
   Ryerson, T
   Aikin, K
   Campos, T
   Weinheimer, A
   Avery, MA
AF Cooper, O. R.
   Parrish, D. D.
   Stohl, A.
   Trainer, M.
   Nedelec, P.
   Thouret, V.
   Cammas, J. P.
   Oltmans, S. J.
   Johnson, B. J.
   Tarasick, D.
   Leblanc, T.
   McDermid, I. S.
   Jaffe, D.
   Gao, R.
   Stith, J.
   Ryerson, T.
   Aikin, K.
   Campos, T.
   Weinheimer, A.
   Avery, M. A.
TI Increasing springtime ozone mixing ratios in the free troposphere over western North America
SO NATURE
LA English
DT Article
ID long-term changes; surface ozone; asian emissions; united-states; aircraft; climatology; transport; pollution; trends
AB In the lowermost layer of the atmosphere-the troposphere-ozone is an important source of the hydroxyl radical, an oxidant that breaks down most pollutants and some greenhouse gases(1). High concentrations of tropospheric ozone are toxic, however, and have a detrimental effect on human health and ecosystem productivity(1). Moreover, tropospheric ozone itself acts as an effective greenhouse gas(2). Much of the present tropospheric ozone burden is a consequence of anthropogenic emissions of ozone precursors(3) resulting in widespread increases in ozone concentrations since the late 1800s(3-7). At present, east Asia has the fastest-growing ozone precursor emissions(8). Much of the springtime east Asian pollution is exported eastwards towards western North America(9). Despite evidence that the exported Asian pollution produces ozone(10), no previous study has found a significant increase in free tropospheric ozone concentrations above the western USA since measurements began in the late 1970s(5,11,12). Here we compile springtime ozone measurements from many different platforms across western North America. We show a strong increase in springtime ozone mixing ratios during 1995-2008 and we have some additional evidence that a similar rate of increase in ozone mixing ratio has occurred since 1984. We find that the rate of increase in ozone mixing ratio is greatest when measurements are more heavily influenced by direct transport from Asia. Our result agrees with previous modelling studies, which indicate that global ozone concentrations should be increasing during the early part of the twenty-first century as a result of increasing precursor emissions, especially at northern mid-latitudes(13), with western North America being particularly sensitive to rising Asian emissions(14). We suggest that the observed increase in springtime background ozone mixing ratio may hinder the USA's compliance with its ozone air quality standard.
C1 [Cooper, O. R.; Aikin, K.] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Cooper, O. R.; Parrish, D. D.; Trainer, M.; Oltmans, S. J.; Johnson, B. J.; Gao, R.; Ryerson, T.; Aikin, K.] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Stohl, A.] Norwegian Inst Air Res, Dept Reg & Global Pollut Issues, N-2027 Kjeller, Norway.
   [Nedelec, P.; Thouret, V.; Cammas, J. P.] Observ Midi Pyrenees, CNRS, Lab Aerol, F-31400 Toulouse, France.
   [Tarasick, D.] Environm Canada, Meteorol Serv Canada, Expt Studies Res Div, Downsview, ON M3H 5T4, Canada.
   [Leblanc, T.; McDermid, I. S.] CALTECH, Jet Prop Lab, Table Mt Facil, Wrightwood, CA 92397 USA.
   [Jaffe, D.] Univ Washington, Dept Atmospher & Environm Chem, Bothell, WA 98011 USA.
   [Stith, J.] Natl Ctr Atmospher Res, Res Aviat Facil, Broomfield, CO 80021 USA.
   [Campos, T.; Weinheimer, A.] Natl Ctr Atmospher Res, Div Atmospher Chem, Boulder, CO 80305 USA.
   [Avery, M. A.] NASA, Langley Res Ctr, Hampton, VA 23681 USA.
C3 University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA; NILU; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); LAERO; Environment & Climate Change Canada; Meteorological Service of Canada; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of Washington; University of Washington Bothell; National Center Atmospheric Research (NCAR) - USA; National Center Atmospheric Research (NCAR) - USA; National Aeronautics & Space Administration (NASA); NASA Langley Research Center
RP Cooper, OR (corresponding author), Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
EM owen.r.cooper@noaa.gov
FU NOAA; European Communities; EADS; National Science Foundation
NR 31
TC 335
Z9 386
U1 1
U2 253
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 344
EP 348
DI 10.1038/nature08708
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100041
PM 20090751
DA 2026-03-09
ER

PT J
AU Jiang, LH
   Fan, XH
   Brandt, WN
   Carilli, CL
   Egami, E
   Hines, DC
   Kurk, JD
   Richards, GT
   Shen, Y
   Strauss, MA
   Vestergaard, M
   Walter, F
AF Jiang, Linhua
   Fan, Xiaohui
   Brandt, W. N.
   Carilli, Chris L.
   Egami, Eiichi
   Hines, Dean C.
   Kurk, Jaron D.
   Richards, Gordon T.
   Shen, Yue
   Strauss, Michael A.
   Vestergaard, Marianne
   Walter, Fabian
TI Dust-free quasars in the early Universe
SO NATURE
LA English
DT Article
ID black-hole masses; near-infrared spectroscopy; z-similar-to-6 quasars; energy-distributions; evolution; galaxy; emission; sample
AB The most distant quasars known, at redshifts z approximate to 6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands(1-3). This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z approximate to 6 quasar was shown not to have any detectable emission from hot dust(4), but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z approximate to 6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z approximate to 6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.
C1 [Jiang, Linhua; Fan, Xiaohui; Egami, Eiichi; Vestergaard, Marianne] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Fan, Xiaohui; Kurk, Jaron D.; Walter, Fabian] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Brandt, W. N.] Penn State Univ, Dept Astron & Astrophys, Davey Lab 525, University Pk, PA 16802 USA.
   [Carilli, Chris L.] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Hines, Dean C.] Space Sci Inst, Boulder, CO 80301 USA.
   [Kurk, Jaron D.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Richards, Gordon T.] Drexel Univ, Dept Phys, Philadelphia, PA 19104 USA.
   [Shen, Yue] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Strauss, Michael A.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Vestergaard, Marianne] Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
C3 University of Arizona; Max Planck Society; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; National Radio Astronomy Observatory (NRAO); Max Planck Society; Drexel University; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; Princeton University; University of Copenhagen; Niels Bohr Institute
RP Jiang, LH (corresponding author), Univ Arizona, Steward Observ, 933 N Cherry Ave, Tucson, AZ 85721 USA.
EM ljiang@email.arizona.edu
FU NASA; JPL/Caltech; NSF AST; Packard Fellowship; John Simon Guggenheim Memorial Fellowship; NASA ADP; Max-Planck-Gesellschaft; Humboldt-Stiftung; DFG; Danish National Research Foundation.
NR 30
TC 95
Z9 103
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 MAR 18
PY 2010
VL 464
IS 7287
BP 380
EP 383
DI 10.1038/nature08877
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100039
PM 20237563
DA 2026-03-09
ER

PT J
AU Olsen, SK
   Capili, AD
   Lu, XQ
   Tan, DS
   Lima, CD
AF Olsen, Shaun K.
   Capili, Allan D.
   Lu, Xuequan
   Tan, Derek S.
   Lima, Christopher D.
TI Active site remodelling accompanies thioester bond formation in the SUMO E1
SO NATURE
LA English
DT Article
ID ubiquitin-activating enzyme; mechanistic insights; protein modification
AB E1 enzymes activate ubiquitin (Ub) and ubiquitin-like (Ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the E1 Cys domain. The structural basis for these intermediates remains unknown. Here we report crystal structures for human SUMO E1 in complex with SUMO adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 angstrom, respectively. These structures show that side chain contacts to ATP.Mg are released after adenylation to facilitate a 130 degree rotation of the Cys domain during thioester bond formation that is accompanied by remodelling of key structural elements including the helix that contains the E1 catalytic cysteine, the crossover and re-entry loops, and refolding of two helices that are required for adenylation. These changes displace side chains required for adenylation with side chains required for thioester bond formation. Mutational and biochemical analyses indicate these mechanisms are conserved in other E1s.
C1 [Lu, Xuequan; Tan, Derek S.] Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
   [Olsen, Shaun K.; Capili, Allan D.; Lima, Christopher D.] Sloan Kettering Inst, Struct Biol Program, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Tan, DS (corresponding author), Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
EM tand@mskcc.org; limac@mskcc.org
FU NCRR at the NIH [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]; NIH [R01 AI068038, R01 GM065872, F32 GM075695]; NYSTAR Watson Investigator Program; Rita Allen Foundation
NR 33
TC 174
Z9 220
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 906
EP U77
DI 10.1038/nature08765
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700037
PM 20164921
DA 2026-03-09
ER

PT J
AU Li, JF
   Huang, YF
   Ding, Y
   Yang, ZL
   Li, SB
   Zhou, XS
   Fan, FR
   Zhang, W
   Zhou, ZY
   Wu, DY
   Ren, B
   Wang, ZL
   Tian, ZQ
AF Li, Jian Feng
   Huang, Yi Fan
   Ding, Yong
   Yang, Zhi Lin
   Li, Song Bo
   Zhou, Xiao Shun
   Fan, Feng Ru
   Zhang, Wei
   Zhou, Zhi You
   Wu, De Yin
   Ren, Bin
   Wang, Zhong Lin
   Tian, Zhong Qun
TI Shell-isolated nanoparticle-enhanced Raman spectroscopy
SO NATURE
LA English
DT Article
ID single molecules; scattering; nanostructures; sers; dna
AB Surface-enhanced Raman scattering (SERS) is a powerful spectroscopy technique that can provide non-destructive and ultrasensitive characterization down to single molecular level, comparable to single-molecule fluorescence spectroscopy(1-15). However, generally substrates based on metals such as Ag, Au and Cu, either with roughened surfaces or in the form of nanoparticles, are required to realise a substantial SERS effect, and this has severely limited the breadth of practical applications of SERS. A number of approaches have extended the technique to non-traditional substrates(14,16,17), most notably tip-enhanced Raman spectroscopy (TERS)(18-20) where the probed substance (molecule or material surface) can be on a generic substrate and where a nanoscale gold tip above the substrate acts as the Raman signal amplifier. The drawback is that the total Raman scattering signal from the tip area is rather weak, thus limiting TERS studies to molecules with large Raman cross-sections. Here, we report an approach, which we name shell-isolated nanoparticle-enhanced Raman spectroscopy, in which the Raman signal amplification is provided by gold nanoparticles with an ultrathin silica or alumina shell. A monolayer of such nanoparticles is spread as 'smart dust' over the surface that is to be probed. The ultrathin coating keeps the nanoparticles from agglomerating, separates them from direct contact with the probed material and allows the nanoparticles to conform to different contours of substrates. High-quality Raman spectra were obtained on various molecules adsorbed at Pt and Au single-crystal surfaces and from Si surfaces with hydrogen monolayers. These measurements and our studies on yeast cells and citrus fruits with pesticide residues illustrate that our method significantly expands the flexibility of SERS for useful applications in the materials and life sciences, as well as for the inspection of food safety, drugs, explosives and environment pollutants.
C1 [Li, Jian Feng; Huang, Yi Fan; Yang, Zhi Lin; Li, Song Bo; Zhou, Xiao Shun; Fan, Feng Ru; Zhang, Wei; Zhou, Zhi You; Wu, De Yin; Ren, Bin; Tian, Zhong Qun] Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
   [Li, Jian Feng; Huang, Yi Fan; Yang, Zhi Lin; Li, Song Bo; Zhou, Xiao Shun; Fan, Feng Ru; Zhang, Wei; Zhou, Zhi You; Wu, De Yin; Ren, Bin; Tian, Zhong Qun] Xiamen Univ, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China.
   [Ding, Yong; Fan, Feng Ru; Wang, Zhong Lin] Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
C3 Xiamen University; Xiamen University; University System of Georgia; Georgia Institute of Technology
RP Tian, ZQ (corresponding author), Xiamen Univ, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
EM zhong.wang@mse.gatech.edu; zqtian@xmu.edu.cn
FU MOST, China [2009CB930703, 2007DFC40440, 2007CB935603]; NSF of China [20620130427, 20533040]; BES DOE [DE-FG02-07ER46394]; US NSF [DMS 0706436, CMMI 0403671]
NR 30
TC 3277
Z9 3580
U1 77
U2 5715
PU NATURE PUBLISHING 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 18
PY 2010
VL 464
IS 7287
BP 392
EP 395
DI 10.1038/nature08907
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100042
PM 20237566
DA 2026-03-09
ER

PT J
AU Ratje, AH
   Loerke, J
   Mikolajka, A
   Brünner, M
   Hildebrand, PW
   Starosta, AL
   Dönhöfer, A
   Connell, SR
   Fucini, P
   Mielke, T
   Whitford, PC
   Onuchic, JN
   Yu, YN
   Sanbonmatsu, KY
   Hartmann, RK
   Penczek, PA
   Wilson, DN
   Spahn, CMT
AF Ratje, Andreas H.
   Loerke, Justus
   Mikolajka, Aleksandra
   Bruenner, Matthias
   Hildebrand, Peter W.
   Starosta, Agata L.
   Doenhoefer, Alexandra
   Connell, Sean R.
   Fucini, Paola
   Mielke, Thorsten
   Whitford, Paul C.
   Onuchic, Jose N.
   Yu, Yanan
   Sanbonmatsu, Karissa Y.
   Hartmann, Roland K.
   Penczek, Pawel A.
   Wilson, Daniel N.
   Spahn, Christian M. T.
TI Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites
SO NATURE
LA English
DT Article
ID electron-microscopy; molecular-dynamics; conformational-changes; intermediate states; messenger-rna; 70s ribosome; translation; mechanism; movement; gtp
AB The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A site(1,2). The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner(3). Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P site) on the 30S head and simultaneously establishes interaction with the exit site (E site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process.
C1 [Ratje, Andreas H.; Loerke, Justus; Bruenner, Matthias; Hildebrand, Peter W.; Mielke, Thorsten; Spahn, Christian M. T.] Charite, Inst Med Phys & Biophys, D-10117 Berlin, Germany.
   [Ratje, Andreas H.; Hartmann, Roland K.] Univ Marburg, Inst Pharmazeut Chem, D-35037 Marburg, Germany.
   [Mikolajka, Aleksandra; Starosta, Agata L.; Doenhoefer, Alexandra; Wilson, Daniel N.] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Mikolajka, Aleksandra; Starosta, Agata L.; Doenhoefer, Alexandra; Wilson, Daniel N.] Univ Munich, Dept Biochem, D-81377 Munich, Germany.
   [Mikolajka, Aleksandra; Wilson, Daniel N.] Univ Munich, Ctr Integrated Prot Sci, D-81377 Munich, Germany.
   [Connell, Sean R.; Fucini, Paola] Goethe Univ Frankfurt, Inst Organ Chem & Chem Biol, Frankfurt Inst Mol Life Sci, D-60438 Frankfurt, Germany.
   [Mielke, Thorsten] Max Planck Inst Mol Genet, UltraStrukturNetzwerk, D-14195 Berlin, Germany.
   [Whitford, Paul C.; Sanbonmatsu, Karissa Y.] Los Alamos Natl Lab, Div Theoret, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA.
   [Onuchic, Jose N.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA.
   [Onuchic, Jose N.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Yu, Yanan] Florida State Univ, Dept Comp Sci, Tallahassee, FL 32306 USA.
   [Penczek, Pawel A.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Philipps University Marburg; University of Munich; University of Munich; University of Munich; Goethe University Frankfurt; Max Planck Society; United States Department of Energy (DOE); Los Alamos National Laboratory; University of California System; University of California San Diego; University of California System; University of California San Diego; State University System of Florida; Florida State University; University of Texas System; University of Texas Health Science Center Houston
RP Spahn, CMT (corresponding author), Charite, Inst Med Phys & Biophys, Ziegelstr 5-9, D-10117 Berlin, Germany.
EM wilson@lmb.uni-muenchen.de; christian.spahn@charite.de
FU Deutsche Forschungsgemeinschaft (DFG) [SFB 740 TP A3, TP Z1, SP 1130/2-1, FU579 1-3, HA 1672/7-5, WI3285/1-1]; European Union 3D-EM Network of Excellence; European Union and Senatsverwaltung fur Wissenschaft, Forschung und Kultur Berlin (UltraStructureNetwork, Anwenderzentrum); US National Institutes of Health (NIH) [GM 60635]; Goethe University Frankfurt (DFG) [EXC 115]; Human Frontiers of Science Program [HFSP67/07]; LANL; National Science Foundation (NSF) [PHY-0822283]; NIH [R01-GM072686]; National Institute of General Medical Sciences [R01GM072686] Funding Source: NIH RePORTER
NR 42
TC 298
Z9 370
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 2
PY 2010
VL 468
IS 7324
BP 713
EP U143
DI 10.1038/nature09547
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700045
PM 21124459
DA 2026-03-09
ER

PT J
AU Reiter, NJ
   Osterman, A
   Torres-Larios, A
   Swinger, KK
   Pan, T
   Mondragón, A
AF Reiter, Nicholas J.
   Osterman, Amy
   Torres-Larios, Alfredo
   Swinger, Kerren K.
   Pan, Tao
   Mondragon, Alfonso
TI Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA
SO NATURE
LA English
DT Article
ID precursor transfer-rna; crystal-structure; escherichia-coli; 2-metal-ion mechanism; thermotoga-maritima; protein-component; conserved core; binding-site; active-site; substrate
AB Ribonuclease (RNase) P is the universal ribozyme responsible for 5'-end tRNA processing. We report the crystal structure of the Thermotoga maritima RNase P holoenzyme in complex with tRNA(Phe). The 154 kDa complex consists of a large catalytic RNA (P RNA), a small protein cofactor and a mature tRNA. The structure shows that RNA-RNA recognition occurs through shape complementarity, specific intermolecular contacts and base-pairing interactions. Soaks with a pre-tRNA 5' leader sequence with and without metal help to identify the 5' substrate path and potential catalytic metal ions. The protein binds on top of a universally conserved structural module in P RNA and interacts with the leader, but not with the mature tRNA. The active site is composed of phosphate backbone moieties, a universally conserved uridine nucleobase, and at least two catalytically important metal ions. The active site structure and conserved RNase P-tRNA contacts suggest a universal mechanism of catalysis by RNase P.
C1 [Reiter, Nicholas J.; Osterman, Amy; Torres-Larios, Alfredo; Swinger, Kerren K.; Mondragon, Alfonso] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
   [Pan, Tao] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 Northwestern University; University of Chicago
RP Mondragón, A (corresponding author), Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
EM a-mondragon@northwestern.edu
FU NIH
NR 50
TC 248
Z9 310
U1 1
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 784
EP 789
DI 10.1038/nature09516
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700037
PM 21076397
DA 2026-03-09
ER

PT J
AU Xie, T
AF Xie, Tao
TI Tunable polymer multi-shape memory effect
SO NATURE
LA English
DT Article
ID biomedical applications; nanocomposites; networks; degradation; recovery; ionomers
AB Shape memory polymers are materials that can memorize temporary shapes and revert to their permanent shape upon exposure to an external stimulus such as heat(1), light(2,3), moisture(4) or magnetic field(5). Such properties have enabled a variety of applications including deployable space structures(6), biomedical devices(7,8), adaptive optical devices(9), smart dry adhesives(10) and fasteners(11). The ultimate potential for a shape memory polymer, however, is limited by the number of temporary shapes it can memorize in each shape memory cycle and the ability to tune the shape memory transition temperature(s) for the targeted applications. Currently known shape memory polymers are capable of memorizing one or two temporary shapes, corresponding to dual-and triple-shape memory effects (also counting the permanent shape), respectively(11-13). At the molecular level, the maximum number of temporary shapes a shape memory polymer can memorize correlates directly to the number of discrete reversible phase transitions (shape memory transitions) in the polymer(11-13). Intuitively, one might deduce that multi-shape memory effects are achievable simply by introducing additional reversible phase transitions. The task of synthesizing a polymer with more than two distinctive and strongly bonded(13) reversible phases, however, is extremely challenging. Tuning shape memory effects, on the other hand, is often achieved through tailoring the shape memory transition temperatures, which requires alteration in the material composition(14-16). Here I show that the perfluoro sulphonic acid ionomer (PFSA), which has only one broad reversible phase transition, exhibits dual-, triple-, and at least quadruple-shape memory effects, all highly tunable without any change to the material composition.
C1 Gen Motors Res & Dev Ctr, Chem Sci & Mat Syst Lab, Warren, MI 48090 USA.
C3 General Motors
RP Xie, T (corresponding author), Gen Motors Res & Dev Ctr, Chem Sci & Mat Syst Lab, Mail Code 480-106-710,30500 Mound Rd, Warren, MI 48090 USA.
EM tao.xie@gm.com
NR 28
TC 1232
Z9 1374
U1 20
U2 1386
PU 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 11
PY 2010
VL 464
IS 7286
BP 267
EP 270
DI 10.1038/nature08863
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100044
PM 20220846
DA 2026-03-09
ER

PT J
AU Thomson, SN
   Brandon, MT
   Tomkin, JH
   Reiners, PW
   Vásquez, C
   Wilson, NJ
AF Thomson, Stuart N.
   Brandon, Mark T.
   Tomkin, Jonathan H.
   Reiners, Peter W.
   Vasquez, Cristian
   Wilson, Nathaniel J.
TI Glaciation as a destructive and constructive control on mountain building
SO NATURE
LA English
DT Article
ID patagonian andes; tectonic evolution; climate; erosion; uplift; transect; belts; chile
AB Theoretical analysis predicts that enhanced erosion related to late Cenozoic global cooling can act as a first-order influence on the internal dynamics of mountain building, leading to a reduction in orogen width and height(1-3). The strongest response is predicted in orogens dominated by highly efficient alpine glacial erosion, producing a characteristic pattern of enhanced erosion on the windward flank of the orogen and maximum elevation controlled by glacier equilibriumline altitude(3,4), where long-term glacier mass gain equals mass loss. However, acquiring definitive field evidence of an active tectonic response to global climate cooling has been elusive(5). Here we present an extensive new low-temperature thermochronologic data set from the Patagonian Andes, a high-latitude active orogen with a well-documented late Cenozoic tectonic, climatic and glacial history. Data from 38 degrees S to 49 degrees S record a marked acceleration in erosion 7 to 5 Myr ago coeval with the onset of major Patagonian glaciation(6) and retreat of deformation from the easternmost thrust front(7). The highest rates and magnitudes of erosion are restricted to the glacial equilibrium line altitude on the windward western flank of the orogen, as predicted in models of glaciated critical taper orogens where erosion rate is a function of ice sliding velocity(3,8). In contrast, towards higher latitudes (49 degrees S to 56 degrees S) a transition to older bedrock cooling ages signifies much reduced late Cenozoic erosion despite dominantly glacial conditions here since the latest Miocene(6). The increased height of the orogenic divide at these latitudes (well above the equilibrium line altitude) leads us to conclude that the southernmost Patagonian Andes represent the first recognized example of regional glacial protection of an active orogen from erosion, leading to constructive growth in orogen height and width.
C1 [Thomson, Stuart N.; Reiners, Peter W.] Univ Arizona, Dept Geosci, Tucson, AZ 85271 USA.
   [Thomson, Stuart N.; Brandon, Mark T.; Wilson, Nathaniel J.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
   [Vasquez, Cristian] Univ Chile, Dept Geol, Santiago, Chile.
   [Tomkin, Jonathan H.] Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
C3 University of Arizona; Yale University; Universidad de Chile; University of Illinois System; University of Illinois Urbana-Champaign
RP Thomson, SN (corresponding author), Univ Arizona, Dept Geosci, Tucson, AZ 85271 USA.
EM thomson@email.arizona.edu
FU NSF [EAR0447140]; Chilean Fondecyt awards [1010412, 1050431, 7010412, 7060240]; Division Of Earth Sciences; Directorate For Geosciences [0732380] Funding Source: National Science Foundation
NR 30
TC 215
Z9 245
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 SEP 16
PY 2010
VL 467
IS 7313
BP 313
EP 317
DI 10.1038/nature09365
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900036
PM 20844534
DA 2026-03-09
ER

PT J
AU Blois, JL
   McGuire, JL
   Hadly, EA
AF Blois, Jessica L.
   McGuire, Jenny L.
   Hadly, Elizabeth A.
TI Small mammal diversity loss in response to late-Pleistocene climatic change
SO NATURE
LA English
DT Article
ID radiocarbon calibration; community; fire
AB Communities have been shaped in numerous ways by past climatic change; this process continues today(1). At the end of the Pleistocene epoch about 11,700 years ago, North American communities were substantially altered by the interplay of two events. The climate shifted from the cold, arid Last Glacial Maximum to the warm, mesic Holocene interglacial, causing many mammal species to shift their geographic distributions substantially(2,3). Populations were further stressed as humans arrived on the continent(4). The resulting megafaunal extinction event, in which 70 of the roughly 220 largest mammals in North America (32%) became extinct 5, has received much attention. However, responses of small mammals to events at the end of the Pleistocene have been much less studied, despite the sensitivity of these animals to current and future environmental change. Here we examine community changes in small mammals in northern California during the last 'natural' global warming event at the Pleistocene-Holocene transition and show that even though no small mammals in the local community became extinct, species losses and gains, combined with changes in abundance, caused declines in both the evenness and richness of communities. Modern mammalian communities are thus depauperate not only as a result of megafaunal extinctions at the end of the Pleistocene but also because of diversity loss among small mammals. Our results suggest that across future landscapes there will be some unanticipated effects of global change on diversity: restructuring of small mammal communities, significant loss of richness, and perhaps the rising dominance of native 'weedy' species.
C1 [Blois, Jessica L.; Hadly, Elizabeth A.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [McGuire, Jenny L.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
C3 Stanford University; University of California System; University of California Berkeley
RP Blois, JL (corresponding author), Univ Wisconsin, Ctr Climat Res, 1225 W Dayton St, Madison, WI 53706 USA.
EM blois@wisc.edu
FU National Science Foundation [EAR-0545648, EAR-0719429]; California Energy Commission; Stanford University Vice Provost for Undergraduate Education; US Forest Service
NR 42
TC 200
Z9 234
U1 1
U2 132
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 771
EP U5
DI 10.1038/nature09077
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800043
PM 20495547
DA 2026-03-09
ER

PT J
AU Banci, L
   Bertini, I
   Ciofi-Baffoni, S
   Kozyreva, T
   Zovo, K
   Palumaa, P
AF Banci, Lucia
   Bertini, Ivano
   Ciofi-Baffoni, Simone
   Kozyreva, Tatiana
   Zovo, Kairit
   Palumaa, Peep
TI Affinity gradients drive copper to cellular destinations
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; menkes-disease protein; superoxide-dismutase; zinc-binding; chaperone; domain; cox17; mechanism; atp7a; metallothionein
AB Copper is an essential trace element for eukaryotes and most prokaryotes(1). However, intracellular free copper must be strictly limited because of its toxic side effects. Complex systems for copper trafficking evolved to satisfy cellular requirements while minimizing toxicity(2). The factors driving the copper transfer between protein partners along cellular copper routes are, however, not fully rationalized. Until now, inconsistent, scattered and incomparable data on the copper-binding affinities of copper proteins have been reported. Here we determine, through a unified electrospray ionization mass spectrometry (ESI-MS)-based strategy, in an environment that mimics the cellular redox milieu, the apparent Cu(I)-binding affinities for a representative set of intracellular copper proteins involved in enzymatic redox catalysis, in copper trafficking to and within various cellular compartments, and in copper storage. The resulting thermodynamic data show that copper is drawn to the enzymes that require it by passing from one copper protein site to another, exploiting gradients of increasing copper-binding affinity. This result complements the finding that fast copper-transfer pathways require metal-mediated protein-protein interactions and therefore protein-protein specific recognition(3). Together with Cu, Zn-SOD1, metallothioneins have the highest affinity for copper(I), and may play special roles in the regulation of cellular copper distribution; however, for kinetic reasons they cannot demetallate copper enzymes. Our study provides the thermodynamic basis for the kinetic processes that lead to the distribution of cellular copper.
C1 [Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone; Kozyreva, Tatiana] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Florence, Italy.
   [Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone; Kozyreva, Tatiana] Univ Florence, Dept Chem, I-50019 Florence, Italy.
   [Zovo, Kairit; Palumaa, Peep] Tallinn Univ Technol, Dept Gene Technol, EE-12618 Tallinn, Estonia.
C3 University of Florence; University of Florence; Tallinn University of Technology
RP Bertini, I (corresponding author), Univ Florence, Magnet Resonance Ctr CERM, Via Luigi Sacconi 6, I-50019 Florence, Italy.
EM ivanobertini@cerm.unifi.it; peepp@staff.ttu.ee
FU Estonian Science Foundation [7191]; Estonian Ministry of Education and Research [SF0140055s08]; SPINE-II-COMPLEXES [LSHG-CT-2006-031220]; FIRB PROTEOMICA MIUR [RBRN07BMCT]; World Federation of Scientists; National Health and Medical Research Council (NHMRC) [7191] Funding Source: National Health and Medical Research Council (NHMRC)
NR 37
TC 428
Z9 491
U1 1
U2 152
PU 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 3
PY 2010
VL 465
IS 7298
BP 645
EP U145
DI 10.1038/nature09018
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000048
PM 20463663
DA 2026-03-09
ER

PT J
AU Henneberger, C
   Papouin, T
   Oliet, SHR
   Rusakov, DA
AF Henneberger, Christian
   Papouin, Thomas
   Oliet, Stephane H. R.
   Rusakov, Dmitri A.
TI Long-term potentiation depends on release of D-serine from astrocytes
SO NATURE
LA English
DT Article
ID glutamate release; synaptic-transmission; transporter currents; receptor activation; glycine site; in-situ; calcium; hippocampus; synapses; brain
AB Long-term potentiation (LTP) of synaptic transmission provides an experimental model for studying mechanisms of memory(1). The classical form of LTP relies on N-methyl-D-aspartate receptors (NMDARs), and it has been shown that astroglia can regulate their activation through Ca2+-dependent release of the NMDAR co-agonist D-serine(2-4). Release of D-serine from glia enables LTP in cultures(5) and explains a correlation between glial coverage of synapses and LTP in the supraoptic nucleus(4). However, increases in Ca2+ concentration in astroglia can also release other signalling molecules, most prominently glutamate(6-8), ATP(9) and tumour necrosis factor-alpha(10,11), whereas neurons themselves can synthesize and supply D-serine(12,13). Furthermore, loading an astrocyte with exogenous Ca2+ buffers does not suppress LTP in hippocampal area CA1 (refs 14-16), and the physiological relevance of experiments in cultures or strong exogenous stimuli applied to astrocytes has been questioned(17,18). The involvement of glia in LTP induction therefore remains controversial. Here we show that clamping internal Ca2+ in individual CA1 astrocytes blocks LTP induction at nearby excitatory synapses by decreasing the occupancy of the NMDAR co-agonist sites. This LTP blockade can be reversed by exogenous D-serine or glycine, whereas depletion of D-serine or disruption of exocytosis in an individual astrocyte blocks local LTP. We therefore demonstrate that Ca2+-dependent release of D-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby.
C1 [Henneberger, Christian; Rusakov, Dmitri A.] UCL, UCL Inst Neurol, London WC1N 3BG, England.
   [Papouin, Thomas; Oliet, Stephane H. R.] INSERM, U862, Neuroctr Magendie, F-33077 Bordeaux, France.
   [Papouin, Thomas; Oliet, Stephane H. R.] Univ Bordeaux, F-33077 Bordeaux, France.
C3 University of London; University College London; Universite de Bordeaux; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux
RP Rusakov, DA (corresponding author), UCL, UCL Inst Neurol, London WC1N 3BG, England.
EM stephane.oliet@inserm.fr; d.rusakov@ion.ucl.ac.uk
FU Human Frontier Science Programme; Wellcome Trust; Medical Research Council (UK); European Union (Promemoria), INSERM, Universite de Bordeaux; Fondation pour la Recherche Medicale; French Ministry of Research; Medical Research Council [G0600368, G0802216, G0900613] Funding Source: researchfish; MRC [G0900613, G0802216, G0600368] Funding Source: UKRI
NR 37
TC 1093
Z9 1263
U1 0
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 232
EP U120
DI 10.1038/nature08673
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700036
PM 20075918
DA 2026-03-09
ER

PT J
AU Crocker, RM
   Jones, DI
   Melia, F
   Ott, J
   Protheroe, RJ
AF Crocker, Roland M.
   Jones, David I.
   Melia, Fulvio
   Ott, Juergen
   Protheroe, Raymond J.
TI A lower limit of 50 microgauss for the magnetic field near the Galactic Centre
SO NATURE
LA English
DT Article
ID radio-continuum survey; interstellar gas; iron line; emission; plane; galaxy; origin; ridge; ghz; arc
AB The amplitude of the magnetic field near the Galactic Centre has been uncertain by two orders of magnitude for several decades. On a scale of similar to 100 parsecs (pc), fields of similar to 1,000 microgauss (mu G; refs 1-3) have been reported, implying a magnetic energy density more than 10,000 times stronger than typical for the Galaxy. Alternatively, the assumption of pressure equilibrium between the various phases of the Galactic Centre interstellar medium (including turbulent molecular gas, the contested(4) 'very hot' plasma, and the magnetic field) suggests fields of similar to 100 mu G over similar to 400 pc size scales(5). Finally, assuming equipartition, fields of only similar to 6 mu G have been inferred from radio observations(6) for 400 pc scales. Here we report a compilation of previous data that reveals a downward break in the region's non-thermal radio spectrum (attributable to a transition from bremsstrahlung to synchrotron cooling of the in situ cosmic-ray electron population). We show that the spectral break requires that the Galactic Centre field be at least similar to 50 mu G on 400 pc scales, lest the synchrotron-emitting electrons produce too much gamma-ray emission, given other existing constraints(7). Other considerations support a field of 100 mu G, implying that over 10% of the Galaxy's magnetic energy is contained in only less than or similar to 0.05% of its volume.
C1 [Crocker, Roland M.] Monash Univ, Sch Phys, Clayton, Vic 3110, Australia.
   [Crocker, Roland M.; Jones, David I.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Jones, David I.; Protheroe, Raymond J.] Univ Adelaide, Sch Phys & Chem, Dept Phys, Adelaide, SA 5005, Australia.
   [Jones, David I.] Australia Telescope Natl Facil, Marsfield, NSW 2122, Australia.
   [Melia, Fulvio] Univ Arizona, Dept Phys, Program Appl Math, Tucson, AZ 85721 USA.
   [Melia, Fulvio] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Ott, Juergen] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Ott, Juergen] CALTECH, Pasadena, CA 91125 USA.
C3 Monash University; Max Planck Society; Adelaide University; University of Adelaide; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility; University of Arizona; University of Arizona; National Radio Astronomy Observatory (NRAO); California Institute of Technology
RP Crocker, RM (corresponding author), Monash Univ, Sch Phys, Clayton, Vic 3110, Australia.
EM Roland.Crocker@mpi-hd.mpg.de
NR 26
TC 150
Z9 159
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 65
EP 67
DI 10.1038/nature08635
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900030
PM 20054391
DA 2026-03-09
ER

PT J
AU Lee, W
   Jiang, ZS
   Liu, JF
   Haverty, PM
   Guan, YH
   Stinson, J
   Yue, P
   Zhang, Y
   Pant, KP
   Bhatt, D
   Ha, C
   Johnson, S
   Kennemer, MI
   Mohan, S
   Nazarenko, I
   Watanabe, C
   Sparks, AB
   Shames, DS
   Gentleman, R
   de Sauvage, FJ
   Stern, H
   Pandita, A
   Ballinger, DG
   Drmanac, R
   Modrusan, Z
   Seshagiri, S
   Zhang, ZM
AF Lee, William
   Jiang, Zhaoshi
   Liu, Jinfeng
   Haverty, Peter M.
   Guan, Yinghui
   Stinson, Jeremy
   Yue, Peng
   Zhang, Yan
   Pant, Krishna P.
   Bhatt, Deepali
   Ha, Connie
   Johnson, Stephanie
   Kennemer, Michael I.
   Mohan, Sankar
   Nazarenko, Igor
   Watanabe, Colin
   Sparks, Andrew B.
   Shames, David S.
   Gentleman, Robert
   de Sauvage, Frederic J.
   Stern, Howard
   Pandita, Ajay
   Ballinger, Dennis G.
   Drmanac, Radoje
   Modrusan, Zora
   Seshagiri, Somasekar
   Zhang, Zemin
TI The mutation spectrum revealed by paired genome sequences from a lung cancer patient
SO NATURE
LA English
DT Article
ID somatic mutations; gene; identification; rearrangement; expression; pathways; patterns; fusion
AB Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease(1,2). Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum(3-8). Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines(9-13). Here we present the complete sequences of a primary lung tumour (603 coverage) and adjacent normal tissue (463). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.
C1 [Lee, William; Jiang, Zhaoshi; Liu, Jinfeng; Haverty, Peter M.; Yue, Peng; Zhang, Yan; Watanabe, Colin; Gentleman, Robert; Zhang, Zemin] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
   [Guan, Yinghui; Stinson, Jeremy; Pant, Krishna P.; Bhatt, Deepali; de Sauvage, Frederic J.; Modrusan, Zora; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Pant, Krishna P.; Kennemer, Michael I.; Nazarenko, Igor; Sparks, Andrew B.; Ballinger, Dennis G.; Drmanac, Radoje] Complete Genom Inc, Mountain View, CA 94043 USA.
   [Johnson, Stephanie; Stern, Howard] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Mohan, Sankar; Shames, David S.; Pandita, Ajay] Genentech Inc, Dept Oncol Diagnost, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech
RP Zhang, ZM (corresponding author), Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
EM zemin@gene.com
NR 29
TC 398
Z9 528
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 473
EP 477
DI 10.1038/nature09004
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700034
PM 20505728
DA 2026-03-09
ER

PT J
AU Zahn, M
   von Storch, H
AF Zahn, Matthias
   von Storch, Hans
TI Decreased frequency of North Atlantic polar lows associated with future climate warming
SO NATURE
LA English
DT Article
ID cold-air outbreaks; model
AB Every winter, the high-latitude oceans are struck by severe storms that are considerably smaller than the weather-dominating synoptic depressions(1). Accompanied by strong winds and heavy precipitation, these often explosively developing mesoscale cyclones-termed polar lows(1)-constitute a threat to offshore activities such as shipping or oil and gas exploitation. Yet owing to their small scale, polar lows are poorly represented in the observational and global reanalysis data(2) often used for climatological investigations of atmospheric features and cannot be assessed in coarse-resolution global simulations of possible future climates. Here we show that in a future anthropogenically warmed climate, the frequency of polar lows is projected to decline. We used a series of regional climate model simulations to downscale a set of global climate change scenarios(3) from the Intergovernmental Panel of Climate Change. In this process, we first simulated the formation of polar low systems in the North Atlantic and then counted the individual cases. A previous study(4) using NCEP/NCAR re-analysis data(5) revealed that polar low frequency from 1948 to 2005 did not systematically change. Now, in projections for the end of the twenty-first century, we found a significantly lower number of polar lows and a northward shift of their mean genesis region in response to elevated atmospheric greenhouse gas concentration. This change can be related to changes in the North Atlantic sea surface temperature and mid-troposphere temperature; the latter is found to rise faster than the former so that the resulting stability is increased, hindering the formation or intensification of polar lows. Our results provide a rare example of a climate change effect in which a type of extreme weather is likely to decrease, rather than increase.
C1 [Zahn, Matthias] Univ Reading, Environm Syst Sci Ctr, Reading RG6 6AL, Berks, England.
   [Zahn, Matthias; von Storch, Hans] GKSS Forschungszentrum Geesthacht GmbH, Inst Coastal Res Syst Anal & Modelling, D-21502 Geesthacht, Germany.
   [von Storch, Hans] Univ Hamburg, Inst Meteorol, D-20146 Hamburg, Germany.
C3 University of Reading; Helmholtz Association; Helmholtz-Zentrum Hereon; University of Hamburg
RP Zahn, M (corresponding author), Univ Reading, Environm Syst Sci Ctr, 3 Earley Gate, Reading RG6 6AL, Berks, England.
EM matthias.zahn@gkss.de
FU DFG [512]; International Detection and Attribution Group (IDAG); DoE; NERC [NE/G015708/1] Funding Source: UKRI; Natural Environment Research Council [NE/G015708/1] Funding Source: researchfish
NR 30
TC 97
Z9 109
U1 1
U2 43
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 309
EP 312
DI 10.1038/nature09388
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900035
PM 20844533
DA 2026-03-09
ER

PT J
AU Rao, P
   Hayden, MS
   Long, MX
   Scott, ML
   West, AP
   Zhang, DK
   Oeckinghaus, A
   Lynch, C
   Hoffmann, A
   Baltimore, D
   Ghosh, S
AF Rao, Ping
   Hayden, Mathew S.
   Long, Meixiao
   Scott, Martin L.
   West, A. Philip
   Zhang, Dekai
   Oeckinghaus, Andrea
   Lynch, Candace
   Hoffmann, Alexander
   Baltimore, David
   Ghosh, Sankar
TI IκBβ acts to inhibit and activate gene expression during the inflammatory response
SO NATURE
LA English
DT Article
ID tumor necrosis factor; c-rel; rheumatoid-arthritis; deficient mice; dna-binding; alpha; phosphorylation; biosynthesis; similarity; sequences
AB The activation of pro-inflammatory gene programs by nuclear factor-kappa B (NF-kappa B) is primarily regulated through cytoplasmic sequestration of NF-kappa B by the inhibitor of kappa B (I kappa B) family of proteins(1). I kappa B beta, a major isoform of I kappa B, can sequester NF-kappa B in the cytoplasm(2), although its biological role remains unclear. Although cells lacking IkBb have been reported(3,4), in vivo studies have been limited and suggested redundancy between I kappa B alpha and I kappa B beta(5). Like I kappa B alpha, I kappa B beta is also inducibly degraded; however, upon stimulation by lipopolysaccharide (LPS), it is degraded slowly and re-synthesized as a hypophosphorylated form that can be detected in the nucleus(6-11). The crystal structure of I kappa B beta bound to p65 suggested this complex might bind DNA(12). In vitro, hypophosphorylated I kappa B beta can bind DNA with p65 and c-Rel, and the DNA-bound NF-kappa B:I kappa B beta complexes are resistant to I kappa B alpha, suggesting hypophosphorylated, nuclear I kappa B beta may prolong the expression of certain genes(9-11). Here we report that in vivo I kappa B beta serves both to inhibit and facilitate the inflammatory response. I kappa B beta degradation releases NF-kappa B dimers which upregulate proinflammatory target genes such as tumour necrosis factor-alpha (TNF-alpha). Surprisingly, absence of I kappa B beta results in a dramatic reduction of TNF-alpha in response to LPS even though activation of NF-kappa B is normal. The inhibition of TNF-alpha messenger RNA (mRNA) expression correlates with the absence of nuclear, hypophosphorylated-I kappa B beta bound to p65:c-Rel heterodimers at a specific kappa B site on the TNF-alpha promoter. Therefore I kappa B beta acts through p65:c-Rel dimers to maintain prolonged expression of TNF-alpha. As a result, I kappa B beta(-/-) mice are resistant to LPS-induced septic shock and collagen-induced arthritis. Blocking I kappa B beta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha production during the inflammatory response.
C1 [Rao, Ping; Hayden, Mathew S.; Long, Meixiao; West, A. Philip; Zhang, Dekai; Oeckinghaus, Andrea; Ghosh, Sankar] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Rao, Ping; Hayden, Mathew S.; Long, Meixiao; West, A. Philip; Zhang, Dekai; Oeckinghaus, Andrea; Ghosh, Sankar] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Hayden, Mathew S.; Long, Meixiao; Oeckinghaus, Andrea; Ghosh, Sankar] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
   [Scott, Martin L.; Baltimore, David] CALTECH, Dept Biol, Pasadena, CA 91125 USA.
   [Lynch, Candace; Hoffmann, Alexander] Univ Calif San Diego, Signaling Syst Lab, Dept Chem & Biochem, La Jolla, CA 92093 USA.
C3 Yale University; Yale University; Columbia University; California Institute of Technology; University of California System; University of California San Diego
RP Ghosh, S (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
EM sg2715@columbia.edu
FU National Institutes of Health [R37-AI03343]
NR 30
TC 165
Z9 194
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1115
EP U132
DI 10.1038/nature09283
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600042
PM 20740013
DA 2026-03-09
ER

PT J
AU Paterson, S
   Vogwill, T
   Buckling, A
   Benmayor, R
   Spiers, AJ
   Thomson, NR
   Quail, M
   Smith, F
   Walker, D
   Libberton, B
   Fenton, A
   Hall, N
   Brockhurst, MA
AF Paterson, Steve
   Vogwill, Tom
   Buckling, Angus
   Benmayor, Rebecca
   Spiers, Andrew J.
   Thomson, Nicholas R.
   Quail, Mike
   Smith, Frances
   Walker, Danielle
   Libberton, Ben
   Fenton, Andrew
   Hall, Neil
   Brockhurst, Michael A.
TI Antagonistic coevolution accelerates molecular evolution
SO NATURE
LA English
DT Article
ID local adaptation; bacteria; phage
AB The Red Queen hypothesis proposes that coevolution of interacting species (such as hosts and parasites) should drive molecular evolution through continual natural selection for adaptation and counter-adaptation(1-3). Although the divergence observed at some host-resistance(4-6) and parasite-infectivity(7-9) genes is consistent with this, the long time periods typically required to study coevolution have so far prevented any direct empirical test. Here we show, using experimental populations of the bacterium Pseudomonas fluorescens SBW25 and its viral parasite, phage Phi 2 (refs 10, 11), that the rate of molecular evolution in the phage was far higher when both bacterium and phage coevolved with each other than when phage evolved against a constant host genotype. Coevolution also resulted in far greater genetic divergence between replicate populations, which was correlated with the range of hosts that coevolved phage were able to infect. Consistent with this, the most rapidly evolving phage genes under coevolution were those involved in host infection. These results demonstrate, at both the genomic and phenotypic level, that antagonistic coevolution is a cause of rapid and divergent evolution, and is likely to be a major driver of evolutionary change within species.
C1 [Paterson, Steve; Vogwill, Tom; Libberton, Ben; Fenton, Andrew; Hall, Neil; Brockhurst, Michael A.] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England.
   [Buckling, Angus; Benmayor, Rebecca] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Spiers, Andrew J.] Univ Abertay Dundee, SIMBIOS Ctr, Dundee DD1 1HG, Scotland.
   [Thomson, Nicholas R.; Quail, Mike; Smith, Frances; Walker, Danielle] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 University of Liverpool; University of Oxford; University of Abertay Dundee; Wellcome Trust Sanger Institute
RP Brockhurst, MA (corresponding author), Univ Liverpool, Sch Biol Sci, Biosci Bldg,Crown St, Liverpool L69 7ZB, Merseyside, England.
EM michael.brockhurst@liverpool.ac.uk
FU Natural Environment Research Council; Wellcome Trust; Leverhulme Trust; European Research Council; Natural Environment Research Council [NBAF010002, NE/F001193/1] Funding Source: researchfish; NERC [NBAF010002, NE/F001193/1] Funding Source: UKRI
NR 27
TC 414
Z9 496
U1 2
U2 305
PU NATURE PUBLISHING 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 11
PY 2010
VL 464
IS 7286
BP 275
EP U154
DI 10.1038/nature08798
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100046
PM 20182425
DA 2026-03-09
ER

PT J
AU Ye, SX
   Zaitseva, E
   Caltabiano, G
   Schertler, GFX
   Sakmar, TP
   Deupi, X
   Vogel, R
AF Ye, Shixin
   Zaitseva, Ekaterina
   Caltabiano, Gianluigi
   Schertler, Gebhard F. X.
   Sakmar, Thomas P.
   Deupi, Xavier
   Vogel, Reiner
TI Tracking G-protein-coupled receptor activation using genetically encoded infrared probes
SO NATURE
LA English
DT Article
ID induced conformational-changes; transmembrane helices; rhodopsin activation; ionic lock; crystallography; spectroscopy; discovery; switches; insights; biology
AB Rhodopsin is a prototypical heptahelical family A G-protein-coupled receptor (GPCR) responsible for dim-light vision(1,2). Light isomerizes rhodopsin's retinal chromophore and triggers concerted movements of transmembrane helices, including an outward tilting of helix 6 (H6) and a smaller movement of H5, to create a site for G-protein binding and activation(3,4). However, the precise temporal sequence and mechanism underlying these helix rearrangements is unclear. We used site-directed non-natural amino acid mutagenesis to engineer rhodopsin with p-azido-L-phenylalanine residues incorporated at selected sites(5), and monitored the azido vibrational signatures using infrared spectroscopy as rhodopsin proceeded along its activation pathway. Here we report significant changes in electrostatic environments of the azido probes even in the inactive photoproduct Meta I, well before the active receptor state was formed. These early changes suggest a significant rotation of H6 and movement of the cytoplasmic part of H5 away from H3. Subsequently, a large outward tilt of H6 leads to opening of the cytoplasmic surface to form the active receptor photoproduct Meta II3. Thus, our results reveal early conformational changes that precede larger rigid-body helix movements, and provide a basis to interpret recent GPCR crystal structures(6,7) and to understand conformational sub-states observed during the activation of other GPCRs(8).
C1 [Zaitseva, Ekaterina; Vogel, Reiner] Univ Freiburg, Inst Mol Med & Cell Res, Biophys Sect, D-79104 Freiburg, Germany.
   [Ye, Shixin; Sakmar, Thomas P.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
   [Caltabiano, Gianluigi; Deupi, Xavier] Univ Autonoma Barcelona, Unitat Bioestadist, Lab Med Computac, Bellaterra 08193, Catalunya, Spain.
   [Schertler, Gebhard F. X.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   [Schertler, Gebhard F. X.] Paul Scherrer Inst, Dept Biol & Chem, Lab Biomol Res, CH-5232 Villigen, Switzerland.
C3 University of Freiburg; Rockefeller University; Autonomous University of Barcelona; MRC Laboratory Molecular Biology; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute
RP Vogel, R (corresponding author), Univ Freiburg, Inst Mol Med & Cell Res, Biophys Sect, Hermann Herder Str 9, D-79104 Freiburg, Germany.
EM sakmar@mail.rockefeller.edu; xavier.deupi@uab.cat; reiner.vogel@biophysik.uni-freiburg.de
FU DFG [Vo 811/4-1, Za 566/2]; C. H. Li Memorial Scholar Award; NIH; Ministerio de Educacion y Ciencia; Instituto de Salud Carlos III
NR 41
TC 226
Z9 258
U1 0
U2 116
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1386
EP U14
DI 10.1038/nature08948
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000054
PM 20383122
DA 2026-03-09
ER

PT J
AU Booth, LN
   Tuch, BB
   Johnson, AD
AF Booth, Lauren N.
   Tuch, Brian B.
   Johnson, Alexander D.
TI Intercalation of a new tier of transcription regulation into an ancient circuit
SO NATURE
LA English
DT Article
ID heterotrimeric g-protein; yeast candida-albicans; cell-cycle arrest; saccharomyces-cerevisiae; kluyveromyces-lactis; gene-expression; evolution; pheromone; identification; meiosis
AB Changes in gene regulatory networks are a major source of evolutionary novelty(1-3). Here we describe a specific type of network rewiring event, one that intercalates a new level of transcriptional control into an ancient circuit. We deduce that, over evolutionary time, the direct ancestral connections between a regulator and its target genes were broken and replaced by indirect connections, preserving the overall logic of the ancestral circuit but producing a new behaviour. The example was uncovered through a series of experiments in three ascomycete yeasts: the bakers' yeast Saccharomyces cerevisiae, the dairy yeast Kluyveromyces lactis and the human pathogen Candida albicans. All three species have three cell types: two mating-competent cell forms (a and alpha) and the product of their mating (a/alpha), which is mating-incompetent. In the ancestral mating circuit, two homeodomain proteins, Mata1 and Mat alpha 2, form a heterodimer that directly represses four genes that are expressed only in a and alpha cells and are required for mating(4-6). In a relatively recent ancestor of K. lactis, a reorganization occurred. The Mata1-Mat alpha 2 heterodimer represses the same four genes (known as the core haploid-specific genes) but now does so indirectly through an intermediate regulatory protein, Rme1. The overall logic of the ancestral circuit is preserved (haploid-specific genes ON in a and alpha cells and OFF in a/alpha cells), but a new phenotype was produced by the rewiring: unlike S. cerevisiae and C. albicans, K. lactis integrates nutritional signals, by means of Rme1, into the decision of whether or not to mate.
C1 [Booth, Lauren N.; Tuch, Brian B.; Johnson, Alexander D.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA.
   [Booth, Lauren N.; Tuch, Brian B.; Johnson, Alexander D.] 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 Johnson, AD (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA.
EM ajohnson@cgl.ucsf.edu
FU National Institutes of Health [RO1 GM037049]; National Institute of General Medical Sciences [R01GM037049] Funding Source: NIH RePORTER
NR 43
TC 61
Z9 87
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 16
PY 2010
VL 468
IS 7326
BP 959
EP U358
DI 10.1038/nature09560
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600046
PM 21164485
DA 2026-03-09
ER

PT J
AU Ide, S
AF Ide, Satoshi
TI Striations, duration, migration and tidal response in deep tremor
SO NATURE
LA English
DT Article
ID slow slip events; non-volcanic tremor; southwest japan; subduction zone; episodic tremor; earthquakes
AB Deep tremor in subduction zones is thought to be caused by small repeating shear slip events on the plate interface with significant slow components(1-4). It occurs at a depth of about 30 kilometres and provides valuable information on deep plate motion and shallow stress accumulation on the fault plane of megathrust earthquakes. Tremor has been suggested to repeat at a regular interval(1,2), migrate at various velocities(4-7) and be modulated by tidal stress(6,8,9). Here I show that some time-invariant interface property controls tremor behaviour, using precise location of tremor sources with event duration in western Shikoku in the Nankai subduction zone, Japan. In areas where tremor duration is short, tremor is more strongly affected by tidal stress and migration is inhibited. Where tremor lasts longer, diffusive migration occurs with a constant diffusivity of 10(4) m(2) s(-1). The control property may be the ratio of brittle to ductile areas, perhaps determined by the influence of mantle wedge serpentinization on the plate interface. The spatial variation of the controlling property seems to be characterized by striations in tremor source distribution, which follows either the current or previous plate subduction directions. This suggests that the striations and corresponding interface properties are formed through the subduction of inhomogeneous structure, such as seamounts, for periods as long as ten million years.
C1 Univ Tokyo, Dept Earth & Planetary Sci, Bunkyo Ku, Tokyo 1130033, Japan.
C3 University of Tokyo
RP Ide, S (corresponding author), Univ Tokyo, Dept Earth & Planetary Sci, Bunkyo Ku, Hongo 7-3-1, Tokyo 1130033, Japan.
EM ide@eps.s.u-tokyo.ac.jp
FU JSPS [20340115]; MEXT [21107007]; Grants-in-Aid for Scientific Research [20340115, 21107007] Funding Source: KAKEN
NR 30
TC 168
Z9 183
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 356
EP U105
DI 10.1038/nature09251
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100046
PM 20631797
DA 2026-03-09
ER

PT J
AU Teslovich, TM
   Musunuru, K
   Smith, AV
   Edmondson, AC
   Stylianou, IM
   Koseki, M
   Pirruccello, JP
   Ripatti, S
   Chasman, DI
   Willer, CJ
   Johansen, CT
   Fouchier, SW
   Isaacs, A
   Peloso, GM
   Barbalic, M
   Ricketts, SL
   Bis, JC
   Aulchenko, YS
   Thorleifsson, G
   Feitosa, MF
   Chambers, J
   Orho-Melander, M
   Melander, O
   Johnson, T
   Li, XH
   Guo, XQ
   Li, MY
   Cho, YS
   Go, MJ
   Kim, YJ
   Lee, JY
   Park, T
   Kim, K
   Sim, X
   Ong, RTH
   Croteau-Chonka, DC
   Lange, LA
   Smith, JD
   Song, K
   Zhao, JH
   Yuan, X
   Luan, JA
   Lamina, C
   Ziegler, A
   Zhang, W
   Zee, RYL
   Wright, AF
   Witteman, JCM
   Wilson, JF
   Willemsen, G
   Wichmann, HE
   Whitfield, JB
   Waterworth, DM
   Wareham, NJ
   Waeber, G
   Vollenweider, P
   Voight, BF
   Vitart, V
   Uitterlinden, AG
   Uda, M
   Tuomilehto, J
   Thompson, JR
   Tanaka, T
   Surakka, I
   Stringham, HM
   Spector, TD
   Soranzo, N
   Smit, JH
   Sinisalo, J
   Silander, K
   Sijbrands, EJG
   Scuteri, A
   Scott, J
   Schlessinger, D
   Sanna, S
   Salomaa, V
   Saharinen, J
   Sabatti, C
   Ruokonen, A
   Rudan, I
   Rose, LM
   Roberts, R
   Rieder, M
   Psaty, BM
   Pramstaller, PP
   Pichler, I
   Perola, M
   Penninx, BWJH
   Pedersen, NL
   Pattaro, C
   Parker, AN
   Pare, G
   Oostra, BA
   O'Donnell, CJ
   Nieminen, MS
   Nickerson, DA
   Montgomery, GW
   Meitinger, T
   McPherson, R
   McCarthy, MI
   McArdle, W
   Masson, D
   Martin, NG
   Marroni, F
   Mangino, M
   Magnusson, PKE
   Lucas, G
   Luben, R
   Loos, RJF
   Lokki, ML
   Lettre, G
   Langenberg, C
   Launer, LJ
   Lakatta, EG
   Laaksonen, R
   Kyvik, KO
   Kronenberg, F
   König, IR
   Khaw, KT
   Kaprio, J
   Kaplan, LM
   Johansson, Å
   Jarvelin, MR
   Janssens, ACJW
   Ingelsson, E
   Igi, W
   Hovingh, GK
   Hottenga, JJ
   Hofman, A
   Hicks, AA
   Hengstenberg, C
   Heid, IM
   Hayward, C
   Havulinna, AS
   Hastie, ND
   Harris, TB
   Haritunians, T
   Hall, AS
   Gyllensten, U
   Guiducci, C
   Groop, LC
   Gonzalez, E
   Gieger, C
   Freimer, NB
   Ferrucci, L
   Erdmann, J
   Elliott, P
   Ejebe, KG
   Doering, A
   Dominiczak, AF
   Demissie, S
   Deloukas, P
   de Geus, EJC
   de Faire, U
   Crawford, G
   Collins, FS
   Chen, YDI
   Caulfield, MJ
   Campbell, H
   Burtt, NP
   Bonnycastle, LL
   Boomsma, DI
   Boekholdt, SM
   Bergman, RN
   Barroso, I
   Bandinelli, S
   Ballantyne, CM
   Assimes, TL
   Quertermous, T
   Altshuler, D
   Seielstad, M
   Wong, TY
   Tai, ES
   Feranil, AB
   Kuzawa, CW
   Adair, LS
   Taylor, HA
   Borecki, IB
   Gabriel, SB
   Wilson, JG
   Holm, H
   Thorsteinsdottir, U
   Gudnason, V
   Krauss, RM
   Mohlke, KL
   Ordovas, JM
   Munroe, PB
   Kooner, JS
   Tall, AR
   Hegele, RA
   Kastelein, JJP
   Schadt, EE
   Rotter, JI
   Boerwinkle, E
   Strachan, DP
   Mooser, V
   Stefansson, K
   Reilly, MP
   Samani, NJ
   Schunkert, H
   Cupples, LA
   Sandhu, MS
   Ridker, PM
   Rader, DJ
   van Duijn, CM
   Peltonen, L
   Abecasis, GR
   Boehnke, M
   Kathiresan, S
AF Teslovich, Tanya M.
   Musunuru, Kiran
   Smith, Albert V.
   Edmondson, Andrew C.
   Stylianou, Ioannis M.
   Koseki, Masahiro
   Pirruccello, James P.
   Ripatti, Samuli
   Chasman, Daniel I.
   Willer, Cristen J.
   Johansen, Christopher T.
   Fouchier, Sigrid W.
   Isaacs, Aaron
   Peloso, Gina M.
   Barbalic, Maja
   Ricketts, Sally L.
   Bis, Joshua C.
   Aulchenko, Yurii S.
   Thorleifsson, Gudmar
   Feitosa, Mary F.
   Chambers, John
   Orho-Melander, Marju
   Melander, Olle
   Johnson, Toby
   Li, Xiaohui
   Guo, Xiuqing
   Li, Mingyao
   Cho, Yoon Shin
   Go, Min Jin
   Kim, Young Jin
   Lee, Jong-Young
   Park, Taesung
   Kim, Kyunga
   Sim, Xueling
   Ong, Rick Twee-Hee
   Croteau-Chonka, Damien C.
   Lange, Leslie A.
   Smith, Joshua D.
   Song, Kijoung
   Zhao, Jing Hua
   Yuan, Xin
   Luan, Jian'an
   Lamina, Claudia
   Ziegler, Andreas
   Zhang, Weihua
   Zee, Robert Y. L.
   Wright, Alan F.
   Witteman, Jacqueline C. M.
   Wilson, James F.
   Willemsen, Gonneke
   Wichmann, H. -Erich
   Whitfield, John B.
   Waterworth, Dawn M.
   Wareham, Nicholas J.
   Waeber, Gerard
   Vollenweider, Peter
   Voight, Benjamin F.
   Vitart, Veronique
   Uitterlinden, Andre G.
   Uda, Manuela
   Tuomilehto, Jaakko
   Thompson, John R.
   Tanaka, Toshiko
   Surakka, Ida
   Stringham, Heather M.
   Spector, Tim D.
   Soranzo, Nicole
   Smit, Johannes H.
   Sinisalo, Juha
   Silander, Kaisa
   Sijbrands, Eric J. G.
   Scuteri, Angelo
   Scott, James
   Schlessinger, David
   Sanna, Serena
   Salomaa, Veikko
   Saharinen, Juha
   Sabatti, Chiara
   Ruokonen, Aimo
   Rudan, Igor
   Rose, Lynda M.
   Roberts, Robert
   Rieder, Mark
   Psaty, Bruce M.
   Pramstaller, Peter P.
   Pichler, Irene
   Perola, Markus
   Penninx, Brenda W. J. H.
   Pedersen, Nancy L.
   Pattaro, Cristian
   Parker, Alex N.
   Pare, Guillaume
   Oostra, Ben A.
   O'Donnell, Christopher J.
   Nieminen, Markku S.
   Nickerson, Deborah A.
   Montgomery, Grant W.
   Meitinger, Thomas
   McPherson, Ruth
   McCarthy, Mark I.
   McArdle, Wendy
   Masson, David
   Martin, Nicholas G.
   Marroni, Fabio
   Mangino, Massimo
   Magnusson, Patrik K. E.
   Lucas, Gavin
   Luben, Robert
   Loos, Ruth J. F.
   Lokki, Marja-Liisa
   Lettre, Guillaume
   Langenberg, Claudia
   Launer, Lenore J.
   Lakatta, Edward G.
   Laaksonen, Reijo
   Kyvik, Kirsten O.
   Kronenberg, Florian
   Koenig, Inke R.
   Khaw, Kay-Tee
   Kaprio, Jaakko
   Kaplan, Lee M.
   Johansson, Asa
   Jarvelin, Marjo-Riitta
   Janssens, A. Cecile J. W.
   Ingelsson, Erik
   Igi, Wilmar
   Hovingh, G. Kees
   Hottenga, Jouke-Jan
   Hofman, Albert
   Hicks, Andrew A.
   Hengstenberg, Christian
   Heid, Iris M.
   Hayward, Caroline
   Havulinna, Aki S.
   Hastie, Nicholas D.
   Harris, Tamara B.
   Haritunians, Talin
   Hall, Alistair S.
   Gyllensten, Ulf
   Guiducci, Candace
   Groop, Leif C.
   Gonzalez, Elena
   Gieger, Christian
   Freimer, Nelson B.
   Ferrucci, Luigi
   Erdmann, Jeanette
   Elliott, Paul
   Ejebe, Kenechi G.
   Doering, Angela
   Dominiczak, Anna F.
   Demissie, Serkalem
   Deloukas, Panagiotis
   de Geus, Eco J. C.
   de Faire, Ulf
   Crawford, Gabriel
   Collins, Francis S.
   Chen, Yii-der I.
   Caulfield, Mark J.
   Campbell, Harry
   Burtt, Noel P.
   Bonnycastle, Lori L.
   Boomsma, Dorret I.
   Boekholdt, S. Matthijs
   Bergman, Richard N.
   Barroso, Ines
   Bandinelli, Stefania
   Ballantyne, Christie M.
   Assimes, Themistocles L.
   Quertermous, Thomas
   Altshuler, David
   Seielstad, Mark
   Wong, Tien Y.
   Tai, E-Shyong
   Feranil, Alan B.
   Kuzawa, Christopher W.
   Adair, Linda S.
   Taylor, Herman A., Jr.
   Borecki, Ingrid B.
   Gabriel, Stacey B.
   Wilson, James G.
   Holm, Hilma
   Thorsteinsdottir, Unnur
   Gudnason, Vilmundur
   Krauss, Ronald M.
   Mohlke, Karen L.
   Ordovas, Jose M.
   Munroe, Patricia B.
   Kooner, Jaspal S.
   Tall, Alan R.
   Hegele, Robert A.
   Kastelein, John J. P.
   Schadt, Eric E.
   Rotter, Jerome I.
   Boerwinkle, Eric
   Strachan, David P.
   Mooser, Vincent
   Stefansson, Kari
   Reilly, Muredach P.
   Samani, Nilesh J.
   Schunkert, Heribert
   Cupples, L. Adrienne
   Sandhu, Manjinder S.
   Ridker, Paul M.
   Rader, Daniel J.
   van Duijn, Cornelia M.
   Peltonen, Leena
   Abecasis, Goncalo R.
   Boehnke, Michael
   Kathiresan, Sekar
TI Biological, clinical and population relevance of 95 loci for blood lipids
SO NATURE
LA English
DT Article
ID genome-wide association; disease; risk; traits; triglycerides; cholesterol; humans
AB Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
C1 [Musunuru, Kiran; Pirruccello, James P.; Voight, Benjamin F.; Bandinelli, Stefania; Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Teslovich, Tanya M.; Willer, Cristen J.; Stringham, Heather M.; Bergman, Richard N.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Musunuru, Kiran; Ballantyne, Christie M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Musunuru, Kiran; Pirruccello, James P.; Voight, Benjamin F.; Guiducci, Candace; Gonzalez, Elena; Ejebe, Kenechi G.; Crawford, Gabriel; Burtt, Noel P.; Altshuler, David; Wong, Tien Y.; Gabriel, Stacey B.; Kathiresan, Sekar] Broad Inst, Cambridge, MA 02142 USA.
   [Musunuru, Kiran; Chasman, Daniel I.; Zee, Robert Y. L.; O'Donnell, Christopher J.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Ridker, Paul M.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Musunuru, Kiran; Pirruccello, James P.; Tai, E-Shyong] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
   [Smith, Albert V.; Feranil, Alan B.; Gudnason, Vilmundur] Iceland Heart Assoc, Heart Prevent Clin & Res Inst, IS-201 Kopavogur, Iceland.
   [Smith, Albert V.; Kuzawa, Christopher W.; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Stefansson, Kari] Univ Iceland, IS-101 Reykjavik, Iceland.
   [Edmondson, Andrew C.; Li, Mingyao; Adair, Linda S.; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Edmondson, Andrew C.; Stylianou, Ioannis M.; Li, Mingyao; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
   [Koseki, Masahiro; Masson, David; Tall, Alan R.] Columbia Univ, Dept Med, Div Mol Med, New York, NY 10032 USA.
   [Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Saharinen, Juha; Perola, Markus; Kaprio, Jaakko] Univ Helsinki, FIMM, FI-00014 Helsinki, Finland.
   [Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Perola, Markus; Kaprio, Jaakko] Natl Inst Hlth & Welf, FI-00251 Helsinki, Finland.
   [Chasman, Daniel I.; Zee, Robert Y. L.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
   [Johansen, Christopher T.; Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada.
   [Fouchier, Sigrid W.; Hovingh, G. Kees; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
   [Isaacs, Aaron; Aulchenko, Yurii S.; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Sijbrands, Eric J. G.; Janssens, A. Cecile J. W.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
   [Peloso, Gina M.; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Peloso, Gina M.; O'Donnell, Christopher J.; Demissie, Serkalem; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
   [Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
   [Ricketts, Sally L.; Luben, Robert; Khaw, Kay-Tee; Sandhu, Manjinder S.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
   [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
   [Thorleifsson, Gudmar; Holm, Hilma; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE, IS-101 Reykjavik, Iceland.
   [Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, Ctr Genome Sci, St Louis, MO 63108 USA.
   [Chambers, John; Zhang, Weihua] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
   [Orho-Melander, Marju; Melander, Olle; Groop, Leif C.] Lund Univ, Dept Clin Sci, SE-20502 Malmo, Sweden.
   [Johnson, Toby; Caulfield, Mark J.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England.
   [Li, Xiaohui; Guo, Xiuqing; Haritunians, Talin; Chen, Yii-der I.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young] Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea.
   [Park, Taesung] Seoul Natl Univ, Coll Nat Sci, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea.
   [Park, Taesung] Seoul Natl Univ, Coll Nat Sci, Dept Stat, Seoul 151742, South Korea.
   [Kim, Kyunga] Sookmyung Womens Univ, Dept Stat, Seoul 140742, South Korea.
   [Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117597, Singapore.
   [Croteau-Chonka, Damien C.; Lange, Leslie A.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Ong, Rick Twee-Hee; Seielstad, Mark] Genome Inst Singapore, Singapore 138672, Singapore.
   [Smith, Joshua D.; Rieder, Mark; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Song, Kijoung; Yuan, Xin; Waterworth, Dawn M.; Mooser, Vincent] GlaxoSmithKline R&D, Div Genet, King Of Prussia, PA 19406 USA.
   [Zhao, Jing Hua; Luan, Jian'an; Wareham, Nicholas J.; Loos, Ruth J. F.; Langenberg, Claudia; Sandhu, Manjinder S.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
   [Lamina, Claudia; Kronenberg, Florian] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
   [Ziegler, Andreas; Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
   [Wright, Alan F.; Vitart, Veronique; Hayward, Caroline; Hastie, Nicholas D.] Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.] NGI, NCHA, NL-2300 RC Leiden, Netherlands.
   [Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.] CMSB, NL-2300 RC Leiden, Netherlands.
   [Wilson, James F.; Rudan, Igor; Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Willemsen, Gonneke; Hottenga, Jouke-Jan; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
   [Wichmann, H. -Erich; Heid, Iris M.; Gieger, Christian; Doering, Angela] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany.
   [Whitfield, John B.; Montgomery, Grant W.; Martin, Nicholas G.] PO Royal Brisbane Hosp, Queensland Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld 4029, Australia.
   [Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
   [Uitterlinden, Andre G.; Sijbrands, Eric J. G.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
   [Uda, Manuela; Sanna, Serena] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy.
   [Tuomilehto, Jaakko; Salomaa, Veikko; Havulinna, Aki S.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland.
   [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 6TP, Leics, England.
   [Tanaka, Toshiko] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
   [Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD 21218 USA.
   [Spector, Tim D.; Soranzo, Nicole; Mangino, Massimo] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Soranzo, Nicole; Deloukas, Panagiotis; Barroso, Ines; Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Smit, Johannes H.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, NL-1007 MB Amsterdam, Netherlands.
   [Sinisalo, Juha; Nieminen, Markku S.] HUCH, Dept Med, Div Cardiol, FI-00029 Helsinki, Finland.
   [Scuteri, Angelo] IRCCS, INRCA, Unita Operat Geriatria, I-00189 Rome, Italy.
   [Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London W12 0NN, England.
   [Schlessinger, David; Lakatta, Edward G.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
   [Sabatti, Chiara] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
   [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, FI-90220 Oulu, Finland.
   [Tanaka, Toshiko] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Gen Ctr, Ottawa, ON K1Y 4W7, Canada.
   [Psaty, Bruce M.] Univ Washington, Dept Med, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
   [Pramstaller, Peter P.; Pichler, Irene; Pattaro, Cristian; Hicks, Andrew A.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Inst Med Genet, Lubeck, Germany.
   [Pedersen, Nancy L.; Magnusson, Patrik K. E.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Parker, Alex N.] Amgen Inc, Thousand Oaks, CA 91320 USA.
   [Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON L8N 3Z5, Canada.
   [Oostra, Ben A.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
   [Meitinger, Thomas] Deutsch Forsch Zentrum Umwelt & Gesundheit, Helmholtz Zentrum Munchen, Inst Humangenet, D-85764 Neuherberg, Germany.
   [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
   [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England.
   [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
   [McArdle, Wendy] Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 2BN, Avon, England.
   [Marroni, Fabio] Inst Appl Genom, I-33100 Udine, Italy.
   [Lucas, Gavin] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
   [Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, FI-00014 Helsinki, Finland.
   [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
   [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
   [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, FI-33521 Tampere, Finland.
   [Kyvik, Kirsten O.] Univ So Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark.
   [Kyvik, Kirsten O.] Univ So Denmark, Danish Twin Registry, Inst Publ Hlth, DK-5000 Odense, Denmark.
   [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Fac Med, FI-00014 Helsinki, Finland.
   [Kaplan, Lee M.] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA.
   [Johansson, Asa; Igi, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden.
   [Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Dept Publ Hlth Sci & Gen Practice, FI-90220 Oulu, Finland.
   [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
   [Heid, Iris M.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
   [Havulinna, Aki S.] Aalto Univ, Sch Sci & Technol, Dept Biomed Engn & Computat Sci, FI-00076 Aalto, Finland.
   [Hall, Alistair S.] Univ Leeds, Fac Med & Hlth, LIGHT Res Inst, Leeds LS2 9JT, W Yorkshire, England.
   [Groop, Leif C.] Helsinki Univ Hosp, Dept Med, FI-00029 Helsinki, Finland.
   [Freimer, Nelson B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat,Ctr Neurobehav Genet, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
   [Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
   [Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
   [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
   [Dominiczak, Anna F.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
   [de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, SE-17177 Stockholm, Sweden.
   [Collins, Francis S.; Bonnycastle, Lori L.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
   [Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
   [Bergman, Richard N.] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
   [Bandinelli, Stefania] ASF, Geriatr Unit, I-50125 Florence, Italy.
   [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   [Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
   [Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 168751, Singapore.
   [Tai, E-Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117597, Singapore.
   [Tai, E-Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol, Singapore 117597, Singapore.
   [Tai, E-Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Publ Hlth, Singapore 117597, Singapore.
   [Feranil, Alan B.] Univ San Carlos, Off Populat Studies Fdn, Cebu 6000, Philippines.
   [Kuzawa, Christopher W.] Northwestern Univ, Dept Anthropol, Evanston, IL 60208 USA.
   [Adair, Linda S.] Univ N Carolina, Carolina Populat Ctr, Dept Nutr, Chapel Hill, NC 27516 USA.
   [Taylor, Herman A., Jr.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39126 USA.
   [Krauss, Ronald M.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
   [Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc, Dept Cardiovasc Epidemiol & Populat Genet, Madrid 28029, Spain.
   [Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Munroe, Patricia B.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.
   [Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
   [Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London SW17 0RE, England.
   [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, NIHR Biomed Res Unit Cardiovasc Dis, Glenfield Hosp, Leicester LE3 9QP, Leics, England.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Michigan System; University of Michigan; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Johns Hopkins University; Icelandic Heart Association; University of Iceland; University of Pennsylvania; University of Pennsylvania; Columbia University; University of Helsinki; Finland National Institute for Health & Welfare; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Western University (University of Western Ontario); University Western Ontario Hospital; University of Amsterdam; Academic Medical Center Amsterdam; Erasmus University Rotterdam; Erasmus MC; Boston University; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Framingham Heart Study; University of Texas System; University of Texas Health Science Center Houston; University of Cambridge; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Washington University (WUSTL); Imperial College London; Lund University; University of London; Queen Mary University London; Cedars Sinai Medical Center; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Genome Science; Seoul National University (SNU); Seoul National University (SNU); Sookmyung Women's University; National University of Singapore; University of North Carolina; University of North Carolina Chapel Hill; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of Washington; University of Washington Seattle; GlaxoSmithKline; Glaxosmithkline USA; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Medical University of Innsbruck; University of Lubeck; University of Edinburgh; University of Edinburgh; Vrije Universiteit Amsterdam; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Royal Brisbane & Women's Hospital; QIMR Berghofer Medical Research Institute; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Erasmus University Rotterdam; Erasmus MC; Consiglio Nazionale delle Ricerche (CNR); University of Cagliari; Finland National Institute for Health & Welfare; University of Leicester; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of London; King's College London; Wellcome Trust Sanger Institute; Vrije Universiteit Amsterdam; IRCCS INRCA; Imperial College London; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Stanford University; University of Oulu; University of Ottawa; Group Health Cooperative; University of Washington; University of Washington Seattle; Group Health Cooperative; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Group Health Cooperative; University of Lubeck; European Academy of Bozen-Bolzano; Karolinska Institutet; Amgen; McMaster University; Erasmus University Rotterdam; Erasmus MC; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; University of Oxford; University of Bristol; University of Helsinki; Universite de Montreal; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Tampere University; Tampere University Hospital; University of Southern Denmark; University of Southern Denmark; University of Helsinki; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Uppsala University; Imperial College London; University of Oulu; University of Regensburg; University of Regensburg; Aalto University; University of Leeds; University of Helsinki; Helsinki University Central Hospital; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Lubeck; Imperial College London; University of Glasgow; Karolinska Institutet; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Amsterdam; Academic Medical Center Amsterdam; University of Amsterdam; Academic Medical Center Amsterdam; University of Southern California; Baylor College of Medicine; Stanford University; National University of Singapore; Singapore National Eye Center; National University of Singapore; National University of Singapore; National University of Singapore; University of San Carlos; Northwestern University; University of North Carolina; University of North Carolina Chapel Hill; University of Mississippi Medical Center; University of Mississippi; Children's Hospital Oakland Research Institute; Children's Hospital Los Angeles; Centro Nacional de Investigaciones Cardiovasculares (CNIC); United States Department of Agriculture (USDA); Tufts University; University of London; Queen Mary University London; City St Georges, University of London; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital
RP Kathiresan, S (corresponding author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org
FU British Heart Foundation [SP/08/005/25115, PG/02/128, RG/07/005/23633, PG/08/094, PG/08/094/26019] Funding Source: Medline; Chief Scientist Office [CZB/4/710] Funding Source: Medline; FIC NIH HHS [TW05596] Funding Source: Medline; Medical Research Council [G0000934, G0601966, MC_QA137934, G9521010D, G0801566, MC_U106179471, G0401527, MC_U127561128, G9521010, G0801056, G0700931, MC_U106188470, G0701863] Funding Source: Medline; NCI NIH HHS [CA 047988] Funding Source: Medline; NCRR NIH HHS [U54 RR020278, RR20649, UL1RR025005, M01-RR00425] Funding Source: Medline; NHGRI NIH HHS [U01HG004402, N01-HG-65403, 1Z01 HG000024, T32 HG000040, T32 HG00040] Funding Source: Medline; NHLBI NIH HHS [N01-HC-45133, 5R01HL08770003, N01-HC-85079, K99 HL098364, 5R01HL08821502, N01-HC-85085, U01 HL069757, U01 HL080295, HL-54776, HL 04381, N01-HC-55018, N01-HC-85082, N01-HC-85084, N01-HC-55021, R01HL086694, N01-HC-85086, RC2 HL101864,, RC1 HL099634, R01HL087652, R01 HL089650, N01-HC-85081, N01-HC-55019, RC1 HL099793, HL085144, R01HL087641, N01-HC-55020, RC2 HL102419, N01-HC-55016, N01-HC-55022, HL 080467, K99HL094535, R01 HL087676, R01 HL089309, N01-HC-35129, N01 HC-55222, N01-HC-75150, R01HL59367, N01-HC-85083, N01-HC-25195, N01-HC-55015, N02-HL-6-4278, 5R01HL087679-02, N01-HC-85080, N01 HC-15103, T32HL007208] Funding Source: Medline; NIA NIH HHS [N01-AG-12100] Funding Source: Medline; NICHD NIH HHS [R24 HD050924] Funding Source: Medline; NIDDK NIH HHS [DK56350, DK072193, R01 DK072193, DK063491, DK078150, DK062370, 5R01DK07568102, U01 DK062370, 5R01DK06833603, U01 DK062418, R01 DK078150] Funding Source: Medline; NIEHS NIH HHS [ES10126] Funding Source: Medline; NIGMS NIH HHS [T32 GM007092] Funding Source: Medline; PHS HHS [HHSN268200625226C] Funding Source: Medline; Wellcome Trust [079895, 077016/Z/05/Z, 076113/B/04/Z, 068545/Z/02] Funding Source: Medline; Intramural NIH HHS Funding Source: Medline; MRC [G0801056, MC_U127561128, G0601966, G0801566, MC_qA137934, MC_U106188470, G0000934, G0700931, G9521010, G0701863] Funding Source: UKRI; British Heart Foundation [PG/08/094/26019] Funding Source: researchfish; Chief Scientist Office [CZB/4/710] Funding Source: researchfish; Medical Research Council [G0801566, G0401527, G0801056, G0801056B, G0601966, G0701863, G9521010, MC_U106179471, MC_U127561128, MC_U106188470, MC_qA137934, G0000934, G0700931] Funding Source: researchfish; National Heart Lung and Blood Institute [R01HL059367, R01HL086694, T32HL007208] Funding Source: NIH RePORTER; National Human Genome Research Institute [T32HG000040] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK072193, P30DK056350, R01DK062370, P30DK063491, U01DK062370] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [P30ES010126] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000965, ZIAAG000799, ZIAAG000675, ZIAAG007380] Funding Source: NIH RePORTER
NR 20
TC 2956
Z9 3301
U1 3
U2 411
PU 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 5
PY 2010
VL 466
IS 7307
BP 707
EP 713
DI 10.1038/nature09270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500029
PM 20686565
DA 2026-03-09
ER

PT J
AU Marcheva, B
   Ramsey, KM
   Buhr, ED
   Kobayashi, Y
   Su, H
   Ko, CH
   Ivanova, G
   Omura, C
   Mo, S
   Vitaterna, MH
   Lopez, JP
   Philipson, LH
   Bradfield, CA
   Crosby, SD
   JeBailey, L
   Wang, XZ
   Takahashi, JS
   Bass, J
AF Marcheva, Biliana
   Ramsey, Kathryn Moynihan
   Buhr, Ethan D.
   Kobayashi, Yumiko
   Su, Hong
   Ko, Caroline H.
   Ivanova, Ganka
   Omura, Chiaki
   Mo, Shelley
   Vitaterna, Martha H.
   Lopez, James P.
   Philipson, Louis H.
   Bradfield, Christopher A.
   Crosby, Seth D.
   JeBailey, Lellean
   Wang, Xiaozhong
   Takahashi, Joseph S.
   Bass, Joseph
TI Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes
SO NATURE
LA English
DT Article
ID circadian gene-expression; insulin-secretion; mouse; liver; mice; transcription; cholesterol; biology
AB The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night(1-3). During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes(4), it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signalling is delayed in circadian mutant mice, and both Clock(5,6) and Bmal1(7) (also called Arntl) mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival and synaptic vesicle assembly. Notably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective beta-cell function at the very latest stage of stimulus-secretion coupling. These results demonstrate a role for the beta-cell clock in coordinating insulin secretion with the sleep-wake cycle, and reveal that ablation of the pancreatic clock can trigger the onset of diabetes mellitus.
C1 [Marcheva, Biliana; Ramsey, Kathryn Moynihan; Kobayashi, Yumiko; Ivanova, Ganka; Omura, Chiaki; Bass, Joseph] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Marcheva, Biliana; Ramsey, Kathryn Moynihan; Buhr, Ethan D.; Kobayashi, Yumiko; Ko, Caroline H.; Ivanova, Ganka; Omura, Chiaki; Bass, Joseph] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA.
   [Su, Hong; Wang, Xiaozhong] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
   [Mo, Shelley] Northwestern Univ, Weinberg Coll Arts & Sci, Evanston, IL 60208 USA.
   [Vitaterna, Martha H.; Bass, Joseph] Northwestern Univ, Ctr Sleep & Circadian Biol, Evanston, IL 60208 USA.
   [Lopez, James P.; Philipson, Louis H.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Bradfield, Christopher A.] Univ Wisconsin, Sch Med & Publ Hlth, McArdle Lab Canc Res, Madison, WI 53706 USA.
   [Crosby, Seth D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA.
   [JeBailey, Lellean] GeneGo Inc, St Joseph, MI 49085 USA.
   [Takahashi, Joseph S.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
   [Takahashi, Joseph S.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
C3 Northwestern University; Feinberg School of Medicine; Northwestern University; Northwestern University; Northwestern University; Northwestern University; University of Chicago; University of Wisconsin System; University of Wisconsin Madison; Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute
RP Bass, J (corresponding author), Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
EM j-bass@northwestern.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [R37-ES-005703]; Chicago Biomedical Consortium; Juvenile Diabetes Research Foundation; National Institute of Mental Health; National Institute on Aging [P01AG011412] Funding Source: NIH RePORTER
NR 30
TC 1214
Z9 1444
U1 4
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 627
EP 631
DI 10.1038/nature09253
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100054
PM 20562852
DA 2026-03-09
ER

PT J
AU Hübel, H
   Hamel, DR
   Fedrizzi, A
   Ramelow, S
   Resch, KJ
   Jennewein, T
AF Huebel, Hannes
   Hamel, Deny R.
   Fedrizzi, Alessandro
   Ramelow, Sven
   Resch, Kevin J.
   Jennewein, Thomas
TI Direct generation of photon triplets using cascaded photon-pair sources
SO NATURE
LA English
DT Article
ID interference
AB Non-classical states of light, such as entangled photon pairs and number states, are essential for fundamental tests of quantum mechanics and optical quantum technologies. The most widespread technique for creating these quantum resources is spontaneous parametric down-conversion of laser light into photon pairs(1). Conservation of energy and momentum in this process, known as phase-matching, gives rise to strong correlations that are used to produce two-photon entanglement in various degrees of freedom(2-9). It has been a longstanding goal in quantum optics to realize a source that can produce analogous correlations in photon triplets, but of the many approaches considered, none has been technically feasible(10-17). Here we report the observation of photon triplets generated by cascaded down-conversion. Each triplet originates from a single pump photon, and therefore quantum correlations will extend over all three photons(18) in a way not achievable with independently created photon pairs(19). Our photon-triplet source will allow experimental interrogation of novel quantum correlations(20), the generation of tripartite entanglement(12,21) without post-selection and the generation of heralded entangled photon pairs suitable for linear optical quantum computing(22). Two of the triplet photons have a wavelength matched for optimal transmission in optical fibres, suitable for three-party quantum communication(23). Furthermore, our results open interesting regimes of non-linear optics, as we observe spontaneous down-conversion pumped by single photons, an interaction also highly relevant to optical quantum computing.
C1 [Huebel, Hannes; Hamel, Deny R.; Resch, Kevin J.; Jennewein, Thomas] Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
   [Huebel, Hannes; Hamel, Deny R.; Resch, Kevin J.; Jennewein, Thomas] Univ Waterloo, Dept Phys & Astron, Waterloo, ON N2L 3G1, Canada.
   [Fedrizzi, Alessandro] Univ Queensland, Dept Phys, Brisbane, Qld 4072, Australia.
   [Fedrizzi, Alessandro] Univ Queensland, Ctr Quantum Comp Technol, Brisbane, Qld 4072, Australia.
   [Ramelow, Sven] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat, A-1090 Vienna, Austria.
   [Ramelow, Sven] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
C3 University of Waterloo; University of Waterloo; University of Queensland; University of Queensland; Austrian Academy of Sciences; University of Vienna
RP Hübel, H (corresponding author), Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
EM hhuebel@iqc.ca; tjennewe@iqc.ca
FU Canadian Institute for Advanced Research; Ontario Centres of Excellence; Ontario Ministry of Research and Innovation; Natural Sciences and Engineering Council of Canada; Canadian Foundation for Innovation; FWF (CoQus); Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 31
TC 159
Z9 178
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 JUL 29
PY 2010
VL 466
IS 7306
BP 601
EP 603
DI 10.1038/nature09175
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100048
PM 20671705
DA 2026-03-09
ER

PT J
AU Tarutani, Y
   Shiba, H
   Iwano, M
   Kakizaki, T
   Suzuki, G
   Watanabe, M
   Isogai, A
   Takayama, S
AF Tarutani, Yoshiaki
   Shiba, Hiroshi
   Iwano, Megumi
   Kakizaki, Tomohiro
   Suzuki, Go
   Watanabe, Masao
   Isogai, Akira
   Takayama, Seiji
TI Trans-acting small RNA determines dominance relationships in Brassica self-incompatibility
SO NATURE
LA English
DT Article
ID ii s-haplotypes; genomic organization; gene-expression; dna methylation; pollen; locus; campestris; paramutation; alleles; region
AB A diploid organism has two copies of each gene, one inherited from each parent. The expression of two inherited alleles is sometimes biased by the effects known as dominant/recessive relationships, which determine the final phenotype of the organism. To explore the mechanisms underlying these relationships, we have examined the monoallelic expression of S-locus protein 11 genes (SP11), which encode the male determinants of self-incompatibility in Brassica. We previously reported that SP11 expression was monoallelic in some S heterozygotes, and that the promoter regions of recessive SP11 alleles were specifically methylated in the anther tapetum(1-3). Here we show that this methylation is controlled by trans-acting small non-coding RNA(sRNA). We identified inverted genomic sequences that were similar to the recessive SP11 promoters in the flanking regions of dominant SP11 alleles. These sequences were specifically expressed in the anther tapetum and processed into 24-nucleotide sRNA, named SP11 methylation inducer (Smi). Introduction of the Smi genomic region into the recessive S homozygotes triggered the methylation of the promoter of recessive SP11 alleles and repressed their transcription. This is an example showing sRNA encoded in the flanking region of a dominant allele acts in trans to induce transcriptional silencing of the recessive allele. Our finding may provide new insights into the widespread monoallelic gene expression systems.
C1 [Tarutani, Yoshiaki; Shiba, Hiroshi; Iwano, Megumi; Isogai, Akira; Takayama, Seiji] Nara Inst Sci & Technol, Grad Sch Biol Sci, Ikoma 6300192, Japan.
   [Kakizaki, Tomohiro] Iwate Univ, Fac Agr, Morioka, Iwate 0208550, Japan.
   [Suzuki, Go] Osaka Kyoiku Univ, Div Nat Sci, Osaka 5828582, Japan.
   [Watanabe, Masao] Tohoku Univ, Grad Sch Life Sci, Aoba Ku, Sendai, Miyagi 9808577, Japan.
C3 Nara Institute of Science & Technology; Iwate University; Osaka University of Education; Tohoku University
RP Takayama, S (corresponding author), Nara Inst Sci & Technol, Grad Sch Biol Sci, 8916-5 Takayama, Ikoma 6300192, Japan.
EM takayama@bs.naist.jp
FU Bio-oriented Technology Research Advancement Institution (BRAIN); Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology (MEXT); Grants-in-Aid for Scientific Research [21112003, 20678001] Funding Source: KAKEN
NR 31
TC 128
Z9 135
U1 0
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 983
EP U110
DI 10.1038/nature09308
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300036
PM 20725042
DA 2026-03-09
ER

PT J
AU Muotri, AR
   Marchetto, MCN
   Coufal, NG
   Oefner, R
   Yeo, G
   Nakashima, K
   Gage, FH
AF Muotri, Alysson R.
   Marchetto, Maria C. N.
   Coufal, Nicole G.
   Oefner, Ruth
   Yeo, Gene
   Nakashima, Kinichi
   Gage, Fred H.
TI L1 retrotransposition in neurons is modulated by MeCP2
SO NATURE
LA English
DT Article
ID cpg-binding protein-2; methyl-cpg; stem-cells; histone deacetylase; adult neurogenesis; rett-syndrome; transcription; hippocampus; sequences; elements
AB Long interspersed nuclear elements-1 (LINE-1 or L1s) are abundant retrotransposons that comprise approximately 20% of mammalian genomes(1-3). Active L1 retrotransposons can impact the genome in a variety of ways, creating insertions, deletions, new splice sites or gene expression fine-tuning(4-6). We have shown previously that L1 retrotransposons are capable of mobilization in neuronal progenitor cells from rodents and humans and evidence of massive L1 insertions was observed in adult brain tissues but not in other somatic tissues(7,8). In addition, L1 mobility in the adult hippocampus can be influenced by the environment(9). The neuronal specificity of somatic L1 retrotransposition in neural progenitors is partially due to the transition of a Sox2/HDAC1 repressor complex to a Wnt-mediated T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activator(7,10). The transcriptional switch accompanies chromatin remodelling during neuronal differentiation, allowing a transient stimulation of L1 transcription(7). The activity of L1 retrotransposons during brain development can have an impact on gene expression and neuronal function, thereby increasing brain-specific genetic mosaicism(11,12). Further understanding of the molecular mechanisms that regulate L1 expression should provide new insights into the role of L1 retrotransposition during brain development. Here we show that L1 neuronal transcription and retrotransposition in rodents are increased in the absence of methyl-CpG-binding protein 2 (MeCP2), a protein involved in global DNA methylation and human neurodevelopmental diseases. Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that L1 retrotransposition can be controlled in a tissue-specific manner and that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition. Our findings add a new level of complexity to the molecular events that can lead to neurological disorders.
C1 [Muotri, Alysson R.] Univ Calif San Diego, Sch Med, Dept Pediat,Dept Cellular & Mol Med, Rady Childrens Hosp San Diego,Stem Cell Program, La Jolla, CA 92093 USA.
   [Marchetto, Maria C. N.; Coufal, Nicole G.; Oefner, Ruth; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Yeo, Gene] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, Stem Cell Program, La Jolla, CA 92093 USA.
   [Nakashima, Kinichi] Nara Inst Sci & Technol, Grad Sch Biol Sci, Lab Mol Neurosci, Ikoma 6300101, Japan.
C3 University of California System; University of California San Diego; Rady Childrens Hospital San Diego; Salk Institute; University of California System; University of California San Diego; Nara Institute of Science & Technology
RP Muotri, AR (corresponding author), Univ Calif San Diego, Sch Med, Dept Pediat,Dept Cellular & Mol Med, Rady Childrens Hosp San Diego,Stem Cell Program, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM muotri@ucsd.edu; gage@salk.edu
FU National Institutes of Health [1-DP2-OD006495-01]; Emerald Foundation; Mathers Foundation; Lookout Fund; NIH/NINDS [R01MH088485]
NR 30
TC 494
Z9 634
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 443
EP 446
DI 10.1038/nature09544
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100044
PM 21085180
DA 2026-03-09
ER

PT J
AU Song, YJ
   Otte, AF
   Kuk, Y
   Hu, YK
   Torrance, DB
   First, PN
   de Heer, WA
   Min, HK
   Adam, S
   Stiles, MD
   MacDonald, AH
   Stroscio, JA
AF Song, Young Jae
   Otte, Alexander F.
   Kuk, Young
   Hu, Yike
   Torrance, David B.
   First, Phillip N.
   de Heer, Walt A.
   Min, Hongki
   Adam, Shaffique
   Stiles, Mark D.
   MacDonald, Allan H.
   Stroscio, Joseph A.
TI High-resolution tunnelling spectroscopy of a graphene quartet
SO NATURE
LA English
DT Article
ID electron-gas; mass
AB Electrons in a single sheet of graphene behave quite differently from those in traditional two-dimensional electron systems. Like massless relativistic particles, they have linear dispersion and chiral eigenstates. Furthermore, two sets of electrons centred at different points in reciprocal space ('valleys') have this dispersion, giving rise to valley degeneracy. The symmetry between valleys, together with spin symmetry, leads to a fourfold quartet degeneracy of the Landau levels, observed as peaks in the density of states produced by an applied magnetic field. Recent electron transport measurements have observed the lifting of the fourfold degeneracy in very large applied magnetic fields, separating the quartet into integer(1-4) and, more recently, fractional(5,6) levels. The exact nature of the broken-symmetry states that form within the Landau levels and lift these degeneracies is unclear at present and is a topic of intense theoretical debate(7-11). Here we study the detailed features of the four quantum states that make up a degenerate graphene Landau level. We use high-resolution scanning tunnelling spectroscopy at temperatures as low as 10 mK in an applied magnetic field to study the top layer of multilayer epitaxial graphene. When the Fermi level lies inside the fourfold Landau manifold, significant electron correlation effects result in an enhanced valley splitting for even filling factors, and an enhanced electron spin splitting for odd filling factors. Most unexpectedly, we observe states with Landau level filling factors of 7/2, 9/2 and 11/2, suggestive of new many-body states in graphene.
C1 [Song, Young Jae; Otte, Alexander F.; Min, Hongki; Adam, Shaffique; Stiles, Mark D.; Stroscio, Joseph A.] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA.
   [Song, Young Jae; Otte, Alexander F.; Min, Hongki] Univ Maryland, Maryland NanoCtr, College Pk, MD 20742 USA.
   [Kuk, Young] Seoul Natl Univ, Dept Phys & Astron, Seoul 1517474, South Korea.
   [Hu, Yike; Torrance, David B.; First, Phillip N.; de Heer, Walt A.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [MacDonald, Allan H.] Univ Texas Austin, Dept Phys, Austin, TX 78712 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; Seoul National University (SNU); University System of Georgia; Georgia Institute of Technology; University of Texas System; University of Texas Austin
RP Stroscio, JA (corresponding author), NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA.
EM joseph.stroscio@nist.gov
FU Korean Government (MOEHRD) [KRF- 2006-214-C00022]; NSF [DMR-0820382 [MRSEC], DMR-0804908, DMR-0606489]; Welch Foundation; Semiconductor Research Corporation
NR 30
TC 170
Z9 195
U1 0
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 185
EP 189
DI 10.1038/nature09330
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300029
PM 20829790
DA 2026-03-09
ER

PT J
AU Kosmrlj, A
   Read, EL
   Qi, Y
   Allen, TM
   Altfeld, M
   Deeks, SG
   Pereyra, F
   Carrington, M
   Walker, BD
   Chakraborty, AK
AF Kosmrlj, Andrej
   Read, Elizabeth L.
   Qi, Ying
   Allen, Todd M.
   Altfeld, Marcus
   Deeks, Steven G.
   Pereyra, Florencia
   Carrington, Mary
   Walker, Bruce D.
   Chakraborty, Arup K.
TI Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection
SO NATURE
LA English
DT Article
ID major histocompatibility complex; responses; peptide; binding; molecules; antigen; cd4(+); lymphocytes; diversity; epitopes
AB Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals ('elite controllers') maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57 (ref. 1). Because HLA molecules present viral peptides that activate CD8(+) T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.
C1 [Kosmrlj, Andrej; Read, Elizabeth L.; Allen, Todd M.; Altfeld, Marcus; Pereyra, Florencia; Carrington, Mary; Walker, Bruce D.; Chakraborty, Arup K.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
   [Kosmrlj, Andrej] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Read, Elizabeth L.; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
   [Read, Elizabeth L.; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Qi, Ying; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94110 USA.
   [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); 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; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Chakraborty, AK (corresponding author), Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
EM bwalker@partners.org; arupc@mit.edu
FU Mark and Lisa Schwartz Foundation; National Institutes of Health (NIH); Philip T and Susan M Ragon Foundation; Jane Coffin Childs Foundation; Bill and Melinda Gates Foundation; NIAID; National Cancer Institute, NIH [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute [ZIABC010791, ZICBC011237] Funding Source: NIH RePORTER; National Institute of Nursing Research; National Institute of Dental and Craniofacial Research; National Institute on Drug Abuse; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Institute on Minority Health and Health Disparities [P30AI060354] Funding Source: NIH RePORTER
NR 40
TC 230
Z9 269
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 MAY 20
PY 2010
VL 465
IS 7296
BP 350
EP U107
DI 10.1038/nature08997
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200041
PM 20445539
DA 2026-03-09
ER

PT J
AU Bao, HM
   Yu, SC
   Tong, DQ
AF Bao, Huiming
   Yu, Shaocai
   Tong, Daniel Q.
TI Massive volcanic SO2 oxidation and sulphate aerosol deposition in Cenozoic North America
SO NATURE
LA English
DT Article
ID volcanogenic sulfate; oxygen; sulfur; origin; atmosphere; oligocene; eruptions; ozone; earth; usa
AB Volcanic eruptions release a large amount of sulphur dioxide (SO2) into the atmosphere(1,2). SO2 is oxidized to sulphate and can subsequently form sulphate aerosol(3), which can affect the Earth's radiation balance, biologic productivity and high-altitude ozone concentrations, as is evident from recent volcanic eruptions(4). SO2 oxidation can occur via several different pathways that depend on its flux and the atmospheric conditions(3). An investigation into how SO2 is oxidized to sulphate-the oxidation product preserved in the rock record-can therefore shed light on past volcanic eruptions and atmospheric conditions. Here we use sulphur and triple oxygen isotope measurements of atmospheric sulphate extracted from tuffaceous deposits to investigate the specific oxidation pathways from which the sulphate was formed. We find that seven eruption-related sulphate aerosol deposition events have occurred during the mid-Cenozoic era (34 to 7 million years ago) in the northern High Plains, North America. Two extensively sampled ash beds display a similar sulphate mixing pattern that has two distinct atmospheric secondary sulphates. A three-dimensional atmospheric sulphur chemistry and transport model study reveals that the observed, isotopically discrete sulphates in sediments can be produced only in initially alkaline cloudwater that favours an ozone-dominated SO2 oxidation pathway in the troposphere. Our finding suggests that, in contrast to the weakly acidic conditions today(5), cloudwater in the northern High Plains may frequently have been alkaline during the mid-Cenozoic era. We propose that atmospheric secondary sulphate preserved in continental deposits represents an unexploited geological archive for atmospheric SO2 oxidation chemistry linked to volcanism and atmospheric conditions in the past.
C1 [Bao, Huiming] Louisiana State Univ, Dept Geol & Geophys, Baton Rouge, LA 70803 USA.
   [Yu, Shaocai] US EPA, Natl Exposure Res Lab, Atmospher Modeling & Anal Div E243 03, Res Triangle Pk, NC 27711 USA.
   [Tong, Daniel Q.] NOAA, Air Resources Lab, Silver Spring, MD 20910 USA.
C3 Louisiana State University System; Louisiana State University; United States Environmental Protection Agency; National Oceanic Atmospheric Admin (NOAA) - USA
RP Bao, HM (corresponding author), Louisiana State Univ, Dept Geol & Geophys, Baton Rouge, LA 70803 USA.
EM bao@lsu.edu; yu.shaocai@epa.gov
FU NSF [EAR-0408986]; United States Environmental Protection Agency through its Office of Research and Development
NR 30
TC 42
Z9 46
U1 3
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 909
EP 912
DI 10.1038/nature09100
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500034
PM 20559384
DA 2026-03-09
ER

PT J
AU Malleshaiah, MK
   Shahrezaei, V
   Swain, PS
   Michnick, SW
AF Malleshaiah, Mohan K.
   Shahrezaei, Vahid
   Swain, Peter S.
   Michnick, Stephen W.
TI The scaffold protein Ste5 directly controls a switch-like mating decision in yeast
SO NATURE
LA English
DT Article
ID map kinase; multisite phosphorylation; signal-transduction; pathway; mechanism; dynamics
AB Evolution has resulted in numerous innovations that allow organisms to increase their fitness by choosing particular mating partners, including secondary sexual characteristics, behavioural patterns, chemical attractants and corresponding sensory mechanisms(1). The haploid yeast Saccharomyces cerevisiae selects mating partners by interpreting the concentration gradient of pheromone secreted by potential mates through a network of mitogen-activated protein kinase (MAPK) signalling proteins(2,3). The mating decision in yeast is an all-or-none, or switch-like, response that allows cells to filter weak pheromone signals, thus avoiding inappropriate commitment to mating by responding only at or above critical concentrations when a mate is sufficiently close(4). The molecular mechanisms that govern the switch-like mating decision are poorly understood. Here we show that the switching mechanism arises from competition between the MAPK Fus3 and a phosphatase Ptc1 for control of the phosphorylation state of four sites on the scaffold protein Ste5. This competition results in a switch-like dissociation of Fus3 from Ste5 that is necessary to generate the switch-like mating response. Thus, the decision to mate is made at an early stage in the pheromone pathway and occurs rapidly, perhaps to prevent the loss of the potential mate to competitors. We argue that the architecture of the Fus3Ste5- Ptc1 circuit generates a novel ultrasensitivity mechanism, which is robust to variations in the concentrations of these proteins. This robustness helps assure that mating can occur despite stochastic or genetic variation between individuals. The role of Ste5 as a direct modulator of a cell-fate decision expands the functional repertoire of scaffold proteins beyond providing specificity and efficiency of information processing(5,6). Similar mechanisms may govern cellular decisions in higher organisms and be disrupted in cancer.
C1 [Malleshaiah, Mohan K.; Michnick, Stephen W.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
   [Michnick, Stephen W.] Univ Montreal, Ctr Robert Cedergren Bioinformat & Genom, Montreal, PQ H3C 3J7, Canada.
   [Shahrezaei, Vahid] Univ London Imperial Coll Sci Technol & Med, Dept Math, London SW7 2AZ, England.
   [Swain, Peter S.] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada.
   [Swain, Peter S.] Univ Edinburgh, Ctr Syst Biol, Edinburgh EH9 3JD, Midlothian, Scotland.
C3 Universite de Montreal; Universite de Montreal; Imperial College London; McGill University; University of Edinburgh
RP Michnick, SW (corresponding author), Univ Montreal, Dept Biochim, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM peter.swain@ed.ac.uk; stephen.michnick@umontreal.ca
FU Canadian Institutes of Health Research [MOP-GMX-152556]; Canada Research Chair in Integrative Genomics; Canada Research Chair in Systems Biology
NR 30
TC 145
Z9 190
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 MAY 6
PY 2010
VL 465
IS 7294
BP 101
EP 105
DI 10.1038/nature08946
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900039
PM 20400943
DA 2026-03-09
ER

PT J
AU Chung, I
   Akita, R
   Vandlen, R
   Toomre, D
   Schlessinger, J
   Mellman, I
AF Chung, Inhee
   Akita, Robert
   Vandlen, Richard
   Toomre, Derek
   Schlessinger, Joseph
   Mellman, Ira
TI Spatial control of EGF receptor activation by reversible dimerization on living cells
SO NATURE
LA English
DT Article
ID live cells; domain; surface; mechanism; family
AB Epidermal growth factor receptor (EGFR) is a type I receptor tyrosine kinase, the deregulation of which has been implicated in a variety of human carcinomas(1-4). EGFR signalling is preceded by receptor dimerization, typically thought to result from a ligand-induced conformational change in the ectodomain that exposes a loop (dimerization arm) required for receptor association. Ligand binding may also trigger allosteric changes in the cytoplasmic domain of the receptor that is crucial for signalling(5-7). Despite these insights, ensemble-averaging approaches have not determined the precise mechanism of receptor activation in situ. Using quantum-dot-based optical tracking of single molecules(8-11) combined with a novel time-dependent diffusivity analysis, here we present the dimerization dynamics of individual EGFRs on living cells. Before ligand addition, EGFRs spontaneously formed finite-lifetime dimers kinetically stabilized by their dimerization arms(12-14). The dimers were primed both for ligand binding and for signalling, such that after EGF addition they rapidly showed a very slow diffusivity state that correlated with activation. Although the kinetic stability of unliganded dimers was in principle sufficient for EGF-independent activation, ligand binding was still required for signalling. Interestingly, dimers were enriched in the cell periphery in an actin-and receptor-expression-dependent fashion, resulting in a peripheral enhancement of EGF-induced signalling that may enable polarized responses to growth factors.
C1 [Chung, Inhee; Akita, Robert; Vandlen, Richard; Mellman, Ira] Genentech Inc, San Francisco, CA 94080 USA.
   [Toomre, Derek] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA.
   [Schlessinger, Joseph] Yale Univ, Sch Med, Deparment Pharmacol, New Haven, CT 06510 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Yale University; Yale University
RP Mellman, I (corresponding author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM mellman.ira@gene.com
FU Research Foundation-Flanders; Agency for Innovation by Science and Technology in Flanders ('Generisch Basisonderzoek aan de Universiteiten'); Ghent University; National Institutes of Health; Spanish Ministerio de Ciencia y Tecnologia; Comunidad de Madrid
NR 30
TC 436
Z9 525
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 783
EP U163
DI 10.1038/nature08827
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000050
PM 20208517
DA 2026-03-09
ER

PT J
AU Naka, K
   Hoshii, T
   Muraguchi, T
   Tadokoro, Y
   Ooshio, T
   Kondo, Y
   Nakao, S
   Motoyama, N
   Hirao, A
AF Naka, Kazuhito
   Hoshii, Takayuki
   Muraguchi, Teruyuki
   Tadokoro, Yuko
   Ooshio, Takako
   Kondo, Yukio
   Nakao, Shinji
   Motoyama, Noboru
   Hirao, Atsushi
TI TGF-β-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; chronic myelogenous leukemia; abl-expressing cells; bcr-abl; transcription factor; oxidative stress; murine model; bone-marrow; apoptosis; mice
AB Chronic myeloid leukaemia (CML) is caused by a defined genetic abnormality that generates BCR-ABL, a constitutively active tyrosine kinase(1). It is widely believed that BCR-ABL activates Akt signalling that suppresses the forkhead O transcription factors (FOXO), supporting the proliferation or inhibiting the apoptosis of CML cells(2-4). Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML(5-8). Here, using a syngeneic transplantation system and a CML-like myeloproliferative disease mouse model, we show that Foxo3a has an essential role in the maintenance of CML LICs. We find that cells with nuclear localization of Foxo3a and decreased Akt phosphorylation are enriched in the LIC population. Serial transplantation of LICs generated from Foxo3a(+/+) and Foxo3a(-/-) mice shows that the ability of LICs to cause disease is significantly decreased by Foxo3a deficiency. Furthermore, we find that TGF-beta is a critical regulator of Akt activation in LICs and controls Foxo3a localization. A combination of TGF-beta inhibition, Foxo3a deficiency and imatinib treatment led to efficient depletion of CML in vivo. Furthermore, the treatment of human CML LICs with a TGF-beta inhibitor impaired their colony-forming ability in vitro. Our results demonstrate a critical role for the TGF-beta-FOXO pathway in the maintenance of LICs, and strengthen our understanding of the mechanisms that specifically maintain CML LICs in vivo.
C1 [Naka, Kazuhito; Hoshii, Takayuki; Muraguchi, Teruyuki; Tadokoro, Yuko; Ooshio, Takako; Hirao, Atsushi] Kanazawa Univ, Div Mol Genet, Ctr Canc & Stem Cell Res, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan.
   [Ooshio, Takako; Hirao, Atsushi] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo 1020075, Japan.
   [Kondo, Yukio; Nakao, Shinji] Kanazawa Univ, Grad Sch Med Sci, Div Canc Med, Kanazawa, Ishikawa 9208641, Japan.
   [Motoyama, Noboru] Natl Ctr Gerontol & Geriatr, Natl Inst Longev Sci, Dept Geriatr Med, Aichi 4748522, Japan.
C3 Kanazawa University; Japan Science & Technology Agency (JST); Kanazawa University
RP Naka, K (corresponding author), Kanazawa Univ, Div Mol Genet, Ctr Canc & Stem Cell Res, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan.
EM kazunaka@kenroku.kanazawa-u.ac.jp; ahirao@kenroku.kanazawa-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan [17GS0419]; Grants-in-Aid for Scientific Research [21390290] Funding Source: KAKEN
NR 28
TC 485
Z9 567
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 676
EP U111
DI 10.1038/nature08734
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900039
PM 20130650
DA 2026-03-09
ER

PT J
AU Hansen, DV
   Lui, JH
   Parker, PRL
   Kriegstein, AR
AF Hansen, David V.
   Lui, Jan H.
   Parker, Philip R. L.
   Kriegstein, Arnold R.
TI Neurogenic radial glia in the outer subventricular zone of human neocortex
SO NATURE
LA English
DT Article
ID gabaergic neurons; cells; pax6; differentiation; telencephalon; evolution; division; origin; cortex; arise
AB Neurons in the developing rodent cortex are generated from radial glial cells that function as neural stem cells. These epithelial cells line the cerebral ventricles and generate intermediate progenitor cells that migrate into the subventricular zone (SVZ) and proliferate to increase neuronal number. The developing human SVZ has a massively expanded outer region (OSVZ) thought to contribute to cortical size and complexity. However, OSVZ progenitor cell types and their contribution to neurogenesis are not well understood. Here we show that large numbers of radial glia-like cells and intermediate progenitor cells populate the human OSVZ. We find that OSVZ radial glia-like cells have a long basal process but, surprisingly, are non-epithelial as they lack contact with the ventricular surface. Using real-time imaging and clonal analysis, we demonstrate that these cells can undergo proliferative divisions and self-renewing asymmetric divisions to generate neuronal progenitor cells that can proliferate further. We also show that inhibition of Notch signalling in OSVZ progenitor cells induces their neuronal differentiation. The establishment of non-ventricular radial glia-like cells may have been a critical evolutionary advance underlying increased cortical size and complexity in the human brain.
C1 [Hansen, David V.; Lui, Jan H.; Parker, Philip R. L.; Kriegstein, Arnold R.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Hansen, David V.; Lui, Jan H.; Parker, Philip R. L.; Kriegstein, Arnold R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Lui, Jan H.] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA.
   [Parker, Philip R. L.] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Kriegstein, AR (corresponding author), Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM KriegsteinA@stemcell.ucsf.edu
FU California Institute for Regenerative Medicine; Bernard Osher Foundation; CIRM
NR 35
TC 999
Z9 1215
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 MAR 25
PY 2010
VL 464
IS 7288
BP 554
EP U110
DI 10.1038/nature08845
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200040
PM 20154730
DA 2026-03-09
ER

PT J
AU Lee, JH
   Durand, R
   Gradinaru, V
   Zhang, F
   Goshen, I
   Kim, DS
   Fenno, LE
   Ramakrishnan, C
   Deisseroth, K
AF Lee, Jin Hyung
   Durand, Remy
   Gradinaru, Viviana
   Zhang, Feng
   Goshen, Inbal
   Kim, Dae-Shik
   Fenno, Lief E.
   Ramakrishnan, Charu
   Deisseroth, Karl
TI Global and local fMRI signals driven by neurons defined optogenetically by type and wiring
SO NATURE
LA English
DT Article
ID optical technology; neural circuitry; cortex; interrogation; projections; systems; bold; rat
AB Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD)(1) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons(2). This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications(3). Using a novel integrated technology unifying optogenetic(4-13) control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKII alpha-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations 14 and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.
C1 [Lee, Jin Hyung] Univ Calif Los Angeles, Dept Elect Engn Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
   [Lee, Jin Hyung; Durand, Remy; Gradinaru, Viviana; Zhang, Feng; Goshen, Inbal; Fenno, Lief E.; Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Kim, Dae-Shik] Korea Adv Inst Sci & Technol, Dept Elect Engn, Taejon 305701, South Korea.
   [Kim, Dae-Shik] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 University of California System; University of California Los Angeles; Stanford University; Korea Advanced Institute of Science & Technology (KAIST); Boston University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Lee, JH (corresponding author), Univ Calif Los Angeles, Dept Elect Engn Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
EM ljinhy@gmail.com; deissero@stanford.edu
FU NIH [(K99/R00) 1K99EB008738]; NSF; SGF; SIGF; Deisseroth laboratory; Keck Foundation; Snyder Foundation; Woo Foundation; Yu Foundation; McKnight Foundation; Coulter Foundation; CIRM; NIMH; NIDA
NR 30
TC 504
Z9 613
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 JUN 10
PY 2010
VL 465
IS 7299
BP 788
EP 792
DI 10.1038/nature09108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800047
PM 20473285
DA 2026-03-09
ER

PT J
AU Hatzivassiliou, G
   Song, K
   Yen, I
   Brandhuber, BJ
   Anderson, DJ
   Alvarado, R
   Ludlam, MJC
   Stokoe, D
   Gloor, SL
   Vigers, G
   Morales, T
   Aliagas, I
   Liu, B
   Sideris, S
   Hoeflich, KP
   Jaiswal, BS
   Seshagiri, S
   Koeppen, H
   Belvin, M
   Friedman, LS
   Malek, S
AF Hatzivassiliou, Georgia
   Song, Kyung
   Yen, Ivana
   Brandhuber, Barbara J.
   Anderson, Daniel J.
   Alvarado, Ryan
   Ludlam, Mary J. C.
   Stokoe, David
   Gloor, Susan L.
   Vigers, Guy
   Morales, Tony
   Aliagas, Ignacio
   Liu, Bonnie
   Sideris, Steve
   Hoeflich, Klaus P.
   Jaiswal, Bijay S.
   Seshagiri, Somasekar
   Koeppen, Hartmut
   Belvin, Marcia
   Friedman, Lori S.
   Malek, Shiva
TI RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
SO NATURE
LA English
DT Article
ID b-raf; selective inhibitor; c-raf; kinase; phosphorylation; efficacy; potent; mutations; mechanism; proteins
AB Activating mutations in KRAS and BRAF are found in more than 30% of all human tumours and 40% of melanoma, respectively, thus targeting this pathway could have broad therapeutic effects(1). Small molecule ATP-competitive RAF kinase inhibitors have potent antitumour effects on mutant BRAF(V600E) tumours but, in contrast to mitogen-activated protein kinase kinase (MEK) inhibitors, are not potent against RAS mutant tumour models, despite RAF functioning as a key effector downstream of RAS and upstream of MEK2,3. Here we show that ATP-competitive RAF inhibitors have two opposing mechanisms of action depending on the cellular context. In BRAF(V600E) tumours, RAF inhibitors effectively block the mitogen-activated protein kinase (MAPK) signalling pathway and decrease tumour growth. Notably, in KRAS mutant and RAS/RAF wild-type tumours, RAF inhibitors activate the RAF-MEK-ERK pathway in a RAS-dependent manner, thus enhancing tumour growth in some xenograft models. Inhibitor binding activates wild-type RAF isoforms by inducing dimerization, membrane localization and interaction with RAS-GTP. These events occur independently of kinase inhibition and are, instead, linked to direct conformational effects of inhibitors on the RAF kinase domain. On the basis of these findings, we demonstrate that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signalling pathways, depending on the cellular context. Furthermore, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors.
C1 [Hatzivassiliou, Georgia; Song, Kyung; Yen, Ivana; Anderson, Daniel J.; Alvarado, Ryan; Ludlam, Mary J. C.; Stokoe, David; Aliagas, Ignacio; Liu, Bonnie; Sideris, Steve; Hoeflich, Klaus P.; Jaiswal, Bijay S.; Seshagiri, Somasekar; Koeppen, Hartmut; Belvin, Marcia; Friedman, Lori S.; Malek, Shiva] Genentech Inc, San Francisco, CA 94080 USA.
   [Brandhuber, Barbara J.; Gloor, Susan L.; Vigers, Guy; Morales, Tony] Array BioPharma, Boulder, CO 80301 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Pfizer; Pfizer USA; Array BioPharma
RP Hatzivassiliou, G (corresponding author), Genentech Inc, San Francisco, CA 94080 USA.
EM hatzivassiliou.georgia@gene.com; malek.shiva@gene.com
NR 33
TC 1336
Z9 1553
U1 3
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 431
EP U132
DI 10.1038/nature08833
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100051
PM 20130576
DA 2026-03-09
ER

PT J
AU Pohl, R
   Antognini, A
   Nez, F
   Amaro, FD
   Biraben, F
   Cardoso, JMR
   Covita, DS
   Dax, A
   Dhawan, S
   Fernandes, LMP
   Giesen, A
   Graf, T
   Hänsch, TW
   Indelicato, P
   Julien, L
   Kao, CY
   Knowles, P
   Le Bigot, EO
   Liu, YW
   Lopes, JAM
   Ludhova, L
   Monteiro, CMB
   Mulhauser, F
   Nebel, T
   Rabinowitz, P
   dos Santos, JMF
   Schaller, LA
   Schuhmann, K
   Schwob, C
   Taqqu, D
   Veloso, JFCA
   Kottmann, F
AF Pohl, Randolf
   Antognini, Aldo
   Nez, Francois
   Amaro, Fernando D.
   Biraben, Francois
   Cardoso, Joao M. R.
   Covita, Daniel S.
   Dax, Andreas
   Dhawan, Satish
   Fernandes, Luis M. P.
   Giesen, Adolf
   Graf, Thomas
   Haensch, Theodor W.
   Indelicato, Paul
   Julien, Lucile
   Kao, Cheng-Yang
   Knowles, Paul
   Le Bigot, Eric-Olivier
   Liu, Yi-Wei
   Lopes, Jose A. M.
   Ludhova, Livia
   Monteiro, Cristina M. B.
   Mulhauser, Francoise
   Nebel, Tobias
   Rabinowitz, Paul
   dos Santos, Joaquim M. F.
   Schaller, Lukas A.
   Schuhmann, Karsten
   Schwob, Catherine
   Taqqu, David
   Veloso, Joao F. C. A.
   Kottmann, Franz
TI The size of the proton
SO NATURE
LA English
DT Article
ID lamb-shift experiment; muonic hydrogen; rydberg constant; atoms; frequency; deuterium; radius; laser; mu
AB The proton is the primary building block of the visible Universe, but many of its properties-such as its charge radius and its anomalous magneticmoment-are not well understood. The root-meansquare charge radius, r(p), has been determined with an accuracy of 2 per cent (at best) by electron-proton scattering experiments(1,2). The present most accurate value of r(p) (with an uncertainty of 1 per cent) is given by the CODATA compilation of physical constants(3). This value is based mainly on precision spectroscopy of atomic hydrogen(4-7) and calculations of bound-state quantum electrodynamics (QED; refs 8, 9). The accuracy of r(p) as deduced from electron-proton scattering limits the testing of bound-state QED in atomic hydrogen as well as the determination of the Rydberg constant (currently the most accurately measured fundamental physical constant 3). An attractive means to improve the accuracy in the measurement of r(p) is provided by muonic hydrogen (a proton orbited by a negative muon); its much smaller Bohr radius compared to ordinary atomic hydrogen causes enhancement of effects related to the finite size of the proton. In particular, the Lamb shift 10 (the energy difference between the 2S(1/2) and 2P(1/2) states) is affected by as much as 2 per cent. Here we use pulsed laser spectroscopy to measure a muonic Lamb shift of 49,881.88(76) GHz. On the basis of present calculations(11-15) of fine and hyperfine splittings and QED terms, we find r(p) = 0.84184(67) fm, which differs by 5.0 standard deviations from the CODATA value(3) of 0.8768(69) fm. Our result implies that either the Rydberg constant has to be shifted by 2110 kHz/c (4.9 standard deviations), or the calculations of the QED effects in atomic hydrogen or muonic hydrogen atoms are insufficient.
C1 [Pohl, Randolf; Antognini, Aldo; Haensch, Theodor W.; Nebel, Tobias] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Nez, Francois; Biraben, Francois; Indelicato, Paul; Julien, Lucile; Le Bigot, Eric-Olivier; Schwob, Catherine] Ecole Normale Super, CNRS, Lab Kastler Brossel, F-75252 Paris 05, France.
   [Nez, Francois; Biraben, Francois; Indelicato, Paul; Julien, Lucile; Le Bigot, Eric-Olivier; Schwob, Catherine] Univ Paris 06, F-75252 Paris 05, France.
   [Amaro, Fernando D.; Cardoso, Joao M. R.; Covita, Daniel S.; Fernandes, Luis M. P.; Lopes, Jose A. M.; Monteiro, Cristina M. B.; dos Santos, Joaquim M. F.] Univ Coimbra, Dept Fis, P-3004516 Coimbra, Portugal.
   [Covita, Daniel S.; Veloso, Joao F. C. A.] Univ Aveiro, Dept Fis, I3N, P-3810193 Aveiro, Portugal.
   [Dax, Andreas; Dhawan, Satish] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Giesen, Adolf; Graf, Thomas] Univ Stuttgart, Inst Strahlwerkzeuge, D-70569 Stuttgart, Germany.
   [Kao, Cheng-Yang; Liu, Yi-Wei] Natl Tsing Hua Univ, Dept Phys, Hsinchu 300, Taiwan.
   [Indelicato, Paul; Ludhova, Livia; Mulhauser, Francoise; Schaller, Lukas A.] Univ Fribourg, Dept Phys, CH-1700 Fribourg, Switzerland.
   [Rabinowitz, Paul] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
   [Schuhmann, Karsten] Dausinger & Giesen GmbH, D-70178 Stuttgart, Germany.
   [Taqqu, David] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
   [Kottmann, Franz] ETH, Inst Teilchenphys, CH-8093 Zurich, Switzerland.
C3 Max Planck Society; Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Sorbonne Universite; Universidade de Coimbra; Universidade de Aveiro; Yale University; University of Stuttgart; National Tsing Hua University; University of Fribourg; Princeton University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Pohl, R (corresponding author), Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
EM randolf.pohl@mpq.mpg.de
FU Max Planck Society; Max Planck Foundation; Swiss National Science Foundation [200020-100632]; Swiss Academy of Engineering Sciences; BQR de l'UFR de physique fondamentale et appliquee de l'Universite Paris 6; ministere des affaires etrangeres France [07819NH]; Fundacao para a Ciencia e a Tecnologia (Portugal); FEDER [PTDC/FIS/82006/2006, SFRH/BPD/46611/2008]; ExtreMe Matter Institute [HA216/EMMI]; Fundação para a Ciência e a Tecnologia [SFRH/BPD/46611/2008, PTDC/FIS/82006/2006] Funding Source: FCT
NR 33
TC 1081
Z9 1236
U1 3
U2 256
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 213
EP 216
DI 10.1038/nature09250
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800031
PM 20613837
DA 2026-03-09
ER

PT J
AU Jacob, Y
   Stroud, H
   LeBlanc, C
   Feng, SH
   Zhuo, LT
   Caro, E
   Hassel, C
   Gutierrez, C
   Michaels, SD
   Jacobsen, SE
AF Jacob, Yannick
   Stroud, Hume
   LeBlanc, Chantal
   Feng, Suhua
   Zhuo, Luting
   Caro, Elena
   Hassel, Christiane
   Gutierrez, Crisanto
   Michaels, Scott D.
   Jacobsen, Steven E.
TI Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; gene repression; methylation; set; protein; rereplication; maintenance; genome; pcna; fork
AB Multiple pathways prevent DNA replication from occurring more than once per cell cycle(1). These pathways block re-replication by strictly controlling the activity of pre-replication complexes, which assemble at specific sites in the genome called origins. Here we show that mutations in the homologous histone 3 lysine 27 (H3K27) monomethyltransferases, ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) and ATXR6, lead to re-replication of specific genomic locations. Most of these locations correspond to transposons and other repetitive and silent elements of the Arabidopsis genome. These sites also correspond to high levels of H3K27 monomethylation, and mutation of the catalytic SET domain is sufficient to cause the re-replication defect. Mutation of ATXR5 and ATXR6 also causes upregulation of transposon expression and has pleiotropic effects on plant development. These results uncover a novel pathway that prevents over-replication of heterochromatin in Arabidopsis.
C1 [Jacob, Yannick; LeBlanc, Chantal; Zhuo, Luting; Hassel, Christiane; Michaels, Scott D.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Stroud, Hume; Caro, Elena; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Gutierrez, Crisanto] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain.
C3 Indiana University System; Indiana University Bloomington; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Biologia Molecular Severo Ochoa (CBM); Autonomous University of Madrid
RP Michaels, SD (corresponding author), Indiana Univ, Dept Biol, 915 E 3rd St, Bloomington, IN 47405 USA.
EM michaels@indiana.edu; jacobsen@ucla.edu
FU Le Fonds Quebecois de la Recherche sur la Nature et les Technologies (FQRNT); National Institutes of Health [GM075060]; Indiana METACyt Initiative of Indiana University; Lilly Endowment, Inc.; Spanish Ministry of Science and Innovation [BFU2009-9783, CSD2007-57B]
NR 29
TC 149
Z9 179
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 AUG 19
PY 2010
VL 466
IS 7309
BP 987
EP U117
DI 10.1038/nature09290
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300037
PM 20631708
DA 2026-03-09
ER

PT J
AU Bilgüvar, K
   Öztürk, AK
   Louvi, A
   Kwan, KY
   Choi, M
   Tatli, B
   Yalnizoglu, D
   Tüysüz, B
   Çaglayan, AO
   Gökben, S
   Kaymakçalan, H
   Barak, T
   Bakircioglu, M
   Yasuno, K
   Ho, W
   Sanders, S
   Zhu, Y
   Yilmaz, S
   Dinçer, A
   Johnson, MH
   Bronen, RA
   Koçer, N
   Per, H
   Mane, S
   Pamir, MN
   Yalçinkaya, C
   Kumandas, S
   Topçu, M
   Özmen, M
   Sestan, N
   Lifton, RP
   State, MW
   Günel, M
AF Bilguvar, Kaya
   Ozturk, Ali Kemal
   Louvi, Angeliki
   Kwan, Kenneth Y.
   Choi, Murim
   Tatli, Burak
   Yalnizoglu, Dilek
   Tuysuz, Beyhan
   Caglayan, Ahmet Okay
   Gokben, Sarenur
   Kaymakcalan, Hande
   Barak, Tanyeri
   Bakircioglu, Mehmet
   Yasuno, Katsuhito
   Ho, Winson
   Sanders, Stephan
   Zhu, Ying
   Yilmaz, Sanem
   Dincer, Alp
   Johnson, Michele H.
   Bronen, Richard A.
   Kocer, Naci
   Per, Hueseyin
   Mane, Shrikant
   Pamir, Mehmet Necmettin
   Yalcinkaya, Cengiz
   Kumandas, Sefer
   Topcu, Meral
   Ozmen, Meral
   Sestan, Nenad
   Lifton, Richard P.
   State, Matthew W.
   Gunel, Murat
TI Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations
SO NATURE
LA English
DT Article
ID human cerebral-cortex; genetic malformations; classification; slitrk1; capture
AB The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers(1,2). An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development(3-6). Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.
C1 [Bilguvar, Kaya; Ozturk, Ali Kemal; Louvi, Angeliki; Choi, Murim; Barak, Tanyeri; Bakircioglu, Mehmet; Yasuno, Katsuhito; Ho, Winson; Sanders, Stephan; Mane, Shrikant; Lifton, Richard P.; State, Matthew W.; Gunel, Murat] Yale Univ, Sch Med, Dept Genet, Ctr Human Genet & Genom, New Haven, CT 06510 USA.
   [Bilguvar, Kaya; Ozturk, Ali Kemal; Louvi, Angeliki; Choi, Murim; Barak, Tanyeri; Bakircioglu, Mehmet; Yasuno, Katsuhito; Ho, Winson; Sanders, Stephan; Mane, Shrikant; Lifton, Richard P.; State, Matthew W.; Gunel, Murat] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT 06510 USA.
   [Bilguvar, Kaya; Ozturk, Ali Kemal; Louvi, Angeliki; Barak, Tanyeri; Bakircioglu, Mehmet; Yasuno, Katsuhito; Ho, Winson; Johnson, Michele H.; Bronen, Richard A.; Gunel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA.
   [Bilguvar, Kaya; Ozturk, Ali Kemal; Louvi, Angeliki; Kwan, Kenneth Y.; Barak, Tanyeri; Bakircioglu, Mehmet; Yasuno, Katsuhito; Ho, Winson; Zhu, Ying; Sestan, Nenad; Gunel, Murat] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
   [Kwan, Kenneth Y.; Zhu, Ying; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
   [Tatli, Burak; Ozmen, Meral] Istanbul Univ, Istanbul Fac Med, Dept Pediat, Div Neurol, TR-34093 Istanbul, Turkey.
   [Yalnizoglu, Dilek; Topcu, Meral] Hacettepe Univ, Sch Med, Dept Pediat, Div Neurol, TR-06100 Ankara, Turkey.
   [Tuysuz, Beyhan] Istanbul Univ, Cerrahpasa Fac Med, Dept Pediat, Div Genet, TR-34098 Istanbul, Turkey.
   [Caglayan, Ahmet Okay] Kayseri Educ & Res Hosp, Dept Med Genet, TR-38010 Kayseri, Turkey.
   [Gokben, Sarenur; Yilmaz, Sanem] Ege Univ, Fac Med, Dept Pediat, Div Neurol, TR-35100 Izmir, Turkey.
   [Kaymakcalan, Hande] Bahcesehir Univ, Fac Arts & Sci, TR-34353 Istanbul, Turkey.
   [Sanders, Stephan; State, Matthew W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
   [Sanders, Stephan; State, Matthew W.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA.
   [Dincer, Alp] Acibadem Univ, Sch Med, Dept Radiol, TR-34742 Istanbul, Turkey.
   [Johnson, Michele H.; Bronen, Richard A.] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA.
   [Johnson, Michele H.] Yale Univ, Sch Med, Dept Otolaryngol, New Haven, CT 06510 USA.
   [Kocer, Naci] Istanbul Univ, Cerrahpasa Fac Med, Dept Radiol, TR-34098 Istanbul, Turkey.
   [Per, Hueseyin; Kumandas, Sefer] Erciyes Univ, Sch Med, Dept Pediat, Div Neurol, TR-38039 Kayseri, Turkey.
   [Mane, Shrikant] Yale Univ, Sch Med, Yale Ctr Genome Anal, New Haven, CT 06510 USA.
   [Pamir, Mehmet Necmettin] Acibadem Univ, Sch Med, Dept Neurosurg, TR-34742 Istanbul, Turkey.
   [Yalcinkaya, Cengiz] Istanbul Univ, Cerrahpasa Fac Med, Dept Neurol, Div Child Neurol, TR-34098 Istanbul, Turkey.
   [Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
C3 Yale University; Yale University; Yale University; Yale University; Yale University; Istanbul University; Hacettepe University; Istanbul University - Cerrahpasa; Istanbul University; Kayseri Training & Research Hospital; Ege University; Bahcesehir University; Yale University; Yale University; Acibadem University; Yale University; Yale University; Istanbul University; Istanbul University - Cerrahpasa; Erciyes University; Yale University; Acibadem University; Istanbul University; Istanbul University - Cerrahpasa; Yale University; Howard Hughes Medical Institute
RP Lifton, RP (corresponding author), Yale Univ, Sch Med, Dept Genet, Ctr Human Genet & Genom, New Haven, CT 06510 USA.
EM richard.lifton@yale.edu; matthew.state@yale.edu; murat.gunel@yale.edu
FU Yale Program on Neurogenetics; Yale Center for Human Genetics and Genomics; National Institutes of Health [RC2 NS070477, UL1 RR024139NIH, UO1MH081896]; National Institutes of Health Neuroscience Microarray Consortium [U24 NS051869-02S1]
NR 25
TC 381
Z9 471
U1 1
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 207
EP U93
DI 10.1038/nature09327
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300034
PM 20729831
DA 2026-03-09
ER

PT J
AU Miyagoshi, T
   Kageyama, A
   Sato, T
AF Miyagoshi, Takehiro
   Kageyama, Akira
   Sato, Tetsuya
TI Zonal flow formation in the Earth's core
SO NATURE
LA English
DT Article
ID deep convection; rayleigh number; driven; field; jets
AB Zonal jets are very common in nature. Well-known examples are those in the atmospheres of giant planets and the alternating jet streams found in the Earth's world ocean(1). Zonal flow formation in nuclear fusion devices is also well studied(2). A common feature of these zonal flows is that they are spontaneously generated in turbulent systems. Because the Earth's outer core is believed to be in a turbulent state, it is possible that there is zonal flow in the liquid iron of the outer core. Here we report an investigation at the current low-viscosity limit of numerical simulations of the geodynamo. We find a previously unknown convection regime of the outer core that has a dual structure comprising inner, sheet-like radial plumes and an outer, westward cylindrical zonal flow. We numerically confirm that the dual-convection structure with such a zonal flow is stable under a strong, self-generated dipole magnetic field.
C1 [Kageyama, Akira] Kobe Univ, Grad Sch Engn, Kobe, Hyogo 6578501, Japan.
   [Miyagoshi, Takehiro] Japan Agcy Marine Earth Sci & Technol, Yokohama, Kanagawa 2360001, Japan.
   [Sato, Tetsuya] Univ Hyogo, Kobe, Hyogo 6500044, Japan.
C3 Kobe University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); University of Hyogo
RP Kageyama, A (corresponding author), Kobe Univ, Grad Sch Engn, Kobe, Hyogo 6578501, Japan.
EM kage@cs.kobe-u.ac.jp
FU KAKENHI [17540404]; Mitsubishi Foundation; Grants-in-Aid for Scientific Research [17540404] Funding Source: KAKEN
NR 26
TC 47
Z9 50
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 793
EP U102
DI 10.1038/nature08754
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300036
PM 20148036
DA 2026-03-09
ER

PT J
AU Ortega, F
   Escaso, F
   Sanz, JL
AF Ortega, Francisco
   Escaso, Fernando
   Sanz, Jose L.
TI A bizarre, humped Carcharodontosauria (Theropoda) from the Lower Cretaceous of Spain
SO NATURE
LA English
DT Article
ID dinosaur; feather; phylogeny; evolution
AB Carcharodontosaurs were the largest predatory dinosaurs, and their early evolutionary history seems to be more intricate than was previously thought. Until recently, carcharodontosaurs were restricted to a group of large theropods inhabiting the Late Cretaceous Gondwanan land masses(1,2), but in the last few years Laurasian evidence(3-5) has been causing a reevaluation of their initial diversification(6). Here we describe an almost complete and exquisitely preserved skeleton of a medium-sized (roughly six metres long) theropod from the Lower Cretaceous series (Barremian stage) Konservat-Lagerstatte of Las Hoyas(7) in Cuenca, Spain. Cladistic analysis supports the idea that the new taxon Concavenator corcovatus is a primitive member of Carcharodontosauria(6), exhibiting two unusual features: elongation of the neurapophyses of two presacral vertebrae forming a pointed, hump-like structure and a series of small bumps on the ulna. We think that these bumps are homologous to quill knobs present on some modern birds; the knobs are related to the insertion area of follicular ligaments that anchor the roots of the flight feathers (remiges) to the arm. We propose that Concavenator has integumentary follicular structures inserted on the ulna, as in modern birds. Because scales do not have follicles, we consider the structures anchored to the Concavenator arms to be non-scale skin appendages homologous to the feathers of modern birds. If this is true, then the phylogenetic bracket for the presence of non-scale skin structures homologous to feathers in theropod dinosaurs would be extended to the Neotetanurae, enlarging the scope for explaining the origin of feathers in theropods.
C1 [Ortega, Francisco; Escaso, Fernando] Univ Nacl Educ Distancia, Fac Ciencias, Dept Fis Matemat & Fluidos, Grp Biol, E-28040 Madrid, Spain.
   [Escaso, Fernando; Sanz, Jose L.] Univ Autonoma Madrid, Fac Ciencias, Dept Biol, Unidad Paleontol, E-28049 Madrid, Spain.
C3 Universidad Nacional de Educacion a Distancia (UNED); Autonomous University of Madrid
RP Ortega, F (corresponding author), Univ Nacl Educ Distancia, Fac Ciencias, Dept Fis Matemat & Fluidos, Grp Biol, Paseo Senda del Rey 9, E-28040 Madrid, Spain.
EM fortega@ccia.uned.es
FU Museo de las Ciencias de Castilla-La Mancha; Spanish Ministerio de Ciencia e Innovacion [CGL2005-05614]
NR 30
TC 97
Z9 115
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 203
EP 206
DI 10.1038/nature09181
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300033
PM 20829793
DA 2026-03-09
ER

PT J
AU Carro, MS
   Lim, WK
   Alvarez, MJ
   Bollo, RJ
   Zhao, XD
   Snyder, EY
   Sulman, EP
   Anne, SL
   Doetsch, F
   Colman, H
   Lasorella, A
   Aldape, K
   Califano, A
   Iavarone, A
AF Carro, Maria Stella
   Lim, Wei Keat
   Alvarez, Mariano Javier
   Bollo, Robert J.
   Zhao, Xudong
   Snyder, Evan Y.
   Sulman, Erik P.
   Anne, Sandrine L.
   Doetsch, Fiona
   Colman, Howard
   Lasorella, Anna
   Aldape, Ken
   Califano, Andrea
   Iavarone, Antonio
TI The transcriptional network for mesenchymal transformation of brain tumours
SO NATURE
LA English
DT Article
ID growth-factor receptor; neural stem-cell; c-myc; expression; differentiation; mechanisms; binding; survival; proliferation; gliogenesis
AB The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBP beta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBP beta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBP beta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells.
C1 [Carro, Maria Stella; Zhao, Xudong; Anne, Sandrine L.; Lasorella, Anna; Califano, Andrea; Iavarone, Antonio] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
   [Lim, Wei Keat; Califano, Andrea] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA.
   [Lim, Wei Keat; Alvarez, Mariano Javier; Califano, Andrea] Columbia Univ, Med Ctr, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Alvarez, Mariano Javier; Califano, Andrea] Columbia Univ, Med Ctr, Joint Ctr Syst Biol, New York, NY 10032 USA.
   [Doetsch, Fiona; Lasorella, Anna; Iavarone, Antonio] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA.
   [Lasorella, Anna] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
   [Iavarone, Antonio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA.
   [Bollo, Robert J.] NYU, Sch Med, Dept Neurosurg, New York, NY 10016 USA.
   [Bollo, Robert J.] NYU, Langone Med Ctr, New York, NY 10016 USA.
   [Snyder, Evan Y.] Burnham Inst Med Res, La Jolla, CA 92037 USA.
   [Sulman, Erik P.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA.
   [Colman, Howard] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
   [Aldape, Ken] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; New York University; NYU Langone Medical Center; New York University; Sanford Burnham Prebys Medical Discovery Institute; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
RP Califano, A (corresponding author), Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA.
EM califano@c2b2.columbia.edu; ai2102@columbia.edu
FU National Institute of Health [R01CA109755, R01CA101644, R01CA085628, R01NS061776]; NCI Grand Opportunities TDDN Network [1RC2CA148308-01]; In Silico Research Centre of Excellence [NCI-caBIG 29XS192]; National Centers for Biomedical Computing NIH Roadmap Initiative [U54CA121852]; National Institute of General Medical Sciences [P20GM075059]; Italian Ministry of Welfare/Provincia di Benevento; Fondation de Recherche Medicale
NR 52
TC 1012
Z9 1159
U1 3
U2 144
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 318
EP U68
DI 10.1038/nature08712
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100036
PM 20032975
DA 2026-03-09
ER

PT J
AU Altshuler, DM
   Gibbs, RA
   Peltonen, L
   Dermitzakis, E
   Schaffner, SF
   Yu, FL
   Bonnen, PE
   de Bakker, PIW
   Deloukas, P
   Gabriel, SB
   Gwilliam, R
   Hunt, S
   Inouye, M
   Jia, XM
   Palotie, A
   Parkin, M
   Whittaker, P
   Chang, K
   Hawes, A
   Lewis, LR
   Ren, YR
   Wheeler, D
   Muzny, DM
   Barnes, C
   Darvishi, K
   Hurles, M
   Korn, JM
   Kristiansson, K
   Lee, C
   McCarroll, SA
   Nemesh, J
   Keinan, A
   Montgomery, SB
   Pollack, S
   Price, AL
   Soranzo, N
   Gonzaga-Jauregui, C
   Anttila, V
   Brodeur, W
   Daly, MJ
   Leslie, S
   McVean, G
   Moutsianas, L
   Nguyen, H
   Zhang, QR
   Ghori, MJR
   McGinnis, R
   McLaren, W
   Takeuchi, F
   Grossman, SR
   Shlyakhter, I
   Hostetter, EB
   Sabeti, PC
   Adebamowo, CA
   Foster, MW
   Gordon, DR
   Licinio, J
   Manca, MC
   Marshall, PA
   Matsuda, I
   Ngare, D
   Wang, VO
   Reddy, D
   Rotimi, CN
   Royal, CD
   Sharp, RR
   Zeng, CQ
   Brooks, LD
   McEwen, JE
AF Altshuler, David M.
   Gibbs, Richard A.
   Peltonen, Leena
   Dermitzakis, Emmanouil
   Schaffner, Stephen F.
   Yu, Fuli
   Bonnen, Penelope E.
   de Bakker, Paul I. W.
   Deloukas, Panos
   Gabriel, Stacey B.
   Gwilliam, Rhian
   Hunt, Sarah
   Inouye, Michael
   Jia, Xiaoming
   Palotie, Aarno
   Parkin, Melissa
   Whittaker, Pamela
   Chang, Kyle
   Hawes, Alicia
   Lewis, Lora R.
   Ren, Yanru
   Wheeler, David
   Muzny, Donna Marie
   Barnes, Chris
   Darvishi, Katayoon
   Hurles, Matthew
   Korn, Joshua M.
   Kristiansson, Kati
   Lee, Charles
   McCarroll, Steven A.
   Nemesh, James
   Keinan, Alon
   Montgomery, Stephen B.
   Pollack, Samuela
   Price, Alkes L.
   Soranzo, Nicole
   Gonzaga-Jauregui, Claudia
   Anttila, Verneri
   Brodeur, Wendy
   Daly, Mark J.
   Leslie, Stephen
   McVean, Gil
   Moutsianas, Loukas
   Nguyen, Huy
   Zhang, Qingrun
   Ghori, Mohammed J. R.
   McGinnis, Ralph
   McLaren, William
   Takeuchi, Fumihiko
   Grossman, Sharon R.
   Shlyakhter, Ilya
   Hostetter, Elizabeth B.
   Sabeti, Pardis C.
   Adebamowo, Clement A.
   Foster, Morris W.
   Gordon, Deborah R.
   Licinio, Julio
   Manca, Maria Cristina
   Marshall, Patricia A.
   Matsuda, Ichiro
   Ngare, Duncan
   Wang, Vivian Ota
   Reddy, Deepa
   Rotimi, Charles N.
   Royal, Charmaine D.
   Sharp, Richard R.
   Zeng, Changqing
   Brooks, Lisa D.
   McEwen, Jean E.
TI Integrating common and rare genetic variation in diverse human populations
SO NATURE
LA English
DT Article
ID genome-wide association; copy number variation; positive selection; haplotype map; variants; diseases; signals; regions; snps
AB Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of <= 5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.
C1 [Altshuler, David M.; Schaffner, Stephen F.; de Bakker, Paul I. W.; Gabriel, Stacey B.; Jia, Xiaoming; Parkin, Melissa; Korn, Joshua M.; McCarroll, Steven A.; Pollack, Samuela; Brodeur, Wendy; Nguyen, Huy; Shlyakhter, Ilya] Broad Inst, Cambridge, MA 02138 USA.
   [Gibbs, Richard A.; Yu, Fuli; Bonnen, Penelope E.; Chang, Kyle; Hawes, Alicia; Lewis, Lora R.; Ren, Yanru; Wheeler, David; Muzny, Donna Marie; Gonzaga-Jauregui, Claudia] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Dermitzakis, Emmanouil; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, Fac Med, CH-1211 Geneva, Switzerland.
   [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA.
   [Deloukas, Panos; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Palotie, Aarno; Whittaker, Pamela; Barnes, Chris; Hurles, Matthew; Kristiansson, Kati; Soranzo, Nicole; Anttila, Verneri; Zhang, Qingrun; Ghori, Mohammed J. R.; McGinnis, Ralph; McLaren, William; Takeuchi, Fumihiko] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge CB10 1HH, England.
   [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland.
   [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Dept Med Genet, FIN-00290 Helsinki, Finland.
   [Palotie, Aarno; Anttila, Verneri] Univ Cent Hosp, Helsinki 00290, Finland.
   [Darvishi, Katayoon; Lee, Charles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Keinan, Alon] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 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.
   [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Ctr, Boston, MA 02114 USA.
   [Leslie, Stephen; McVean, Gil; Moutsianas, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Grossman, Sharon R.; Hostetter, Elizabeth B.; Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02215 USA.
   [Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Preventat Med, Inst Human Virol N406, Baltimore, MD 21201 USA.
   [Foster, Morris W.] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA.
   [Gordon, Deborah R.] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA.
   [Licinio, Julio] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2603, Australia.
   [Manca, Maria Cristina] Inst Oncol Study & Prevent, I-50139 Florence, Italy.
   [Marshall, Patricia A.] Case Western Reserve Univ, Dept Bioeth, Sch Med TA200, Cleveland, OH 44106 USA.
   [Matsuda, Ichiro] Hlth Sci Univ Hokkaido, Tobetsu, Hokkaido 0610293, Japan.
   [Ngare, Duncan] Moi Univ, Dept Populat & Family Hlth, Eldoret 30100, Kenya.
   [Wang, Vivian Ota; Brooks, Lisa D.; McEwen, Jean E.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Reddy, Deepa] Univ Houston Clear Lake City, Dept Anthropol, Houston, TX 77058 USA.
   [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
   [Royal, Charmaine D.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Sharp, Richard R.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44124 USA.
   [Zeng, Changqing] Chinese Acad Sci, Beijing Inst Genom, Beijing 101300, Peoples R China.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Baylor College of Medicine; University of Geneva; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Wellcome Trust Sanger Institute; University of Helsinki; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Cornell University; 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; Massachusetts General Hospital; University of Oxford; Harvard University; University System of Maryland; University of Maryland Baltimore; University of Oklahoma System; University of Oklahoma - Norman; University of California System; University of California San Francisco; Australian National University; John Curtin School of Medical Research; University System of Ohio; Case Western Reserve University; Health Sciences University of Hokkaido; Moi University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Houston System; University of Houston; University of Houston Clear Lake; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Duke University; Cleveland Clinic Foundation; Chinese Academy of Sciences; Beijing Institute of Genomics, CAS
RP Altshuler, DM (corresponding author), Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02138 USA.
EM altshuler@molbio.mgh.harvard.edu; agibbs@bcm.edu
FU USA National Institutes of Health; National Human Genome Research Institute; National Institute on Deafness and Other Communication Disorders; Wellcome Trust [068545/Z/02, 076113]; Louis-Jeantet Foundation; NCCR 'Frontiers in Genetics' (Swiss National Science Foundation); UK Medical Research Council [G0000934]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER; Medical Research Council [G0000934] Funding Source: researchfish; MRC [G0000934] Funding Source: UKRI
NR 27
TC 2170
Z9 2541
U1 2
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 SEP 2
PY 2010
VL 467
IS 7311
BP 52
EP 58
DI 10.1038/nature09298
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200033
PM 20811451
DA 2026-03-09
ER

PT J
AU Li, SL
   Miller, N
   Lin, DNC
   Fortney, JJ
AF Li, Shu-lin
   Miller, N.
   Lin, Douglas N. C.
   Fortney, Jonathan J.
TI WASP-12b as a prolate, inflated and disrupting planet from tidal dissipation
SO NATURE
LA English
DT Article
ID giant planets; extrasolar planet; stars; period; disks; accretion; evolution; radii; orbit; mass
AB The class of exotic Jupiter-mass planets that orbit very close to their parent stars were not explicitly expected before their discovery(1). The recently discovered(2) transiting planet WASP-12b has a mass M = 1.4 +/- 0.1 Jupiter masses (M-J), a mean orbital distance of only 3.1 stellar radii ( meaning it is subject to intense tidal forces), and a period of 1.1 days. Its radius 1.79 +/- 0.09 R-J is unexpectedly large and its orbital eccentricity 0.049 +/- 0.015 is even more surprising because such close orbits are usually quickly circularized. Here we report an analysis of its properties, which reveals that the planet is losing mass to its host star at a rate of about 10(-7) M-J per year. The planet's surface is distorted by the star's gravity and the light curve produced by its prolate shape will differ by about ten per cent from that of a spherical planet. We conclude that dissipation of the star's tidal perturbation in the planet's convective envelope provides the energy source for its large volume. We predict up to 10 mJy CO band-head (2.292 mu m) emission from a tenuous disk around the host star, made up of tidally stripped planetary gas. It may also contain a detectable resonant super-Earth, as a hypothetical perturber that continually stirs up WASP-12b's eccentricity.
C1 [Li, Shu-lin] Peking Univ, Dept Astron, Beijing 100871, Peoples R China.
   [Li, Shu-lin; Lin, Douglas N. C.] Peking Univ, Kavli Inst Astron & Astrophys, Beijing 100871, Peoples R China.
   [Miller, N.; Lin, Douglas N. C.; Fortney, Jonathan J.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
C3 Peking University; Peking University; University of California System; University of California Santa Cruz
RP Lin, DNC (corresponding author), Chinese Acad Sci, Natl Astron Observ China, Beijing 100012, Peoples R China.
EM lin@ucolick.org
FU Kavli Foundation; NASA; JPL; NSF; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908807] Funding Source: National Science Foundation
NR 26
TC 112
Z9 129
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 FEB 25
PY 2010
VL 463
IS 7284
BP 1054
EP 1056
DI 10.1038/nature08715
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400030
PM 20182506
DA 2026-03-09
ER

PT J
AU Cafaro, J
   Rieke, F
AF Cafaro, Jon
   Rieke, Fred
TI Noise correlations improve response fidelity and stimulus encoding
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; feedforward inhibition; firing rate; cortex; variability; selectivity; excitation; neurons; information; integration
AB Computation in the nervous system often relies on the integration of signals from parallel circuits with different functional properties. Correlated noise in these inputs can, in principle, have diverse and dramatic effects on the reliability of the resulting computations(1-8). Such theoretical predictions have rarely been tested experimentally because of a scarcity of preparations that permit measurement of both the covariation of a neuron's input signals and the effect on a cell's output of manipulating such covariation. Here we introduce a method to measure covariation of the excitatory and inhibitory inputs a cell receives. This method revealed strong correlated noise in the inputs to two types of retinal ganglion cell. Eliminating correlated noise without changing other input properties substantially decreased the accuracy with which a cell's spike outputs encoded light inputs. Thus, covariation of excitatory and inhibitory inputs can be a critical determinant of the reliability of neural coding and computation.
C1 [Rieke, Fred] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Cafaro, Jon; Rieke, Fred] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
C3 Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Rieke, F (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM rieke@u.washington.edu
FU HHMI; NIH [EY-11850]
NR 32
TC 109
Z9 136
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 964
EP U363
DI 10.1038/nature09570
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600047
PM 21131948
DA 2026-03-09
ER

PT J
AU Frank, DC
   Esper, J
   Raible, CC
   Büntgen, U
   Trouet, V
   Stocker, B
   Joos, F
AF Frank, David C.
   Esper, Jan
   Raible, Christoph C.
   Buentgen, Ulf
   Trouet, Valerie
   Stocker, Benjamin
   Joos, Fortunat
TI Ensemble reconstruction constraints on the global carbon cycle sensitivity to climate
SO NATURE
LA English
DT Article
ID northern-hemisphere temperatures; atmospheric co2; last millennium; antarctic ice; feedbacks; commitments; resolution; holocene; core
AB The processes controlling the carbon flux and carbon storage of the atmosphere, ocean and terrestrial biosphere are temperature sensitive(1-4) and are likely to provide a positive feedback leading to amplified anthropogenic warming(3). Owing to this feedback, at time-scales ranging from interannual to the 20-100-kyr cycles of Earth's orbital variations(1,5-7), warming of the climate system causes a net release of CO2 into the atmosphere; this in turn amplifies warming. But the magnitude of the climate sensitivity of the global carbon cycle (termed gamma), and thus of its positive feedback strength, is under debate, giving rise to large uncertainties in global warming projections(8,9). Here we quantify the median gamma as 7.7 p. p. m. v. CO2 per degrees C warming, with a likely range of 1.7-21.4 p. p. m. v. CO2 per degrees C. Sensitivity experiments exclude significant influence of pre-industrial land-use change on these estimates. Our results, based on the coupling of a probabilistic approach with an ensemble of proxy-based temperature reconstructions and pre-industrial CO2 data from three ice cores, provide robust constraints for gamma on the policy-relevant multi-decadal to centennial timescales. By using an ensemble of >200,000 members, quantification of gamma is not only improved, but also likelihoods can be assigned, thereby providing a benchmark for future model simulations. Although uncertainties do not at present allow exclusion of gamma calculated from any of ten coupled carbon-climate models, we find that gamma is about twice as likely to fall in the lowermost than in the uppermost quartile of their range. Our results are incompatibly lower (P < 0.05) than recent pre-industrial empirical estimates of similar to 40 p. p. m. v. CO2 per degrees C (refs 6, 7), and correspondingly suggest similar to 80% less potential amplification of ongoing global warming.
C1 [Frank, David C.; Buentgen, Ulf; Trouet, Valerie] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Frank, David C.; Raible, Christoph C.; Stocker, Benjamin; Joos, Fortunat] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Esper, Jan] Johannes Gutenberg Univ Mainz, Dept Geog, D-55099 Mainz, Germany.
   [Raible, Christoph C.; Stocker, Benjamin; Joos, Fortunat] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Bern; Johannes Gutenberg University of Mainz; University of Bern
RP Frank, DC (corresponding author), Swiss Fed Res Inst WSL, Zurcherstr 111, CH-8903 Birmensdorf, Switzerland.
EM david.frank@wsl.ch
FU Swiss National Science Foundation (NCCR-Climate); European Union [226701, 017008]
NR 46
TC 216
Z9 236
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 JAN 28
PY 2010
VL 463
IS 7280
BP 527
EP U143
DI 10.1038/nature08769
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100048
PM 20110999
DA 2026-03-09
ER

PT J
AU Pakull, MW
   Soria, R
   Motch, C
AF Pakull, Manfred W.
   Soria, Roberto
   Motch, Christian
TI A 300-parsec-long jet-inflated bubble around a powerful microquasar in the galaxy NGC 7793
SO NATURE
LA English
DT Article
ID x-ray sources; supernova-remnants; radio; model
AB Black-hole accretion states near or above the Eddington luminosity (the point at which radiation force outwards overcomes gravity) are still poorly known because of the rarity of such sources. Ultraluminous X-ray sources 1 are the most luminous class of black hole (L-X approximate to 10(40) erg s(-1)) located outside the nuclei of active galaxies. They are likely to be accreting at super-Eddington rates, if they are powered by black holes with masses less than 100 solar masses. They are often associated with shock-ionized nebulae 2,3, though with no evidence of collimated jets. Microquasars with steady jets are much less luminous. Here we report that the large nebula S26 (ref. 4) in the nearby galaxy NGC 7793 is powered by a black hole with a pair of collimated jets. It is similar to the famous Galactic source SS433 (ref. 5), but twice as large and a few times more powerful. We determine a mechanical power of around a few 10(40) erg s(-1). The jets therefore seem 10(4) times more energetic than the X-ray emission from the core. S26 has the structure of a Fanaroff-Riley type II (FRII-type) active galaxy: X-ray and optical core, X-ray hot spots, radio lobes 6 and an optical and X-ray cocoon. It is a microquasar where most of the jet power is dissipated in thermal particles in the lobes rather than relativistic electrons.
C1 [Pakull, Manfred W.; Motch, Christian] Univ Strasbourg, CNRS, UMR 7550, Astron Observ, F-67000 Strasbourg, France.
   [Soria, Roberto] Univ Coll London, MSSL, Holmbury RH5 6NT, Surrey, England.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of London; University College London
RP Pakull, MW (corresponding author), Univ Strasbourg, CNRS, UMR 7550, Astron Observ, 11 Rue Univ, F-67000 Strasbourg, France.
EM manfred.pakull@astro.unistra.fr; rsoria@physics.usyd.edu.au
FU Early-Career Leverhulme Fellowship
NR 27
TC 124
Z9 129
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 209
EP 212
DI 10.1038/nature09168
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800030
PM 20613836
DA 2026-03-09
ER

PT J
AU Hare, S
   Gupta, SS
   Valkov, E
   Engelman, A
   Cherepanov, P
AF Hare, Stephen
   Gupta, Saumya Shree
   Valkov, Eugene
   Engelman, Alan
   Cherepanov, Peter
TI Retroviral intasome assembly and inhibition of DNA strand transfer
SO NATURE
LA English
DT Article
ID automated structure solution; hiv-1 integrase; crystal-structure; active-site; terminal domains; structural basis; virus integrase; binding domain; protein; mechanism
AB Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein-DNA and protein-protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs.
C1 [Hare, Stephen; Gupta, Saumya Shree; Valkov, Eugene; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1PG, England.
   [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
C3 Imperial College London; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Cherepanov, P (corresponding author), Univ London Imperial Coll Sci Technol & Med, Div Med, St Marys Campus,Norfolk Pl, London W2 1PG, England.
EM p.cherepanov@imperial.ac.uk
FU UK Medical Research Council; US National Institutes of Health; Medical Research Council [G0900116] Funding Source: researchfish; MRC [G0900116] Funding Source: UKRI; National Heart Lung and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute on Aging; National Institute on Drug Abuse; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Institute on Minority Health and Health Disparities; National Institute of Diabetes and Digestive and Kidney Diseases [P30AI060354] Funding Source: NIH RePORTER
NR 50
TC 561
Z9 657
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 MAR 11
PY 2010
VL 464
IS 7286
BP 232
EP U108
DI 10.1038/nature08784
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100037
PM 20118915
DA 2026-03-09
ER

PT J
AU Lassance, JM
   Groot, AT
   Liénard, MA
   Antony, B
   Borgwardt, C
   Andersson, F
   Hedenström, E
   Heckel, DG
   Löfstedt, C
AF Lassance, Jean-Marc
   Groot, Astrid T.
   Lienard, Marjorie A.
   Antony, Binu
   Borgwardt, Christin
   Andersson, Fredrik
   Hedenstrom, Erik
   Heckel, David G.
   Lofstedt, Christer
TI Allelic variation in a fatty-acyl reductase gene causes divergence in moth sex pheromones
SO NATURE
LA English
DT Article
ID european corn-borer; desaturase gene; lepidoptera; polymorphism; evolution; specificity; speciation; software; linkage; system
AB Pheromone-based behaviours are crucial in animals from insects to mammals(1,2), and reproductive isolation is often based on pheromone differences(1-4). However, the genetic mechanisms by which pheromone signals change during the evolution of new species are largely unknown(4). In the sexual communication system of moths (Insecta: Lepidoptera), females emit a species-specific pheromone blend that attracts males over long distances(1,2,4). The European corn borer, Ostrinia nubilalis, consists of two sex pheromone races, Z and E, that use different ratios of the cis and trans isomers of acetate pheromone components(5). This subtle difference leads to strong reproductive isolation in the field between the two races(6,7), which could represent a first step in speciation. Female sex pheromone production and male behavioural response are under the control of different major genes(8,9), but the identity of these genes is unknown. Here we show that allelic variation in a fatty-acyl reductase gene essential for pheromone biosynthesis accounts for the phenotypic variation in female pheromone production, leading to race-specific signals. Both the cis and trans isomers of the pheromone precursors are produced by both races, but the precursors are differentially reduced to yield opposite ratios in the final pheromone blend as a result of the substrate specificity of the enzymes encoded by the Z and E alleles. This is the first functional characterization of a gene contributing to intraspecific behavioural reproductive isolation in moths, highlighting the importance of evolutionary diversification in a lepidopteran-specific family of reductases. Accumulation of substitutions in the coding region of a single biosynthetic enzyme can produce pheromone differences resulting in reproductive isolation, with speciation as a potential end result.
C1 [Lassance, Jean-Marc; Lienard, Marjorie A.; Antony, Binu; Lofstedt, Christer] Lund Univ, Dept Biol, S-22362 Lund, Sweden.
   [Groot, Astrid T.; Borgwardt, Christin; Heckel, David G.] Max Planck Inst Chem Ecol, Dept Entomol, D-07745 Jena, Germany.
   [Andersson, Fredrik; Hedenstrom, Erik] Mid Sweden Univ, Dept Nat Sci Engn & Math, S-85170 Sundsvall, Sweden.
C3 Lund University; Max Planck Society; Mid-Sweden University
RP Lassance, JM (corresponding author), Lund Univ, Dept Biol, S-22362 Lund, Sweden.
EM jean-marc.lassance@ekol.lu.se; christer.lofstedt@ekol.lu.se
FU Swedish Research Council (VR); Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); Max-Planck-Gesellschaft
NR 37
TC 177
Z9 207
U1 1
U2 99
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 486
EP U7
DI 10.1038/nature09058
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200035
PM 20592730
DA 2026-03-09
ER

PT J
AU Tobin, VA
   Hashimoto, H
   Wacker, DW
   Takayanagi, Y
   Langnaese, K
   Caquineau, C
   Noack, J
   Landgraf, R
   Onaka, T
   Leng, G
   Meddle, SL
   Engelmann, M
   Ludwig, M
AF Tobin, Vicky A.
   Hashimoto, Hirofumi
   Wacker, Douglas W.
   Takayanagi, Yuki
   Langnaese, Kristina
   Caquineau, Celine
   Noack, Julia
   Landgraf, Rainer
   Onaka, Tatsushi
   Leng, Gareth
   Meddle, Simone L.
   Engelmann, Mario
   Ludwig, Mike
TI An intrinsic vasopressin system in the olfactory bulb is involved in social recognition
SO NATURE
LA English
DT Article
ID hypothalamic magnocellular vasopressin; neurons in-vivo; mitral cells; oxytocin; receptor; release; expression; responses; ablation; nucleus
AB Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain, where they have fundamentally important roles in social behaviours(1). In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders and obsessive-compulsive disorder, and polymorphisms of V1a vasopressin receptor have been linked to autism(2,3). Here we report that the rat olfactory bulb contains a large population of interneurons which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurons. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system.
C1 [Tobin, Vicky A.; Hashimoto, Hirofumi; Wacker, Douglas W.; Caquineau, Celine; Leng, Gareth; Meddle, Simone L.; Ludwig, Mike] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
   [Takayanagi, Yuki; Onaka, Tatsushi] Jichi Med Univ, Dept Physiol, Shimotsuke, Tochigi 3290498, Japan.
   [Langnaese, Kristina; Noack, Julia; Engelmann, Mario] Otto VonGuericke Univ Magdegurg, Inst Biochem & Cell Biol, D-39120 Magdeburg, Germany.
   [Noack, Julia] Otto VonGuericke Univ Magdegurg, Ctr Cellular Imaging & Innovat Dis Models, D-39120 Magdeburg, Germany.
   [Landgraf, Rainer] Max Planck Inst Psychiat, D-80804 Munich, Germany.
   [Meddle, Simone L.] Univ Edinburgh, Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland.
   [Meddle, Simone L.] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland.
C3 University of Edinburgh; Jichi Medical University; Otto von Guericke University; Otto von Guericke University; Max Planck Society; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh
RP Ludwig, M (corresponding author), Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
EM mike.ludwig@ed.ac.uk
FU Biotechnology and Biological Sciences Research Council; Japan Ministry of Education, Culture, Sports, Science and Technology; Deutsche Forschungsgemeinschaft; German Academic Exchange Service/Academic Research Collaboration; Japan Society for the Promotion of Science; BBSRC [BB/F019009/1] Funding Source: UKRI; MRC [G0700176] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F019009/1] Funding Source: researchfish; Medical Research Council [G0700176] Funding Source: researchfish
NR 38
TC 170
Z9 197
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 18
PY 2010
VL 464
IS 7287
BP 413
EP U110
DI 10.1038/nature08826
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100047
PM 20182426
DA 2026-03-09
ER

PT J
AU Lestas, I
   Vinnicombe, G
   Paulsson, J
AF Lestas, Ioannis
   Vinnicombe, Glenn
   Paulsson, Johan
TI Fundamental limits on the suppression of molecular fluctuations
SO NATURE
LA English
DT Article
ID plasmid replication; feedback-control; gene-expression; poisson-type; single-cell; noise; performance; information; limitations; robustness
AB Negative feedback is common in biological processes and can increase a system's stability to internal and external perturbations. But at the molecular level, control loops always involve signalling steps with finite rates for random births and deaths of individual molecules. Here we show, by developing mathematical tools that merge control and information theory with physical chemistry, that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctuations. Specifically, the minimum standard deviation in abundances decreases with the quartic root of the number of signalling events, making it extremely expensive to increase accuracy. Our results are formulated in terms of experimental observables, and existing data show that cells use brute force when noise suppression is essential; for example, regulatory genes are transcribed tens of thousands of times per cell cycle. The theory challenges conventional beliefs about biochemical accuracy and presents an approach to the rigorous analysis of poorly characterized biological systems.
C1 [Lestas, Ioannis; Vinnicombe, Glenn] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
   [Paulsson, Johan] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
C3 University of Cambridge; Harvard University
RP Vinnicombe, G (corresponding author), Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
EM gv@eng.cam.ac.uk; johan_paulsson@hms.harvard.edu
FU BBSRC [BB/C008073/1]; National Science Foundation [DMS-074876-0, 0720056]; National Institutes of Health [GM081563-02, GM068763-06]; BBSRC [BB/C008073/1] Funding Source: UKRI; National Institute of General Medical Sciences [R01GM081563] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [0748760, 0720056] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BB/C008073/1] Funding Source: researchfish
NR 32
TC 326
Z9 389
U1 0
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 SEP 9
PY 2010
VL 467
IS 7312
BP 174
EP 178
DI 10.1038/nature09333
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300027
PM 20829788
DA 2026-03-09
ER

PT J
AU Long, F
   Su, CC
   Zimmermann, MT
   Boyken, SE
   Rajashankar, KR
   Jernigan, RL
   Yu, EW
AF Long, Feng
   Su, Chih-Chia
   Zimmermann, Michael T.
   Boyken, Scott E.
   Rajashankar, Kanagalaghatta R.
   Jernigan, Robert L.
   Yu, Edward W.
TI Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport
SO NATURE
LA English
DT Article
ID membrane-fusion protein; multidrug efflux; recognition; system; cu(i); crystallography; resistance; software; dynamics; complex
AB Gram-negative bacteria, such as Escherichia coli, frequently use tripartite efflux complexes in the resistance-nodulation-cell division (RND) family to expel various toxic compounds from the cell(1,2). The efflux system CusCBA is responsible for extruding biocidal Cu(I) and Ag(I) ions(3,4). No previous structural information was available for the heavy-metal efflux (HME) subfamily of the RND efflux pumps. Here we describe the crystal structures of the inner-membrane transporter CusA in the absence and presence of bound Cu(I) or Ag(I). These CusA structures provide new structural information about the HME subfamily of RND efflux pumps. The structures suggest that the metal-binding sites, formed by a three-methionine cluster, are located within the cleft region of the periplasmic domain. This cleft is closed in the apo-CusA form but open in the CusA-Cu(I) and CusA-Ag(I) structures, which directly suggests a plausible pathway for ion export. Binding of Cu(I) and Ag(I) triggers significant conformational changes in both the periplasmic and transmembrane domains. The crystal structure indicates that CusA has, in addition to the three-methionine metal-binding site, four methionine pairs-three located in the transmembrane region and one in the periplasmic domain. Genetic analysis and transport assays suggest that CusA is capable of actively picking up metal ions from the cytosol, using these methionine pairs or clusters to bind and export metal ions. These structures suggest a stepwise shuttle mechanism for transport between these sites.
C1 [Long, Feng; Yu, Edward W.] Iowa State Univ, Mol Cellular & Dev Biol Interdept Grad Program, Ames, IA 50011 USA.
   [Su, Chih-Chia; Yu, Edward W.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
   [Zimmermann, Michael T.; Boyken, Scott E.; Jernigan, Robert L.; Yu, Edward W.] Iowa State Univ, Bioinformat & Computat Biol Interdept Grad Progra, Ames, IA 50011 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Dept Chem & Chem Biol, Argonne Natl Lab, Argonne, IL 60439 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, NE CAT, Argonne Natl Lab, 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; Iowa State University; Cornell University; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University; Iowa State University; Iowa State University
RP Yu, EW (corresponding author), Iowa State Univ, Mol Cellular & Dev Biol Interdept Grad Program, Ames, IA 50011 USA.
EM ewyu@iastate.edu
FU National Institutes of Health (NIH), National Center for Research Resources [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]; NIH [GM074027, GM086431, GM081680, GM072014]
NR 44
TC 209
Z9 235
U1 1
U2 89
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 484
EP U140
DI 10.1038/nature09395
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200048
PM 20865003
DA 2026-03-09
ER

PT J
AU Garneau, JE
   Dupuis, ME
   Villion, M
   Romero, DA
   Barrangou, R
   Boyaval, P
   Fremaux, C
   Horvath, P
   Magadán, AH
   Moineau, S
AF Garneau, Josiane E.
   Dupuis, Marie-Eve
   Villion, Manuela
   Romero, Dennis A.
   Barrangou, Rodolphe
   Boyaval, Patrick
   Fremaux, Christophe
   Horvath, Philippe
   Magadan, Alfonso H.
   Moineau, Sylvain
TI The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA
SO NATURE
LA English
DT Article
ID escherichia-coli; repeats; identification; rnas; expression; resistance; defense; gene; diversity; sequences
AB Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.
C1 [Garneau, Josiane E.; Dupuis, Marie-Eve; Villion, Manuela; Magadan, Alfonso H.; Moineau, Sylvain] Univ Laval, Felix dHerelle Reference Ctr Bacterial Viruses, Dept Biochim Microbiol & Bioinformat, Fac Med Dent,Grp Rech Ecol Buccale,Fac Sci & Geni, Quebec City, PQ G1V 0A6, Canada.
   [Romero, Dennis A.; Barrangou, Rodolphe] Danisco USA Inc, Madison, WI 53716 USA.
   [Boyaval, Patrick; Fremaux, Christophe; Horvath, Philippe] Danisco France SAS, F-86220 Dange St Romain, France.
C3 Laval University
RP Moineau, S (corresponding author), Univ Laval, Felix dHerelle Reference Ctr Bacterial Viruses, Dept Biochim Microbiol & Bioinformat, Fac Med Dent,Grp Rech Ecol Buccale,Fac Sci & Geni, Quebec City, PQ G1V 0A6, Canada.
EM Sylvain.Moineau@bcm.ulaval.ca
FU Novalait/FQRNT; Clarin/FICYT; NSERC; CIHR
NR 36
TC 1748
Z9 2574
U1 18
U2 972
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 67
EP 71
DI 10.1038/nature09523
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900036
PM 21048762
DA 2026-03-09
ER

PT J
AU Kikuchi, K
   Holdway, JE
   Werdich, AA
   Anderson, RM
   Fang, Y
   Egnaczyk, GF
   Evans, T
   MacRae, CA
   Stainier, DYR
   Poss, KD
AF Kikuchi, Kazu
   Holdway, Jennifer E.
   Werdich, Andreas A.
   Anderson, Ryan M.
   Fang, Yi
   Egnaczyk, Gregory F.
   Evans, Todd
   MacRae, Calum A.
   Stainier, Didier Y. R.
   Poss, Kenneth D.
TI Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes
SO NATURE
LA English
DT Article
ID adult mammalian cardiomyocytes; cell-based therapy; ventral morphogenesis; transcription factor; tube formation; growth; differentiation; proliferation; injury; expression
AB Recent studies indicate that mammals, including humans, maintain some capacity to renew cardiomyocytes throughout postnatal life(1,2). Yet, there is little or no significant cardiac muscle regeneration after an injury such as acute myocardial infarction(3). By contrast, zebrafish efficiently regenerate lost cardiac muscle, providing a model for understanding how natural heart regeneration may be blocked or enhanced(4,5). In the absence of lineage-tracing technology applicable to adult zebrafish, the cellular origins of newly regenerated cardiac muscle have remained unclear. Using new genetic fate-mapping approaches, here we identify a population of cardiomyocytes that become activated after resection of the ventricular apex and contribute prominently to cardiac muscle regeneration. Through the use of a transgenic reporter strain, we found that cardiomyocytes throughout the subepicardial ventricular layer trigger expression of the embryonic cardiogenesis gene gata4 within a week of trauma, before expression localizes to proliferating cardiomyocytes surrounding and within the injury site. Cre-recombinase-based lineage-tracing of cells expressing gata4 before evident regeneration, or of cells expressing the contractile gene cmlc2 before injury, each labelled most cardiac muscle in the ensuing regenerate. By optical voltage mapping of surface myocardium in whole ventricles, we found that electrical conduction is re-established between existing and regenerated cardiomyocytes between 2 and 4 weeks post-injury. After injury and prolonged fibroblast growth factor receptor inhibition to arrest cardiac regeneration and enable scar formation, experimental release of the signalling block led to gata4 expression and morphological improvement of the injured ventricular wall without loss of scar tissue. Our results indicate that electrically coupled cardiac muscle regenerates after resection injury, primarily through activation and expansion of cardiomyocyte populations. These findings have implications for promoting regeneration of the injured human heart.
C1 [Kikuchi, Kazu; Holdway, Jennifer E.; Fang, Yi; Egnaczyk, Gregory F.; Poss, Kenneth D.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   [Kikuchi, Kazu; Holdway, Jennifer E.; Fang, Yi; Egnaczyk, Gregory F.; Poss, Kenneth D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
   [Egnaczyk, Gregory F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Werdich, Andreas A.; MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
   [Anderson, Ryan M.; Stainier, Didier Y. R.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Evans, Todd] Cornell Univ, Dept Surg, Weill Cornell Med Coll, New York, NY 10021 USA.
C3 Duke University; Duke University; Howard Hughes Medical Institute; Duke University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of California System; University of California San Francisco; Cornell University; Weill Cornell Medicine
RP Poss, KD (corresponding author), Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
EM k.poss@cellbio.duke.edu
FU AHA; JDRF; JSPS; NIH at Massachusetts General Hospital [HL007208]; NIH at Duke University Medical Center [HL007101]; NHLBI [HL064282, HL054737, HL081674]; NIGMS [GM075846]; March of Dimes; Pew Charitable Trusts; Whitehead Foundation; National Heart Lung and Blood Institute [T32HL007208] Funding Source: NIH RePORTER
NR 36
TC 865
Z9 1050
U1 1
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 MAR 25
PY 2010
VL 464
IS 7288
BP 601
EP U162
DI 10.1038/nature08804
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200050
PM 20336144
DA 2026-03-09
ER

PT J
AU Fisher, HS
   Hoekstra, HE
AF Fisher, Heidi S.
   Hoekstra, Hopi E.
TI Competition drives cooperation among closely related sperm of deer mice
SO NATURE
LA English
DT Article
ID natural-populations; swimming speed; peromyscus; fertility; velocity; evolution; rodent; size; gene
AB Among the extraordinary adaptations driven by sperm competition is the cooperative behaviour of spermatozoa(1). By forming cooperative groups, sperm can increase their swimming velocity and thereby gain an advantage in intermale sperm competition(1,2). Accordingly, selection should favour cooperation of the most closely related sperm to maximize fitness(3). Here we show that sperm of deer mice (genus Peromyscus) form motile aggregations, then we use this system to test predictions of sperm cooperation. We find that sperm aggregate more often with conspecific than heterospecific sperm, suggesting that individual sperm can discriminate on the basis of genetic relatedness. Next, we provide evidence that the cooperative behaviour of closely related sperm is driven by sperm competition. In a monogamous species lacking sperm competition, Peromyscus polionotus, sperm indiscriminately group with unrelated conspecific sperm. In contrast, in the highly promiscuous deer mouse, Peromyscus maniculatus, sperm are significantly more likely to aggregate with those obtained from the same male than with sperm from an unrelated conspecific donor. Even when we test sperm from sibling males, we continue to see preferential aggregations of related sperm in P. maniculatus. These results suggest that sperm from promiscuous deer mice discriminate among relatives and thereby cooperate with the most closely related sperm, an adaptation likely to have been driven by sperm competition.
C1 [Fisher, Heidi S.; Hoekstra, Hopi E.] Harvard Univ, Museum Comparat Zool, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Fisher, Heidi S.; Hoekstra, Hopi E.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Fisher, HS (corresponding author), Harvard Univ, Museum Comparat Zool, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
EM hfisher@oeb.harvard.edu
FU NIH; Arnold and Mabel Beckman Foundation
NR 31
TC 102
Z9 130
U1 2
U2 207
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 801
EP 803
DI 10.1038/nature08736
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300038
PM 20090679
DA 2026-03-09
ER

PT J
AU Lee, CTA
   Luffi, P
   Höink, T
   Li, J
   Dasgupta, R
   Hernlund, J
AF Lee, Cin-Ty A.
   Luffi, Peter
   Hoeink, Tobias
   Li, Jie
   Dasgupta, Rajdeep
   Hernlund, John
TI Upside-down differentiation and generation of a 'primordial' lower mantle
SO NATURE
LA English
DT Article
ID equation-of-state; thermal evolution; high-pressure; melt; earth; density; petrogenesis; segregation; stability; elements
AB Except for the first 50-100 million years or so of the Earth's history, when most of the mantle may have been subjected to melting, the differentiation of Earth's silicate mantle has been controlled by solid-state convection(1). As the mantle upwells and decompresses across its solidus, it partially melts. These low-density melts rise to the surface and form the continental and oceanic crusts, driving the differentiation of the silicate part of the Earth. Because many trace elements, such as heat-producing U, Th and K, as well as the noble gases, preferentially partition into melts (here referred to as incompatible elements), melt extraction concentrates these elements into the crust (or atmosphere in the case of noble gases), where nearly half of the Earth's budget of these elements now resides(2). In contrast, the upper mantle, as sampled by mid-ocean ridge basalts, is highly depleted in incompatible elements, suggesting a complementary relationship with the crust. Mass balance arguments require that the other half of these incompatible elements be hidden in the Earth's interior. Hypotheses abound for the origin of this hidden reservoir(3-6). The most widely held view has been that this hidden reservoir represents primordial material never processed by melting or degassing. Here, we suggest that a necessary by-product of whole-mantle convection during the Earth's first billion years is deep and hot melting, resulting in the generation of dense liquids that crystallized and sank into the lower mantle. These sunken lithologies would have 'primordial' chemical signatures despite a non-primordial origin.
C1 [Lee, Cin-Ty A.; Luffi, Peter; Hoeink, Tobias; Dasgupta, Rajdeep] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Li, Jie] Univ Michigan, Dept Geol Sci, Ann Arbor, MI 48109 USA.
   [Hernlund, John] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 Rice University; University of Michigan System; University of Michigan; University of California System; University of California Berkeley
RP Lee, CTA (corresponding author), Rice Univ, Dept Earth Sci, MS-126,6100 Main St, Houston, TX 77005 USA.
EM ctlee@rice.edu
FU Packard Foundation; NSF; University of Illinois; Directorate For Geosciences; Division Of Earth Sciences [0855737] Funding Source: National Science Foundation
NR 41
TC 152
Z9 178
U1 1
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 930
EP U102
DI 10.1038/nature08824
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700042
PM 20164926
DA 2026-03-09
ER

PT J
AU Hollander, JA
   Im, HI
   Amelio, AL
   Kocerha, J
   Bali, P
   Lu, Q
   Willoughby, D
   Wahlestedt, C
   Conkright, MD
   Kenny, PJ
AF Hollander, Jonathan A.
   Im, Heh-In
   Amelio, Antonio L.
   Kocerha, Jannet
   Bali, Purva
   Lu, Qun
   Willoughby, David
   Wahlestedt, Claes
   Conkright, Michael D.
   Kenny, Paul J.
TI Striatal microRNA controls cocaine intake through CREB signalling
SO NATURE
LA English
DT Article
ID addiction-like behavior; gene-expression; dorsal striatum; drug-addiction; raf inhibitor; activation; seeking; brain; neuroplasticity; plasticity
AB Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling. This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB; also known as CRTC). Our findings indicate that striatal miR-212 signalling has a key role in determining vulnerability to cocaine addiction, reveal new molecular regulators that control the complex actions of cocaine in brain reward circuitries and provide an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs.
C1 [Hollander, Jonathan A.; Im, Heh-In; Bali, Purva; Lu, Qun; Kenny, Paul J.] Scripps Res Inst, Dept Mol Therapeut, Lab Behav & Mol Neurosci, Jupiter, FL 33458 USA.
   [Amelio, Antonio L.; Conkright, Michael D.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
   [Kocerha, Jannet; Wahlestedt, Claes] Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA.
   [Kocerha, Jannet; Wahlestedt, Claes] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
   [Willoughby, David] Ocean Ridge Biosci, Palm Beach Gardens, FL 33410 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
RP Kenny, PJ (corresponding author), Scripps Res Inst, Dept Mol Therapeut, Lab Behav & Mol Neurosci, Jupiter, FL 33458 USA.
EM pjkenny@scripps.edu
FU National Institute on Drug Abuse (NIDA)
NR 59
TC 323
Z9 399
U1 1
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 JUL 8
PY 2010
VL 466
IS 7303
BP 197
EP U66
DI 10.1038/nature09202
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800028
PM 20613834
DA 2026-03-09
ER

PT J
AU Gibson, P
   Tong, YA
   Robinson, G
   Thompson, MC
   Currle, DS
   Eden, C
   Kranenburg, TA
   Hogg, T
   Poppleton, H
   Martin, J
   Finkelstein, D
   Pounds, S
   Weiss, A
   Patay, Z
   Scoggins, M
   Ogg, R
   Pei, YX
   Yang, ZJ
   Brun, S
   Lee, Y
   Zindy, F
   Lindsey, JC
   Taketo, MM
   Boop, FA
   Sanford, RA
   Gajjar, A
   Clifford, SC
   Roussel, MF
   McKinnon, PJ
   Gutmann, DH
   Ellison, DW
   Wechsler-Reya, R
   Gilbertson, RJ
AF Gibson, Paul
   Tong, Yiai
   Robinson, Giles
   Thompson, Margaret C.
   Currle, D. Spencer
   Eden, Christopher
   Kranenburg, Tanya A.
   Hogg, Twala
   Poppleton, Helen
   Martin, Julie
   Finkelstein, David
   Pounds, Stanley
   Weiss, Aaron
   Patay, Zoltan
   Scoggins, Matthew
   Ogg, Robert
   Pei, Yanxin
   Yang, Zeng-Jie
   Brun, Sonja
   Lee, Youngsoo
   Zindy, Frederique
   Lindsey, Janet C.
   Taketo, Makoto M.
   Boop, Frederick A.
   Sanford, Robert A.
   Gajjar, Amar
   Clifford, Steven C.
   Roussel, Martine F.
   McKinnon, Peter J.
   Gutmann, David H.
   Ellison, David W.
   Wechsler-Reya, Robert
   Gilbertson, Richard J.
TI Subtypes of medulloblastoma have distinct developmental origins
SO NATURE
LA English
DT Article
ID cell; progenitors; p53; hindbrain; model; mice
AB Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour(1-4). These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype)(3-8). The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype) 1,3,4 arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1(+) precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.
C1 [Gibson, Paul; Tong, Yiai; Robinson, Giles; Currle, D. Spencer; Eden, Christopher; Kranenburg, Tanya A.; Hogg, Twala; Poppleton, Helen; Martin, Julie; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Robinson, Giles; Gajjar, Amar; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Finkelstein, David] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [Pounds, Stanley] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Patay, Zoltan; Scoggins, Matthew; Ogg, Robert] St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA.
   [Lee, Youngsoo; Zindy, Frederique; Roussel, Martine F.; McKinnon, Peter J.] St Jude Childrens Res Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA.
   [Boop, Frederick A.; Sanford, Robert A.] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA.
   [Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Thompson, Margaret C.] Cleveland Clin, Dept Pediat Hematol Oncol, Cleveland, OH 44195 USA.
   [Weiss, Aaron] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA.
   [Pei, Yanxin; Yang, Zeng-Jie; Brun, Sonja; Wechsler-Reya, Robert] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Lindsey, Janet C.; Clifford, Steven C.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan.
   [Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Cleveland Clinic Foundation; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Duke University; Newcastle University - UK; Kyoto University; Washington University (WUSTL)
RP Gilbertson, RJ (corresponding author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM Richard.Gilbertson@stjude.org
FU National Institutes of Health [R01CA129541, P01CA96832, P30CA021765]; Collaborative Ependymoma Research Network; American Lebanese Syrian Associated Charities; National Cancer Institute [P01CA096832, P30CA021765] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS037956] Funding Source: NIH RePORTER
NR 29
TC 620
Z9 768
U1 0
U2 57
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1095
EP 1099
DI 10.1038/nature09587
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800057
PM 21150899
DA 2026-03-09
ER

PT J
AU Craddock, N
   Hurles, ME
   Cardin, N
   Pearson, RD
   Plagnol, V
   Robson, S
   Vukcevic, D
   Barnes, C
   Conrad, DF
   Giannoulatou, E
   Holmes, C
   Marchini, JL
   Stirrups, K
   Tobin, MD
   Wain, LV
   Yau, C
   Aerts, J
   Ahmad, T
   Andrews, TD
   Arbury, H
   Attwood, A
   Auton, A
   Ball, SG
   Balmforth, AJ
   Barrett, JC
   Barroso, I
   Barton, A
   Bennett, AJ
   Bhaskar, S
   Blaszczyk, K
   Bowes, J
   Brand, OJ
   Braund, PS
   Bredin, F
   Breen, G
   Brown, MJ
   Bruce, IN
   Bull, J
   Burren, OS
   Burton, J
   Byrnes, J
   Caesar, S
   Clee, CM
   Coffey, AJ
   Connell, JMC
   Cooper, JD
   Dominiczak, AF
   Downes, K
   Drummond, HE
   Dudakia, D
   Dunham, A
   Ebbs, B
   Eccles, D
   Edkins, S
   Edwards, C
   Elliot, A
   Emery, P
   Evans, DM
   Evans, G
   Eyre, S
   Farmer, A
   Ferrier, IN
   Feuk, L
   Fitzgerald, T
   Flynn, E
   Forbes, A
   Forty, L
   Franklyn, JA
   Freathy, RM
   Gibbs, P
   Gilbert, P
   Gokumen, O
   Gordon-Smith, K
   Gray, E
   Green, E
   Groves, CJ
   Grozeva, D
   Gwilliam, R
   Hall, A
   Hammond, N
   Hardy, M
   Harrison, P
   Hassanali, N
   Hebaishi, H
   Hines, S
   Hinks, A
   Hitman, GA
   Hocking, L
   Howard, E
   Howard, P
   Howson, JMM
   Hughes, D
   Hunt, S
   Isaacs, JD
   Jain, M
   Jewell, DP
   Johnson, T
   Jolley, JD
   Jones, IR
   Jones, LA
   Kirov, G
   Langford, CF
   Lango-Allen, H
   Lathrop, GM
   Lee, J
   Lee, KL
   Lees, C
   Lewis, K
   Lindgren, CM
   Maisuria-Armer, M
   Maller, J
   Mansfield, J
   Martin, P
   Massey, DCO
   McArdle, WL
   McGuffin, P
   McLay, KE
   Mentzer, A
   Mimmack, ML
   Morgan, AE
   Morris, AP
   Mowat, C
   Myers, S
   Newman, W
   Nimmo, ER
   O'Donovan, MC
   Onipinla, A
   Onyiah, I
   Ovington, NR
   Owen, MJ
   Palin, K
   Parnell, K
   Pernet, D
   Perry, JRB
   Phillips, A
   Pinto, D
   Prescott, NJ
   Prokopenko, I
   Quail, MA
   Rafelt, S
   Rayner, NW
   Redon, R
   Reid, DM
   Renwick, A
   Ring, SM
   Robertson, N
   Russell, E
   St Clair, D
   Sambrook, JG
   Sanderson, JD
   Schuilenburg, H
   Scott, CE
   Scott, R
   Seal, S
   Shaw-Hawkins, S
   Shields, BM
   Simmonds, MJ
   Smyth, DJ
   Somaskantharajah, E
   Spanova, K
   Steer, S
   Stephens, J
   Stevens, HE
   Stone, MA
   Su, Z
   Symmons, DPM
   Thompson, JR
   Thomson, W
   Travers, ME
   Turnbull, C
   Valsesia, A
   Walker, M
   Walker, NM
   Wallace, C
   Warren-Perry, M
   Watkins, NA
   Webster, J
   Weedon, MN
   Wilson, AG
   Woodburn, M
   Wordsworth, BP
   Young, AH
   Zeggini, E
   Carter, NP
   Frayling, TM
   Lee, C
   McVean, G
   Munroe, PB
   Palotie, A
   Sawcer, SJ
   Scherer, SW
   Strachan, DP
   Tyler-Smith, C
   Brown, MA
   Burton, PR
   Caulfield, MJ
   Compston, A
   Farrall, M
   Gough, SCL
   Hall, AS
   Hattersley, AT
   Hill, AVS
   Mathew, CG
   Pembrey, M
   Satsangi, J
   Stratton, MR
   Worthington, J
   Deloukas, P
   Duncanson, A
   Kwiatkowski, DP
   McCarthy, MI
   Ouwehand, WH
   Parkes, M
   Rahman, N
   Todd, JA
   Samani, NJ
   Donnelly, P
AF Craddock, Nick
   Hurles, Matthew E.
   Cardin, Niall
   Pearson, Richard D.
   Plagnol, Vincent
   Robson, Samuel
   Vukcevic, Damjan
   Barnes, Chris
   Conrad, Donald F.
   Giannoulatou, Eleni
   Holmes, Chris
   Marchini, Jonathan L.
   Stirrups, Kathy
   Tobin, Martin D.
   Wain, Louise V.
   Yau, Chris
   Aerts, Jan
   Ahmad, Tariq
   Andrews, T. Daniel
   Arbury, Hazel
   Attwood, Anthony
   Auton, Adam
   Ball, Stephen G.
   Balmforth, Anthony J.
   Barrett, Jeffrey C.
   Barroso, Ines
   Barton, Anne
   Bennett, Amanda J.
   Bhaskar, Sanjeev
   Blaszczyk, Katarzyna
   Bowes, John
   Brand, Oliver J.
   Braund, Peter S.
   Bredin, Francesca
   Breen, Gerome
   Brown, Morris J.
   Bruce, Ian N.
   Bull, Jaswinder
   Burren, Oliver S.
   Burton, John
   Byrnes, Jake
   Caesar, Sian
   Clee, Chris M.
   Coffey, Alison J.
   Connell, John M. C.
   Cooper, Jason D.
   Dominiczak, Anna F.
   Downes, Kate
   Drummond, Hazel E.
   Dudakia, Darshna
   Dunham, Andrew
   Ebbs, Bernadette
   Eccles, Diana
   Edkins, Sarah
   Edwards, Cathryn
   Elliot, Anna
   Emery, Paul
   Evans, David M.
   Evans, Gareth
   Eyre, Steve
   Farmer, Anne
   Ferrier, I. Nicol
   Feuk, Lars
   Fitzgerald, Tomas
   Flynn, Edward
   Forbes, Alistair
   Forty, Liz
   Franklyn, Jayne A.
   Freathy, Rachel M.
   Gibbs, Polly
   Gilbert, Paul
   Gokumen, Omer
   Gordon-Smith, Katherine
   Gray, Emma
   Green, Elaine
   Groves, Chris J.
   Grozeva, Detelina
   Gwilliam, Rhian
   Hall, Anita
   Hammond, Naomi
   Hardy, Matt
   Harrison, Pile
   Hassanali, Neelam
   Hebaishi, Husam
   Hines, Sarah
   Hinks, Anne
   Hitman, Graham A.
   Hocking, Lynne
   Howard, Eleanor
   Howard, Philip
   Howson, Joanna M. M.
   Hughes, Debbie
   Hunt, Sarah
   Isaacs, John D.
   Jain, Mahim
   Jewell, Derek P.
   Johnson, Toby
   Jolley, Jennifer D.
   Jones, Ian R.
   Jones, Lisa A.
   Kirov, George
   Langford, Cordelia F.
   Lango-Allen, Hana
   Lathrop, G. Mark
   Lee, James
   Lee, Kate L.
   Lees, Charlie
   Lewis, Kevin
   Lindgren, Cecilia M.
   Maisuria-Armer, Meeta
   Maller, Julian
   Mansfield, John
   Martin, Paul
   Massey, Dunecan C. O.
   McArdle, Wendy L.
   McGuffin, Peter
   McLay, Kirsten E.
   Mentzer, Alex
   Mimmack, Michael L.
   Morgan, Ann E.
   Morris, Andrew P.
   Mowat, Craig
   Myers, Simon
   Newman, William
   Nimmo, Elaine R.
   O'Donovan, Michael C.
   Onipinla, Abiodun
   Onyiah, Ifejinelo
   Ovington, Nigel R.
   Owen, Michael J.
   Palin, Kimmo
   Parnell, Kirstie
   Pernet, David
   Perry, John R. B.
   Phillips, Anne
   Pinto, Dalila
   Prescott, Natalie J.
   Prokopenko, Inga
   Quail, Michael A.
   Rafelt, Suzanne
   Rayner, Nigel W.
   Redon, Richard
   Reid, David M.
   Renwick, Anthony
   Ring, Susan M.
   Robertson, Neil
   Russell, Ellie
   St Clair, David
   Sambrook, Jennifer G.
   Sanderson, Jeremy D.
   Schuilenburg, Helen
   Scott, Carol E.
   Scott, Richard
   Seal, Sheila
   Shaw-Hawkins, Sue
   Shields, Beverley M.
   Simmonds, Matthew J.
   Smyth, Debbie J.
   Somaskantharajah, Elilan
   Spanova, Katarina
   Steer, Sophia
   Stephens, Jonathan
   Stevens, Helen E.
   Stone, Millicent A.
   Su, Zhan
   Symmons, Deborah P. M.
   Thompson, John R.
   Thomson, Wendy
   Travers, Mary E.
   Turnbull, Clare
   Valsesia, Armand
   Walker, Mark
   Walker, Neil M.
   Wallace, Chris
   Warren-Perry, Margaret
   Watkins, Nicholas A.
   Webster, John
   Weedon, Michael N.
   Wilson, Anthony G.
   Woodburn, Matthew
   Wordsworth, B. Paul
   Young, Allan H.
   Zeggini, Eleftheria
   Carter, Nigel P.
   Frayling, Timothy M.
   Lee, Charles
   McVean, Gil
   Munroe, Patricia B.
   Palotie, Aarno
   Sawcer, Stephen J.
   Scherer, Stephen W.
   Strachan, David P.
   Tyler-Smith, Chris
   Brown, Matthew A.
   Burton, Paul R.
   Caulfield, Mark J.
   Compston, Alastair
   Farrall, Martin
   Gough, Stephen C. L.
   Hall, Alistair S.
   Hattersley, Andrew T.
   Hill, Adrian V. S.
   Mathew, Christopher G.
   Pembrey, Marcus
   Satsangi, Jack
   Stratton, Michael R.
   Worthington, Jane
   Deloukas, Panos
   Duncanson, Audrey
   Kwiatkowski, Dominic P.
   McCarthy, Mark I.
   Ouwehand, Willem H.
   Parkes, Miles
   Rahman, Nazneen
   Todd, John A.
   Samani, Nilesh J.
   Donnelly, Peter
TI Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
SO NATURE
LA English
DT Article
ID copy-number variation; large-scale; susceptibility; polymorphisms; deletion; heritability; health
AB Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
C1 [Craddock, Nick; Forty, Liz; Green, Elaine; Grozeva, Detelina; Jones, Ian R.; Kirov, George; O'Donovan, Michael C.; Owen, Michael J.; Russell, Ellie] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Sch Med, Cardiff CF14 4XN, Wales.
   [Hurles, Matthew E.; Robson, Samuel; Barnes, Chris; Conrad, Donald F.; Stirrups, Kathy; Aerts, Jan; Andrews, T. Daniel; Arbury, Hazel; Attwood, Anthony; Barrett, Jeffrey C.; Barroso, Ines; Bhaskar, Sanjeev; Burton, John; Clee, Chris M.; Coffey, Alison J.; Dunham, Andrew; Edkins, Sarah; Fitzgerald, Tomas; Gray, Emma; Gwilliam, Rhian; Hammond, Naomi; Hebaishi, Husam; Howard, Eleanor; Hunt, Sarah; Langford, Cordelia F.; Lewis, Kevin; McLay, Kirsten E.; Mimmack, Michael L.; Onyiah, Ifejinelo; Palin, Kimmo; Quail, Michael A.; Redon, Richard; Scott, Carol E.; Somaskantharajah, Elilan; Valsesia, Armand; Zeggini, Eleftheria; Carter, Nigel P.; Palotie, Aarno; Tyler-Smith, Chris; Stratton, Michael R.; Deloukas, Panos; Kwiatkowski, Dominic P.; Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Cardin, Niall; Giannoulatou, Eleni; Holmes, Chris; Marchini, Jonathan L.; Yau, Chris; Auton, Adam; Myers, Simon; Su, Zhan; McVean, Gil; Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Pearson, Richard D.; Vukcevic, Damjan; Byrnes, Jake; Jain, Mahim; Lindgren, Cecilia M.; Maller, Julian; Morris, Andrew P.; Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil; Zeggini, Eleftheria; Hill, Adrian V. S.; Kwiatkowski, Dominic P.; McCarthy, Mark I.; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Plagnol, Vincent; Burren, Oliver S.; Cooper, Jason D.; Downes, Kate; Hardy, Matt; Howson, Joanna M. M.; Maisuria-Armer, Meeta; Ovington, Nigel R.; Schuilenburg, Helen; Smyth, Debbie J.; Stevens, Helen E.; Walker, Neil M.; Wallace, Chris; Woodburn, Matthew; Todd, John A.] Univ Cambridge, Cambridge Inst Med Res, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0XY, England.
   [Tobin, Martin D.; Wain, Louise V.; Thompson, John R.; Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
   [Tobin, Martin D.; Wain, Louise V.; Thompson, John R.; Burton, Paul R.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
   [Ahmad, Tariq; Freathy, Rachel M.; Lango-Allen, Hana; Parnell, Kirstie; Perry, John R. B.; Shields, Beverley M.; Weedon, Michael N.; Frayling, Timothy M.; Hattersley, Andrew T.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
   [Attwood, Anthony; Jolley, Jennifer D.; Sambrook, Jennifer G.; Stephens, Jonathan; Watkins, Nicholas A.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.
   [Attwood, Anthony; Jolley, Jennifer D.; Sambrook, Jennifer G.; Stephens, Jonathan; Watkins, Nicholas A.; Ouwehand, Willem H.] Cambridge Ctr, Natl Hlth Serv Blood & Transplant, Cambridge CB2 0PT, England.
   [Ball, Stephen G.; Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, LIGHT, MCRC, Leeds LS2 9JT, W Yorkshire, England.
   [Barton, Anne; Bowes, John; Bruce, Ian N.; Eyre, Steve; Flynn, Edward; Gilbert, Paul; Hinks, Anne; Martin, Paul; Symmons, Deborah P. M.; Thomson, Wendy; Worthington, Jane] Univ Manchester, Arc Epidemiol Unit, Manchester M13 9PT, Lancs, England.
   [Bennett, Amanda J.; Groves, Chris J.; Hassanali, Neelam; Lindgren, Cecilia M.; Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil; Travers, Mary E.; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England.
   [Blaszczyk, Katarzyna; Prescott, Natalie J.; Mathew, Christopher G.] Kings Coll London, Sch Med, Dept Med & Mol Genet, Guys Hosp, London SE1 9RT, England.
   [Brand, Oliver J.; Franklyn, Jayne A.; Simmonds, Matthew J.; Gough, Stephen C. L.] Univ Birmingham, Inst Biomed Res, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands, England.
   [Braund, Peter S.; Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
   [Bredin, Francesca; Lee, James; Massey, Dunecan C. O.; Parkes, Miles] Addenbrookes Hosp, IBD Genet Res Grp, Cambridge CB2 0QQ, England.
   [Breen, Gerome; St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.
   [Breen, Gerome; Farmer, Anne; McGuffin, Peter] Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England.
   [Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
   [Bull, Jaswinder; Dudakia, Darshna; Ebbs, Bernadette; Elliot, Anna; Gibbs, Polly; Hall, Anita; Hines, Sarah; Hughes, Debbie; Pernet, David; Renwick, Anthony; Scott, Richard; Seal, Sheila; Spanova, Katarina; Turnbull, Clare; Warren-Perry, Margaret; Stratton, Michael R.; Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England.
   [Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa A.] Univ Birmingham, Natl Ctr Mental Hlth, Dept Psychiat, Birmingham B15 2FG, W Midlands, England.
   [Connell, John M. C.; Dominiczak, Anna F.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
   [Drummond, Hazel E.; Lees, Charlie; Nimmo, Elaine R.; Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Div Med Sci,Sch Mol & Clin Med, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Eccles, Diana] Univ Southampton, Acad Unit Genet Med, Southampton SO16 5YA, Hants, England.
   [Edwards, Cathryn] Torbay Hosp, Endoscopy Reg Training Unit, Torquay TQ2 7AA, England.
   [Emery, Paul] Univ Leeds, Chapel Allerton Hosp, Acad Unit Musculoskeletal Dis, Leeds LS7 4SA, W Yorkshire, England.
   [Evans, David M.] Univ Bristol, MRC, Ctr Causal Analyses Translat Epidemiol, Dept Social Med, Bristol BS8 2BN, Avon, England.
   [Evans, Gareth; Newman, William] Univ Manchester, MAHSC, Dept Med Genet, Manchester M13 0JH, Lancs, England.
   [Ferrier, I. Nicol; Young, Allan H.] Royal Victoria Infirm, Sch Neurol Neurobiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Feuk, Lars; Pinto, Dalila; Scherer, Stephen W.] Hosp Sick Children, MaRS Ctr, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada.
   [Feuk, Lars; Pinto, Dalila; Scherer, Stephen W.] Hosp Sick Children, MaRS Ctr, Program Genet & Genom Biol, Toronto, ON M5G 1L7, Canada.
   [Feuk, Lars] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, S-75185 Uppsala, Sweden.
   [Forbes, Alistair] Univ Coll London Hosp Trust, Inst Digest Dis, London NW1 2BU, England.
   [Franklyn, Jayne A.; Gough, Stephen C. L.] Univ Hosp Birmingham NHS Fdn Trust, Birmingham B15 2TT, W Midlands, England.
   [Gokumen, Omer; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Gokumen, Omer; Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Harrison, Pile] Univ Oxford, Inst Musculoskeletal Sci, Botnar Res Ctr, Oxford OX3 7LD, England.
   [Hitman, Graham A.] Barts & London Royal London Hosp, Ctr Diabet & Metab Med, London E1 1BB, England.
   [Hocking, Lynne; Reid, David M.] Univ Aberdeen, Bone Res Grp, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland.
   [Howard, Philip; Johnson, Toby; Lee, Kate L.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Munroe, Patricia B.; Caulfield, Mark J.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London EC1M 6BQ, England.
   [Isaacs, John D.] Sch Med, Musculoskeletal Res Grp, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Jewell, Derek P.] Univ Oxford, Gastroenterol Unit, Radcliffe Infirm, Oxford OX2 6HE, England.
   [Lathrop, G. Mark] Ctr Natl Genotypage, F-91057 Paris, France.
   [Mansfield, John] Newcastle Univ, Royal Victoria Infirm, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [McArdle, Wendy L.; Ring, Susan M.] Univ Bristol, Dept Social Med, ALSPAC Lab, Bristol BS8 2BN, Avon, England.
   [Mentzer, Alex; Sanderson, Jeremy D.] Kings Coll London, Sch Biomed & Hlth Sci, Div Nutr Sci, London SE1 9NH, England.
   [Morgan, Ann E.] Univ Leeds, Chapel Allerton Hosp, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds LS7 4SA, W Yorkshire, England.
   [Mowat, Craig; Phillips, Anne] Univ Dundee, Ninewells Hosp & Med Sch, Dept Gen Internal Med, Dundee DD1 9SY, Scotland.
   [Redon, Richard] INSERM, UMR915, Inst Thorax, F-44035 Nantes, France.
   [Steer, Sophia] Kings Coll Hosp Natl Hlth Serv Fdn Trust, London SE5 9RS, England.
   [Stone, Millicent A.] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
   [Stone, Millicent A.] Univ Bath, Bath BA2 7AY, Somerset, England.
   [Walker, Mark] Newcastle Univ, Diabet Res Grp, Sch Clin Med Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Webster, John] Aberdeen Royal Infirm, Aberdeen AB9 2ZB, Grampian, Scotland.
   [Wilson, Anthony G.] Univ Sheffield, Sch Med & Biomed Sci, Sheffield S10 2JF, S Yorkshire, England.
   [Wordsworth, B. Paul; Brown, Matthew A.] Univ Oxford, Nuffield Orthopaed Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7LD, England.
   [Young, Allan H.] Univ British Columbia, Inst Mental Hlth, Vancouver, BC V6T 1Z3, Canada.
   [Sawcer, Stephen J.; Compston, Alastair] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
   [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Strachan, David P.] Univ London, Div Community Hlth Sci, London SW17 0RE, England.
   [Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld 4102, Australia.
   [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Hattersley, Andrew T.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX2 5DW, Devon, England.
   [Pembrey, Marcus] UCL, Inst Child Hlth, Clin & Mol Genet Unit, London WC1N 1EH, England.
   [Duncanson, Audrey] Wellcome Trust Res Labs, London NW1 2BE, England.
   [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
   [Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
C3 Cardiff University; Wellcome Trust Sanger Institute; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; University of Cambridge; University of Leicester; University of Leicester; University of Exeter; University of Plymouth; University of Cambridge; NHS Blood & Transplant (NHSBT); University of Leeds; University of Manchester; University of Oxford; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; University of Birmingham; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Aberdeen; University of London; King's College London; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of London; Institute of Cancer Research - UK; University of Birmingham; University of Glasgow; University of Edinburgh; University of Southampton; University of Leeds; Chapel Allerton Hospital; University of Bristol; University of Manchester; Newcastle University - UK; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Uppsala University; University of London; University College London; University of Birmingham; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Oxford; Barts Health NHS Trust; Royal London Hospital; University of Aberdeen; University of London; Queen Mary University London; Newcastle University - UK; University of Oxford; Radcliffe Infirmary; CEA; Newcastle University - UK; University of Bristol; University of London; King's College London; Chapel Allerton Hospital; Leeds Biomedical Research Centre; University of Leeds; University of Dundee; Nantes Universite; CHU de Nantes; Institut National de la Sante et de la Recherche Medicale (Inserm); King's College Hospital NHS Foundation Trust; King's College Hospital; University of Toronto; Saint Michaels Hospital Toronto; University of Bath; Newcastle University - UK; University of Aberdeen; University of Sheffield; Nuffield Orthopaedic Centre; University of Oxford; University of British Columbia; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Toronto; University of London; University of Queensland; Princess Alexandra Hospital; University of Oxford; Wellcome Centre for Human Genetics; University of Exeter; University of Plymouth; University of London; University College London; University of Oxford; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital
RP Craddock, N (corresponding author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Sch Med, Heath Pk, Cardiff CF14 4XN, Wales.
FU Wellcome Trust; MRC [G19/9, G9521010, G0800675, G0800759, MC_UP_A390_1107, G0700491, G0600329, G0500115, G0800509, G0701420, G0600705, G0400874, G0501942, G0701810, G0000934, G0701003, G0800383, G90/106] Funding Source: UKRI; British Heart Foundation [RG/09/012/28096, RG/08/014/24067] Funding Source: researchfish; Cancer Research UK; Versus Arthritis [18475] Funding Source: researchfish; Chief Scientist Office [CZB/4/540] Funding Source: researchfish; Medical Research Council [G0701420, G0801418B, MC_UP_A390_1107, G0501942, G9817803B, G0800759, G0700491, G0600705, G0500115, G0400874, G90/106, G0600329, G0000934, G0800675, G0800509, G0701003, G0800383, G9521010, G0701810, G0600718B, G19/9] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10299, NF-SI-0508-10335] Funding Source: researchfish
NR 33
TC 625
Z9 736
U1 0
U2 121
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 713
EP U86
DI 10.1038/nature08979
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000036
PM 20360734
DA 2026-03-09
ER

PT J
AU Pavelka, N
   Rancati, G
   Zhu, J
   Bradford, WD
   Saraf, A
   Florens, L
   Sanderson, BW
   Hattem, GL
   Li, R
AF Pavelka, Norman
   Rancati, Giulia
   Zhu, Jin
   Bradford, William D.
   Saraf, Anita
   Florens, Laurence
   Sanderson, Brian W.
   Hattem, Gaye L.
   Li, Rong
TI Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast
SO NATURE
LA English
DT Article
ID identification technology; saccharomyces-cerevisiae; cells; evolution; peptides
AB Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer and adaptive evolution in experimental organisms(1-9). However, it remains unresolved how aneuploidy impacts gene expression and whether aneuploidy could directly bring about phenotypic variation and improved fitness over that of euploid counterparts. Here we show, using quantitative mass spectrometry-based proteomics and phenotypic profiling, that levels of protein expression in aneuploid yeast strains largely scale with chromosome copy numbers, following the same trend as that observed for the transcriptome, and that aneuploidy confers diverse phenotypes. We designed a novel scheme to generate, through random meiotic segregation, 38 stable and fully isogenic aneuploid yeast strains with distinct karyotypes and genome contents between 1N and 3N without involving any genetic selection. Through quantitative growth assays under various conditions or in the presence of a panel of chemotherapeutic or antifungal drugs, we found that some aneuploid strains grew significantly better than euploid control strains under conditions suboptimal for the latter. These results provide strong evidence that aneuploidy directly affects gene expression at both the transcriptome and proteome levels and can generate significant phenotypic variation that could bring about fitness gains under diverse conditions. Our findings suggest that the fitness ranking between euploid and aneuploid cells is dependent on context and karyotype, providing the basis for the notion that aneuploidy can directly underlie phenotypic evolution and cellular adaptation.
C1 [Pavelka, Norman; Rancati, Giulia; Zhu, Jin; Bradford, William D.; Saraf, Anita; Florens, Laurence; Sanderson, Brian W.; Hattem, Gaye L.; Li, Rong] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Li, Rong] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center
RP Li, R (corresponding author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA.
EM rli@stowers.org
FU NIH [RO1GM059964]
NR 25
TC 469
Z9 554
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 321
EP 325
DI 10.1038/nature09529
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000054
PM 20962780
DA 2026-03-09
ER

PT J
AU Duncan, AW
   Taylor, MH
   Hickey, RD
   Newell, AEH
   Lenzi, ML
   Olson, SB
   Finegold, MJ
   Grompe, M
AF Duncan, Andrew W.
   Taylor, Matthew H.
   Hickey, Raymond D.
   Newell, Amy E. Hanlon
   Lenzi, Michelle L.
   Olson, Susan B.
   Finegold, Milton J.
   Grompe, Markus
TI The ploidy conveyor of mature hepatocytes as a source of genetic variation
SO NATURE
LA English
DT Article
ID tyrosinemia type-i; murine model; cell-fusion; mouse model; stem-cells; liver; mice; vivo; fumarylacetoacetate; polyploidization
AB Mononucleated and binucleated polyploid hepatocytes (4n, 8n, 16n and higher) are found in all mammalian species, but the functional significance of this conserved phenomenon remains unknown(1-4). Polyploidization occurs through failed cytokinesis, begins at weaning in rodents and increases with age(2,5-7). Previously, we demonstrated that the opposite event, ploidy reversal, also occurs in polyploid hepatocytes generated by artificial cell fusion(8-10). This raised the possibility that somatic 'reductive mitoses' can also happen in normal hepatocytes. Here we show that multipolar mitotic spindles form frequently in mouse polyploid hepatocytes and can result in one-step ploidy reversal to generate offspring with halved chromosome content. Proliferating hepatocytes produce a highly diverse population of daughter cells with multiple numerical chromosome imbalances as well as uniparental origins. Our findings support a dynamic model of hepatocyte polyploidization, ploidy reversal and aneuploidy, a phenomenon that we term the 'ploidy conveyor'. We propose that this mechanism evolved to generate genetic diversity and permits adaptation of hepatocytes to xenobiotic or nutritional injury.
C1 [Duncan, Andrew W.; Hickey, Raymond D.; Grompe, Markus] Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Oregon Stem Cell Ctr, Portland, OR 97239 USA.
   [Taylor, Matthew H.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA.
   [Hickey, Raymond D.; Newell, Amy E. Hanlon; Lenzi, Michelle L.; Olson, Susan B.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
   [Finegold, Milton J.] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon Health & Science University; Baylor College of Medicine; Baylor College Medical Hospital
RP Duncan, AW (corresponding author), Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Oregon Stem Cell Ctr, Portland, OR 97239 USA.
EM duncanan@ohsu.edu
FU Advanced Light Microscopy Core at OHSU [S10-RR023432]; Morphology Core of the Texas Medical Center [DK56338]; National Institute of Health [R01DK067636, F32DK076232]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056338] Funding Source: NIH RePORTER
NR 26
TC 392
Z9 471
U1 1
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 OCT 7
PY 2010
VL 467
IS 7316
BP 707
EP U93
DI 10.1038/nature09414
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500038
PM 20861837
DA 2026-03-09
ER

PT J
AU Bean, JL
   Kempton, EMR
   Homeier, D
AF Bean, Jacob L.
   Kempton, Eliza Miller-Ricci
   Homeier, Derek
TI A ground-based transmission spectrum of the super-Earth exoplanet GJ 1214b
SO NATURE
LA English
DT Article
ID ocean-planets; mass; atmospheres; search; rich
AB In contrast to planets with masses similar to that of Jupiter and higher, the bulk compositions of planets in the so-called super-Earth regime (masses 2-10 times that of the Earth) cannot be uniquely determined from a measurement of mass and radius alone. For these planets, there is a degeneracy between the mass and composition of both the interior and a possible atmosphere in theoretical models(1,2). The recently discovered transiting super-Earth exoplanet GJ 1214b is one example of this problem(3). Three distinct models for the planet that are consistent with its mass and radius have been suggested(4). Breaking the degeneracy between these models requires obtaining constraints on the planet's atmospheric composition(5,6). Here we report a ground-based measurement of the transmission spectrum of GJ 1214b between wavelengths of 780 and 1,000 nm. The lack of features in this spectrum rules out (at 4.9 sigma confidence) cloud-free atmospheres composed primarily of hydrogen. If the planet's atmosphere is hydrogen-dominated, then it must contain clouds or hazes that are optically thick at the observed wavelengths at pressures less than 200 mbar. Alternatively, the featureless transmission spectrum is also consistent with the presence of a dense, water vapour atmosphere.
C1 [Bean, Jacob L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Bean, Jacob L.; Homeier, Derek] Univ Gottingen, Inst Astrophys, D-37077 Gottingen, Germany.
   [Kempton, Eliza Miller-Ricci] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
C3 Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of Gottingen; University of California System; University of California Santa Cruz
RP Bean, JL (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM jbean@cfa.harvard.edu
FU European Commissions; NASA
NR 22
TC 296
Z9 338
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 DEC 2
PY 2010
VL 468
IS 7324
BP 669
EP 672
DI 10.1038/nature09596
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700035
PM 21124452
DA 2026-03-09
ER

PT J
AU Danino, T
   Mondragón-Palomino, O
   Tsimring, L
   Hasty, J
AF Danino, Tal
   Mondragon-Palomino, Octavio
   Tsimring, Lev
   Hasty, Jeff
TI A synchronized quorum of genetic clocks
SO NATURE
LA English
DT Article
ID bacillus-thuringiensis; quenching lactonase; cell communication; escherichia-coli; toggle switch; expression; network; behavior; oscillators; rhythms
AB The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level.
C1 [Danino, Tal; Mondragon-Palomino, Octavio; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Tsimring, Lev; Hasty, Jeff] Univ Calif San Diego, BioCircuits Inst, La Jolla, CA 92093 USA.
   [Hasty, Jeff] Univ Calif, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Hasty, J (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM hasty@bioeng.ucsd.edu
FU National Institutes of Health and General Medicine [GM69811]; DOE CSGF; CONACyT (Mexico) [184646]; National Institute of General Medical Sciences [R01GM069811] Funding Source: NIH RePORTER
NR 49
TC 775
Z9 982
U1 6
U2 355
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 326
EP 330
DI 10.1038/nature08753
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100037
PM 20090747
DA 2026-03-09
ER

PT J
AU Planavsky, NJ
   Rouxel, OJ
   Bekker, A
   Lalonde, SV
   Konhauser, KO
   Reinhard, CT
   Lyons, TW
AF Planavsky, Noah J.
   Rouxel, Olivier J.
   Bekker, Andrey
   Lalonde, Stefan V.
   Konhauser, Kurt O.
   Reinhard, Christopher T.
   Lyons, Timothy W.
TI The evolution of the marine phosphate reservoir
SO NATURE
LA English
DT Article
ID silica cycle; phosphorus; iron; depletion; sediments
AB Phosphorus is a biolimiting nutrient that has an important role in regulating the burial of organic matter and the redox state of the ocean-atmosphere system(1). The ratio of phosphorus to iron in iron-oxide-rich sedimentary rocks can be used to track dissolved phosphate concentrations if the dissolved silica concentration of sea water is estimated(2-5). Here we present iron and phosphorus concentration ratios from distal hydrothermal sediments and iron formations through time to study the evolution of the marine phosphate reservoir. The data suggest that phosphate concentrations have been relatively constant over the Phanerozoic eon, the past 542 million years (Myr) of Earth's history. In contrast, phosphate concentrations seem to have been elevated in Precambrian oceans. Specifically, there is a peak in phosphorus-to-iron ratios in Neoproterozoic iron formations dating from 750 to 635 Myr ago, indicating unusually high dissolved phosphate concentrations in the aftermath of widespread, low-latitude 'snowball Earth' glaciations. An enhanced postglacial phosphate flux would have caused high rates of primary productivity and organic carbon burial and a transition to more oxidizing conditions in the ocean and atmosphere. The snowball Earth glaciations and Neoproterozoic oxidation are both suggested as triggers for the evolution and radiation of metazoans(6,7). We propose that these two factors are intimately linked; a glacially induced nutrient surplus could have led to an increase in atmospheric oxygen, paving the way for the rise of metazoan life.
C1 [Planavsky, Noah J.; Reinhard, Christopher T.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Planavsky, Noah J.; Rouxel, Olivier J.] Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
   [Rouxel, Olivier J.] Univ Europeene Bretagne, European Inst Marine Studies, F-29280 Plouzane, France.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
   [Lalonde, Stefan V.; Konhauser, Kurt O.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
C3 University of California System; University of California Riverside; Woods Hole Oceanographic Institution; Universite de Bretagne Occidentale; Institut Universitaire Europeen de la Mer (IUEM); University of Manitoba; University of Alberta
RP Lyons, TW (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM timothy.lyons@ucr.edu
FU NSF; NASA Astrobiology Institute; NASA; NSF-EAR; NSERC; NSF-OCE; NSF-GSF; Directorate For Geosciences [0951998] Funding Source: National Science Foundation; Division Of Earth Sciences [0951998] Funding Source: National Science Foundation
NR 30
TC 401
Z9 477
U1 7
U2 290
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1088
EP 1090
DI 10.1038/nature09485
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600043
PM 20981096
DA 2026-03-09
ER

PT J
AU Swinbank, AM
   Smail, I
   Longmore, S
   Harris, AI
   Baker, AJ
   De Breuck, C
   Richard, J
   Edge, AC
   Ivison, RJ
   Blundell, R
   Coppin, KEK
   Cox, P
   Gurwell, M
   Hainline, LJ
   Krips, M
   Lundgren, A
   Neri, R
   Siana, B
   Siringo, G
   Stark, DP
   Wilner, D
   Younger, JD
AF Swinbank, A. M.
   Smail, I.
   Longmore, S.
   Harris, A. I.
   Baker, A. J.
   De Breuck, C.
   Richard, J.
   Edge, A. C.
   Ivison, R. J.
   Blundell, R.
   Coppin, K. E. K.
   Cox, P.
   Gurwell, M.
   Hainline, L. J.
   Krips, M.
   Lundgren, A.
   Neri, R.
   Siana, B.
   Siringo, G.
   Stark, D. P.
   Wilner, D.
   Younger, J. D.
TI Intense star formation within resolved compact regions in a galaxy at z=2.3
SO NATURE
LA English
DT Article
ID submillimeter galaxy; high-redshift; molecular clouds; big-bang; resolution; population; luminosity; continuum; starburst; emission
AB Massive galaxies in the early Universe have been shown to be forming stars at surprisingly high rates(1-3). Prominent examples are dust-obscured galaxies which are luminous when observed at sub-millimetre wavelengths and which may be forming stars at a rate of 1,000 solar masses (M(circle dot)) per year(4-7). These intense bursts of star formation are believed to be driven by mergers between gas-rich galaxies(8-9). Probing the properties of individual star-forming regions within these galaxies, however, is beyond the spatial resolution and sensitivity of even the largest telescopes at present. Here we report observations of the sub-millimetre galaxy SMMJ2135-0102 at redshift z = 2.3259, which has been gravitationally magnified by a factor of 32 by a massive foreground galaxy cluster lens. This magnification, when combined with high-resolution sub-millimetre imaging, resolves the star-forming regions at a linear scale of only 100 parsecs. We find that the luminosity densities of these star-forming regions are comparable to the dense cores of giant molecular clouds in the local Universe, but they are about a hundred times larger and 10(7) times more luminous. Although vigorously star-forming, the underlying physics of the star-formation processes at z approximate to 2 appears to be similar to that seen in local galaxies, although the energetics are unlike anything found in the present-day Universe.
C1 [Swinbank, A. M.; Smail, I.; Richard, J.; Edge, A. C.; Coppin, K. E. K.] Univ Durham, Inst Computat Cosmol, Durham DH1 3LE, England.
   [Longmore, S.; Blundell, R.; Gurwell, M.; Wilner, D.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Harris, A. I.; Hainline, L. J.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Baker, A. J.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [De Breuck, C.] European So Observ, D-85748 Garching, Germany.
   [Ivison, R. J.] Royal Observ, Sci & Technol Facil Council, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Ivison, R. J.] Royal Observ Edinburgh, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Cox, P.; Krips, M.; Neri, R.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Lundgren, A.; Siringo, G.] European So Observ, Santiago 19, Chile.
   [Siana, B.] CALTECH, Pasadena, CA 91125 USA.
   [Stark, D. P.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Younger, J. D.] Inst Adv Study, Princeton, NJ 08540 USA.
C3 Durham University; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University System of Maryland; University of Maryland College Park; Rutgers University System; Rutgers University New Brunswick; European Southern Observatory; University of Edinburgh; University of Edinburgh; European Southern Observatory; California Institute of Technology; University of Cambridge; Institute for Advanced Study - USA
RP Swinbank, AM (corresponding author), Univ Durham, Inst Computat Cosmol, South Rd, Durham DH1 3LE, England.
EM a.m.swinbank@dur.ac.uk
FU Royal Astronomical Society Sir Norman Lockyer Fellowship; Marie Curie fellowship; Science Technology and Facilities Council fellowship; NASA through a Hubble Fellowship; Smithsonian Institution; Academia Sinica; INSU/CNRS (France); Max Planck Gesellschaft (MPG; Germany); Instituto Geografico Nacional (IGN; Spain); STFC [ST/F002963/1, ST/H005234/1, ST/H001913/1, ST/H008519/1, ST/F002289/1, ST/F002300/1, ST/F008694/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H001913/1, ST/H008519/1, ST/F002289/1, ST/F002300/1, PP/E001181/1, ST/F002963/1, ST/H005234/1, ST/F008694/1] Funding Source: researchfish
NR 28
TC 310
Z9 328
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 APR 1
PY 2010
VL 464
IS 7289
BP 733
EP 736
DI 10.1038/nature08880
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000039
PM 20305639
DA 2026-03-09
ER

PT J
AU Zheng, YM
   Bai, H
   Huang, ZB
   Tian, XL
   Nie, FQ
   Zhao, Y
   Zhai, J
   Jiang, L
AF Zheng, Yongmei
   Bai, Hao
   Huang, Zhongbing
   Tian, Xuelin
   Nie, Fu-Qiang
   Zhao, Yong
   Zhai, Jin
   Jiang, Lei
TI Directional water collection on wetted spider silk
SO NATURE
LA English
DT Article
ID mechanical-property; surfaces; capture; droplet; motion
AB Many biological surfaces in both the plant and animal kingdom possess unusual structural features at the micro-and nanometre-scale that control their interaction with water and hence wettability(1-5). An intriguing example is provided by desert beetles, which use micrometre-sized patterns of hydrophobic and hydrophilic regions on their backs to capture water from humid air(6). As anyone who has admired spider webs adorned with dew drops will appreciate, spider silk is also capable of efficiently collecting water from air. Here we show that the water-collecting ability of the capture silk of the cribellate spider Uloborus walckenaerius is the result of a unique fibre structure that forms after wetting, with the 'wet-rebuilt' fibres characterized by periodic spindle-knots made of random nanofibrils and separated by joints made of aligned nanofibrils. These structural features result in a surface energy gradient between the spindle-knots and the joints and also in a difference in Laplace pressure, with both factors acting together to achieve continuous condensation and directional collection of water drops around spindle-knots. Submillimetre-sized liquid drops have been driven by surface energy gradients(7-9) or a difference in Laplace pressure(10), but until now neither force on its own has been used to overcome the larger hysteresis effects that make the movement of micrometre-sized drops more difficult. By tapping into both driving forces, spider silk achieves this task. Inspired by this finding, we designed artificial fibres that mimic the structural features of silk and exhibit its directional water-collecting ability.
C1 [Huang, Zhongbing; Tian, Xuelin; Nie, Fu-Qiang; Zhao, Yong; Jiang, Lei] Chinese Acad Sci, Inst Chem, BNLMS, Beijing 100190, Peoples R China.
   [Zheng, Yongmei; Zhai, Jin] Beijing Univ Aeronaut & Astronaut, Sch Chem & Environm, Beijing 100083, Peoples R China.
   [Bai, Hao] Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Chemistry, CAS; Beihang University; Chinese Academy of Sciences; National Center for Nanoscience & Technology, CAS
RP Jiang, L (corresponding author), Chinese Acad Sci, Inst Chem, BNLMS, Beijing 100190, Peoples R China.
EM zhaoyong@iccas.ac.cn; jianglei@iccas.ac.cn
FU State Basic Research Program of China [2007CB936403]; Key Program in the National Natural Science Foundation of China [119030601101]; Knowledge Innovation Program in the Chinese Academy of Sciences [2A200522222200301]
NR 27
TC 1980
Z9 2191
U1 68
U2 3330
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 640
EP 643
DI 10.1038/nature08729
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900031
PM 20130646
DA 2026-03-09
ER

PT J
AU Guiguemde, WA
   Shelat, AA
   Bouck, D
   Duffy, S
   Crowther, GJ
   Davis, PH
   Smithson, DC
   Connelly, M
   Clark, J
   Zhu, FY
   Jiménez-Díaz, MB
   Martinez, MS
   Wilson, EB
   Tripathi, AK
   Gut, J
   Sharlow, ER
   Bathurst, I
   El Mazouni, F
   Fowble, JW
   Forquer, I
   McGinley, PL
   Castro, S
   Angulo-Barturen, I
   Ferrer, S
   Rosenthal, PJ
   DeRisi, JL
   Sullivan, DJ
   Lazo, JS
   Roos, DS
   Riscoe, MK
   Phillips, MA
   Rathod, PK
   Van Voorhis, WC
   Avery, VM
   Guy, RK
AF Guiguemde, W. Armand
   Shelat, Anang A.
   Bouck, David
   Duffy, Sandra
   Crowther, Gregory J.
   Davis, Paul H.
   Smithson, David C.
   Connelly, Michele
   Clark, Julie
   Zhu, Fangyi
   Jimenez-Diaz, Maria B.
   Martinez, Maria S.
   Wilson, Emily B.
   Tripathi, Abhai K.
   Gut, Jiri
   Sharlow, Elizabeth R.
   Bathurst, Ian
   El Mazouni, Farah
   Fowble, Joseph W.
   Forquer, Isaac
   McGinley, Paula L.
   Castro, Steve
   Angulo-Barturen, Inigo
   Ferrer, Santiago
   Rosenthal, Philip J.
   DeRisi, Joseph L.
   Sullivan, David J., Jr.
   Lazo, John S.
   Roos, David S.
   Riscoe, Michael K.
   Phillips, Margaret A.
   Rathod, Pradipsinh K.
   Van Voorhis, Wesley C.
   Avery, Vicky M.
   Guy, R. Kiplin
TI Chemical genetics of Plasmodium falciparum
SO NATURE
LA English
DT Article
ID malaria; identification; disruption; resistance; survival; growth
AB Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.
C1 [Guiguemde, W. Armand; Shelat, Anang A.; Bouck, David; Smithson, David C.; Connelly, Michele; Clark, Julie; Zhu, Fangyi; Guy, R. Kiplin] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA.
   [Duffy, Sandra; Avery, Vicky M.] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia.
   [Crowther, Gregory J.; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Davis, Paul H.; Roos, David S.] Univ Penn, Penn Genome Frontiers Inst, Philadelphia, PA 19104 USA.
   [Davis, Paul H.; Roos, David S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Jimenez-Diaz, Maria B.; Martinez, Maria S.; Angulo-Barturen, Inigo; Ferrer, Santiago] GlaxoSmithKline, Dis Developing World, Tres Cantos 28760, Spain.
   [Wilson, Emily B.; DeRisi, Joseph L.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Tripathi, Abhai K.; Sullivan, David J., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
   [Gut, Jiri; Rosenthal, Philip J.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA.
   [Sharlow, Elizabeth R.; Lazo, John S.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA.
   [Bathurst, Ian] Med Malaria Venture, CH-1215 Geneva, Switzerland.
   [El Mazouni, Farah; Phillips, Margaret A.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
   [Fowble, Joseph W.; Rathod, Pradipsinh K.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   [Forquer, Isaac; Riscoe, Michael K.] Portland VA Med Ctr, Expt Chemotherapy Lab, Portland, OR 97239 USA.
   [McGinley, Paula L.; Castro, Steve] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
C3 St Jude Children's Research Hospital; Griffith University; University of Washington; University of Washington Seattle; University of Pennsylvania; University of Pennsylvania; GlaxoSmithKline; Glaxosmithkline United Kingdom; University of California System; University of California San Francisco; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; University of California System; University of California San Francisco; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Texas System; University of Texas Southwestern Medical Center; University of Washington; University of Washington Seattle; US Department of Veterans Affairs; Veterans Health Administration (VHA); Portland VA Medical Center; Rutgers University System; Rutgers University New Brunswick
RP Guy, RK (corresponding author), St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM kip.guy@stjude.org
FU American Lebanese Syrian Associated Charities (ALSAC); St Jude Children's Research Hospital (SJCRH); Medicines for Malaria Venture; National Institute of Allergy and Infectious Diseases [AI772682, AI075517, AI067921, AI080625, AI28724, AI53862, AI35707, AI053680, AI075594, AI082617, AI045774]; National Cancer Institute [CA78039]; Welch Foundation [I-1257]; Doris Duke Charitable Foundation; Ellison Medical Foundation
NR 27
TC 474
Z9 550
U1 1
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 311
EP 315
DI 10.1038/nature09099
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200032
PM 20485428
DA 2026-03-09
ER

PT J
AU Degroote, P
   Aerts, C
   Baglin, A
   Miglio, A
   Briquet, M
   Noels, A
   Niemczura, E
   Montalban, J
   Bloemen, S
   Oreiro, R
   Vuckovic, M
   Smolders, K
   Auvergne, M
   Baudin, F
   Catala, C
   Michel, E
AF Degroote, Pieter
   Aerts, Conny
   Baglin, Annie
   Miglio, Andrea
   Briquet, Maryline
   Noels, Arlette
   Niemczura, Ewa
   Montalban, Josefina
   Bloemen, Steven
   Oreiro, Raquel
   Vuckovic, Maja
   Smolders, Kristof
   Auvergne, Michel
   Baudin, Frederic
   Catala, Claude
   Michel, Eric
TI Deviations from a uniform period spacing of gravity modes in a massive star
SO NATURE
LA English
DT Article
ID whole earth telescope; stellar; asteroseismology; oscillations; pulsations; sun
AB The life of a star is dominantly determined by the physical processes in the stellar interior. Unfortunately, we still have a poor understanding of how the stellar gas mixes near the stellar core, preventing precise predictions of stellar evolution(1). The unknown nature of the mixing processes as well as the extent of the central mixed region is particularly problematic for massive stars(2). Oscillations in stars with masses a few times that of the Sun offer a unique opportunity to disentangle the nature of various mixing processes, through the distinct signature they leave on period spacings in the gravity mode spectrum(3). Here we report the detection of numerous gravity modes in a young star with a mass of about seven solar masses. The mean period spacing allows us to estimate the extent of the convective core, and the clear periodic deviation from the mean constrains the location of the chemical transition zone to be at about 10 per cent of the radius and rules out a clearcut profile.
C1 [Degroote, Pieter; Aerts, Conny; Briquet, Maryline; Bloemen, Steven; Oreiro, Raquel; Vuckovic, Maja; Smolders, Kristof] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Aerts, Conny] Radboud Univ Nijmegen, Dept Astrophys, IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Baglin, Annie; Auvergne, Michel; Catala, Claude; Michel, Eric] Univ Paris 07, Univ Paris 06, Observ Paris, LESIA,UMR8109, F-92195 Meudon, France.
   [Miglio, Andrea; Noels, Arlette; Montalban, Josefina] Univ Liege, Inst Astrophys & Geophys, B-4000 Liege, Belgium.
   [Niemczura, Ewa] Univ Wroclaw, Astron Inst, PL-51622 Wroclaw, Poland.
   [Baudin, Frederic] Inst Astrophys Spatiale, F-91405 Orsay, France.
C3 KU Leuven; Radboud University Nijmegen; Universite Paris Cite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Liege; University of Wroclaw; Universite Paris Saclay; Sorbonne Universite
RP Degroote, P (corresponding author), Katholieke Univ Leuven, Inst Sterrenkunde, Celestijnenlaan 200D, B-3001 Louvain, Belgium.
EM pieter.degroote@ster.kuleuven.ac.be
FU European Research Council under the European Community; Research Council of KU Leuven; Belgian Federal Science Policy
NR 30
TC 144
Z9 147
U1 0
U2 211
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 259
EP 261
DI 10.1038/nature08864
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100042
PM 20220844
DA 2026-03-09
ER

PT J
AU Alvarez, SE
   Harikumar, KB
   Hait, NC
   Allegood, J
   Strub, GM
   Kim, EY
   Maceyka, M
   Jiang, HL
   Luo, C
   Kordula, T
   Milstien, S
   Spiegel, S
AF Alvarez, Sergio E.
   Harikumar, Kuzhuvelil B.
   Hait, Nitai C.
   Allegood, Jeremy
   Strub, Graham M.
   Kim, Eugene Y.
   Maceyka, Michael
   Jiang, Hualiang
   Luo, Cheng
   Kordula, Tomasz
   Milstien, Sheldon
   Spiegel, Sarah
TI Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2
SO NATURE
LA English
DT Article
ID sphingosine 1-phosphate; tnf-alpha; activation; kinase; rip1; ikk; ubiquitylation; binding; cells; p38
AB Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-kappa B signalling triggered by TNF-alpha(1,2). Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1)(3) that then serves as a platform for recruitment and stimulation of I kappa B kinase, leading to activation of the transcription factor NF-kappa B. Although TRAF2 is a RING domain ubiquitin ligase, direct evidence that TRAF2 catalyses the ubiquitination of RIP1 is lacking. TRAF2 binds to sphingosine kinase 1 (SphK1)(4), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) inside cells. Here we show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of I kappa B kinase and I kappa B alpha, and I kappa B alpha degradation, leading to NF-kappa B activation. These responses were mediated by intracellular S1P independently of its cell surface G-protein-coupled receptors. S1P specifically binds to TRAF2 at the amino-terminal RING domain and stimulates its E3 ligase activity. S1P, but not dihydro-S1P, markedly increased recombinant TRAF2-catalysed lysine-63-linked, but not lysine-48-linked, polyubiquitination of RIP1 in vitro in the presence of the ubiquitin conjugating enzymes (E2) UbcH13 or UbcH5a. Our data show that TRAF2 is a novel intracellular target of S1P, and that S1P is the missing cofactor for TRAF2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination. These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappa B activation pathway important in inflammatory, antiapoptotic and immune processes.
C1 [Alvarez, Sergio E.; Harikumar, Kuzhuvelil B.; Hait, Nitai C.; Allegood, Jeremy; Strub, Graham M.; Kim, Eugene Y.; Maceyka, Michael; Kordula, Tomasz; Milstien, Sheldon; Spiegel, Sarah] Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Sch Med, Richmond, VA 23298 USA.
   [Alvarez, Sergio E.; Harikumar, Kuzhuvelil B.; Hait, Nitai C.; Allegood, Jeremy; Strub, Graham M.; Kim, Eugene Y.; Maceyka, Michael; Kordula, Tomasz; Milstien, Sheldon; Spiegel, Sarah] Virginia Commonwealth Univ, Massey Canc Ctr, Sch Med, Richmond, VA 23298 USA.
   [Jiang, Hualiang; Luo, Cheng] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
C3 Virginia Commonwealth University; Virginia Commonwealth University; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS
RP Spiegel, S (corresponding author), Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA.
EM sspiegel@vcu.edu
FU National Institute of Health [R37GM043880, R01CA61774, R01AI50094, U19AI077435]; Ministry of Scientific and Technology of China [2009CB918502]
NR 30
TC 623
Z9 745
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 24
PY 2010
VL 465
IS 7301
BP 1084
EP U149
DI 10.1038/nature09128
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900054
PM 20577214
DA 2026-03-09
ER

PT J
AU Boiko, AD
   Razorenova, OV
   van de Rijn, M
   Swetter, SM
   Johnson, DL
   Ly, DP
   Butler, PD
   Yang, GP
   Joshua, B
   Kaplan, MJ
   Longaker, MT
   Weissman, IL
AF Boiko, Alexander D.
   Razorenova, Olga V.
   van de Rijn, Matt
   Swetter, Susan M.
   Johnson, Denise L.
   Ly, Daphne P.
   Butler, Paris D.
   Yang, George P.
   Joshua, Benzion
   Kaplan, Michael J.
   Longaker, Michael T.
   Weissman, Irving L.
TI Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271
SO NATURE
LA English
DT Article
ID cancer stem-cells; prospective identification; progenitors
AB The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years(1). Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation(1,2). The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-) gamma c(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-) gamma c(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(-) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.
C1 [Boiko, Alexander D.; Longaker, Michael T.; Weissman, Irving L.] Stanford Univ, Sch Med, Stanford Canc Ctr, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94304 USA.
   [Razorenova, Olga V.] Stanford Univ, Med Ctr, Stanford Canc Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA.
   [van de Rijn, Matt; Weissman, Irving L.] Stanford Univ, Med Ctr, Stanford Canc Ctr, Dept Pathol, Stanford, CA 94305 USA.
   [Swetter, Susan M.] Stanford Univ, Med Ctr, Stanford Canc Ctr, Dept Dermatol,Pigmented Les & Melanoma Program, Stanford, CA 94305 USA.
   [Swetter, Susan M.; Yang, George P.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
   [Johnson, Denise L.; Ly, Daphne P.; Butler, Paris D.; Yang, George P.; Longaker, Michael T.] Stanford Univ, Med Ctr, Stanford Canc Ctr, Dept Surg, Stanford, CA 94305 USA.
   [Ly, Daphne P.; Butler, Paris D.; Yang, George P.; Longaker, Michael T.] Stanford Univ, Sch Med, Dept Surg, Hagey Lab Pediat Regenerat Med,Div Plast & Recons, Stanford, CA 94305 USA.
   [Joshua, Benzion; Kaplan, Michael J.] Stanford Univ, Med Ctr, Stanford Canc Ctr, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA.
C3 Stanford Cancer Institute; Stanford University; Stanford Medicine; Stanford University; Stanford Medicine; Stanford Cancer Institute; Stanford Cancer Institute; Stanford University; Stanford Medicine; Stanford University; Stanford Medicine; Stanford Cancer Institute; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Stanford Cancer Institute; Stanford University; Stanford Medicine; Stanford University; Stanford University; Stanford Medicine; Stanford Cancer Institute
RP Boiko, AD (corresponding author), Stanford Univ, Sch Med, Stanford Canc Ctr, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94304 USA.
EM aboiko@stanford.edu; irv@stanford.edu
FU American Cancer Society; NIH [F32 CA126252, 1RC2 DE02077-01]; Virginia & D.K. Ludwig Fund for Cancer Research; NIH/NCRR [UL1 RR025744]; Oak Foundation; Ellenburg Faculty Scholar Endowment
NR 30
TC 588
Z9 678
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 JUL 1
PY 2010
VL 466
IS 7302
BP 133
EP U155
DI 10.1038/nature09161
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800049
PM 20596026
DA 2026-03-09
ER

PT J
AU Scherber, C
   Eisenhauer, N
   Weisser, WW
   Schmid, B
   Voigt, W
   Fischer, M
   Schulze, ED
   Roscher, C
   Weigelt, A
   Allan, E
   Bessler, H
   Bonkowski, M
   Buchmann, N
   Buscot, F
   Clement, LW
   Ebeling, A
   Engels, C
   Halle, S
   Kertscher, I
   Klein, AM
   Koller, R
   König, S
   Kowalski, E
   Kummer, V
   Kuu, A
   Lange, M
   Lauterbach, D
   Middelhoff, C
   Migunova, VD
   Milcu, A
   Müller, R
   Partsch, S
   Petermann, JS
   Renker, C
   Rottstock, T
   Sabais, A
   Scheu, S
   Schumacher, J
   Temperton, VM
   Tscharntke, T
AF Scherber, Christoph
   Eisenhauer, Nico
   Weisser, Wolfgang W.
   Schmid, Bernhard
   Voigt, Winfried
   Fischer, Markus
   Schulze, Ernst-Detlef
   Roscher, Christiane
   Weigelt, Alexandra
   Allan, Eric
   Bessler, Holger
   Bonkowski, Michael
   Buchmann, Nina
   Buscot, Francois
   Clement, Lars W.
   Ebeling, Anne
   Engels, Christof
   Halle, Stefan
   Kertscher, Ilona
   Klein, Alexandra-Maria
   Koller, Robert
   Koenig, Stephan
   Kowalski, Esther
   Kummer, Volker
   Kuu, Annely
   Lange, Markus
   Lauterbach, Dirk
   Middelhoff, Cornelius
   Migunova, Varvara D.
   Milcu, Alexandru
   Mueller, Ramona
   Partsch, Stephan
   Petermann, Jana S.
   Renker, Carsten
   Rottstock, Tanja
   Sabais, Alexander
   Scheu, Stefan
   Schumacher, Jens
   Temperton, Vicky M.
   Tscharntke, Teja
TI Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment
SO NATURE
LA English
DT Article
ID trophic groups; top-down
AB Biodiversity is rapidly declining(1), and this may negatively affect ecosystem processes(2), including economically important ecosystem services(3). Previous studies have shown that biodiversity has positive effects on organisms and processes(4) across trophic levels(5). However, only a few studies have so far incorporated an explicit food-web perspective(6). In an eight-year biodiversity experiment, we studied an unprecedented range of above-and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades.
C1 [Scherber, Christoph; Ebeling, Anne; Tscharntke, Teja] Univ Gottingen, Dept Crop Sci, D-37077 Gottingen, Germany.
   [Scherber, Christoph; Weisser, Wolfgang W.; Voigt, Winfried; Roscher, Christiane; Weigelt, Alexandra; Allan, Eric; Clement, Lars W.; Ebeling, Anne; Halle, Stefan; Kertscher, Ilona; Klein, Alexandra-Maria; Kowalski, Esther; Lange, Markus; Lauterbach, Dirk; Mueller, Ramona] Univ Jena, Inst Ecol, D-07743 Jena, Germany.
   [Eisenhauer, Nico; Partsch, Stephan; Sabais, Alexander; Scheu, Stefan] Univ Gottingen, JF Blumenbach Inst Zool & Anthropol, D-37073 Gottingen, Germany.
   [Eisenhauer, Nico] Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA.
   [Schmid, Bernhard; Petermann, Jana S.] Univ Zurich, Inst Environm Sci, CH-8057 Zurich, Switzerland.
   [Fischer, Markus] Univ Bern, CH-3013 Bern, Switzerland.
   [Fischer, Markus; Kummer, Volker; Rottstock, Tanja] Univ Potsdam, Inst Biochem & Biol, D-14469 Potsdam, Germany.
   [Schulze, Ernst-Detlef; Middelhoff, Cornelius; Schumacher, Jens; Temperton, Vicky M.] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Roscher, Christiane] UFZ Helmholtz Ctr Environm Res, Dept Community Ecol, D-06120 Halle, Germany.
   [Weigelt, Alexandra] Univ Leipzig, Inst Biol 1, D-04103 Leipzig, Germany.
   [Bessler, Holger; Engels, Christof] Humboldt Univ, Dept Plant Nutr, D-14195 Berlin, Germany.
   [Bonkowski, Michael; Koller, Robert] Univ Cologne, Cologne Bioctr, Dept Terr Ecol, D-50674 Cologne, Germany.
   [Buchmann, Nina] Swiss Fed Inst Technol, Inst Plant Anim & Agroecosyst Sci, LFW C56, CH-8092 Zurich, Switzerland.
   [Buscot, Francois; Koenig, Stephan] UFZ Helmholtz Ctr Environm Res, Dept Soil Ecol, D-06102 Halle, Germany.
   [Klein, Alexandra-Maria] Leuphana Univ Lueneburg, Inst Ecol & Environm Chem, D-21335 Luneburg, Germany.
   [Kuu, Annely] Tallinn Univ Technol, Tartu Coll, EE-51008 Tartu, Estonia.
   [Migunova, Varvara D.] KI Skryabin All Russian Inst Helminthol, Moscow 117218, Russia.
   [Milcu, Alexandru] Imperial Coll London, Div Biol, NERC Ctr Populat Biol, Ascot SL5 7PY, Berks, England.
   [Petermann, Jana S.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [Renker, Carsten] Mainz Museum Nat Hist, D-55116 Mainz, Germany.
   [Schumacher, Jens] Univ Jena, Inst Stochast, D-07743 Jena, Germany.
   [Temperton, Vicky M.] Forschungszentrum Julich GmbH, Phytosphere Inst ICG 3, D-52425 Julich, Germany.
C3 University of Gottingen; Friedrich Schiller University of Jena; University of Gottingen; University of Minnesota System; University of Minnesota Twin Cities; University of Zurich; University of Bern; University of Potsdam; Max Planck Society; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); Leipzig University; Humboldt University of Berlin; University of Cologne; Swiss Federal Institutes of Technology Domain; ETH Zurich; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ); Leuphana University Luneburg; Tallinn University of Technology; Federal Scientific Centre VIEV; Imperial College London; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); University of British Columbia; Friedrich Schiller University of Jena; Helmholtz Association; Julich Research Centre
RP Scherber, C (corresponding author), Univ Gottingen, Dept Crop Sci, Grisebachstr 6, D-37077 Gottingen, Germany.
EM christoph.scherber@agr.uni-goettingen.de
FU Deutsche Forschungsgemeinschaft [FOR 456]; NERC [cpb010001] Funding Source: UKRI; Natural Environment Research Council [cpb010001] Funding Source: researchfish
NR 29
TC 825
Z9 949
U1 23
U2 968
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 553
EP 556
DI 10.1038/nature09492
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200040
PM 20981010
DA 2026-03-09
ER

PT J
AU Chandrashekar, J
   Kuhn, C
   Oka, Y
   Yarmolinsky, DA
   Hummler, E
   Ryba, NJP
   Zuker, CS
AF Chandrashekar, Jayaram
   Kuhn, Christina
   Oka, Yuki
   Yarmolinsky, David A.
   Hummler, Edith
   Ryba, Nicholas J. P.
   Zuker, Charles S.
TI The cells and peripheral representation of sodium taste in mice
SO NATURE
LA English
DT Article
ID single chorda tympani; glossopharyngeal nerve; receptor-cells; bitter taste; salt taste; amiloride; channel; mouse; nacl; rat
AB Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion(1-5). Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a nonselective detector for a wide range of salts(1-3,6-9). Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system(1,3,6-14). Previously, we showed that four of the five basic taste qualities-sweet, sour, bitter and umami-are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses(5,15-18). Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC19,20, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaC alpha in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.
C1 [Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurobiol, La Jolla, CA 92093 USA.
   [Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Kuhn, Christina; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
   [Hummler, Edith] Univ Lausanne, Fac Biol & Med, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); University of Lausanne
RP Zuker, CS (corresponding author), Columbia Univ, Columbia Coll Phys & Surg, Howard Hughes Med Inst, Dept Biochem, New York, NY 10032 USA.
EM cz2195@columbia.edu
FU NIH, NIDCR; National Institute of Dental and Craniofacial Research [ZIADE000561] Funding Source: NIH RePORTER
NR 30
TC 522
Z9 655
U1 4
U2 269
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 297
EP U182
DI 10.1038/nature08783
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100051
PM 20107438
DA 2026-03-09
ER

PT J
AU Block, M
   Ackermann, D
   Blaum, K
   Droese, C
   Dworschak, M
   Eliseev, S
   Fleckenstein, T
   Haettner, E
   Herfurth, F
   Hessberger, FP
   Hofmann, S
   Ketelaer, J
   Ketter, J
   Kluge, HJ
   Marx, G
   Mazzocco, M
   Novikov, YN
   Plass, WR
   Popeko, A
   Rahaman, S
   Rodríguez, D
   Scheidenberger, C
   Schweikhard, L
   Thirolf, PG
   Vorobyev, GK
   Weber, C
AF Block, M.
   Ackermann, D.
   Blaum, K.
   Droese, C.
   Dworschak, M.
   Eliseev, S.
   Fleckenstein, T.
   Haettner, E.
   Herfurth, F.
   Hessberger, F. P.
   Hofmann, S.
   Ketelaer, J.
   Ketter, J.
   Kluge, H. -J.
   Marx, G.
   Mazzocco, M.
   Novikov, Yu. N.
   Plass, W. R.
   Popeko, A.
   Rahaman, S.
   Rodriguez, D.
   Scheidenberger, C.
   Schweikhard, L.
   Thirolf, P. G.
   Vorobyev, G. K.
   Weber, C.
TI Direct mass measurements above uranium bridge the gap to the island of stability
SO NATURE
LA English
DT Article
ID nuclear-structure investigations; superheavy nuclei; heaviest nuclei; shiptrap; accuracy; elements
AB The mass of an atom incorporates all its constituents and their interactions(1). The difference between the mass of an atom and the sum of its building blocks (the binding energy) is a manifestation of Einstein's famous relation E = mc(2). The binding energy determines the energy available for nuclear reactions and decays (and thus the creation of elements by stellar nucleosynthesis), and holds the key to the fundamental question of how heavy the elements can be. Superheavy elements have been observed in challenging production experiments(2-4), but our present knowledge of the binding energy of these nuclides is based only on the detection of their decay products. The reconstruction from extended decay chains introduces uncertainties that render the interpretation difficult. Here we report direct mass measurements of transuranium nuclides. Located at the farthest tip of the actinide species on the proton number-neutron number diagram, these nuclides represent the gateway to the predicted island of stability. In particular, we have determined the mass values of No252-254 (atomic number 102) with the Penning trap mass spectrometer SHIPTRAP(5). The uncertainties are of the order of 10 keV/c(2) (representing a relative precision of 0.05 p.p.m.), despite minute production rates of less than one atom per second. Our experiments advance direct mass measurements by ten atomic numbers with no loss in accuracy, and provide reliable anchor points en route to the island of stability.
C1 [Block, M.; Ackermann, D.; Dworschak, M.; Herfurth, F.; Hessberger, F. P.; Hofmann, S.; Kluge, H. -J.; Novikov, Yu. N.; Plass, W. R.; Scheidenberger, C.; Vorobyev, G. K.] GSI Helmholtzzentrum Schwerionenforsch GmbH, D-64291 Darmstadt, Germany.
   [Blaum, K.; Eliseev, S.; Ketter, J.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Droese, C.; Marx, G.; Schweikhard, L.] Ernst Moritz Arndt Univ Greifswald, D-17489 Greifswald, Germany.
   [Fleckenstein, T.; Haettner, E.; Plass, W. R.; Scheidenberger, C.] Univ Giessen, D-35390 Giessen, Germany.
   [Ketelaer, J.] Johannes Gutenberg Univ Mainz, D-55128 Mainz, Germany.
   [Kluge, H. -J.] Heidelberg Univ, D-69120 Heidelberg, Germany.
   [Mazzocco, M.] Univ Padua, Dipartimento Fis, I-35131 Padua, Italy.
   [Mazzocco, M.] Ist Nazl Fis Nucl, Sez Padova, I-35131 Padua, Italy.
   [Novikov, Yu. N.] PNPIRAS, Gatchina 188300, Russia.
   [Popeko, A.] Joint Inst Nucl Res, Flerov Lab Nucl React, Dubna 141980, Russia.
   [Rahaman, S.; Weber, C.] Univ Jyvaskyla, Jyvaskyla 40014, Finland.
   [Rodriguez, D.] Univ Granada, Dept FAMN, E-18071 Granada, Spain.
   [Thirolf, P. G.] Univ Munich, D-85748 Garching, Germany.
C3 Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Max Planck Society; Universitat Greifswald; Justus Liebig University Giessen; Johannes Gutenberg University of Mainz; Ruprecht Karls University Heidelberg; University of Padua; Istituto Nazionale di Fisica Nucleare (INFN); National Research Centre - Kurchatov Institute; Petersburg Nuclear Physics Institute; Joint Institute for Nuclear Research - Russia; University of Jyvaskyla; University of Granada; University of Munich
RP Block, M (corresponding author), GSI Helmholtzzentrum Schwerionenforsch GmbH, Planckstr 1, D-64291 Darmstadt, Germany.
EM m.block@gsi.de
FU German Federal Ministry of Education and Research; Max-Planck Society; Helmholtz Association; Junta de Andalucia
NR 30
TC 167
Z9 176
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 FEB 11
PY 2010
VL 463
IS 7282
BP 785
EP 788
DI 10.1038/nature08774
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300034
PM 20148034
DA 2026-03-09
ER

PT J
AU Olmedo-Monfil, V
   Durán-Figueroa, N
   Arteaga-Vázquez, M
   Demesa-Arévalo, E
   Autran, D
   Grimanelli, D
   Slotkin, RK
   Martienssen, RA
   Vielle-Calzada, JP
AF Olmedo-Monfil, Vianey
   Duran-Figueroa, Noe
   Arteaga-Vazquez, Mario
   Demesa-Arevalo, Edgar
   Autran, Daphne
   Grimanelli, Daniel
   Slotkin, R. Keith
   Martienssen, Robert A.
   Vielle-Calzada, Jean-Philippe
TI Control of female gamete formation by a small RNA pathway in Arabidopsis
SO NATURE
LA English
DT Article
ID trans-acting sirnas; gene; biogenesis; expression; genome
AB In the ovules of most sexual flowering plants female gametogenesis is initiated from a single surviving gametic cell, the functional megaspore, formed after meiosis of the somatically derived megaspore mother cell (MMC)(1,2). Because some mutants and certain sexual species exhibit more than one MMC2-4, and many others are able to form gametes without meiosis (by apomixis)(5), it has been suggested that somatic cells in the ovule are competent to respond to a local signal likely to have an important function in determination(6). Here we show that the Arabidopsis protein ARGONAUTE 9 (AGO9) controls female gamete formation by restricting the specification of gameto-phyte precursors in a dosage-dependent, non-cell-autonomous manner. Mutations in AGO9 lead to the differentiation of multiple gametic cells that are able to initiate gametogenesis. The AGO9 protein is not expressed in the gamete lineage; instead, it is expressed in cytoplasmic foci of somatic companion cells. Mutations in SUPPRESSOR OF GENE SILENCING 3 and RNA-DEPENDENT RNA POLYMERASE 6 exhibit an identical defect to ago9 mutants, indicating that the movement of small RNA (sRNAs) silencing out of somatic companion cells is necessary for controlling the specification of gametic cells. AGO9 preferentially interacts with 24-nucleotide sRNAs derived from transposable elements (TEs), and its activity is necessary to silence TEs in female gametes and their accessory cells. Our results show that AGO9-dependent sRNA silencing is crucial to specify cell fate in the Arabidopsis ovule, and that epigenetic reprogramming in companion cells is necessary for sRNA-dependent silencing in plant gametes.
C1 [Olmedo-Monfil, Vianey; Duran-Figueroa, Noe; Arteaga-Vazquez, Mario; Demesa-Arevalo, Edgar; Vielle-Calzada, Jean-Philippe] Cinvestav Irapuato, Lab Nacl Genom Biodiversidad, Grp Desarrollo Reprod & Apomixis, Guanajuato 36500, Mexico.
   [Olmedo-Monfil, Vianey; Duran-Figueroa, Noe; Arteaga-Vazquez, Mario; Demesa-Arevalo, Edgar; Vielle-Calzada, Jean-Philippe] Cinvestav Irapuato, Dept Ingn Genet Plantas, Guanajuato 36500, Mexico.
   [Autran, Daphne; Grimanelli, Daniel] Inst Rech Dev, UMR 5096, F-34394 Montpellier, France.
   [Slotkin, R. Keith; Martienssen, Robert A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut de Recherche pour le Developpement (IRD); Universite Perpignan Via Domitia; Cold Spring Harbor Laboratory
RP Vielle-Calzada, JP (corresponding author), Cinvestav Irapuato, Lab Nacl Genom Biodiversidad, Grp Desarrollo Reprod & Apomixis, Guanajuato 36500, Mexico.
EM vielle@ira.cinvestav.mx
FU IRD-France; ANR; NIH; NSF; Consejo Nacional de Ciencia y Tecnologia; Consejo Estatal de Ciencia y Tecnologia de Guanajuato; Howard Hughes Medical Institute; Direct For Biological Sciences; Div Of Biological Infrastructure [0963400] Funding Source: National Science Foundation
NR 33
TC 464
Z9 528
U1 4
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 628
EP U200
DI 10.1038/nature08828
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200056
PM 20208518
DA 2026-03-09
ER

PT J
AU Rauzi, M
   Lenne, PF
   Lecuit, T
AF Rauzi, Matteo
   Lenne, Pierre-Francois
   Lecuit, Thomas
TI Planar polarized actomyosin contractile flows control epithelial junction remodelling
SO NATURE
LA English
DT Article
ID adherens junctions; apical constriction; cell-shape; tissue morphogenesis; alpha-catenin; e-cadherin; drosophila; network; forces; intercalation
AB Force generation by Myosin-II motors on actin filaments drives cell and tissue morphogenesis(1-15). In epithelia, contractile forces are resisted at apical junctions by adhesive forces dependent on E-cadherin(16), which also transmits tension(6,17-19). During Drosophila embryonic germband extension, tissue elongation is driven by cell intercalation(20), which requires an irreversible and planar polarized remodelling of epithelial cell junctions(4,5). We investigate how cell deformations emerge from the interplay between force generation and cortical force transmission during this remodelling in Drosophila melanogaster. The shrinkage of dorsal-ventral-oriented ('vertical') junctions during this process is known to require planar polarized junctional contractility by Myosin II (refs 4,5,7,12). Here we show that this shrinkage is not produced by junctional Myosin II itself, but by the polarized flow of medial actomyosin pulses towards 'vertical' junctions. This anisotropic flow is oriented by the planar polarized distribution of E-cadherin complexes, in that medial Myosin II flows towards 'vertical' junctions, which have relatively less E-cadherin than transverse junctions. Our evidence suggests that the medial flow pattern reflects equilibrium properties of force transmission and coupling to E-cadherin by a-Catenin. Thus, epithelial morphogenesis is not properly reflected by Myosin II steady state distribution but by polarized contractile actomyosin flows that emerge from interactions between E-cadherin and actomyosin networks.
C1 [Rauzi, Matteo; Lenne, Pierre-Francois; Lecuit, Thomas] Univ Aix Marseille 2, CNRS, IBDML, UMR6216, F-13288 Marseille 09, France.
C3 Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite
RP Lecuit, T (corresponding author), Univ Aix Marseille 2, CNRS, IBDML, UMR6216, Campus Luminy,Case 907, F-13288 Marseille 09, France.
EM lenne@ibdml.univ-mrs.fr; lecuit@ibdml.univ-mrs.fr
FU HFSP; CNRS; Fondation pour la Recherche Medicale; ANR-Blanc; Region PACA; ANR-PCV; Amplitude Systems
NR 36
TC 493
Z9 600
U1 1
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1110
EP U515
DI 10.1038/nature09566
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800060
PM 21068726
DA 2026-03-09
ER

PT J
AU Moro, K
   Yamada, T
   Tanabe, M
   Takeuchi, T
   Ikawa, T
   Kawamoto, H
   Furusawa, J
   Ohtani, M
   Fujii, H
   Koyasu, S
AF Moro, Kazuyo
   Yamada, Taketo
   Tanabe, Masanobu
   Takeuchi, Tsutomu
   Ikawa, Tomokatsu
   Kawamoto, Hiroshi
   Furusawa, Jun-ichi
   Ohtani, Masashi
   Fujii, Hideki
   Koyasu, Shigeo
TI Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
SO NATURE
LA English
DT Article
ID natural-killer-cells; ror-gamma-t; inducer cells; mice lacking; il-33; expression; differentiation; lymphocytes; generation; expulsion
AB Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines(1,2). Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors(3) and lymphoid tissue inducer cells(4). These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells(5-7). Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection(8,9). After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.
C1 [Moro, Kazuyo; Furusawa, Jun-ichi; Ohtani, Masashi; Fujii, Hideki; Koyasu, Shigeo] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Yamada, Taketo] Keio Univ, Sch Med, Dept Pathol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Tanabe, Masanobu; Takeuchi, Tsutomu] Keio Univ, Sch Med, Dept Trop Med & Parasitol, Shinjuku Ku, Tokyo 1608582, Japan.
   [Moro, Kazuyo] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo 1020075, Japan.
   [Ikawa, Tomokatsu; Kawamoto, Hiroshi] Riken Res Ctr Allergy & Immunol, Lab Lymphocyte Dev, Kanagawa 2300045, Japan.
   [Ohtani, Masashi] Kansai Med Univ, Inst Biomed Sci, Dept Cell Signalling, Osaka 5708506, Japan.
   [Koyasu, Shigeo] Japan Soc Promot Sci, Res Ctr Sci Syst, Chiyoda Ku, Tokyo 1028472, Japan.
C3 Keio University; Keio University; Keio University; Japan Science & Technology Agency (JST); RIKEN; Kansai Medical University; Japan Society for the Promotion of Science
RP Koyasu, S (corresponding author), Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan.
EM koyasu@sc.itc.keio.ac.jp
FU Japan Society for the Promotion of Science [20790378, 14370116, 16390146, 18390155]; Ministry of Education, Culture, Sports, Science and Technology, Japan; Grants-in-Aid for Scientific Research [18390155, 20790378, 16390146, 22590437, 14370116] Funding Source: KAKEN
NR 33
TC 1632
Z9 1893
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 JAN 28
PY 2010
VL 463
IS 7280
BP 540
EP U160
DI 10.1038/nature08636
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100051
PM 20023630
DA 2026-03-09
ER

PT J
AU Bénazéraf, B
   Francois, P
   Baker, RE
   Denans, N
   Little, CD
   Pourquié, O
AF Benazeraf, Bertrand
   Francois, Paul
   Baker, Ruth E.
   Denans, Nicolas
   Little, Charles D.
   Pourquie, Olivier
TI A random cell motility gradient downstream of FGF controls elongation of an amniote embryo
SO NATURE
LA English
DT Article
ID chick-embryo; movement; somitogenesis; gastrulation; boundary; dynamics; matrix
AB Vertebrate embryos are characterized by an elongated anteroposterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogenactivated protein kinase (MAPK) gradient(1), which has been implicated in the control of cell motility in this tissue(2). Both FGF signalling gain-and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements.
C1 [Benazeraf, Bertrand; Pourquie, Olivier] Howard Hughes Med Inst, Kansas City, MO 64110 USA.
   [Benazeraf, Bertrand; Denans, Nicolas; Pourquie, Olivier] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Benazeraf, Bertrand; Denans, Nicolas; Pourquie, Olivier] Univ Strasbourg, CNRS, INSERM, IGBMC,UMR 7104,U964, F-67400 Illkirch Graffenstaden, France.
   [Francois, Paul] Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10065 USA.
   [Baker, Ruth E.] Univ Oxford, Math Inst, Ctr Math Biol, Oxford OX1 3LB, England.
   [Little, Charles D.; Pourquie, Olivier] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
C3 Howard Hughes Medical Institute; Stowers Institute for Medical Research; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Rockefeller University; University of Oxford; University of Kansas; University of Kansas Medical Center
RP Pourquié, O (corresponding author), Howard Hughes Med Inst, Kansas City, MO 64110 USA.
EM pourquie@igbmc.fr
FU Howard Hughes Medical Institute; Stowers Institute for Medical Research; NIH [R02 HD043158]; Chaire d'excellence; NSF [DMR-0129848]; Lavoisier Fellowship; RCUK Fellowship in Mathematical Biology; Microsoft European Postdoctoral Research Fellowship; Mathers Charitable Foundation
NR 30
TC 250
Z9 298
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 8
PY 2010
VL 466
IS 7303
BP 248
EP 252
DI 10.1038/nature09151
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800039
PM 20613841
DA 2026-03-09
ER

PT J
AU Holt, JW
   Fishbaugh, KE
   Byrne, S
   Christian, S
   Tanaka, K
   Russell, PS
   Herkenhoff, KE
   Safaeinili, A
   Putzig, NE
   Phillips, RJ
AF Holt, J. W.
   Fishbaugh, K. E.
   Byrne, S.
   Christian, S.
   Tanaka, K.
   Russell, P. S.
   Herkenhoff, K. E.
   Safaeinili, A.
   Putzig, N. E.
   Phillips, R. J.
TI The construction of Chasma Boreale on Mars
SO NATURE
LA English
DT Article
ID north polar-region; stratigraphy; deposits; history; origin
AB The polar layered deposits of Mars contain the planet's largest known reservoir of water ice(1,2) and the prospect of revealing a detailed Martian palaeoclimate record(3,4), but the mechanisms responsible for the formation of the dominant features of the north polar layered deposits (NPLD) are unclear, despite decades of debate. Stratigraphic analyses of the exposed portions of Chasma Boreale-a large canyon 500 km long, up to 100 km wide, and nearly 2 km deep-have led most researchers to favour an erosional process for its formation following initial NPLD accumulation. Candidate mechanisms include the catastrophic outburst of water(5), protracted basal melting(6), erosional undercutting(7), aeolian downcutting(7-9) and a combination of these processes(10). Here we use new data from the Mars Reconnaissance Orbiter to show that Chasma Boreale is instead a long-lived, complex feature resulting primarily from non-uniform accumulation of the NPLD. The initial valley that later became Chasma Boreale was matched by a second, equally large valley that was completely filled in by subsequent deposition, leaving no evidence on the surface to indicate its former presence. We further demonstrate that topography existing before the NPLD began accumulating influenced successive episodes of deposition and erosion, resulting in most of the present-day topography. Long-term and large-scale patterns of mass balance achieved through sedimentary processes, rather than catastrophic events, ice flow or highly focused erosion, have produced the largest geomorphic anomaly in the north polar ice of Mars.
C1 [Holt, J. W.; Christian, S.] Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
   [Fishbaugh, K. E.] Smithsonian Natl Air & Space Museum, Washington, DC 20560 USA.
   [Byrne, S.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Christian, S.] Bryn Mawr Coll, Bryn Mawr, PA 19010 USA.
   [Tanaka, K.; Herkenhoff, K. E.] US Geol Survey, Astrogeol Sci Ctr, Flagstaff, AZ 86001 USA.
   [Russell, P. S.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Safaeinili, A.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Putzig, N. E.; Phillips, R. J.] SW Res Inst, Boulder, CO 80302 USA.
C3 University of Texas System; University of Texas Austin; Smithsonian Institution; Smithsonian National Air & Space Museum; University of Arizona; Bryn Mawr College; United States Department of the Interior; United States Geological Survey; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology
RP Holt, JW (corresponding author), Univ Texas Austin, Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
EM jack@ig.utexas.edu
FU Institute for Geophysics of the Jackson School of Geosciences; NASA [NAG5-12693]; Mars Reconnaissance Orbiter (MRO); Italian Space Agency
NR 26
TC 50
Z9 53
U1 0
U2 20
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 446
EP 449
DI 10.1038/nature09050
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700027
PM 20505721
DA 2026-03-09
ER

PT J
AU Christodoulou, F
   Raible, F
   Tomer, R
   Simakov, O
   Trachana, K
   Klaus, S
   Snyman, H
   Hannon, GJ
   Bork, P
   Arendt, D
AF Christodoulou, Foteini
   Raible, Florian
   Tomer, Raju
   Simakov, Oleg
   Trachana, Kalliopi
   Klaus, Sebastian
   Snyman, Heidi
   Hannon, Gregory J.
   Bork, Peer
   Arendt, Detlev
TI Ancient animal microRNAs and the evolution of tissue identity
SO NATURE
LA English
DT Article
ID nematostella-vectensis; spatial expression; genes; let-7; drosophila; system
AB The spectacular escalation in complexity in early bilaterian evolution correlates with a strong increase in the number of microRNAs(1,2). To explore the link between the birth of ancient microRNAs and body plan evolution, we set out to determine the ancient sites of activity of conserved bilaterian microRNA families in a comparative approach. We reason that any specific localization shared between protostomes and deuterostomes (the two major superphyla of bilaterian animals) should probably reflect an ancient specificity of that microRNA in their last common ancestor. Here, we investigate the expression of conserved bilaterian microRNAs in Platynereis dumerilii, a protostome retaining ancestral bilaterian features(3,4), in Capitella, another marine annelid, in the sea urchin Strongylocentrotus, a deuterostome, and in sea anemone Nematostella, representing an outgroup to the bilaterians. Our comparative data indicate that the oldest known animal microRNA, miR-100, and the related miR-125 and let-7 were initially active in neurosecretory cells located around the mouth. Other sets of ancient microRNAs were first present in locomotor ciliated cells, specific brain centres, or, more broadly, one of four major organ systems: central nervous system, sensory tissue, musculature and gut. These findings reveal that microRNA evolution and the establishment of tissue identities were closely coupled in bilaterian evolution. Also, they outline a minimum set of cell types and tissues that existed in the protostome-deuterostome ancestor.
C1 [Christodoulou, Foteini; Raible, Florian; Tomer, Raju; Simakov, Oleg; Klaus, Sebastian; Snyman, Heidi; Arendt, Detlev] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
   [Raible, Florian; Trachana, Kalliopi; Bork, Peer] European Mol Biol Lab, Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Hannon, Gregory J.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Cold Spring Harbor Laboratory
RP Arendt, D (corresponding author), European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
EM arendt@embl.de
FU National Cancer Institute [P01CA013106] Funding Source: NIH RePORTER; NCI NIH HHS [P01 CA013106] Funding Source: Medline
NR 38
TC 232
Z9 277
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1084
EP U105
DI 10.1038/nature08744
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400037
PM 20118916
DA 2026-03-09
ER

PT J
AU Zhao, YF
   Terry, D
   Shi, L
   Weinstein, H
   Blanchard, SC
   Javitch, JA
AF Zhao, Yongfang
   Terry, Daniel
   Shi, Lei
   Weinstein, Harel
   Blanchard, Scott C.
   Javitch, Jonathan A.
TI Single-molecule dynamics of gating in a neurotransmitter transporter homologue
SO NATURE
LA English
DT Article
ID bacterial homolog; leut; fluorescence; substrate; binding; na+; rna; mechanism; reveals; protein
AB Neurotransmitter: Na+ symporters (NSS) remove neurotransmitters from the synapse in a reuptake process that is driven by the Na+ gradient. Drugs that interfere with this reuptake mechanism, such as cocaine and antidepressants, profoundly influence behaviour and mood. To probe the nature of the conformational changes that are associated with substrate binding and transport, we have developed a single-molecule fluorescence imaging assay and combined it with functional and computational studies of the prokaryotic NSS homologue LeuT. Here we show molecular details of the modulation of intracellular gating of LeuT by substrates and inhibitors, as well as by mutations that alter binding, transport or both. Our direct observations of single-molecule transitions, reflecting structural dynamics of the intracellular region of the transporter that might be masked by ensemble averaging or suppressed under crystallographic conditions, are interpreted in the context of an allosteric mechanism that couples ion and substrate binding to transport.
C1 [Zhao, Yongfang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA.
   [Zhao, Yongfang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Zhao, Yongfang; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
   [Terry, Daniel; Shi, Lei; Weinstein, Harel; Blanchard, Scott C.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
   [Shi, Lei; Weinstein, Harel] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA.
   [Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; New York State Psychiatry Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Columbia University
RP Javitch, JA (corresponding author), Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, 630 W 168th, New York, NY 10032 USA.
EM scb2005@med.cornell.edu; jaj2@columbia.edu
FU National Institutes of Health [DA17293, DA022413, DA12408, DA023694]; Tri-Institutional Training Program in Computational Biology and Medicine
NR 51
TC 220
Z9 263
U1 0
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 188
EP U73
DI 10.1038/nature09057
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500028
PM 20463731
DA 2026-03-09
ER

PT J
AU van Os, J
   Kenis, G
   Rutten, BPF
AF van Os, Jim
   Kenis, Gunter
   Rutten, Bart P. F.
TI The environment and schizophrenia
SO NATURE
LA English
DT Article
ID daily-life stress; psychotic symptoms; childhood trauma; cannabis use; nonpsychotic disorders; familial liability; birth-cohort; brain-injury; risk-factors; urbanicity
AB Psychotic syndromes can be understood as disorders of adaptation to social context. Although heritability is often emphasized, onset is associated with environmental factors such as early life adversity, growing up in an urban environment, minority group position and cannabis use, suggesting that exposure may have an impact on the developing 'social' brain during sensitive periods. Therefore heritability, as an index of genetic influence, may be of limited explanatory power unless viewed in the context of interaction with social effects. Longitudinal research is needed to uncover gene-environment interplay that determines how expression of vulnerability in the general population may give rise to more severe psychopathology.
C1 [van Os, Jim; Kenis, Gunter; Rutten, Bart P. F.] Maastricht Univ, Med Ctr, SEARCH, European Grad Sch Neurosci, NL-6200 MD Maastricht, Netherlands.
   [van Os, Jim] Kings Coll London, Dept Psychosis Studies, Inst Psychiat, London SE5 8AF, England.
C3 Maastricht University; University of London; King's College London
RP van Os, J (corresponding author), Maastricht Univ, Med Ctr, SEARCH, European Grad Sch Neurosci, NL-6200 MD Maastricht, Netherlands.
EM j.vanos@sp.unimaas.nl
FU Dutch Health Research Council [10-000-1002]; European Community [HEALTH-F2-2009-241909]
NR 99
TC 1161
Z9 1303
U1 3
U2 367
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 203
EP 212
DI 10.1038/nature09563
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000036
PM 21068828
DA 2026-03-09
ER

PT J
AU Lowe, AR
   Siegel, JJ
   Kalab, P
   Siu, M
   Weis, K
   Liphardt, JT
AF Lowe, Alan R.
   Siegel, Jake J.
   Kalab, Petr
   Siu, Merek
   Weis, Karsten
   Liphardt, Jan T.
TI Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking
SO NATURE
LA English
DT Article
ID phenylalanine-glycine nucleoporins; protein import; translocation; transport; molecule; diffusion; hydrogel; beta
AB The nuclear pore complex (NPC) mediates all exchange between the cytoplasm and the nucleus. Small molecules can passively diffuse through the NPC, whereas larger cargos require transport receptors to translocate(1). How the NPC facilitates the translocation of transport receptor/cargo complexes remains unclear. To investigate this process, we tracked single protein-functionalized quantum dot cargos as they moved through human NPCs. Here we show that import proceeds by successive substeps comprising cargo capture, filtering and translocation, and release into the nucleus. Most quantum dots are rejected at one of these steps and return to the cytoplasm, including very large cargos that abort at a size-selective barrier. Cargo movement in the central channel is subdiffusive and cargos that can bind more transport receptors diffuse more freely. Without Ran GTPase, a critical regulator of transport directionality(1), cargos still explore the entire NPC, but have a markedly reduced probability of exit into the nucleus, suggesting that NPC entry and exit steps are not equivalent and that the pore is functionally asymmetric to importing cargos. The overall selectivity of the NPC seems to arise from the cumulative action of multiple reversible substeps and a final irreversible exit step.
C1 [Lowe, Alan R.; Siegel, Jake J.; Weis, Karsten; Liphardt, Jan T.] Univ Calif Berkeley, QB3, Berkeley, CA 94720 USA.
   [Lowe, Alan R.; Liphardt, Jan T.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Lowe, Alan R.; Liphardt, Jan T.] Univ Calif Berkeley, Bay Area Phys Sci Oncol Ctr, Berkeley, CA 94720 USA.
   [Siegel, Jake J.; Siu, Merek; Liphardt, Jan T.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Kalab, Petr; Weis, Karsten] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA.
   [Lowe, Alan R.; Liphardt, Jan T.] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, 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; 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 Weis, K (corresponding author), Univ Calif Berkeley, QB3, Berkeley, CA 94720 USA.
EM kweis@berkeley.edu
FU NIH [GM058065, GM77856]; NCI [U54CA143836]
NR 28
TC 133
Z9 151
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 SEP 15
PY 2010
VL 467
IS 7315
BP 600
EP U126
DI 10.1038/nature09285
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100041
PM 20811366
DA 2026-03-09
ER

PT J
AU Governato, F
   Brook, C
   Mayer, L
   Brooks, A
   Rhee, G
   Wadsley, J
   Jonsson, P
   Willman, B
   Stinson, G
   Quinn, T
   Madau, P
AF Governato, F.
   Brook, C.
   Mayer, L.
   Brooks, A.
   Rhee, G.
   Wadsley, J.
   Jonsson, P.
   Willman, B.
   Stinson, G.
   Quinn, T.
   Madau, P.
TI Bulgeless dwarf galaxies and dark matter cores from supernova-driven outflows
SO NATURE
LA English
DT Article
ID stellar feedback; radiative-transfer; star-formation; disk galaxy; simulations; universe; resolution; rotation; origin; haloes
AB For almost two decades the properties of 'dwarf' galaxies have challenged the cold dark matter (CDM) model of galaxy formation(1). Most observed dwarf galaxies consist of a rotating stellar disk(2) embedded in a massive dark-matter halo with a near-constant-density core(3). Models based on the dominance of CDM, however, invariably form galaxies with dense spheroidal stellar bulges and steep central dark-matter profiles(4-6), because low-angular-momentum baryons and dark matter sink to the centres of galaxies through accretion and repeated mergers(7). Processes that decrease the central density of CDM halos(8) have been identified, but have not yet reconciled theory with observations of present-day dwarfs. This failure is potentially catastrophic for the CDM model, possibly requiring a different dark-matter particle candidate(9). Here we report hydrodynamical simulations (in a framework(10) assuming the presence of CDM and a cosmological constant) in which the inhomogeneous interstellar medium is resolved. Strong outflows from supernovae remove low-angular-momentum gas, which inhibits the formation of bulges and decreases the dark-matter density to less than half of what it would otherwise be within the central kiloparsec. The analogues of dwarf galaxies-bulgeless and with shallow central dark-matter profiles-arise naturally in these simulations.
C1 [Governato, F.; Quinn, T.] Univ Washington, Dept Astron, Seattle, WA 98195 USA.
   [Brook, C.] Univ Cent Lancashire, Jeremiah Horrocks Inst, Preston PR1 2HE, Lancs, England.
   [Mayer, L.] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
   [Brooks, A.] CALTECH, Pasadena, CA 91125 USA.
   [Rhee, G.] Univ Nevada, Dept Phys & Astron, Las Vegas, NV 89154 USA.
   [Wadsley, J.; Stinson, G.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Jonsson, P.] Univ Calif Santa Cruz, Inst Particle Phys, Santa Cruz, CA 95064 USA.
   [Madau, P.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Willman, B.] Haverford Coll, Dept Astron, Haverford, PA 19041 USA.
C3 University of Washington; University of Washington Seattle; University of Lancashire; University of Zurich; California Institute of Technology; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; McMaster University; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Haverford College
RP Governato, F (corresponding author), Univ Washington, Dept Astron, Seattle, WA 98195 USA.
EM fabio@astro.washington.edu
NR 30
TC 886
Z9 975
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 14
PY 2010
VL 463
IS 7278
BP 203
EP 206
DI 10.1038/nature08640
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700029
PM 20075915
DA 2026-03-09
ER

PT J
AU Zegerman, P
   Diffley, JFX
AF Zegerman, Philip
   Diffley, John F. X.
TI Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation
SO NATURE
LA English
DT Article
ID s-phase checkpoint; budding yeast; saccharomyces-cerevisiae; progression; forks; origins; activation; kinases; pathway; stress
AB The initiation of eukaryotic DNA replication is regulated by three protein kinase classes: cyclin-dependent kinases (CDK), Dbf4-dependent kinase (DDK) and the DNA damage checkpoint kinases(1). CDK phosphorylation of two key initiation factors, Sld2 and Sld3, promotes essential interactions with Dpb11 (refs 2-4), whereas DDK acts by phosphorylating subunits of the Mcm2-7 helicase(5). CDK has an additional role in replication by preventing the re-loading of Mcm2-7 during the S, G2 and M phases(6), thus preventing origin re-firing and re-replication. During the G1 phase, both CDK and DDK are downregulated, which allows origin licensing and prevents premature replication initiation(3). Origin firing is also inhibited during the S phase when DNA damage or replication fork stalling activates the checkpoint kinases(7-10). Here we show that, analogous to the situation in the G1 phase, the Saccharomyces cerevisiae checkpoint kinase Rad53 inhibits both CDK- and DDK-dependent pathways, which acts redundantly to block further origin firing. Rad53 acts on DDK directly by phosphorylating Dbf4, whereas the CDK pathway is blocked by Rad53-mediated phosphorylation of the downstream CDK substrate, Sld3. This allows CDK to remain active during the S phase in the presence of DNA damage, which is crucial to prevent re-loading of Mcm2-7 onto origins that have already fired(6). Our results explain how checkpoints regulate origin firing and demonstrate that the slowing of S phase by the 'intra-S checkpoint' is primarily due to the inhibition of origin firing.
C1 [Zegerman, Philip; Diffley, John F. X.] Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
C3 Cancer Research UK
RP Diffley, JFX (corresponding author), Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
EM John.Diffley@cancer.org.uk
FU Cancer Research UK
NR 30
TC 226
Z9 269
U1 0
U2 21
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 474
EP 478
DI 10.1038/nature09373
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200046
PM 20835227
DA 2026-03-09
ER

PT J
AU Campins, H
   Hargrove, K
   Pinilla-Alonso, N
   Howell, ES
   Kelley, MS
   Licandro, J
   Mothé-Diniz, T
   Fernández, Y
   Ziffer, J
AF Campins, Humberto
   Hargrove, Kelsey
   Pinilla-Alonso, Noemi
   Howell, Ellen S.
   Kelley, Michael S.
   Licandro, Javier
   Mothe-Diniz, T.
   Fernandez, Y.
   Ziffer, Julie
TI Water ice and organics on the surface of the asteroid 24 Themis
SO NATURE
LA English
DT Article
AB It has been suggested(1-3) that Earth's current supply of water was delivered by asteroids, some time after the collision that produced the Moon (which would have vaporized any of the pre-existing water). So far, no measurements of water ice on asteroids(4,5) have been made, but its presence has been inferred from the comet-like activity of several small asteroids, including two members of the Themis dynamical family(6). Here we report infrared spectra of the asteroid 24 Themis which show that ice and organic compounds are not only present on its surface but also prevalent. Infrared spectral differences between it and other asteroids make 24 Themis unique so far, and our identification of ice and organics agrees with independent results(7) that rule out other compounds as possible sources of the observed spectral structure. The widespread presence of surface ice on 24 Themis is somewhat unexpected because of the relatively short lifetime of exposed ice at this distance (similar to 3.2 AU) from the Sun. Nevertheless, there are several plausible sources, such as a subsurface reservoir that brings water to the surface through 'impact gardening' and/or sublimation.
C1 [Campins, Humberto; Hargrove, Kelsey; Fernandez, Y.] Univ Cent Florida, Orlando, FL 32816 USA.
   [Pinilla-Alonso, Noemi] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Howell, Ellen S.] NAIC Arecibo Observ, Arecibo, PR 00612 USA.
   [Kelley, Michael S.] Univ Maryland, College Pk, MD 20742 USA.
   [Licandro, Javier] Inst Astrofis Canarias, E-38200 San Cristobal la Laguna, Spain.
   [Mothe-Diniz, T.] Univ Fed Rio de Janeiro, BR-20080090 Rio De Janeiro, RJ, Brazil.
   [Licandro, Javier] Univ La Laguna, Dept Astrophys, E-38205 San Cristobal la Laguna, Spain.
   [Ziffer, Julie] Univ So Maine, Dept Phys, Portland, ME 04104 USA.
C3 State University System of Florida; University of Central Florida; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; University System of Maryland; University of Maryland College Park; Instituto de Astrofisica de Canarias; Universidade Federal do Rio de Janeiro; Universidad de la Laguna; University of Maine System; University of Southern Maine
RP Campins, H (corresponding author), Univ Cent Florida, POB 162385, Orlando, FL 32816 USA.
EM campins@physics.ucf.edu
FU NASA; US National Science Foundation; Spanish 'Ministerio de Ciencia e Innovacion'; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908276] Funding Source: National Science Foundation
NR 21
TC 281
Z9 308
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 APR 29
PY 2010
VL 464
IS 7293
BP 1320
EP 1321
DI 10.1038/nature09029
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000039
PM 20428164
DA 2026-03-09
ER

PT J
AU Green, AW
   Glazebrook, K
   McGregor, PJ
   Abraham, RG
   Poole, GB
   Damjanov, I
   McCarthy, PJ
   Colless, M
   Sharp, RG
AF Green, Andrew W.
   Glazebrook, Karl
   McGregor, Peter J.
   Abraham, Roberto G.
   Poole, Gregory B.
   Damjanov, Ivana
   McCarthy, Patrick J.
   Colless, Matthew
   Sharp, Robert G.
TI High star formation rates as the origin of turbulence in early and modern disk galaxies
SO NATURE
LA English
DT Article
ID to 2-3 galaxy; forming galaxy; h-alpha; physical-property; high-redshift; kinematics; spectroscopy; dynamics; universe; ghasp
AB Observations of star formation and kinematics in early galaxies at high spatial and spectral resolution have shown that two-thirds are massive rotating disk galaxies(1-5), with the remainder being less massive non-rotating objects(2,4,6-8). The line-of-sight-averaged velocity dispersions are typically five times higher than in today's disk galaxies. This suggests that gravitationally unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos(9,10). These accreting flows, however, have not been observed(11), and cosmic accretion cannot power the observed level of turbulence(12). Here we report observations of a sample of rare, high-velocity-dispersion disk galaxies in the nearby Universe where cold accretion is unlikely to drive their high star formation rates. We find that their velocity dispersions are correlated with their star formation rates, but not their masses or gas fractions, which suggests that star formation is the energetic driver of galaxy disk turbulence at all cosmic epochs.
C1 [Green, Andrew W.; Glazebrook, Karl; Poole, Gregory B.] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [McGregor, Peter J.] Australian Natl Univ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Abraham, Roberto G.; Damjanov, Ivana] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [McCarthy, Patrick J.] Observ Carnegie Inst Washington, Pasadena, CA 91101 USA.
   [Colless, Matthew; Sharp, Robert G.] Australian Astron Observ, Epping, NSW 1710, Australia.
C3 Swinburne University of Technology; Australian National University; University of Toronto; Carnegie Institution for Science
RP Green, AW (corresponding author), Swinburne Univ Technol, Ctr Astrophys & Supercomp, POB 218, Hawthorn, Vic 3122, Australia.
EM agreen@astro.swin.edu.au
FU Australian Research Council; Swinburne University of Technology; Anglo-Australian Observatory; ANU2.3-m telescope
NR 29
TC 112
Z9 117
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 7
PY 2010
VL 467
IS 7316
BP 684
EP 686
DI 10.1038/nature09452
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500032
PM 20930839
DA 2026-03-09
ER

PT J
AU Heinig, M
   Petretto, E
   Wallace, C
   Bottolo, L
   Rotival, M
   Lu, H
   Li, YY
   Sarwar, R
   Langley, SR
   Bauerfeind, A
   Hummel, O
   Lee, YA
   Paskas, S
   Rintisch, C
   Saar, K
   Cooper, J
   Buchan, R
   Gray, EE
   Cyster, JG
   Erdmann, J
   Hengstenberg, C
   Maouche, S
   Ouwehand, WH
   Rice, CM
   Samani, NJ
   Schunkert, H
   Goodall, AH
   Schulz, H
   Roider, HG
   Vingron, M
   Blankenberg, S
   Münzel, T
   Zeller, T
   Szymczak, S
   Ziegler, A
   Tiret, L
   Smyth, DJ
   Pravenec, M
   Aitman, TJ
   Cambien, F
   Clayton, D
   Todd, JA
   Hubner, N
   Cook, SA
AF Heinig, Matthias
   Petretto, Enrico
   Wallace, Chris
   Bottolo, Leonardo
   Rotival, Maxime
   Lu, Han
   Li, Yoyo
   Sarwar, Rizwan
   Langley, Sarah R.
   Bauerfeind, Anja
   Hummel, Oliver
   Lee, Young-Ae
   Paskas, Svetlana
   Rintisch, Carola
   Saar, Kathrin
   Cooper, Jason
   Buchan, Rachel
   Gray, Elizabeth E.
   Cyster, Jason G.
   Erdmann, Jeanette
   Hengstenberg, Christian
   Maouche, Seraya
   Ouwehand, Willem H.
   Rice, Catherine M.
   Samani, Nilesh J.
   Schunkert, Heribert
   Goodall, Alison H.
   Schulz, Herbert
   Roider, Helge G.
   Vingron, Martin
   Blankenberg, Stefan
   Muenzel, Thomas
   Zeller, Tanja
   Szymczak, Silke
   Ziegler, Andreas
   Tiret, Laurence
   Smyth, Deborah J.
   Pravenec, Michal
   Aitman, Timothy J.
   Cambien, Francois
   Clayton, David
   Todd, John A.
   Hubner, Norbert
   Cook, Stuart A.
TI A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
SO NATURE
LA English
DT Article
ID genome-wide association; transcription factors; molecular networks; gene-expression; disease; inflammation; responses; ifih1; snps; rat
AB Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches(1,2). Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7(3))-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration(4,5), is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-amacrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 x 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 x 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.
C1 [Heinig, Matthias; Bauerfeind, Anja; Hummel, Oliver; Lee, Young-Ae; Paskas, Svetlana; Rintisch, Carola; Saar, Kathrin; Schulz, Herbert; Hubner, Norbert] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Heinig, Matthias; Roider, Helge G.; Vingron, Martin] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Petretto, Enrico; Bottolo, Leonardo; Lu, Han; Li, Yoyo; Sarwar, Rizwan; Langley, Sarah R.; Buchan, Rachel; Aitman, Timothy J.; Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Med Res Council,Clin Sci Ctr, London W12 0NN, England.
   [Petretto, Enrico; Bottolo, Leonardo] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Wallace, Chris; Cooper, Jason; Smyth, Deborah J.; Clayton, David; Todd, John A.] Univ Cambridge, Cambridge Inst Med Res, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab, Cambridge CB2 0XY, England.
   [Rotival, Maxime; Maouche, Seraya; Tiret, Laurence; Cambien, Francois] Univ Paris 06, INSERM, UMRS 937, F-75013 Paris, France.
   [Rotival, Maxime; Maouche, Seraya; Tiret, Laurence; Cambien, Francois] Sch Med, F-75013 Paris, France.
   [Lee, Young-Ae] Charite, D-13353 Berlin, Germany.
   [Gray, Elizabeth E.; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Gray, Elizabeth E.; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
   [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
   [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.
   [Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 0PT, England.
   [Ouwehand, Willem H.; Rice, Catherine M.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Samani, Nilesh J.; Goodall, Alison H.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
   [Samani, Nilesh J.; Goodall, Alison H.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
   [Blankenberg, Stefan; Muenzel, Thomas; Zeller, Tanja] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, D-55131 Mainz, Germany.
   [Szymczak, Silke; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Univ Klinikum Schleswig Holstein, D-23562 Lubeck, Germany.
   [Pravenec, Michal] Acad Sci Czech Republic, Inst Physiol, Prague 14220 4, Czech Republic.
   [Pravenec, Michal] Ctr Appl Genom, Prague 14220 4, Czech Republic.
   [Hubner, Norbert] Charite, CC4, D-10117 Berlin, Germany.
   [Cook, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England.
C3 Helmholtz Association; Max Delbruck Center for Molecular Medicine; Max Planck Society; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); Imperial College London; Imperial College London; University of Cambridge; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Lubeck; University of Regensburg; University of Cambridge; NHS Blood & Transplant (NHSBT); Wellcome Trust Sanger Institute; University of Leicester; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; Johannes Gutenberg University of Mainz; University of Kiel; Schleswig Holstein University Hospital; University of Lubeck; Czech Academy of Sciences; Institute of Physiology of the Czech Academy of Sciences; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Imperial College London
RP Hubner, N (corresponding author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany.
EM nhuebner@mdc-berlin.de; stuart.cook@csc.mrc.ac.uk
FU German National Genome Research Network; Helmholtz Association Alliance on Systems Biology; EURATools [LSHG-CT-2005-019015]; European Union [LSHM-CT-2006-037593]; PHC ALLIANCE [19419PH]; UK National Institute for Health Research Biomedical Research Unit (Royal Brompton and Harefield NHS Trusts, University Hospitals of Leicester NHS Trusts); Biomedical Research Centre (Imperial College NHS Trust); British Heart Foundation; Grant Agency of the Czech Republic [P301/10/0290]; Ministry of Education of the Czech Republic [1M6837805002]; Fondation Leducq; Medical Research Council UK; Research Councils UK; Juvenile Diabetes Research Foundation International; National Institute for Health Research (UK); National Institute of Diabetes and Digestive and Kidney Diseases (USA); Wellcome Trust; European Community [HEALTH-F4-2010-241504]; MRC [MC_U120085815, MC_U120061454, MC_U120097112] Funding Source: UKRI; Medical Research Council [MC_U120085815, MC_U120097112, MC_U120061454] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10275] Funding Source: researchfish
NR 29
TC 229
Z9 261
U1 0
U2 25
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 460
EP 464
DI 10.1038/nature09386
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200043
PM 20827270
DA 2026-03-09
ER

PT J
AU Boyce, DG
   Lewis, MR
   Worm, B
AF Boyce, Daniel G.
   Lewis, Marlon R.
   Worm, Boris
TI Global phytoplankton decline over the past century
SO NATURE
LA English
DT Article
ID ocean chlorophyll; fish production; climate-change; variability; plankton
AB In the oceans, ubiquitous microscopic phototrophs (phytoplankton) account for approximately half the production of organic matter on Earth. Analyses of satellite-derived phytoplankton concentration (available since 1979) have suggested decadal-scale fluctuations linked to climate forcing, but the length of this record is insufficient to resolve longer-term trends. Here we combine available ocean transparency measurements and in situ chlorophyll observations to estimate the time dependence of phytoplankton biomass at local, regional and global scales since 1899. We observe declines in eight out of ten ocean regions, and estimate a global rate of decline of similar to 1% of the global median per year. Our analyses further reveal interannual to decadal phytoplankton fluctuations superimposed on long-term trends. These fluctuations are strongly correlated with basin-scale climate indices, whereas long-term declining trends are related to increasing sea surface temperatures. We conclude that global phytoplankton concentration has declined over the past century; this decline will need to be considered in future studies of marine ecosystems, geochemical cycling, ocean circulation and fisheries.
C1 [Boyce, Daniel G.; Worm, Boris] Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
   [Lewis, Marlon R.] Dalhousie Univ, Dept Oceanog, Halifax, NS B3H 4J1, Canada.
C3 Dalhousie University; Dalhousie University
RP Boyce, DG (corresponding author), Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
EM dboyce@dal.ca
FU Natural Sciences and Engineering Research Council of Canada; US Office of Naval Research; Canada Foundation for Climate and Atmospheric Sciences; National Aeronautics and Space Administration; Sloan Foundation; Lenfest Ocean Program
NR 39
TC 1024
Z9 1178
U1 14
U2 703
PU NATURE PUBLISHING 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 29
PY 2010
VL 466
IS 7306
BP 591
EP 596
DI 10.1038/nature09268
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100046
PM 20671703
DA 2026-03-09
ER

PT J
AU Perfettini, H
   Avouac, JP
   Tavera, H
   Kositsky, A
   Nocquet, JM
   Bondoux, F
   Chlieh, M
   Sladen, A
   Audin, L
   Farber, DL
   Soler, P
AF Perfettini, Hugo
   Avouac, Jean-Philippe
   Tavera, Hernando
   Kositsky, Andrew
   Nocquet, Jean-Mathieu
   Bondoux, Francis
   Chlieh, Mohamed
   Sladen, Anthony
   Audin, Laurence
   Farber, Daniel L.
   Soler, Pierre
TI Seismic and aseismic slip on the Central Peru megathrust
SO NATURE
LA English
DT Article
ID strain accumulation; earthquake; deformation; locking
AB Slip on a subduction megathrust can be seismic or aseismic, with the two modes of slip complementing each other in time and space to accommodate the long-term plate motions. Although slip is almost purely aseismic at depths greater than about 40 km, heterogeneous surface strain(1-8) suggests that both modes of slip occur at shallower depths, with aseismic slip resulting from steady or transient creep in the interseismic and postseismic periods(9-11). Thus, active faults seem to comprise areas that slip mostly during earthquakes, and areas that mostly slip aseismically. The size, location and frequency of earthquakes that a megathrust can generate thus depend on where and when aseismic creep is taking place, and what fraction of the long-term slip rate it accounts for. Here we address this issue by focusing on the central Peru megathrust. We show that the Pisco earthquake, with moment magnitude M-w = 8.0, ruptured two asperities within a patch that had remained locked in the interseismic period, and triggered aseismic frictional afterslip on two adjacent patches. The most prominent patch of afterslip coincides with the subducting Nazca ridge, an area also characterized by low interseismic coupling, which seems to have repeatedly acted as a barrier to seismic rupture propagation in the past. The seismogenic portion of the megathrust thus appears to be composed of interfingering rate-weakening and rate-strengthening patches. The rate-strengthening patches contribute to a high proportion of aseismic slip, and determine the extent and frequency of large interplate earthquakes. Aseismic slip accounts for as much as 50-70% of the slip budget on the seismogenic portion of the megathrust in central Peru, and the return period of earthquakes with M-w = 8.0 in the Pisco area is estimated to be 250 years.
C1 [Perfettini, Hugo; Bondoux, Francis; Chlieh, Mohamed; Audin, Laurence; Soler, Pierre] Inst Rech Dev, F-13572 Marseille 02, France.
   [Perfettini, Hugo; Tavera, Hernando; Bondoux, Francis; Audin, Laurence] Inst Geofis Peru, Lima, Peru.
   [Avouac, Jean-Philippe; Kositsky, Andrew; Sladen, Anthony] CALTECH, Div Geol & Planetary Sci, Tecton Observ, Pasadena, CA 91125 USA.
   [Nocquet, Jean-Mathieu; Chlieh, Mohamed] GeoAzur, F-06560 Valbonne, France.
   [Farber, Daniel L.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Perfettini, Hugo; Bondoux, Francis] Univ Grenoble 1, CNRS, Observ Sci, Lab Geophys Interne & Tectonophys,LCPC,IRD, F-38041 Grenoble 9, France.
   [Perfettini, Hugo; Audin, Laurence] Univ Toulouse 3, CNRS, Observ Midi Pyrenees, Lab Mecanismes Transfert Geol,IRD, F-31400 Toulouse, France.
   [Farber, Daniel L.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Kositsky, Andrew] Ashima Res, Pasadena, CA 91106 USA.
C3 Institut de Recherche pour le Developpement (IRD); California Institute of Technology; Universite Cote d'Azur; Observatoire de la Cote d'Azur; University of California System; University of California Santa Cruz; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); Universite Gustave-Eiffel; Laboratoire Central des Ponts et Chaussees (LCPC); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National d'Etudes Spatiales (CNES); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Perfettini, H (corresponding author), Inst Rech Dev, 44 Blvd Dunkerque, F-13572 Marseille 02, France.
EM hugo.perfettini@ird.fr
FU Institute de Recherche pour le Developpement; Gordon and Betty Moore Foundation; National Science Foundation [EAR-0838495]
NR 29
TC 242
Z9 274
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 78
EP 81
DI 10.1038/nature09062
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900034
PM 20445628
DA 2026-03-09
ER

PT J
AU Zhang, J
   Wagh, P
   Guay, D
   Sanchez-Pulido, L
   Padhi, BK
   Korzh, V
   Andrade-Navarro, MA
   Akimenko, MA
AF Zhang, Jing
   Wagh, Purva
   Guay, Danielle
   Sanchez-Pulido, Luis
   Padhi, Bhaja K.
   Korzh, Vladimir
   Andrade-Navarro, Miguel A.
   Akimenko, Marie-Andree
TI Loss of fish actinotrichia proteins and the fin-to-limb transition
SO NATURE
LA English
DT Article
ID apical ectodermal ridge; in-situ hybridization; gene-expression; sonic-hedgehog; pectoral fin; caudal fin; zebrafish; gli3; morphogenesis; regeneration
AB The early development of teleost paired fins is strikingly similar to that of tetrapod limb buds and is controlled by similar mechanisms(1,2). One early morphological divergence between pectoral fins and limbs is in the fate of the apical ectodermal ridge (AER), the distal epidermis that rims the bud. Whereas the AER of tetrapods regresses after specification of the skeletal progenitors(3), the AER of teleost fishes forms a fold that elongates(4,5). Formation of the fin fold is accompanied by the synthesis of two rows of rigid, unmineralized fibrils called actinotrichia, which keep the fold straight(6,7) and guide the migration of mesenchymal cells within the fold(5,8). The actinotrichia are made of elastoidin, the components of which, apart from collagen, are unknown. Here we show that two zebrafish proteins, which we name actinodin 1 and 2 (And1 and And2), are essential structural components of elastoidin. The presence of actinodin sequences in several teleost fishes and in the elephant shark (Callorhinchus milii, which occupies a basal phylogenetic position), but not in tetrapods, suggests that these genes have been lost during tetrapod species evolution. Double gene knockdown of and1 and and2 in zebrafish embryos results in the absence of actinotrichia and impaired fin folds. Gene expression profiles in embryos lacking and1 and and2 function are consistent with pectoral fin truncation and may offer a potential explanation for the polydactyly observed in early tetrapod fossils. We propose that the loss of both actinodins and actinotrichia during evolution may have led to the loss of lepidotrichia and may have contributed to the fin-to-limb transition.
C1 [Zhang, Jing; Wagh, Purva; Guay, Danielle; Akimenko, Marie-Andree] Univ Ottawa, Dept Biol, CAREG, Ottawa, ON K1N 6N5, Canada.
   [Sanchez-Pulido, Luis] Univ Oxford, Funct Genom Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Padhi, Bhaja K.] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0L2, Canada.
   [Korzh, Vladimir] Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Andrade-Navarro, Miguel A.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
C3 University of Ottawa; University of Oxford; Health Canada; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Akimenko, MA (corresponding author), Univ Ottawa, Dept Biol, CAREG, Ottawa, ON K1N 6N5, Canada.
EM makimen@uottawa.ca
FU European Modular Biology Organization [ALT 325-2008]; Natural Science Engineering and Research Council of Canada; Canadian Institutes of Health Research; Canada Research Chairs; Helmholtz Alliance on Systems Biology; Agency for Science, Technology and Research of Singapore; MRC [MC_U137761446] Funding Source: UKRI; Medical Research Council [MC_U137761446] Funding Source: researchfish
NR 35
TC 117
Z9 140
U1 0
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 234
EP U106
DI 10.1038/nature09137
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800036
PM 20574421
DA 2026-03-09
ER

PT J
AU Tsai, WW
   Wang, ZX
   Yiu, TT
   Akdemir, KC
   Xia, WY
   Winter, S
   Tsai, CY
   Shi, XB
   Schwarzer, D
   Plunkett, W
   Aronow, B
   Gozani, O
   Fischle, W
   Hung, MC
   Patel, DJ
   Barton, MC
AF Tsai, Wen-Wei
   Wang, Zhanxin
   Yiu, Teresa T.
   Akdemir, Kadir C.
   Xia, Weiya
   Winter, Stefan
   Tsai, Cheng-Yu
   Shi, Xiaobing
   Schwarzer, Dirk
   Plunkett, William
   Aronow, Bruce
   Gozani, Or
   Fischle, Wolfgang
   Hung, Mien-Chie
   Patel, Dinshaw J.
   Barton, Michelle Craig
TI TRIM24 links a non-canonical histone signature to breast cancer
SO NATURE
LA English
DT Article
ID gene-expression; phd finger; nuclear receptors; binding modules; chromatin regulation; coactivator htif1; transcription; estrogen; complex; alpha
AB Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.
C1 [Wang, Zhanxin; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Tsai, Wen-Wei; Yiu, Teresa T.; Shi, Xiaobing; Barton, Michelle Craig] Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Program Genes & Dev, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Yiu, Teresa T.; Akdemir, Kadir C.; Shi, Xiaobing; Barton, Michelle Craig] Univ Texas MD Anderson Canc Ctr, Ctr Canc Epigenet, Houston, TX 77030 USA.
   [Yiu, Teresa T.; Akdemir, Kadir C.; Shi, Xiaobing; Barton, Michelle Craig] Univ Texas MD Anderson Canc Ctr, Ctr Stem Cell & Dev Biol, Houston, TX 77030 USA.
   [Xia, Weiya; Hung, Mien-Chie] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Akdemir, Kadir C.] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Bioinformat, Houston, TX 77030 USA.
   [Winter, Stefan; Fischle, Wolfgang] Max Planck Inst Biophys Chem, Lab Chromatin Biochem, D-37077 Gottingen, Germany.
   [Tsai, Cheng-Yu; Plunkett, William] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
   [Schwarzer, Dirk] Leibniz Inst Mol Pharmakol FMP, Dept Chem Biol Prot Chem, D-13125 Berlin, Germany.
   [Aronow, Bruce] Cincinnati Childrens Hosp Med Ctr, Computat Med Ctr, Cincinnati, OH 45229 USA.
   [Gozani, Or] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA.
   [Hung, Mien-Chie] China Med Univ & Hosp, Grad Inst Canc Biol, Taichung 404, Taiwan.
   [Hung, Mien-Chie] China Med Univ & Hosp, Ctr Mol Med, Taichung 404, Taiwan.
C3 Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Max Planck Society; University of Texas System; UTMD Anderson Cancer Center; Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Cincinnati Children's Hospital Medical Center; Stanford University; China Medical University Taiwan; China Medical University Hospital - Taiwan; China Medical University Taiwan; China Medical University Hospital - Taiwan
RP Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pateld@mskcc.org; mbarton@mdanderson.org
FU National Institutes of Health (NIH) [GM081627, U54 RR025216, P30DK078392-01, GM079641]; George and Cynthia Mitchell Foundation; China Medical University and Hospital; MDACC; Starr Foundation; Leukemia and Lymphoma Society; Max Planck Society; NCI Cancer Center; Sowell-Huggins Foundation; EMBO; Center for Cancer Epigenetics;  [T32 HD07325]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK078392] Funding Source: NIH RePORTER
NR 54
TC 359
Z9 415
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 927
EP U320
DI 10.1038/nature09542
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600039
PM 21164480
DA 2026-03-09
ER

PT J
AU Klaers, J
   Schmitt, J
   Vewinger, F
   Weitz, M
AF Klaers, Jan
   Schmitt, Julian
   Vewinger, Frank
   Weitz, Martin
TI Bose-Einstein condensation of photons in an optical microcavity
SO NATURE
LA English
DT Article
ID exciton polaritons; phase-transition; cavity; gas; lasers
AB Bose-Einstein condensation (BEC)-the macroscopic ground-state accumulation of particles with integer spin (bosons) at low temperature and high density-has been observed in several physical systems(1-9), including cold atomic gases and solid-state quasiparticles. However, the most omnipresent Bose gas, blackbody radiation (radiation in thermal equilibrium with the cavity walls) does not show this phase transition. In such systems photons have a vanishing chemical potential, meaning that their number is not conserved when the temperature of the photon gas is varied(10); at low temperatures, photons disappear in the cavity walls instead of occupying the cavity ground state. Theoretical works have considered thermalization processes that conserve photon number (a prerequisite for BEC), involving Compton scattering with a gas of thermal electrons(11) or photon-photon scattering in a nonlinear resonator configuration(12,13). Number-conserving thermalization was experimentally observed(14) for a two-dimensional photon gas in a dye-filled optical microcavity, which acts as a 'white-wall' box. Here we report the observation of a Bose-Einstein condensate of photons in this system. The cavity mirrors provide both a confining potential and a nonvanishing effective photon mass, making the system formally equivalent to a two-dimensional gas of trapped, massive bosons. The photons thermalize to the temperature of the dye solution (room temperature) by multiple scattering with the dye molecules. Upon increasing the photon density, we observe the following BEC signatures: the photon energies have a Bose-Einstein distribution with a massively populated ground-state mode on top of a broad thermal wing; the phase transition occurs at the expected photon density and exhibits the predicted dependence on cavity geometry; and the ground-state mode emerges even for a spatially displaced pump spot. The prospects of the observed effects include studies of extremely weakly interacting low-dimensional Bose gases(9) and new coherent ultraviolet sources(15).
C1 [Klaers, Jan; Schmitt, Julian; Vewinger, Frank; Weitz, Martin] Univ Bonn, Inst Angew Phys, D-53115 Bonn, Germany.
C3 University of Bonn
RP Weitz, M (corresponding author), Univ Bonn, Inst Angew Phys, Wegelerstr 8, D-53115 Bonn, Germany.
EM martin.weitz@uni-bonn.de
FU Deutsche Forschungsgemeinschaft within the focused research unit [FOR557]; IFRAF at LKB Paris
NR 30
TC 590
Z9 669
U1 2
U2 205
PU 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 25
PY 2010
VL 468
IS 7323
BP 545
EP 548
DI 10.1038/nature09567
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200038
PM 21107426
DA 2026-03-09
ER

PT J
AU Charnoz, S
   Salmon, J
   Crida, A
AF Charnoz, Sebastien
   Salmon, Julien
   Crida, Aurelien
TI The recent formation of Saturn's moonlets from viscous spreading of the main rings
SO NATURE
LA English
DT Article
ID satellites; accretion; evolution; planets; disk
AB The regular satellites of the giant planets are believed to have finished their accretion concurrent with the planets, about 4.5 Gyr ago(1-4). A population of Saturn's small moons orbiting just outside the main rings are dynamically young(5,6) (less than 10(7) yr old), which is inconsistent with the formation timescale for the regular satellites. They are also underdense(7) (similar to 600 kgm(-3)) and show spectral characteristics similar to those of the main rings(8,9). It has been suggested that they accreted at the rings' edge(7,10,11), but hitherto it has been impossible to model the formation process fully owing to a lack of computational power. Here we report a hybrid simulation in which the viscous spreading of Saturn's rings beyond the Roche limit (the distance beyond which the rings are gravitationally unstable) gives rise to the small moons. The moonlets' mass distribution and orbital architecture are reproduced. The current confinement of the main rings and the existence of the dusty F ring are shown to be direct consequences of the coupling of viscous evolution and satellite formation. Saturn's rings, like a mini protoplanetary disk, may be the last place where accretion was recently active in the Solar System, some 10(6)-10(7) yr ago.
C1 [Charnoz, Sebastien; Salmon, Julien] Univ Paris Diderot, CEA, CNRS, Lab AIM, F-91191 Gif Sur Yvette, France.
   [Crida, Aurelien] Univ Cambridge, Dept Appl Math & Theoret Phys, Cambridge CB3 0WA, England.
   [Crida, Aurelien] Univ Nice Sophia Antipolis, CNRS, Observ Cote Azur, Lab Cassiopee, F-06304 Nice 4, France.
C3 Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of Cambridge; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Observatoire de la Cote d'Azur
RP Charnoz, S (corresponding author), Univ Paris Diderot, CEA, CNRS, Lab AIM, F-91191 Gif Sur Yvette, France.
EM charnoz@cea.fr
FU Universite Paris Diderot; CEA/IRFU/SAp
NR 27
TC 121
Z9 128
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 JUN 10
PY 2010
VL 465
IS 7299
BP 752
EP 754
DI 10.1038/nature09096
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800038
PM 20535205
DA 2026-03-09
ER

PT J
AU Zhang, P
   Wang, JW
   Shi, YG
AF Zhang, Peng
   Wang, Jiawei
   Shi, Yigong
TI Structure and mechanism of the S component of a bacterial ECF transporter
SO NATURE
LA English
DT Article
ID abc transporters; binding
AB The energy-coupling factor (ECF) transporters, responsible for vitamin uptake in prokaryotes, are a unique family of membrane transporters(1,2). Each ECF transporter contains a membrane-embedded, substrate-binding protein (known as the S component), an energy-coupling module that comprises two ATP-binding proteins (known as the A and A' components) and a transmembrane protein (known as the T component). The structure and transport mechanism of the ECF family remain unknown. Here we report the crystal structure of RibU, the S component of the ECF-type riboflavin transporter from Staphylococcus aureus at 3.6-angstrom resolution. RibU contains six transmembrane segments, adopts a previously unreported transporter fold and contains a riboflavin molecule bound to the L1 loop and the periplasmic portion of transmembrane segments 4-6. Structural analysis reveals the essential ligand-binding residues, identifies the putative transport path and, with sequence alignment, uncovers conserved structural features and suggests potential mechanisms of action among the ECF transporters. [GRAPHICS] .
C1 [Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Prot Sci Lab, Beijing 100084, Peoples R China.
   [Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Zhang, Peng] Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Wang, Jiawei] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Wang, Jiawei] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Princeton University; Tsinghua University; Tsinghua University
RP Shi, YG (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Prot Sci Lab, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU National Institutes of Health [R01 GM084964]; Ministry of Science and Technology of China [2009CB918801]; National Natural Science Foundation of China [30888001]
NR 25
TC 80
Z9 103
U1 0
U2 132
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 717
EP U148
DI 10.1038/nature09488
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700046
PM 20972419
DA 2026-03-09
ER

PT J
AU Daigaku, Y
   Davies, AA
   Ulrich, HD
AF Daigaku, Yasukazu
   Davies, Adelina A.
   Ulrich, Helle D.
TI Ubiquitin-dependent DNA damage bypass is separable from genome replication
SO NATURE
LA English
DT Article
ID cell nuclear antigen; saccharomyces-cerevisiae; postreplication repair; translesion synthesis; ultraviolet-light; polymerase-eta; budding yeast; error-free; pol-eta; s-phase
AB Post-replication repair (PRR) is a pathway that allows cells to bypass or overcome lesions during DNA replication(1). In eukaryotes, damage bypass is activated by ubiquitylation of the replication clamp PCNA through components of the RAD6 pathway(2). Whereas monoubiquitylation of PCNA allows mutagenic translesion synthesis by damage-tolerant DNA polymerases(3-5), polyubiquitylation is required for an error-free pathway that probably involves a template switch to the undamaged sister chromatid(6). Both the timing of PRR events during the cell cycle and their location relative to replication forks, as well as the factors required downstream of PCNA ubiquitylation, have remained poorly characterized. Here we demonstrate that the RAD6 pathway normally operates during S phase. However, using an inducible system of DNA damage bypass in budding yeast (Saccharomyces cerevisiae), we show that the process is separable in time and space from genome replication, thus allowing direct visualization and quantification of productive PRR tracts. We found that both during and after S phase ultraviolet-radiation-induced lesions are bypassed predominantly via translesion synthesis, whereas the error-free pathway functions as a backup system. Our approach has revealed the distribution of PRR tracts in a synchronized cell population. It will allow an in-depth mechanistic analysis of how cells manage the processing of lesions to their genomes during and after replication.
C1 [Daigaku, Yasukazu; Davies, Adelina A.; Ulrich, Helle D.] Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
C3 Cancer Research UK
RP Ulrich, HD (corresponding author), Canc Res UK London Res Inst, Clare Hall Labs, Blanche Lane, S Mimms EN6 3LD, Herts, England.
EM helle.ulrich@cancer.org.uk
FU Cancer Research UK
NR 30
TC 219
Z9 250
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 951
EP U13
DI 10.1038/nature09097
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500043
PM 20453836
DA 2026-03-09
ER

PT J
AU Specchia, V
   Piacentini, L
   Tritto, P
   Fanti, L
   D'Alessandro, R
   Palumbo, G
   Pimpinelli, S
   Bozzetti, MP
AF Specchia, Valeria
   Piacentini, Lucia
   Tritto, Patrizia
   Fanti, Laura
   D'Alessandro, Rosalba
   Palumbo, Gioacchino
   Pimpinelli, Sergio
   Bozzetti, Maria P.
TI Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons
SO NATURE
LA English
DT Article
ID drosophila-melanogaster; genetic-analysis; y-chromosome; stellate; spermatogenesis; evolution; protein; hsp83; organization; capacitor
AB The canalization concept(1) describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways(2-5), indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability(6,7.) Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis.
C1 [Specchia, Valeria; Bozzetti, Maria P.] Univ Salento, DiSTeBA, I-73100 Lecce, Italy.
   [Piacentini, Lucia; Fanti, Laura; Pimpinelli, Sergio] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy.
   [Piacentini, Lucia; Fanti, Laura; Pimpinelli, Sergio] Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy.
   [Tritto, Patrizia; D'Alessandro, Rosalba; Palumbo, Gioacchino] Univ Bari, DIGEMI, I-70126 Bari, Italy.
C3 University of Salento; Pasteur Network; Fondazione Cenci Bolognetti; Sapienza University Rome; Sapienza University Rome; Universita degli Studi di Bari Aldo Moro
RP Bozzetti, MP (corresponding author), Univ Salento, DiSTeBA, I-73100 Lecce, Italy.
EM maria.bozzetti@unisalento.it
FU Ministero dell'Universita e della Ricerca (MIUR)
NR 30
TC 216
Z9 247
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 FEB 4
PY 2010
VL 463
IS 7281
BP 662
EP U92
DI 10.1038/nature08739
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900036
PM 20062045
DA 2026-03-09
ER

PT J
AU Szabo, E
   Rampalli, S
   Risueño, RM
   Schnerch, A
   Mitchell, R
   Fiebig-Comyn, A
   Levadoux-Martin, M
   Bhatia, M
AF Szabo, Eva
   Rampalli, Shravanti
   Risueno, Ruth M.
   Schnerch, Angelique
   Mitchell, Ryan
   Fiebig-Comyn, Aline
   Levadoux-Martin, Marilyne
   Bhatia, Mickie
TI Direct conversion of human fibroblasts to multilineage blood progenitors
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; stem-cells; mice lacking; ips cells; expression; transcription; hematopoiesis; induction; transplantation; circuitry
AB As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise to granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human pluripotent stem cells.
C1 [Szabo, Eva; Rampalli, Shravanti; Risueno, Ruth M.; Schnerch, Angelique; Mitchell, Ryan; Fiebig-Comyn, Aline; Levadoux-Martin, Marilyne; Bhatia, Mickie] McMaster Univ, Stem Cell & Canc Res Inst, Hamilton, ON L8N 3Z5, Canada.
   [Schnerch, Angelique; Mitchell, Ryan; Bhatia, Mickie] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada.
C3 McMaster University; McMaster University
RP Bhatia, M (corresponding author), McMaster Univ, Stem Cell & Canc Res Inst, Hamilton, ON L8N 3Z5, Canada.
EM mbhatia@mcmaster.ca
FU Canadian Institute of Health Research (CIHR); Canadian Cancer Society Research Institute (CCS-RI); StemCell Network; Ontario Ministry of Research Innovation (MRI); Canadian Chair; Ministry of Research and Innovation (MRI); MITACS; Ontario Graduate Scholarship (OGS)
NR 47
TC 557
Z9 735
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 25
PY 2010
VL 468
IS 7323
BP 521
EP U191
DI 10.1038/nature09591
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200033
PM 21057492
DA 2026-03-09
ER

PT J
AU Gillet, N
   Jault, D
   Canet, E
   Fournier, A
AF Gillet, Nicolas
   Jault, Dominique
   Canet, Elisabeth
   Fournier, Alexandre
TI Fast torsional waves and strong magnetic field within the Earth's core
SO NATURE
LA English
DT Article
ID length-of-day; secular variation; angular-momentum; motions; oscillations; rotation; flows
AB The magnetic field inside the Earth's fluid and electrically conducting outer core cannot be directly probed. The root-mean-squared (r.m.s.) intensity for the resolved part of the radial magnetic field at the core-mantle boundary is 0.3 mT, but further assumptions are needed to infer the strength of the field inside the core. Recent diagnostics obtained from numerical geodynamo models(1) indicate that the magnitude of the dipole field at the surface of a fluid dynamo is about ten times weaker than the r.m.s. field strength in its interior, which would yield an intensity of the order of several millitesla within the Earth's core. However, a 60-year signal found in the variation in the length of day(2) has long been associated with magneto-hydrodynamic torsional waves carried by a much weaker internal field(3,4). According to these studies, the r.m.s. strength of the field in the cylindrical radial direction (calculated for all length scales) is only 0.2 mT, a figure even smaller than the r.m.s. strength of the large-scale (spherical harmonic degree n <= 13) field visible at the core-mantle boundary. Here we reconcile numerical geodynamo models with studies of geostrophic motions in the Earth's core that rely on geomagnetic data. From an ensemble inversion of core flow models, we find a torsional wave recurring every six years, the angular momentum of which accounts well for both the phase and the amplitude of the six-year signal for change in length of day detected over the second half of the twentieth century(5). It takes about four years for the wave to propagate throughout the fluid outer core, and this travel time translates into a slowness for Alfven waves that corresponds to a r.m.s. field strength in the cylindrical radial direction of approximately 2 mT. Assuming isotropy, this yields a r.m.s. field strength of 4 mT inside the Earth's core.
C1 [Gillet, Nicolas; Jault, Dominique; Canet, Elisabeth] Univ Grenoble 1, CNRS, Lab Geophys Interne & Tectonophys, F-38041 Grenoble 9, France.
   [Fournier, Alexandre] Univ Paris Diderot, CNRS, Inst Phys Globe Paris, Equipe Geomagnetisme, F-75252 Paris 5, France.
C3 Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite
RP Gillet, N (corresponding author), Univ Grenoble 1, CNRS, Lab Geophys Interne & Tectonophys, BP 53, F-38041 Grenoble 9, France.
EM nicolas.gillet@obs.ujf-grenoble.fr
FU French Agence Nationale de la Recherche [BLAN06-2.155316]; French Centre National d'Etudes Spatiales
NR 30
TC 259
Z9 275
U1 2
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 74
EP 77
DI 10.1038/nature09010
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900033
PM 20445627
DA 2026-03-09
ER

PT J
AU Wu, Y
   Cain-Hom, C
   Choy, L
   Hagenbeek, TJ
   de Leon, GP
   Chen, YM
   Finkle, D
   Venook, R
   Wu, XM
   Ridgway, J
   Schahin-Reed, D
   Dow, GJ
   Shelton, A
   Stawicki, S
   Watts, RJ
   Zhang, J
   Choy, R
   Howard, P
   Kadyk, L
   Yan, MH
   Zha, JP
   Callahan, CA
   Hymowitz, SG
   Siebel, CW
AF Wu, Yan
   Cain-Hom, Carol
   Choy, Lisa
   Hagenbeek, Thijs J.
   de Leon, Gladys P.
   Chen, Yongmei
   Finkle, David
   Venook, Rayna
   Wu, Xiumin
   Ridgway, John
   Schahin-Reed, Dorreyah
   Dow, Graham J.
   Shelton, Amy
   Stawicki, Scott
   Watts, Ryan J.
   Zhang, Jeff
   Choy, Robert
   Howard, Peter
   Kadyk, Lisa
   Yan, Minhong
   Zha, Jiping
   Callahan, Christopher A.
   Hymowitz, Sarah G.
   Siebel, Christian W.
TI Therapeutic antibody targeting of individual Notch receptors
SO NATURE
LA English
DT Article
ID inhibits tumor-growth; gamma-secretase; anti-p185her2 antibody; malignant-melanoma; regulatory region; cancer-therapy; b-cells; mutations; leukemia; angiogenesis
AB The four receptors of the Notch family are widely expressed transmembrane proteins that function as key conduits through which mammalian cells communicate to regulate cell fate and growth(1,2). Ligand binding triggers a conformational change in the receptor negative regulatory region (NRR) that enables ADAM protease cleavage(3,4) at a juxtamembrane site that otherwise lies buried within the quiescent NRR5,6. Subsequent intramembrane proteolysis catalysed by the c-secretase complex liberates the intracellular domain (ICD) to initiate the downstream Notch transcriptional program. Aberrant signalling through each receptor has been linked to numerous diseases, particularly cancer(7), making the Notch pathway a compelling target for new drugs. Although gamma-secretase inhibitors (GSIs) have progressed into the clinic(8), GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways(9) and cause intestinal toxicity(10), attributed to dual inhibition of Notch1 and 2 (ref. 11). To elucidate the discrete functions of Notch1 and Notch2 and develop clinically relevant inhibitors that reduce intestinal toxicity, we used phage display technology to generate highly specialized antibodies that specifically antagonize each receptor paralogue and yet cross-react with the human and mouse sequences, enabling the discrimination of Notch1 versus Notch2 function in human patients and rodent models. Our co-crystal structure shows that the inhibitory mechanism relies on stabilizing NRR quiescence. Selective blocking of Notch1 inhibits tumour growth in pre-clinical models through two mechanisms: inhibition of cancer cell growth and deregulation of angiogenesis. Whereas inhibition of Notch1 plus Notch2 causes severe intestinal toxicity, inhibition of either receptor alone reduces or avoids this effect, demonstrating a clear advantage over pan-Notch inhibitors. Our studies emphasize the value of paralogue-specific antagonists in dissecting the contributions of distinct Notch receptors to differentiation and disease and reveal the therapeutic promise in targeting Notch1 and Notch2 independently.
C1 [Cain-Hom, Carol; Choy, Lisa; Hagenbeek, Thijs J.; Dow, Graham J.; Shelton, Amy; Siebel, Christian W.] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Wu, Yan; Chen, Yongmei; Stawicki, Scott] Genentech Inc, Dept Antibody Engn, San Francisco, CA 94080 USA.
   [Zha, Jiping; Callahan, Christopher A.] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Finkle, David; Venook, Rayna] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA.
   [Wu, Xiumin; Ridgway, John; Yan, Minhong] Genentech Inc, Dept Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA.
   [Schahin-Reed, Dorreyah; Watts, Ryan J.] Genentech Inc, Dept Neurodegenerat, San Francisco, CA 94080 USA.
   [de Leon, Gladys P.; Hymowitz, Sarah G.] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA.
   [Zhang, Jeff; Choy, Robert; Howard, Peter; Kadyk, Lisa] Exelixis Inc, San Francisco, CA 94083 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Exelixis, Inc.
RP Siebel, CW (corresponding author), Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM csiebel@gene.com
FU Department of Energy, National Institutes of Health; National Institute of General Medical Sciences
NR 38
TC 601
Z9 776
U1 1
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1052
EP U122
DI 10.1038/nature08878
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000041
PM 20393564
DA 2026-03-09
ER

PT J
AU Abdo, AA
   Ackermann, M
   Ajello, M
   Axelsson, M
   Baldini, L
   Ballet, J
   Barbiellini, G
   Bastieri, D
   Baughman, BM
   Bechtol, K
   Bellazzini, R
   Berenji, B
   Blandford, RD
   Bloom, ED
   Bock, DCJ
   Bogart, JR
   Bonamente, E
   Borgland, AW
   Bouvier, A
   Bregeon, J
   Brez, A
   Brigida, M
   Bruel, P
   Burnett, TH
   Buson, S
   Caliandro, GA
   Cameron, RA
   Caraveo, PA
   Casandjian, JM
   Cavazzuti, E
   Cecchi, C
   Çelik, Ö
   Chekhtman, A
   Cheung, CC
   Chiang, J
   Ciprini, S
   Claus, R
   Cohen-Tanugi, J
   Collmar, W
   Cominsky, LR
   Conrad, J
   Corbel, S
   Corbet, R
   Costamante, L
   Cutini, S
   Dermer, CD
   de Angelis, A
   de Palma, F
   Digel, SW
   Silva, EDE
   Drell, PS
   Dubois, R
   Dumora, D
   Farnier, C
   Favuzzi, C
   Fegan, SJ
   Ferrara, EC
   Focke, WB
   Fortin, P
   Frailis, M
   Fuhrmann, L
   Fukazawa, Y
   Funk, S
   Fusco, P
   Gargano, F
   Gasparrini, D
   Gehrels, N
   Germani, S
   Giebels, B
   Giglietto, N
   Giommi, P
   Giordano, F
   Giroletti, M
   Glanzman, T
   Godfrey, G
   Grenier, IA
   Grove, JE
   Guillemot, L
   Guiriec, S
   Hanabata, Y
   Harding, AK
   Hayashida, M
   Hays, E
   Horan, D
   Hughes, RE
   Iafrate, G
   Itoh, R
   Jackson, MS
   Jóhannesson, G
   Johnson, AS
   Johnson, WN
   Kadler, M
   Kamae, T
   Katagiri, H
   Kataoka, J
   Kawai, N
   Kerr, M
   Knödlseder, J
   Kocian, ML
   Kuss, M
   Lande, J
   Larsson, S
   Latronico, L
   Lemoine-Goumard, M
   Longo, F
   Loparco, F
   Lott, B
   Lovellette, MN
   Lubrano, P
   Macquart, J
   Madejski, GM
   Makeev, A
   Max-Moerbeck, W
   Mazziotta, MN
   McConville, W
   McEnery, JE
   McGlynn, S
   Meurer, C
   Michelson, F
   Mitthumsiri, W
   Mizuno, T
   Moiseev, AA
   Monte, C
   Monzani, ME
   Morselli, A
   Moskalenko, IV
   Murgia, S
   Nestoras, I
   Nolan, PL
   Norris, JP
   Nuss, E
   Ohsugi, T
   Okumura, A
   Omodei, N
   Orlando, E
   Ormes, JF
   Paneque, D
   Panetta, JH
   Parent, D
   Pavlidou, V
   Pearson, TJ
   Pelassa, V
   Pepe, M
   Pesce-Rollins, M
   Piron, F
   Porter, TA
   Rainò, S
   Rando, R
   Razzano, M
   Readhead, A
   Reimer, A
   Reimer, O
   Reposeur, T
   Reyes, LC
   Richards, JL
   Rochester, LS
   Rodriguez, AY
   Roth, M
   Ryde, F
   Sadrozinski, HFW
   Sanchez, D
   Sander, A
   Parkinson, PMS
   Scargle, JD
   Sgrò, C
   Shaw, MS
   Shrader, C
   Siskind, EJ
   Smith, DA
   Smith, PD
   Spandre, G
   Spinelli, P
   Stawarz, L
   Stevenson, M
   Strickman, MS
   Suson, DJ
   Tajima, H
   Takahashi, H
   Takahashi, T
   Tanaka, T
   Taylor, GB
   Thayer, JB
   Thayer, JG
   Thompson, DJ
   Tibaldo, L
   Torres, DF
   Tosti, G
   Tramacere, A
   Uchiyama, Y
   Usher, TL
   Vasileiou, V
   Vilchez, N
   Vitale, V
   Waite, AP
   Wang, P
   Wehrle, AE
   Winer, BL
   Wood, KS
   Ylinen, T
   Zensus, JA
   Ziegler, M
   Uemura, M
   Ikejiri, Y
   Kawabata, KS
   Kino, M
   Sakimoto, K
   Sasada, M
   Sato, S
   Yamanaka, M
   Villata, M
   Raiteri, CM
   Agudo, I
   Aller, HD
   Aller, MF
   Angelakis, E
   Arkharov, AA
   Bach, U
   Benítez, E
   Berdyugin, A
   Blinov, DA
   Boettcher, M
   Buemi, CS
   Chen, WP
   Dolci, M
   Dultzin, D
   Efimova, NV
   Gurwell, MA
   Gusbar, C
   Gómez, JL
   Heidt, J
   Hiriart, D
   Hovatta, T
   Jorstad, SG
   Konstantinova, TS
   Kopatskaya, EN
   Koptelova, E
   Kurtanidze, OM
   Lahteenmaki, A
   Larionov, VM
   Larionova, EG
   Leto, P
   Lin, HC
   Lindfors, E
   Marscher, AP
   McHardy, IM
   Melnichuk, DA
   Mommert, M
   Nilsson, K
   Di Paola, A
   Reinthal, R
   Richter, GM
   Roca-Sogorb, M
   Roustazadeh, P
   Sigua, LA
   Takalo, LO
   Tornikoski, M
   Trigilio, C
   Troitsky, IS
   Umana, G
   Villforth, C
   Grainge, K
   Moderski, R
   Nalewajko, K
   Sikora, M
AF Abdo, A. A.
   Ackermann, M.
   Ajello, M.
   Axelsson, M.
   Baldini, L.
   Ballet, J.
   Barbiellini, G.
   Bastieri, D.
   Baughman, B. M.
   Bechtol, K.
   Bellazzini, R.
   Berenji, B.
   Blandford, R. D.
   Bloom, E. D.
   Bock, D. C. -J.
   Bogart, J. R.
   Bonamente, E.
   Borgland, A. W.
   Bouvier, A.
   Bregeon, J.
   Brez, A.
   Brigida, M.
   Bruel, P.
   Burnett, T. H.
   Buson, S.
   Caliandro, G. A.
   Cameron, R. A.
   Caraveo, P. A.
   Casandjian, J. M.
   Cavazzuti, E.
   Cecchi, C.
   Celik, Oe
   Chekhtman, A.
   Cheung, C. C.
   Chiang, J.
   Ciprini, S.
   Claus, R.
   Cohen-Tanugi, J.
   Collmar, W.
   Cominsky, L. R.
   Conrad, J.
   Corbel, S.
   Corbet, R.
   Costamante, L.
   Cutini, S.
   Dermer, C. D.
   de Angelis, A.
   de Palma, F.
   Digel, S. W.
   do Couto e Silva, E.
   Drell, P. S.
   Dubois, R.
   Dumora, D.
   Farnier, C.
   Favuzzi, C.
   Fegan, S. J.
   Ferrara, E. C.
   Focke, W. B.
   Fortin, P.
   Frailis, M.
   Fuhrmann, L.
   Fukazawa, Y.
   Funk, S.
   Fusco, P.
   Gargano, F.
   Gasparrini, D.
   Gehrels, N.
   Germani, S.
   Giebels, B.
   Giglietto, N.
   Giommi, P.
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   Nilsson, K.
   Di Paola, A.
   Reinthal, R.
   Richter, G. M.
   Roca-Sogorb, M.
   Roustazadeh, P.
   Sigua, L. A.
   Takalo, L. O.
   Tornikoski, M.
   Trigilio, C.
   Troitsky, I. S.
   Umana, G.
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   Grainge, K.
   Moderski, R.
   Nalewajko, K.
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TI A change in the optical polarization associated with a γ-ray flare in the blazar 3C 279
SO NATURE
LA English
DT Article
ID active galactic nucleus; radio; variability; telescope; radiation; quasar; jet; ultraviolet; emission; model
AB It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight(1). The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma (gamma)-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10(5) gravitational radii.
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   [Moderski, R.; Nalewajko, K.; Sikora, M.] Nicolaus Copernicus Astron Ctr, PL-00716 Warsaw, Poland.
C3 Stanford University; United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake; National Academies of Sciences, Engineering & Medicine; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stockholm University; Oskar Klein Centre; Istituto Nazionale di Fisica Nucleare (INFN); Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Istituto Nazionale di Fisica Nucleare (INFN); University of Trieste; Istituto Nazionale di Fisica Nucleare (INFN); University of Padua; University System of Ohio; Ohio State University; University of California System; University of California Berkeley; Istituto Nazionale di Fisica Nucleare (INFN); University of Perugia; Politecnico di Bari; Istituto Nazionale di Fisica Nucleare (INFN); Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); University of Washington; University of Washington Seattle; Institut d'Estudis Espacials de Catalunya (IEEC); University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Istituto Nazionale Astrofisica (INAF); Agenzia Spaziale Italiana (ASI); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Aeronautics & Space Administration (NASA); University System of Maryland; University of Maryland Baltimore County; University System of Maryland; University of Maryland Baltimore County; George Mason University; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Max Planck Society; California State University System; Sonoma State University; Stockholm University; Institut Universitaire de France; University of Udine; 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); Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Istituto Nazionale Astrofisica (INAF); Max Planck Society; Hiroshima University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; Istituto Nazionale Astrofisica (INAF); University of Alabama System; University of Alabama Huntsville; Royal Institute of Technology; University of Erlangen Nuremberg; University of Erlangen Nuremberg; Universities Space Research Association (USRA); Waseda University; Institute of Science Tokyo; Tokyo Institute of Technology; RIKEN; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); University of Western Australia; California Institute of Technology; Istituto Nazionale di Fisica Nucleare (INFN); University of Denver; University of Tokyo; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of Innsbruck; University of Innsbruck; University of Chicago; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Nycb Real-Time Computing Inc.; Jagiellonian University; Purdue University System; Purdue University Northwest; Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); University of New Mexico; ICREA; University of Rome Tor Vergata; University of Kalmar; Linnaeus University; Hiroshima University; Nagoya University; Istituto Nazionale Astrofisica (INAF); University of Turin; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); University of Michigan System; University of Michigan; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; Pulkovo Main Astronomic Observatory; Universidad Nacional Autonoma de Mexico; University of Turku; Saint Petersburg State University; University System of Ohio; Ohio University; Istituto Nazionale Astrofisica (INAF); National Central University; Istituto Nazionale Astrofisica (INAF); Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Ruprecht Karls University Heidelberg; Universidad Nacional Autonoma de Mexico; Aalto University; Boston University; Ilia State University; University of Southampton; Istituto Nazionale Astrofisica (INAF); University of Cambridge; Polish Academy of Sciences; Nicolaus Copernicus Astronomical Center of the Polish Academy of Sciences
RP Hayashida, M (corresponding author), Stanford Univ, Dept Phys, WW Hansen Expt Phys Lab, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
EM hayasida@stanford.edu; madejski@slac.stanford.edu
FU Georgian National Science Foundation; Spanish "Ministerio de Ciencia e Innovacion''; NSF; NASA; Smithsonian Institution in the United States; UK Science and Technology Facilities Council; Academia Sinica in Taiwan; Russian RFBR; Academy of Finland; JSPS; K. A. Wallenberg Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0808050] Funding Source: National Science Foundation; ICREA Funding Source: Custom; Science and Technology Facilities Council [ST/G009465/1, ST/G003084/1] Funding Source: researchfish; STFC [ST/G003084/1, ST/G009465/1] Funding Source: UKRI
NR 25
TC 282
Z9 295
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 18
PY 2010
VL 463
IS 7283
BP 919
EP 923
DI 10.1038/nature08841
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700039
PM 20164923
DA 2026-03-09
ER

PT J
AU Ai, M
   Min, S
   Grosjean, Y
   Leblanc, C
   Bell, R
   Benton, R
   Suh, GSB
AF Ai, Minrong
   Min, Soohong
   Grosjean, Yael
   Leblanc, Charlotte
   Bell, Rati
   Benton, Richard
   Suh, Greg S. B.
TI Acid sensing by the Drosophila olfactory system
SO NATURE
LA English
DT Article
ID carbon-dioxide; chemosensory receptors; targeted expression; avoidance; neurons; transmission; behavior; reveals; minos; map
AB The odour of acids has a distinct quality that is perceived as sharp, pungent and often irritating(1). How acidity is sensed and translated into an appropriate behavioural response is poorly understood. Here we describe a functionally segregated population of olfactory sensory neurons in the fruitfly, Drosophila melanogaster, that are highly selective for acidity. These olfactory sensory neurons express IR64a, a member of the recently identified ionotropic receptor (IR) family of putative olfactory receptors(2). In vivo calcium imaging showed that IR64a+ neurons projecting to the DC4 glomerulus in the antennal lobe are specifically activated by acids. Flies in which the function of IR64a+ neurons or the IR64a gene is disrupted had defects in acid-evoked physiological and behavioural responses, but their responses to non-acidic odorants remained unaffected. Furthermore, artificial stimulation of IR64a+ neurons elicited avoidance responses. Taken together, these results identify cellular and molecular substrates for acid detection in the Drosophila olfactory system and support a labelled-line mode of acidity coding at the periphery.
C1 [Ai, Minrong; Min, Soohong; Leblanc, Charlotte; Suh, Greg S. B.] NYU, Sch Med, Dept Cell Biol, Skirball Inst Biomol Med,Mol Neurobiol Program, New York, NY 10016 USA.
   [Grosjean, Yael; Bell, Rati; Benton, Richard] Univ Lausanne, Fac Biol & Med, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
C3 New York University; University of Lausanne
RP Suh, GSB (corresponding author), NYU, Sch Med, Dept Cell Biol, Skirball Inst Biomol Med,Mol Neurobiol Program, New York, NY 10016 USA.
EM greg.suh@med.nyu.edu
FU National Research Service Award; Boehringer Ingelheim Foundation; Centre National de la Recherche Scientifique; European Research Council; Swiss National Science Foundation; Alfred P. Sloan Foundation; Whitehall Foundation; Whitehead President Award; NIH [1RO1GM089746]
NR 25
TC 268
Z9 334
U1 5
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 DEC 2
PY 2010
VL 468
IS 7324
BP 691
EP U112
DI 10.1038/nature09537
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700040
PM 21085119
DA 2026-03-09
ER

PT J
AU Bochukova, EG
   Huang, N
   Keogh, J
   Henning, E
   Purmann, C
   Blaszczyk, K
   Saeed, S
   Hamilton-Shield, J
   Clayton-Smith, J
   O'Rahilly, S
   Hurles, ME
   Farooqi, IS
AF Bochukova, Elena G.
   Huang, Ni
   Keogh, Julia
   Henning, Elana
   Purmann, Carolin
   Blaszczyk, Kasia
   Saeed, Sadia
   Hamilton-Shield, Julian
   Clayton-Smith, Jill
   O'Rahilly, Stephen
   Hurles, Matthew E.
   Farooqi, I. Sadaf
TI Large, rare chromosomal deletions associated with severe early-onset obesity
SO NATURE
LA English
DT Article
ID clinical spectrum; adult obesity; autism; microdeletion; receptor; 16p11.2; gene; rearrangements; sensitivity; childhood
AB Obesity is a highly heritable and genetically heterogeneous disorder(1). Here we investigated the contribution of copy number variation to obesity in 300 Caucasian patients with severe early-onset obesity, 143 of whom also had developmental delay. Large (>500 kilobases), rare (<1%) deletions were significantly enriched in patients compared to 7,366 controls (P<0.001). We identified several rare copy number variants that were recurrent in patients but absent or at much lower prevalence in controls. We identified five patients with overlapping deletions on chromosome 16p11.2 that were found in 2 out of 7,366 controls (P<5 x 10(-5)). In three patients the deletion co-segregated with severe obesity. Two patients harboured a larger de novo 16p11.2 deletion, extending through a 593-kilobase region previously associated with autism(2-4) and mental retardation(5); both of these patients had mild developmental delay in addition to severe obesity. In an independent sample of 1,062 patients with severe obesity alone, the smaller 16p11.2 deletion was found in an additional two patients. All 16p11.2 deletions encompass several genes but include SH2B1, which is known to be involved in leptin and insulin signalling(6). Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity. We show that copy number variation contributes significantly to the genetic architecture of human obesity.
C1 [Bochukova, Elena G.; Keogh, Julia; Henning, Elana; Purmann, Carolin; Blaszczyk, Kasia; Saeed, Sadia; O'Rahilly, Stephen; Farooqi, I. Sadaf] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England.
   [Huang, Ni; Hurles, Matthew E.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Hamilton-Shield, Julian] Bristol Childrens Hosp, Bristol BS2 8BG, Avon, England.
   [Clayton-Smith, Jill] St Marys Hosp, Manchester M13 9WL, Lancs, England.
C3 Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Wellcome Trust Sanger Institute; Bristol Royal Hospital For Children; University of Manchester
RP Farooqi, IS (corresponding author), Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England.
EM meh@sanger.ac.uk; isf20@cam.ac.uk
FU Wellcome Trust [077014/Z/05/0Z, 082390/Z/07/Z, 085475]; MRC Centre for Obesity and Related Disorders; NIHR Cambridge Biomedical Research Centre; NIH; Wellcome Trust [082390/Z/07/Z] Funding Source: Wellcome Trust; Medical Research Council [G0900554] Funding Source: researchfish; MRC [G0900554] Funding Source: UKRI
NR 25
TC 414
Z9 492
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 4
PY 2010
VL 463
IS 7281
BP 666
EP 670
DI 10.1038/nature08689
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900037
PM 19966786
DA 2026-03-09
ER

PT J
AU Sibanda, BL
   Chirgadze, DY
   Blundell, TL
AF Sibanda, Bancinyane L.
   Chirgadze, Dimitri Y.
   Blundell, Tom L.
TI Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats
SO NATURE
LA English
DT Article
ID dependent protein-kinase; catalytic subunit; 3-dimensional structure; complex; domain; end; suggests; 3-kinase; damage
AB Broken chromosomes arising from DNA double-strand breaks result from endogenous events such as the production of reactive oxygen species during cellular metabolism, as well as from exogenous sources such as ionizing radiation(1-3). Left unrepaired or incorrectly repaired they can lead to genomic changes that may result in cell death or cancer. DNA-dependent protein kinase (DNA-PK), a holoenzyme that comprises the DNA-PK catalytic subunit (DNA-PKcs) 4,5 and the heterodimer Ku70/Ku80, has a major role in non-homologous end joining-the main pathway in mammals used to repair double-strand breaks(6-8). DNA-PKcs is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids and belonging to the phosphatidylinositol-3-OH kinase (PI(3) K)-related protein family(9). DNA-PKcs is involved in the sensing and transmission of DNA damage signals to proteins such as p53, setting off events that lead to cell cycle arrest(10,11). It phosphorylates a wide range of substrates in vitro, including Ku70/Ku80, which is translocated along DNA(12). Here we present the crystal structure of human DNA-PKcs at 6.6 angstrom resolution, in which the overall fold is clearly visible, to our knowledge, for the first time. The many alpha-helical HEAT repeats (helix-turn-helix motifs) facilitate bending and allow the polypeptide chain to fold into a hollow circular structure. The carboxy-terminal kinase domain is located on top of this structure, and a small HEAT repeat domain that probably binds DNA is inside. The structure provides a flexible cradle to promote DNA double-strand-break repair.
C1 [Sibanda, Bancinyane L.; Chirgadze, Dimitri Y.; Blundell, Tom L.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
C3 University of Cambridge
RP Sibanda, BL (corresponding author), Univ Cambridge, Dept Biochem, Old Addenbrookes Site,80 Tennis Court Rd, Cambridge CB2 1GA, England.
EM lynn@cryst.bioc.cam.ac.uk; dima@cryst.bioc.cam.ac.uk
FU Wellcome Trust; CR-UK
NR 40
TC 180
Z9 210
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 118
EP U132
DI 10.1038/nature08648
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900042
PM 20023628
DA 2026-03-09
ER

PT J
AU Willenbring, JK
   von Blanckenburg, F
AF Willenbring, Jane K.
   von Blanckenburg, Friedhelm
TI Long-term stability of global erosion rates and weathering during late-Cenozoic cooling
SO NATURE
LA English
DT Article
ID climate-change; accumulation rates; beryllium; sediment; water
AB Over geologic timescales, CO2 is emitted from the Earth's interior and is removed from the atmosphere by silicate rock weathering and organic carbon burial. This balance is thought to have stabilized greenhouse conditions within a range that ensured habitable conditions(1). Changes in this balance have been attributed to changes in topographic relief, where varying rates of continental rock weathering and erosion(1,2) are superimposed on fluctuations in organic carbon burial(3). Geological strata provide an indirect yet imperfectly preserved record of this change through changing rates of sedimentation(1,2,4). Widespread observations of a recent (0-5-Myr) fourfold increase in global sedimentation rates require a global mechanism to explain them(4-6). Accelerated uplift and global cooling have been given as possible causes(2,4,6,7), but because of the links between rates of erosion and the correlated rate of weathering(8,9), an increase in the drawdown of CO2 that is predicted to follow may be the cause of global climate change instead(2). However, globally, rates of uplift cannot increase everywhere in the way that apparent sedimentation rates do(4,10). Moreover, proxy records of past atmospheric CO2 provide no evidence for this large reduction in recent CO2 concentrations(11,12). Here we question whether this increase in global weathering and erosion actually occurred and whether the apparent increase in the sedimentation rate is due to observational biases in the sedimentary record(13). As evidence, we recast the ocean dissolved Be-10/Be-9 isotope system as a weathering proxy spanning the past similar to 12 Myr (ref. 14). This proxy indicates stable weathering fluxes during the late-Cenozoic era. The sum of these observations shows neither clear evidence for increased erosion nor clear evidence for a pulse in weathered material to the ocean. We conclude that processes different from an increase in denudation caused Cenozoic global cooling, and that global cooling had no profound effect on spatially and temporally averaged weathering rates.
C1 [Willenbring, Jane K.; von Blanckenburg, Friedhelm] Deutsch GeoForschungsZentrum, Sect Earth Surface Geochem 3 4, D-14473 Potsdam, Germany.
C3 Helmholtz Association; GFZ Helmholtz Centre for Geosciences
RP von Blanckenburg, F (corresponding author), Deutsch GeoForschungsZentrum, Sect Earth Surface Geochem 3 4, D-14473 Potsdam, Germany.
EM jane.willenbring@sas.upenn.edu; fvb@gfz-potsdam.de
FU Alexander von Humboldt Postdoctoral Fellowship
NR 30
TC 332
Z9 391
U1 4
U2 263
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 211
EP 214
DI 10.1038/nature09044
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500033
PM 20463736
DA 2026-03-09
ER

PT J
AU Brinks, D
   Stefani, FD
   Kulzer, F
   Hildner, R
   Taminiau, TH
   Avlasevich, Y
   Müllen, K
   Van Hulst, NF
AF Brinks, Daan
   Stefani, Fernando D.
   Kulzer, Florian
   Hildner, Richard
   Taminiau, Tim H.
   Avlasevich, Yuri
   Muellen, Klaus
   Van Hulst, Niek F.
TI Visualizing and controlling vibrational wave packets of single molecules
SO NATURE
LA English
DT Article
ID coherent control; quantum control; laser-pulses; dynamics; spectroscopy; fluorescence; chemistry; bond
AB The active steering of the pathways taken by chemical reactions and the optimization of energy conversion processes(1-3) provide striking examples of the coherent control of quantum interference through the use of shaped laser pulses. Experimentally, coherence is usually established by synchronizing a subset of molecules in an ensemble(4-7) with ultra-short laser pulses(8). But in complex systems where even chemically identical molecules exist with different conformations and in diverse environments, the synchronized subset will have an intrinsic inhomogeneity that limits the degree of coherent control that can be achieved. A natural-and, indeed, the ultimate-solution to overcoming intrinsic inhomogeneities is the investigation of the behaviour of one molecule at a time. The single-molecule approach(9,10) has provided useful insights into phenomena as diverse as biomolecular interactions(11-13), cellular processes(14) and the dynamics of supercooled liquids(15) and conjugated polymers(16.) Coherent state preparation of single molecules has so far been restricted to cryogenic conditions(17), whereas at room temperature only incoherent vibrational relaxation pathways have been probed(18). Here we report the observation and manipulation of vibrational wave-packet interference in individual molecules at ambient conditions. We show that adapting the time and phase distribution of the optical excitation field to the dynamics of each molecule results in a high degree of control, and expect that the approach can be extended to achieve single-molecule coherent control in other complex inhomogeneous systems.
C1 [Brinks, Daan; Stefani, Fernando D.; Kulzer, Florian; Hildner, Richard; Taminiau, Tim H.; Van Hulst, Niek F.] ICFO, Barcelona 08860, Spain.
   [Avlasevich, Yuri; Muellen, Klaus] Max Planck Inst Polymer Res, D-55128 Mainz, Germany.
   [Van Hulst, Niek F.] ICREA, Barcelona 08015, Spain.
C3 Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); Max Planck Society; ICREA
RP Stefani, FD (corresponding author), ICFO, Mediterranean Technol Pk, Barcelona 08860, Spain.
EM Fernando.Stefani@df.uba.ar; Niek.vanHulst@ICFO.es
FU Koerber foundation (Hamburg); Spanish Ministry of Science and Innovation [CSD2007-046-NanoLight.es, MAT2006-08184]; ICREA Funding Source: Custom
NR 30
TC 157
Z9 171
U1 2
U2 151
PU 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 17
PY 2010
VL 465
IS 7300
BP 905
EP U5
DI 10.1038/nature09110
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500033
PM 20559383
DA 2026-03-09
ER

PT J
AU Green, DH
   Hibberson, WO
   Kovács, I
   Rosenthal, A
AF Green, David H.
   Hibberson, William O.
   Kovacs, Istvan
   Rosenthal, Anja
TI Water and its influence on the lithosphere-asthenosphere boundary
SO NATURE
LA English
DT Article
ID quantitative-analysis; midocean ridges; phase-relations; high-pressures; mantle; melt; h2o; peridotite; amphibole; olivine
AB The Earth has distinctive convective behaviour, described by the plate tectonics model, in which lateral motion of the oceanic lithosphere of basaltic crust and peridotitic uppermost mantle is decoupled from the underlying mechanically weaker upper mantle (asthenosphere). The reason for differentiation at the lithosphere-asthenosphere boundary is currently being debated with relevant observations from geophysics (including seismology) and geo-chemistry (including experimental petrology). Water is thought to have an important effect on mantle rheology, either by weakening the crystal structure of olivine and pyroxenes by dilute solid solution(1), or by causing low-temperature partial melting(2). Here we present a novel experimental approach to clarify the role of water in the uppermost mantle at pressures up to 6 GPa, equivalent to a depth of 190 km. We found that for lherzolite in which a water-rich vapour is present, the temperature at which a silicate melt first appears (the vapour-saturated solidus) increases from a minimum of 970 degrees C at 1.5 GPa to 1,350 degrees C at 6 GPa. We have measured the water content in lherzolite to be approximately 180 parts per million, retained in nominally anhydrous minerals at 2.5 and 4 GPa at temperatures above and below the vapour-saturated solidus. The hydrous mineral pargasite is the main water-storage site in the uppermost mantle, and the instability of pargasite at pressures greater than 3 GPa (equivalent to more than about 90 km depth) causes a sharp drop in both the water-storage capacity and the solidus temperature of fertile upper-mantle lherzolite. The presence of interstitial melt in mantle with more than 180 parts per million of water at pressures greater than 3 GPa alters mantle rheology and defines the lithosphere-asthenosphere boundary. Modern asthenospheric mantle acting as the source for mid-oceanic ridge basalts has a water content of 50-200 parts per million (refs 3-5). We show that this matches the water content of residual nominally anhydrous minerals after incipient melting of lherzolite at the vapour-saturated solidus at high pressure.
C1 [Green, David H.] Univ Tasmania, Sch Earth Sci, Hobart, Tas 7001, Australia.
   [Green, David H.] Univ Tasmania, Ctr Ore Deposit Studies, Hobart, Tas 7001, Australia.
   [Green, David H.; Hibberson, William O.; Kovacs, Istvan; Rosenthal, Anja] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Kovacs, Istvan] Eotvos Lorand Geophys Inst Hungary, Dept Data Management, H-1145 Budapest, Hungary.
C3 University of Tasmania; University of Tasmania; Australian National University
RP Green, DH (corresponding author), Univ Tasmania, Sch Earth Sci, Hobart, Tas 7001, Australia.
EM David.H.Green@utas.edu.au
FU Australian Research Council; A.E. Ringwood Memorial Scholarship; Australian International Postgraduate Research Scholarship; Marie Curie International Reintegration Grant [NAMS-230937]; Australian National University
NR 30
TC 299
Z9 361
U1 2
U2 177
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 448
EP U97
DI 10.1038/nature09369
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200040
PM 20865000
DA 2026-03-09
ER

PT J
AU Salazar-Ciudad, I
   Jernvall, J
AF Salazar-Ciudad, Isaac
   Jernvall, Jukka
TI A computational model of teeth and the developmental origins of morphological variation
SO NATURE
LA English
DT Article
ID expression patterns; mammalian teeth; evolution; simulation; morphogenesis; dynamics; ontogeny
AB The relationship between the genotype and the phenotype, or the genotype-phenotype map, is generally approached with the tools of multivariate quantitative genetics and morphometrics(1-4). Whereas studies of development(5-7) and mathematical models of development(4,8-12) may offer new insights into the genotype-phenotype map, the challenge is to make them useful at the level of microevolution. Here we report a computational model of mammalian tooth development that combines parameters of genetic and cellular interactions to produce a three-dimensional tooth from a simple tooth primordia. We systematically tinkered with each of the model parameters to generate phenotypic variation and used geometric morphometric analyses to identify, or developmentally ordinate, parameters best explaining population-level variation of real teeth. To model the full range of developmentally possible morphologies, we used a population sample of ringed seals (Phoca hispida ladogensis)(13). Seal dentitions show a high degree of variation, typically linked to the lack of exact occlusion(13-16). Our model suggests that despite the complexity of development and teeth, there may be a simple basis for dental variation. Changes in single parameters regulating signalling during cusp development may explain shape variation among individuals, whereas a parameter regulating epithelial growth may explain serial, tooth-to-tooth variation along the jaw. Our study provides a step towards integrating the genotype, development and the phenotype.
C1 [Salazar-Ciudad, Isaac] Univ Autonoma Barcelona, Dept Genet & Microbiol, Fac Biociencies, E-08193 Barcelona, Spain.
   [Salazar-Ciudad, Isaac; Jernvall, Jukka] Univ Helsinki, Inst Biotechnol, Dev Biol Program, FIN-00014 Helsinki, Finland.
   [Jernvall, Jukka] SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA.
C3 Autonomous University of Barcelona; University of Helsinki; State University of New York (SUNY) System; Stony Brook University
RP Salazar-Ciudad, I (corresponding author), Univ Autonoma Barcelona, Dept Genet & Microbiol, Fac Biociencies, E-08193 Barcelona, Spain.
EM isaac.salazar@uab.cat; jernvall@fastmail.fm
FU Ramon y Cajal Program [RYC-2007-00149]; Academy of Finland
NR 39
TC 270
Z9 308
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 583
EP U138
DI 10.1038/nature08838
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200046
PM 20220757
DA 2026-03-09
ER

PT J
AU Makde, RD
   England, JR
   Yennawar, HP
   Tan, S
AF Makde, Ravindra D.
   England, Joseph R.
   Yennawar, Hemant P.
   Tan, Song
TI Structure of RCC1 chromatin factor bound to the nucleosome core particle
SO NATURE
LA English
DT Article
ID chromosome condensation rcc1; crystal-structure; angstrom resolution; nuclear transport; mitotic spindle; beta-gamma; ran; dna; complex; binding
AB The small GTPase Ran enzyme regulates critical eukaryotic cellular functions including nuclear transport and mitosis through the creation of a RanGTP gradient around the chromosomes. This concentration gradient is created by the chromatin-bound RCC1 (regulator of chromosome condensation) protein, which recruits Ran to nucleosomes and activates Ran's nucleotide exchange activity. Although RCC1 has been shown to bind directly with the nucleosome, the molecular details of this interaction were not known. Here we determine the crystal structure of a complex of Drosophila RCC1 and the nucleosome core particle at 2.9 angstrom resolution, providing an atomic view of how a chromatin protein interacts with the histone and DNA components of the nucleosome. Our structure also suggests that the Widom 601 DNA positioning sequence present in the nucleosomes forms a 145-base-pair nucleosome core particle, not the expected canonical 147-base-pair particle.
C1 [Makde, Ravindra D.; England, Joseph R.; Yennawar, Hemant P.; Tan, Song] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Tan, S (corresponding author), Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
EM sxt30@psu.edu
FU NIGMS NIH HHS [R01 GM088236] Funding Source: Medline
NR 50
TC 313
Z9 378
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 562
EP U81
DI 10.1038/nature09321
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100032
PM 20739938
DA 2026-03-09
ER

PT J
AU Tan, KR
   Brown, M
   Labouèbe, G
   Yvon, C
   Creton, C
   Fritschy, JM
   Rudolph, U
   Lüscher, C
AF Tan, Kelly R.
   Brown, Matthew
   Labouebe, Gwenael
   Yvon, Cedric
   Creton, Cyril
   Fritschy, Jean-Marc
   Rudolph, Uwe
   Luescher, Christian
TI Neural bases for addictive properties of benzodiazepines
SO NATURE
LA English
DT Article
ID ventral tegmental area; evoked synaptic plasticity; dopamine neurons; in-vivo; gaba(b) receptors; modulation; abuse; cells; acid; alpha-1-beta-2-gamma-2
AB Benzodiazepines are widely used in clinics and for recreational purposes, but will lead to addiction in vulnerable individuals. Addictive drugs increase the levels of dopamine and also trigger long-lasting synaptic adaptations in the mesolimbic reward system that ultimately may induce the pathological behaviour. The neural basis for the addictive nature of benzodiazepines, however, remains elusive. Here we show that benzodiazepines increase firing of dopamine neurons of the ventral tegmental area through the positive modulation of GABA(A) (gamma-aminobutyric acid type A) receptors in nearby interneurons. Such disinhibition, which relies on alpha 1-containing GABA(A) receptors expressed in these cells, triggers drug-evoked synaptic plasticity in excitatory afferents onto dopamine neurons and underlies drug reinforcement. Taken together, our data provide evidence that benzodiazepines share defining pharmacological features of addictive drugs through cell-type-specific expression of alpha 1-containing GABA(A) receptors in the ventral tegmental area. The data also indicate that subunit-selective benzodiazepines sparing alpha 1 may be devoid of addiction liability.
C1 [Tan, Kelly R.; Brown, Matthew; Labouebe, Gwenael; Yvon, Cedric; Creton, Cyril; Luescher, Christian] Univ Geneva, Dept Basic Neurosci, Fac Med, CH-1211 Geneva, Switzerland.
   [Fritschy, Jean-Marc] Univ Zurich, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland.
   [Rudolph, Uwe] Harvard Univ, Sch Med, Lab Genet Neuropharmacol, McLean Hosp, Belmont, MA 02478 USA.
   [Rudolph, Uwe] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA.
   [Luescher, Christian] Univ Hosp Geneva, Dept Clin Neurosci, Neurol Clin, CH-1211 Geneva, Switzerland.
   [Luescher, Christian] Geneva Neurosci Ctr, CH-1211 Geneva, Switzerland.
C3 University of Geneva; University of Zurich; Harvard University; Harvard University Medical Affiliates; McLean Hospital; Harvard University; University of Geneva
RP Lüscher, C (corresponding author), Univ Geneva, Dept Basic Neurosci, Fac Med, CH-1211 Geneva, Switzerland.
EM christian.luscher@unige.ch
FU National Institute on Drug Abuse (NIDA) [DA019022]; Swiss National Science Foundation; Swiss Initiative in Systems Biology; European Commission [LSHM-CT-2005-19063]
NR 48
TC 294
Z9 356
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 769
EP U78
DI 10.1038/nature08758
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300031
PM 20148031
DA 2026-03-09
ER

PT J
AU Ji, H
   Ehrlich, LIR
   Seita, J
   Murakami, P
   Doi, A
   Lindau, P
   Lee, H
   Aryee, MJ
   Irizarry, RA
   Kim, K
   Rossi, DJ
   Inlay, MA
   Serwold, T
   Karsunky, H
   Ho, LN
   Daley, GQ
   Weissman, IL
   Feinberg, AP
AF Ji, Hong
   Ehrlich, Lauren I. R.
   Seita, Jun
   Murakami, Peter
   Doi, Akiko
   Lindau, Paul
   Lee, Hwajin
   Aryee, Martin J.
   Irizarry, Rafael A.
   Kim, Kitai
   Rossi, Derrick J.
   Inlay, Matthew A.
   Serwold, Thomas
   Karsunky, Holger
   Ho, Lena
   Daley, George Q.
   Weissman, Irving L.
   Feinberg, Andrew P.
TI Comprehensive methylome map of lineage commitment from haematopoietic progenitors
SO NATURE
LA English
DT Article
ID dna methyltransferase; transcription factor; stem; methylation; cells; mice; meis1
AB Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs(1), a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
C1 [Ji, Hong; Murakami, Peter; Doi, Akiko; Lee, Hwajin; Irizarry, Rafael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA.
   [Ji, Hong; Murakami, Peter; Doi, Akiko; Lee, Hwajin; Irizarry, Rafael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Ehrlich, Lauren I. R.; Seita, Jun; Lindau, Paul; Rossi, Derrick J.; Inlay, Matthew A.; Serwold, Thomas; Karsunky, Holger; Ho, Lena; Weissman, Irving L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Aryee, Martin J.; Irizarry, Rafael A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
   [Aryee, Martin J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Kim, Kitai; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA.
   [Kim, Kitai; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Kim, Kitai; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Kim, Kitai; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Kim, Kitai; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
C3 Johns Hopkins University; Johns Hopkins University; Stanford University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins University; Johns Hopkins Medicine; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University
RP Feinberg, AP (corresponding author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, 570 Rangos,725 N Wolfe St, Baltimore, MD 21205 USA.
EM afeinberg@jhu.edu
FU National Institutes of Health [R37CA053458, P50HG003233, R01AI047457, R01AI047458, R00AGO29760, CA09151, F32AI058521]; Thomas and Stacey Siebel Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine [T1-00001]; National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER
NR 30
TC 509
Z9 602
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 338
EP U120
DI 10.1038/nature09367
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900041
PM 20720541
DA 2026-03-09
ER

PT J
AU Cresci, G
   Mannucci, F
   Maiolino, R
   Marconi, A
   Gnerucci, A
   Magrini, L
AF Cresci, G.
   Mannucci, F.
   Maiolino, R.
   Marconi, A.
   Gnerucci, A.
   Magrini, L.
TI Gas accretion as the origin of chemical abundance gradients in distant galaxies
SO NATURE
LA English
DT Article
ID integral field spectroscopy; star-forming galaxy; lyman-break galaxy; similar-to 2; evolution; metallicity; stellar; mass; z-similar-to-2; diagnostics
AB It has recently been suggested(1,2) that galaxies in the early Universe could have grown through the accretion of cold gas, and that this may have been the main driver of star formation and stellar mass growth(3-5). Because the cold gas is essentially primordial, it has a very low abundance of elements heavier than helium (referred to as metallicity). If funnelled to the centre of a galaxy, it will result in the central gas having an overall lower metallicity than gas further from the centre, because the gas further out has been enriched by supernovae and stellar winds, and not diluted by the primordial gas. Here we report chemical abundances across three rotationally supported star-forming galaxies at redshift z approximate to 3, only 2 Gyr after the Big Bang. We find 'inverse' gradients, with the central, star-forming regions having lower metallicities than less active ones, which is opposite to what is seen in local galaxies(6,7). We conclude that the central gas has been diluted by the accretion of primordial gas, as predicted by 'cold flow' models.
C1 [Cresci, G.; Mannucci, F.; Magrini, L.] INAF Osservatorio Astrofis Arcetri, I-50125 Florence, Italy.
   [Cresci, G.] Max Planck Inst Extraterr Phys MPE, D-85748 Garching, Germany.
   [Maiolino, R.] INAF Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Marconi, A.; Gnerucci, A.] Univ Florence, Dipartimento Fis & Astron, I-50125 Florence, Italy.
C3 Istituto Nazionale Astrofisica (INAF); Max Planck Society; Istituto Nazionale Astrofisica (INAF); University of Florence
RP Cresci, G (corresponding author), INAF Osservatorio Astrofis Arcetri, Largo E Fermi 5, I-50125 Florence, Italy.
EM gcresci@arcetri.astro.it
FU ESO; INAF; ASI
NR 30
TC 215
Z9 234
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 811
EP 813
DI 10.1038/nature09451
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700059
PM 20944741
DA 2026-03-09
ER

PT J
AU Jopling, C
   Sleep, E
   Raya, M
   Marti, M
   Raya, A
   Belmonte, JCI
AF Jopling, Chris
   Sleep, Eduard
   Raya, Marina
   Marti, Merce
   Raya, Angel
   Izpisua Belmonte, Juan Carlos
TI Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation
SO NATURE
LA English
DT Article
ID cell-cycle; injury; myocardium; expression
AB Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts(1-3), including the zebrafish(4,5), which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse(6). Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.
C1 [Jopling, Chris; Sleep, Eduard; Raya, Marina; Marti, Merce; Raya, Angel; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
   [Sleep, Eduard; Raya, Angel; Izpisua Belmonte, Juan Carlos] Networking Ctr Biomed Res Bioengn Biomat & Nanome, Barcelona 08003, Spain.
   [Raya, Angel] ICREA, Barcelona 08010, Spain.
   [Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; University of Barcelona; ICREA; Salk Institute
RP Belmonte, JCI (corresponding author), Ctr Regenerat Med Barcelona, Dr Aiguader St 88, Barcelona 08003, Spain.
EM belmonte@salk.edu
FU Ministry of Innovation, Universities and Enterprise (DIUE), Generalitat de Catalunya; Fundacion Cellex; Ipsen Foundation; G. Harold and Leila Y. Mathers Charitable Foundation; Sanofi-Aventis; Ministry of Science and Innovation (MICINN); CIBER; National Institutes of Health; ICREA Funding Source: Custom
NR 25
TC 1071
Z9 1299
U1 3
U2 208
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 606
EP U168
DI 10.1038/nature08899
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200051
PM 20336145
DA 2026-03-09
ER

PT J
AU Zheng, Y
   Josefowicz, S
   Chaudhry, A
   Peng, XP
   Forbush, K
   Rudensky, AY
AF Zheng, Ye
   Josefowicz, Steven
   Chaudhry, Ashutosh
   Peng, Xiao P.
   Forbush, Katherine
   Rudensky, Alexander Y.
TI Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
SO NATURE
LA English
DT Article
ID transcription factor foxp3; human genome; expression; methylation; lineage
AB Immune homeostasis is dependent on tight control over the size of a population of regulatory T (T-reg) cells capable of suppressing over-exuberant immune responses. The T-reg cell subset is comprised of cells that commit to the T-reg lineage by upregulating the transcription factor Foxp3 either in the thymus (tT(reg)) or in the periphery (iT(reg))(1,2). Considering a central role for Foxp3 in T-reg cell differentiation and function(3,4), we proposed that conserved non-coding DNA sequence (CNS) elements at the Foxp3 locus encode information defining the size, composition and stability of the T-reg cell population. Here we describe the function of three Foxp3 CNS elements (CNS1-3) in T-reg cell fate determination in mice. The pioneer element CNS3, which acts to potently increase the frequency of T-reg cells generated in the thymus and the periphery, binds c-Rel in in vitro assays. In contrast, CNS1, which contains a TGF-beta-NFAT response element, is superfluous for tT(reg) cell differentiation, but has a prominent role in iT(reg) cell generation in gut-associated lymphoid tissues. CNS2, although dispensable for Foxp3 induction, is required for Foxp3 expression in the progeny of dividing T-reg cells. Foxp3 binds to CNS2 in a Cbf-beta-Runx1 and CpG DNA demethylation-dependent manner, suggesting that Foxp3 recruitment to this 'cellular memory module' facilitates the heritable maintenance of the active state of the Foxp3 locus and, therefore, T-reg lineage stability. Together, our studies demonstrate that the composition, size and maintenance of the T-reg cell population are controlled by Foxp3 CNS elements engaged in response to distinct cell-extrinsic or -intrinsic cues.
C1 [Zheng, Ye; Josefowicz, Steven; Chaudhry, Ashutosh; Forbush, Katherine; Rudensky, Alexander Y.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Zheng, Ye; Josefowicz, Steven; Chaudhry, Ashutosh; Forbush, Katherine; Rudensky, Alexander Y.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
   [Zheng, Ye; Josefowicz, Steven; Chaudhry, Ashutosh; Peng, Xiao P.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Zheng, Ye; Josefowicz, Steven; Chaudhry, Ashutosh; Peng, Xiao P.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Rudensky, AY (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM rudenska@mskcc.org
FU National Institutes of Health; CRI-Irvington Institute; CRI
NR 24
TC 971
Z9 1173
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 FEB 11
PY 2010
VL 463
IS 7282
BP 808
EP U120
DI 10.1038/nature08750
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300040
PM 20072126
DA 2026-03-09
ER

PT J
AU Karunatilaka, KS
   Solem, A
   Pyle, AM
   Rueda, D
AF Karunatilaka, Krishanthi S.
   Solem, Amanda
   Pyle, Anna Marie
   Rueda, David
TI Single-molecule analysis of Mss116-mediated group II intron folding
SO NATURE
LA English
DT Article
ID dead-box protein; chaperone activity; atp hydrolysis; spectroscopy; requires; ribozyme; fret
AB DEAD-box helicases are conserved enzymes involved in nearly all aspects of RNA metabolism, but their mechanisms of action remain unclear. Here, we investigated the mechanism of the DEAD-box protein Mss116 on its natural substrate, the group II intron ai5 gamma. Group II introns are structurally complex catalytic RNAs considered evolutionarily related to the eukaryotic spliceosome, and an interesting paradigm for large RNA folding. We used single-molecule fluorescence to monitor the effect of Mss116 on folding dynamics of a minimal active construct, ai5 gamma-D135. The data show that Mss116 stimulates dynamic sampling between states along the folding pathway, an effect previously observed only with high Mg2+ concentrations. Furthermore, the data indicate that Mss116 promotes folding through discrete ATP-independent and ATP-dependent steps. We propose that Mss116 stimulates group II intron folding through a multi-step process that involves electrostatic stabilization of early intermediates and ATP hydrolysis during the final stages of native state assembly.
C1 [Karunatilaka, Krishanthi S.; Solem, Amanda; Rueda, David] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA.
   [Pyle, Anna Marie] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Pyle, Anna Marie] Yale Univ, Dept Chem, New Haven, CT 06520 USA.
   [Pyle, Anna Marie] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA.
C3 Wayne State University; Yale University; Yale University; Yale University; Howard Hughes Medical Institute
RP Rueda, D (corresponding author), Wayne State Univ, Dept Chem, 5101 Cass Ave, Detroit, MI 48202 USA.
EM anna.pyle@yale.edu; david.rueda@wayne.edu
FU National Institutes of Health [R01GM085116, R01GM050313]; National Science Foundation [MCB-0747285]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0747285] Funding Source: National Science Foundation
NR 35
TC 69
Z9 82
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 OCT 21
PY 2010
VL 467
IS 7318
BP 935
EP U75
DI 10.1038/nature09422
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700031
PM 20944626
DA 2026-03-09
ER

PT J
AU West, XZ
   Malinin, NL
   Merkulova, AA
   Tischenko, M
   Kerr, BA
   Borden, EC
   Podrez, EA
   Salomon, RG
   Byzova, TV
AF West, Xiaoxia Z.
   Malinin, Nikolay L.
   Merkulova, Alona A.
   Tischenko, Mira
   Kerr, Bethany A.
   Borden, Ernest C.
   Podrez, Eugene A.
   Salomon, Robert G.
   Byzova, Tatiana V.
TI Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands
SO NATURE
LA English
DT Article
ID toll-like receptor-2; macular degeneration; chronic inflammation; pattern-recognition; innate immunity; system; cancer; cells; cd36
AB Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression(1,2). Whereas the mechanism of hypoxia-driven angiogenesis is well understood(3,4), the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, omega-(2-carboxyethyl) pyrrole (CEP) and other related pyrroles(5), are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
C1 [West, Xiaoxia Z.; Malinin, Nikolay L.; Merkulova, Alona A.; Tischenko, Mira; Kerr, Bethany A.; Podrez, Eugene A.; Byzova, Tatiana V.] Cleveland Clin Fdn, Dept Mol Cardiol, JJ Jacobs Ctr Thrombosis & Vasc Biol, Cleveland, OH 44195 USA.
   [West, Xiaoxia Z.; Salomon, Robert G.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
   [Borden, Ernest C.; Byzova, Tatiana V.] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA.
C3 Cleveland Clinic Foundation; University System of Ohio; Case Western Reserve University; Cleveland Clinic Foundation
RP Byzova, TV (corresponding author), Cleveland Clin Fdn, Dept Mol Cardiol, JJ Jacobs Ctr Thrombosis & Vasc Biol, NB50,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM byzovat@ccf.org
FU NIH [HL073311, HL071625, CA126847, HL077213, GM021249]; American Heart Association [10SDG4300062]; National Heart Lung and Blood Institute [R01HL071625] Funding Source: NIH RePORTER; American Heart Association (AHA) [10SDG4300062] Funding Source: American Heart Association (AHA)
NR 32
TC 374
Z9 420
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 OCT 21
PY 2010
VL 467
IS 7318
BP 972
EP U150
DI 10.1038/nature09421
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700040
PM 20927103
DA 2026-03-09
ER

PT J
AU Ammann, MW
   Brodholt, JP
   Wookey, J
   Dobson, DP
AF Ammann, M. W.
   Brodholt, J. P.
   Wookey, J.
   Dobson, D. P.
TI First-principles constraints on diffusion in lower-mantle minerals and a weak D" layer
SO NATURE
LA English
DT Article
ID post-perovskite phase; fe-mg interdiffusion; mgsio3 perovskite; seismic anisotropy; self-diffusion; pressure; silicon; beneath; oxygen
AB Post-perovskite MgSiO3 is believed to be present in the D '' region of the Earth's lower most mantle(1-4). Its existence has been used to explain a number of seismic observations, such as the D '' reflector and the high degree of seismic anisotropy within the D '' layer(5-8). Ionic diffusion in post-perovskite controls its viscosity, which in turn controls the thermal and chemical coupling between the core and the mantle, the development of plumes and the stability of deep chemical reservoirs(9). Here we report the use of first-principles methods to calculate absolute diffusion rates in post-perovskite under the conditions found in the Earth's lower mantle. We find that the diffusion of Mg2+ and Si4+ in post-perovskite is extremely anisotropic, with almost eight orders of magnitude difference between the fast and slow directions. If post-perovskite in the D '' layer shows significant lattice-preferred orientation, the fast diffusion direction will render post-perovskite up to four orders of magnitude weaker than perovskite. The presence of weak postperovskite strongly increases the heat flux across the core-mantle boundary and alters the geotherm(9). It also provides an explanation for laterally varying viscosity in the lowermost mantle, as required by long-period geoid models(10). Moreover, the behaviour of very weak post-perovskite can reconcile seismic observation of a D '' reflector with recent experiments showing that the width of the perovskite-to-post-perovskite transition is too wide to cause sharp reflectors(11). We suggest that the observed sharp D '' reflector is caused by a rapid change in seismic anisotropy. Once sufficient perovskite has transformed into post-perovskite, post-perovskite becomes interconnected and strain is partitioned into this weaker phase. At this point, the weaker post-perovskite will start to deform rapidly, thereby developing a strong crystallographic texture. We show that the expected seismic contrast between the deformed perovskite-plus-post-perovskite assemblage and the overlying isotropic perovskite-plus-post-perovskite assemblage is consistent with seismic observations.
C1 [Ammann, M. W.; Brodholt, J. P.; Dobson, D. P.] UCL, Dept Earth Sci, London WC1E 6BT, England.
   [Wookey, J.] Univ Bristol, Dept Earth Sci, Bristol BS6 6LL, Avon, England.
C3 University of London; University College London; University of Bristol
RP Ammann, MW (corresponding author), UCL, Dept Earth Sci, Gower St, London WC1E 6BT, England.
EM m.ammann@ucl.ac.uk; j.brodholt@ucl.ac.uk
FU European Commission [MRTN-CT-2006-035957]; Office of Science and Technology; Natural Environment Research Council [hpc010001] Funding Source: researchfish; NERC [hpc010001] Funding Source: UKRI
NR 32
TC 205
Z9 222
U1 0
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 462
EP 465
DI 10.1038/nature09052
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700031
PM 20505725
DA 2026-03-09
ER

PT J
AU Allen, HL
   Estrada, K
   Lettre, G
   Berndt, SI
   Weedon, MN
   Rivadeneira, F
   Willer, CJ
   Jackson, AU
   Vedantam, S
   Raychaudhuri, S
   Ferreira, T
   Wood, AR
   Weyant, RJ
   Segré, AV
   Speliotes, EK
   Wheeler, E
   Soranzo, N
   Park, JH
   Yang, J
   Gudbjartsson, D
   Heard-Costa, NL
   Randall, JC
   Qi, L
   Smith, AV
   Mägi, R
   Pastinen, T
   Liang, L
   Heid, IM
   Luan, J
   Thorleifsson, G
   Winkler, TW
   Goddard, ME
   Lo, KS
   Palmer, C
   Workalemahu, T
   Aulchenko, YS
   Johansson, Å
   Zillikens, MC
   Feitosa, MF
   Esko, T
   Johnson, T
   Ketkar, S
   Kraft, P
   Mangino, M
   Prokopenko, I
   Absher, D
   Albrecht, E
   Ernst, F
   Glazer, NL
   Hayward, C
   Hottenga, JJ
   Jacobs, KB
   Knowles, JW
   Kutalik, Z
   Monda, KL
   Polasek, O
   Preuss, M
   Rayner, NW
   Robertson, NR
   Steinthorsdottir, V
   Tyrer, JP
   Voight, BF
   Wiklund, F
   Xu, JF
   Zhao, JH
   Nyholt, DR
   Pellikka, N
   Perola, M
   Perry, JRB
   Surakka, I
   Tammesoo, ML
   Altmaier, EL
   Amin, N
   Aspelund, T
   Bhangale, T
   Boucher, G
   Chasman, DI
   Chen, C
   Coin, L
   Cooper, MN
   Dixon, AL
   Gibson, Q
   Grundberg, E
   Hao, K
   Junttila, MJ
   Kaplan, LM
   Kettunen, J
   König, IR
   Kwan, T
   Lawrence, RW
   Levinson, DF
   Lorentzon, M
   McKnight, B
   Morris, AP
   Müller, M
   Ngwa, JS
   Purcell, S
   Rafelt, S
   Salem, RM
   Salvi, E
   Sanna, S
   Shi, JX
   Sovio, U
   Thompson, JR
   Turchin, MC
   Vandenput, L
   Verlaan, DJ
   Vitart, V
   White, CC
   Ziegler, A
   Almgren, P
   Balmforth, AJ
   Campbell, H
   Citterio, L
   De Grandi, A
   Dominiczak, A
   Duan, J
   Elliott, P
   Elosua, R
   Eriksson, JG
   Freimer, NB
   Geus, EJC
   Glorioso, N
   Haiqing, S
   Hartikainen, AL
   Havulinna, AS
   Hicks, AA
   Hui, JN
   Igl, W
   Illig, T
   Jula, A
   Kajantie, E
   Kilpelaeinen, TO
   Koiranen, M
   Kolcic, I
   Koskinen, S
   Kovacs, P
   Laitinen, J
   Liu, JJ
   Lokki, ML
   Marusic, A
   Maschio, A
   Meitinger, T
   Mulas, A
   Pare, G
   Parker, AN
   Peden, JF
   Petersmann, A
   Pichler, I
   Pietiläinen, KH
   Pouta, A
   Riddertråle, M
   Rotter, JI
   Sambrook, JG
   Sanders, AR
   Schmidt, CO
   Sinisalo, J
   Smit, JH
   Stringham, HM
   Walters, GB
   Widen, E
   Wild, SH
   Willemsen, G
   Zagato, L
   Zgaga, L
   Zitting, P
   Alavere, H
   Farrall, M
   McArdle, WL
   Nelis, M
   Peters, MJ
   Ripatti, S
   Meurs, JBJ
   Aben, KK
   Ardlie, KG
   Beckmann, JS
   Beilby, JP
   Bergman, RN
   Bergmann, S
   Collins, FS
   Cusi, D
   den Heijer, M
   Eiriksdottir, G
   Gejman, PV
   Hall, AS
   Hamsten, A
   Huikuri, HV
   Iribarren, C
   Kähönen, M
   Kaprio, J
   Kathiresan, S
   Kiemeney, L
   Kocher, T
   Launer, LJ
   Lehtimäki, T
   Melander, O
   Mosley, TH
   Musk, AW
   Nieminen, MS
   O'Donnell, CJ
   Ohlsson, C
   Oostra, B
   Palmer, LJ
   Raitakari, O
   Ridker, PM
   Rioux, JD
   Rissanen, A
   Rivolta, C
   Schunkert, H
   Shuldiner, AR
   Siscovick, DS
   Stumvoll, M
   Tönjes, A
   Tuomilehto, J
   van Ommen, GJ
   Viikari, J
   Heath, AC
   Martin, NG
   Montgomery, GW
   Province, MA
   Kayser, M
   Arnold, AM
   Atwood, LD
   Boerwinkle, E
   Chanock, SJ
   Deloukas, P
   Gieger, C
   Grönberg, H
   Hall, P
   Hattersley, AT
   Hengstenberg, C
   Hoffman, W
   Lathrop, GM
   Salomaa, V
   Schreiber, S
   Uda, M
   Waterworth, D
   Wright, AF
   Assimes, TL
   Barroso, I
   Hofman, A
   Mohlke, KL
   Boomsma, DI
   Caulfield, MJ
   Cupples, LA
   Erdmann, J
   Fox, CS
   Gudnason, V
   Gyllensten, U
   Harris, TB
   Hayes, RB
   Jarvelin, MR
   Mooser, V
   Munroe, PB
   Ouwehand, WH
   Penninx, BW
   Pramstaller, PP
   Quertermous, T
   Rudan, I
   Samani, NJ
   Spector, TD
   Völzke, H
   Watkins, H
   Wilson, JF
   Groop, LC
   Haritunians, T
   Hu, FB
   Kaplan, RC
   Metspalu, A
   North, KE
   Schlessinger, D
   Wareham, NJ
   Hunter, DJ
   O'Connell, JR
   Strachan, DP
   Schadt, HE
   Thorsteinsdottir, U
   Peltonen, L
   Uitterlinden, AG
   Visscher, PM
   Chatterjee, N
   Loos, RJF
   Boehnke, M
   McCarthy, MI
   Ingelsson, E
   Lindgren, CM
   Abecasis, GR
   Stefansson, K
   Frayling, TM
   Hirschhorn, JN
AF Allen, Hana Lango
   Estrada, Karol
   Lettre, Guillaume
   Berndt, Sonja I.
   Weedon, Michael N.
   Rivadeneira, Fernando
   Willer, Cristen J.
   Jackson, Anne U.
   Vedantam, Sailaja
   Raychaudhuri, Soumya
   Ferreira, Teresa
   Wood, Andrew R.
   Weyant, Robert J.
   Segre, Ayellet V.
   Speliotes, Elizabeth K.
   Wheeler, Eleanor
   Soranzo, Nicole
   Park, Ju-Hyun
   Yang, Jian
   Gudbjartsson, Daniel
   Heard-Costa, Nancy L.
   Randall, Joshua C.
   Qi, Lu
   Smith, Albert Vernon
   Maegi, Reedik
   Pastinen, Tomi
   Liang, Liming
   Heid, Iris M.
   Luan, Jian'an
   Thorleifsson, Gudmar
   Winkler, Thomas W.
   Goddard, Michael E.
   Lo, Ken Sin
   Palmer, Cameron
   Workalemahu, Tsegaselassie
   Aulchenko, Yurii S.
   Johansson, Asa
   Zillikens, M. Carola
   Feitosa, Mary F.
   Esko, Tonu
   Johnson, Toby
   Ketkar, Shamika
   Kraft, Peter
   Mangino, Massimo
   Prokopenko, Inga
   Absher, Devin
   Albrecht, Eva
   Ernst, Florian
   Glazer, Nicole L.
   Hayward, Caroline
   Hottenga, Jouke-Jan
   Jacobs, Kevin B.
   Knowles, Joshua W.
   Kutalik, Zoltan
   Monda, Keri L.
   Polasek, Ozren
   Preuss, Michael
   Rayner, Nigel W.
   Robertson, Neil R.
   Steinthorsdottir, Valgerdur
   Tyrer, Jonathan P.
   Voight, Benjamin F.
   Wiklund, Fredrik
   Xu, Jianfeng
   Zhao, Jing Hua
   Nyholt, Dale R.
   Pellikka, Niina
   Perola, Markus
   Perry, John R. B.
   Surakka, Ida
   Tammesoo, Mari-Liis
   Altmaier, Elizabeth L.
   Amin, Najaf
   Aspelund, Thor
   Bhangale, Tushar
   Boucher, Gabrielle
   Chasman, Daniel I.
   Chen, Constance
   Coin, Lachlan
   Cooper, Matthew N.
   Dixon, Anna L.
   Gibson, Quince
   Grundberg, Elin
   Hao, Ke
   Junttila, M. Juhani
   Kaplan, Lee M.
   Kettunen, Johannes
   Koenig, Inke R.
   Kwan, Tony
   Lawrence, Robert W.
   Levinson, Douglas F.
   Lorentzon, Mattias
   McKnight, Barbara
   Morris, Andrew P.
   Mueller, Martina
   Ngwa, Julius Suh
   Purcell, Shaun
   Rafelt, Suzanne
   Salem, Rany M.
   Salvi, Erika
   Sanna, Serena
   Shi, Jianxin
   Sovio, Ulla
   Thompson, John R.
   Turchin, Michael C.
   Vandenput, Liesbeth
   Verlaan, Dominique J.
   Vitart, Veronique
   White, Charles C.
   Ziegler, Andreas
   Almgren, Peter
   Balmforth, Anthony J.
   Campbell, Harry
   Citterio, Lorena
   De Grandi, Alessandro
   Dominiczak, Anna
   Duan, Jubao
   Elliott, Paul
   Elosua, Roberto
   Eriksson, Johan G.
   Freimer, Nelson B.
   Geus, Eco J. C.
   Glorioso, Nicola
   Haiqing, Shen
   Hartikainen, Anna-Liisa
   Havulinna, Aki S.
   Hicks, Andrew A.
   Hui, Jennie
   Igl, Wilmar
   Illig, Thomas
   Jula, Antti
   Kajantie, Eero
   Kilpelaeinen, Tuomas O.
   Koiranen, Markku
   Kolcic, Ivana
   Koskinen, Seppo
   Kovacs, Peter
   Laitinen, Jaana
   Liu, Jianjun
   Lokki, Marja-Liisa
   Marusic, Ana
   Maschio, Andrea
   Meitinger, Thomas
   Mulas, Antonella
   Pare, Guillaume
   Parker, Alex N.
   Peden, John F.
   Petersmann, Astrid
   Pichler, Irene
   Pietilainen, Kirsi H.
   Pouta, Anneli
   Riddertrale, Martin
   Rotter, Jerome I.
   Sambrook, Jennifer G.
   Sanders, Alan R.
   Schmidt, Carsten Oliver
   Sinisalo, Juha
   Smit, Jan H.
   Stringham, Heather M.
   Walters, G. Bragi
   Widen, Elisabeth
   Wild, Sarah H.
   Willemsen, Gonneke
   Zagato, Laura
   Zgaga, Lina
   Zitting, Paavo
   Alavere, Helene
   Farrall, Martin
   McArdle, Wendy L.
   Nelis, Mari
   Peters, Marjolein J.
   Ripatti, Samuli
   vVan Meurs, Joyce B. J.
   Aben, Katja K.
   Ardlie, Kristin G.
   Beckmann, Jacques S.
   Beilby, John P.
   Bergman, Richard N.
   Bergmann, Sven
   Collins, Francis S.
   Cusi, Daniele
   den Heijer, Martin
   Eiriksdottir, Gudny
   Gejman, Pablo V.
   Hall, Alistair S.
   Hamsten, Anders
   Huikuri, Heikki V.
   Iribarren, Carlos
   Kahonen, Mika
   Kaprio, Jaakko
   Kathiresan, Sekar
   Kiemeney, Lambertus
   Kocher, Thomas
   Launer, Lenore J.
   Lehtimaki, Terho
   Melander, Olle
   Mosley, Tom H., Jr.
   Musk, Arthur W.
   Nieminen, Markku S.
   O'Donnell, Christopher J.
   Ohlsson, Claes
   Oostra, Ben
   Palmer, Lyle J.
   Raitakari, Olli
   Ridker, Paul M.
   Rioux, John D.
   Rissanen, Aila
   Rivolta, Carlo
   Schunkert, Heribert
   Shuldiner, Alan R.
   Siscovick, David S.
   Stumvoll, Michael
   Toenjes, Anke
   Tuomilehto, Jaakko
   van Ommen, Gert-Jan
   Viikari, Jorma
   Heath, Andrew C.
   Martin, Nicholas G.
   Montgomery, Grant W.
   Province, Michael A.
   Kayser, Manfred
   Arnold, Alice M.
   Atwood, Larry D.
   Boerwinkle, Eric
   Chanock, Stephen J.
   Deloukas, Panos
   Gieger, Christian
   Gronberg, Henrik
   Hall, Per
   Hattersley, Andrew T.
   Hengstenberg, Christian
   Hoffman, Wolfgang
   Lathrop, G. Mark
   Salomaa, Veikko
   Schreiber, Stefan
   Uda, Manuela
   Waterworth, Dawn
   Wright, Alan F.
   Assimes, Themistocles L.
   Barroso, Ines
   Hofman, Albert
   Mohlke, Karen L.
   Boomsma, Dorret I.
   Caulfield, Mark J.
   Cupples, L. Adrienne
   Erdmann, Jeanette
   Fox, Caroline S.
   Gudnason, Vilmundur
   Gyllensten, Ulf
   Harris, Tamara B.
   Hayes, Richard B.
   Jarvelin, Marjo-Ritta
   Mooser, Vincent
   Munroe, Patricia B.
   Ouwehand, Willem H.
   Penninx, Brenda W.
   Pramstaller, Peter P.
   Quertermous, Thomas
   Rudan, Igor
   Samani, Nilesh J.
   Spector, Timothy D.
   Voelzke, Henry
   Watkins, Hugh
   Wilson, James F.
   Groop, Leif C.
   Haritunians, Talin
   Hu, Frank B.
   Kaplan, Robert C.
   Metspalu, Andres
   North, Kari E.
   Schlessinger, David
   Wareham, Nicholas J.
   Hunter, David J.
   O'Connell, Jeffrey R.
   Strachan, David P.
   Schadt, H. -Erich
   Thorsteinsdottir, Unnur
   Peltonen, Leena
   Uitterlinden, Andre G.
   Visscher, Peter M.
   Chatterjee, Nilanjan
   Loos, Ruth J. F.
   Boehnke, Michael
   McCarthy, Mark I.
   Ingelsson, Erik
   Lindgren, Cecilia M.
   Abecasis, Goncalo R.
   Stefansson, Kari
   Frayling, Timothy M.
   Hirschhorn, Joel N.
TI Hundreds of variants clustered in genomic loci and biological pathways affect human height
SO NATURE
LA English
DT Article
ID wide association; common variants; heritability; adult
AB Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
C1 [Allen, Hana Lango; Weedon, Michael N.; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
   [Estrada, Karol; Rivadeneira, Fernando; Aulchenko, Yurii S.; Amin, Najaf; vVan Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
   [Estrada, Karol; Rivadeneira, Fernando; Zillikens, M. Carola; Peters, Marjolein J.; vVan Meurs, Joyce B. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [Estrada, Karol; Rivadeneira, Fernando; Aulchenko, Yurii S.; Peters, Marjolein J.; vVan Meurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre G.] NCHA, NGI, NL-42300 RC Leiden, Netherlands.
   [Lettre, Guillaume; Lo, Ken Sin; Boucher, Gabrielle; Rioux, John D.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
   [Lettre, Guillaume; Rioux, John D.] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.
   [Berndt, Sonja I.; Park, Ju-Hyun; Shi, Jianxin; Chatterjee, Nilanjan] Natl Canc Inst, Natl Inst Hlth, Divis Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Willer, Cristen J.; Jackson, Anne U.; Weyant, Robert J.; Stringham, Heather M.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Vedantam, Sailaja; Palmer, Cameron; Altmaier, Elizabeth L.; Salem, Rany M.; Turchin, Michael C.] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA.
   [Vedantam, Sailaja; Palmer, Cameron; Altmaier, Elizabeth L.; Salem, Rany M.; Turchin, Michael C.] Childrens Hosp, Program Gen, Boston, MA 02115 USA.
   [Vedantam, Sailaja; Palmer, Cameron; Altmaier, Elizabeth L.; Salem, Rany M.; Turchin, Michael C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Raychaudhuri, Soumya; Segre, Ayellet V.; Voight, Benjamin F.; Ardlie, Kristin G.; Kathiresan, Sekar] MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Raychaudhuri, Soumya; Segre, Ayellet V.; Voight, Benjamin F.; Ardlie, Kristin G.; Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
   [Ferreira, Teresa; Randall, Joshua C.; Maegi, Reedik; Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Morris, Andrew P.; Peden, John F.; Farrall, Martin; Watkins, Hugh; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Segre, Ayellet V.; Voight, Benjamin F.; Purcell, Shaun; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Segre, Ayellet V.; Voight, Benjamin F.] Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA.
   [Speliotes, Elizabeth K.; Kaplan, Lee M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
   [Wheeler, Eleanor; Soranzo, Nicole; Grundberg, Elin; Chanock, Stephen J.; Deloukas, Panos; Barroso, Ines; Ouwehand, Willem H.; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Soranzo, Nicole; Mangino, Massimo; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Yang, Jian; Visscher, Peter M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Queensland 4006, Australia.
   [Gudbjartsson, Daniel; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Heard-Costa, Nancy L.; Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Qi, Lu; Workalemahu, Tsegaselassie; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Qi, Lu; Pietilainen, Kirsi H.; Kaprio, Jaakko; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA 02115 USA.
   [Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
   [Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
   [Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland.
   [Pastinen, Tomi; Grundberg, Elin; Kwan, Tony; Verlaan, Dominique J.] McGill Univ, Montreal, PQ H3A 1A4, Canada.
   [Pastinen, Tomi; Grundberg, Elin; Kwan, Tony; Verlaan, Dominique J.] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada.
   [Pastinen, Tomi; Grundberg, Elin; Kwan, Tony; Verlaan, Dominique J.] McGill Univ, Ctr Hlth, Dept Human Genet, Montreal, PQ H3G 1A4, Canada.
   [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA.
   [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA.
   [Heid, Iris M.; Winkler, Thomas W.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
   [Heid, Iris M.; Albrecht, Eva; Mueller, Martina; Illig, Thomas; Gieger, Christian; Schadt, H. -Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany.
   [Luan, Jian'an; Zhao, Jing Hua; Kilpelaeinen, Tuomas O.; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Met Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
   [Goddard, Michael E.] Univ Melbourne, Fac Land & Environm, Parkville, Vic 3010, Australia.
   [Goddard, Michael E.] Dept Primary Ind, Bundoora, Vic 3086, Australia.
   [Johansson, Asa; Igl, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden.
   [Johansson, Asa] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, Fac Med, N-7489 Trondheim, Norway.
   [Feitosa, Mary F.; Ketkar, Shamika; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Esko, Tonu; Tammesoo, Mari-Liis; Alavere, Helene; Nelis, Mari] Univ Tartu, Estonian Genome Ctr, EE-50410 Tartu, Estonia.
   [Esko, Tonu; Nelis, Mari; Metspalu, Andres] Estonian Bioctr, EE-51010 Tartu, Estonia.
   [Esko, Tonu; Nelis, Mari; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
   [Johnson, Toby; Kutalik, Zoltan; Beckmann, Jacques S.; Bergmann, Sven; Rivolta, Carlo] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Johnson, Toby; Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Johnson, Toby] Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.
   [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Univ London, William Harvey Res Inst, Barts & London Genome Ctr, Barts & London Sch Med & Dent, London EC1M6BQ, England.
   [Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Prokopenko, Inga; Rayner, Nigel W.; Robertson, Neil R.; Lindgren, Cecilia M.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [Absher, Devin] Hudson Alpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, D-17487 Greifswald, Germany.
   [Glazer, Nicole L.; Wiklund, Fredrik] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Glazer, Nicole L.; Wiklund, Fredrik] Univ Washington, Dept Med, Seattle, WA 98101 USA.
   [Hayward, Caroline; Xu, Jianfeng; Vitart, Veronique; Wright, Alan F.; Rudan, Igor] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Hottenga, Jouke-Jan; Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
   [Jacobs, Kevin B.] NCI Frederick, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Knowles, Joshua W.; Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA.
   [Polasek, Ozren; Kolcic, Ivana; Zgaga, Lina] Univ Zagreb, Andrija Stampar Sch Publ Hlth, Sch Med, Zagreb 10000, Croatia.
   [Polasek, Ozren] Gen Info Ltd, Zagreb 10000, Croatia.
   [Preuss, Michael; Koenig, Inke R.] Univ Lubeck, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
   [Tyrer, Jonathan P.] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
   [Gronberg, Henrik; Hall, Per; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostatist, S-17177 Stockholm, Sweden.
   [Shuldiner, Alan R.] Wake Forest Univ, Ctr Human Genome, Winston Salem, NC 27157 USA.
   [Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Queensland 4006, Australia.
   [Pellikka, Niina; Perola, Markus; Surakka, Ida; Kettunen, Johannes; Widen, Elisabeth; Ripatti, Samuli; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00014, Finland.
   [Pellikka, Niina; Perola, Markus; Surakka, Ida; Kettunen, Johannes; Ripatti, Samuli; Peltonen, Leena] Natl Inst Hlth & Welfare, Dept Chron Dis Prevent, Unit Publ Hlth Gen, FIN-00014 Helsinki, Finland.
   [Bhangale, Tushar] Univ Washington, Dept Gen Sci, Seattle, WA 98195 USA.
   [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
   [Chasman, Daniel I.; Kaplan, Lee M.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Chen, Constance] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
   [Coin, Lachlan; Sovio, Ulla; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London W2 1PG, England.
   [Cooper, Matthew N.; Lawrence, Robert W.; Hui, Jennie; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostatist, Crawley, WA 6009, Australia.
   [Dixon, Anna L.] Univ Bath, Bath BA1 1RL, Avon, England.
   [Dixon, Anna L.] Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England.
   [Gibson, Quince; Haiqing, Shen; Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
   [Hao, Ke] Rosetta Inpharmat Wholly Owned Subsidiary Merck&C, Dept Genet, Seattle, WA 98109 USA.
   [Junttila, M. Juhani; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Oulu 90014, Finland.
   [Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA.
   [Levinson, Douglas F.] Stanford Univ, Sch ofMedicine, Stanford, CA 93405 USA.
   [Lorentzon, Mattias; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Inst Med, Dept Internal Med, Sahlgrenska Acad, S-41345 Gothenburg, Sweden.
   [McKnight, Barbara; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Mueller, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, D-81377 Munich, Germany.
   [Mueller, Martina; Schadt, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany.
   [Ngwa, Julius Suh; White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Purcell, Shaun; Schreiber, Stefan; Peltonen, Leena] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Purcell, Shaun; Peltonen, Leena] MIT, Cambridge, MA 02142 USA.
   [Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
   [Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
   [Salvi, Erika; Cusi, Daniele] Univ Milan, Dept Med Surg & Dent, I-20139 Milan, Italy.
   [Salvi, Erika] KOS Genet Srl, I-20123 Milan, Italy.
   [Sanna, Serena; Maschio, Andrea; Mulas, Antonella; Uda, Manuela] Ist Neurogenet & Neurofarmacol CNR, I-09042 Cagliari, Italy.
   [Thompson, John R.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
   [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
   [Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
   [Almgren, Peter; Groop, Leif C.] Lund Univ, Ctr Diabet, Dept Clin Sci, S-20502 Malmo, Sweden.
   [Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England.
   [Campbell, Harry; Wild, Sarah H.; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Citterio, Lorena; Zagato, Laura] Univ Vita Salute San Raffaele, Div Nephrol & Dialysis, I-20132 Milan, Italy.
   [De Grandi, Alessandro; Dominiczak, Anna; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, I-39100 Bolzano, Italy.
   [De Grandi, Alessandro; Dominiczak, Anna; Hicks, Andrew A.; Pichler, Irene; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
   [Strachan, David P.] Univ Glasgow, British Heart Fdn Glasgow Cardiovascular Res Ct, Glasgow G12 8TA, Lanark, Scotland.
   [Duan, Jubao; Sanders, Alan R.; Gejman, Pablo V.] Northshore Univ Healthsyst, Evanston, IL 60201 USA.
   [Elosua, Roberto; Eriksson, Johan G.] Inst Municipal Invest Medica & CIBER Epidemiol &, Barcelona, Spain.
   Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland.
   [Eriksson, Johan G.; Kajantie, Eero] Natl Inst Hlth & Welf, Helsinki 00271, Finland.
   [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki 00280, Finland.
   [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki 00250, Finland.
   [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa 65130, Finland.
   [Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
   [Glorioso, Nicola] Univ Sassari, Hypertens & Cardiovasc Prevent Ctr, I-07100 Sassari, Italy.
   [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu 90014, Finland.
   [Havulinna, Aki S.; Koskinen, Seppo; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki 00014, Finland.
   [Hui, Jennie; Beilby, John P.] QEII Med Ctr, PathW Lab Western Australia, Dept Mol Genet, Nedlands, WA 6009, Australia.
   [Hui, Jennie; Beilby, John P.; Musk, Arthur W.; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn Inc, Nedlands, WA, Australia.
   [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku 20720, Finland.
   [Koiranen, Markku; Jarvelin, Marjo-Ritta] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland.
   [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, D-04103 Leipzig, Germany.
   [Laitinen, Jaana] Finnish Inst Occupat Hlth, Oulu 90220, Finland.
   [Liu, Jianjun] Genome Inst Singapore, Singapore 138672, Singapore.
   [Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki 00014, Finland.
   [Marusic, Ana; Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split 21000, Croatia.
   [Meitinger, Thomas] Klinikum Rechts Isar Techn Univ Mu nchen, Inst Human Genet, D-81675 Munich, Germany.
   [Meitinger, Thomas] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada.
   [Parker, Alex N.] Amgen Inc, Cambridge, MA 02139 USA.
   [Peden, John F.; Farrall, Martin; Watkins, Hugh; Procardis Consortium] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England.
   [Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem, D-17475 Greifswald, Germany.
   [Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Lab Med, D-17475 Greifswald, Germany.
   [Pietilainen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland.
   [Pietilainen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res unit, Helsinki, Finland.
   [Pouta, Anneli; Jarvelin, Marjo-Ritta] Natl Inst Hlth & Welf, Oulu 90101, Finland.
   [Riddertrale, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, S-20502 Maimo, Sweden.
   [Sambrook, Jennifer G.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 OPT, England.
   [Sambrook, Jennifer G.; Ouwehand, Willem H.] Cambridge Ctr, Cambridge CB2 0PT, England.
   [Schmidt, Carsten Oliver; Hoffman, Wolfgang; Voelzke, Henry] Inst Community Med, D-17489 Greifswald, Germany.
   [Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki 00029, Finland.
   [Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiatry EMGO Inst, NL-1081 BT Amsterdam, Netherlands.
   [Zitting, Paavo] Lapland Cent Hosp, Dept Physiat, Rovaniemi 96101, Finland.
   [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [McArdle, Wendy L.] Univ Bristol, Dept Social Med, ALSPAC, Bristol BS8 2BN, Avon, England.
   [Aben, Katja K.; Kiemeney, Lambertus] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands.
   [Beckmann, Jacques S.] CHU Vaudois, Univ Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
   [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Phys & Biophys, Los Angeles, CA 90033 USA.
   [Collins, Francis S.] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20892 USA.
   [den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands.
   [Hamsten, Anders] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Atherosclerosis Res Unit, S-17176 Solna, Sweden.
   [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
   [Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
   [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Tampere 33520, Finland.
   [Kahonen, Mika] Tampere Univ Hosp, Tampere 33520, Finland.
   [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Unit Child & Adolescent Mental Hlth, Helsinki 00271, Finland.
   [Kathiresan, Sekar; McCarthy, Mark I.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Kathiresan, Sekar; McCarthy, Mark I.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   [Kathiresan, Sekar; O'Donnell, Christopher J.] Boston Univ, Framingham, MA 01702 USA.
   [Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
   [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Kiemeney, Lambertus] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostatist & HTA, NL-6500 HB Nijmegen, Netherlands.
   [Kiemeney, Lambertus] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands.
   [Kocher, Thomas] Zentrum Zahn Mund & Kieferheilkunde, D-17489 Greifswald, Germany.
   [Launer, Lenore J.; Harris, Tamara B.] Natl Inst Hlth, NIA, Lab Epidemiol Demog, Bethesda, MD 20892 USA.
   [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Tampere 33520, Finland.
   [Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Tampere 33520, Finland.
   [Mosley, Tom H., Jr.] Univ Mississippi, Div Geriatr, Med Ctr, Dept Med, Jackson, MS 39216 USA.
   [Musk, Arthur W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
   [O'Donnell, Christopher J.] Natl Inst Hlth, Nat Lung & Blood Inst, Framingham, MA 01702 USA.
   [Oostra, Ben] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands.
   [Raitakari, Olli] Turku Univ, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland.
   [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, Turku 20520, Finland.
   [Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, D-23562 Lubeck, Germany.
   [Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
   [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
   [Stumvoll, Michael] Univ Leipzig, LIFE Study Ctr, Leipzig, Germany.
   [Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, D-04103 Leipzig, Germany.
   [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.
   [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands.
   [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, NL-2333 ZC Leiden, Netherlands.
   [Viikari, Jorma] Univ Turku, Dept Med, Turku 20520, Finland.
   [Viikari, Jorma] Turku Univ Hosp, Turku 20520, Finland.
   [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat & Midwest, Res Inst Alcoholism, St Louis, MO 63108 USA.
   [Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Province, Michael A.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
   [Kayser, Manfred] Erasmus MC, Dept Forens Mol Biol, NL-3015 GE Rotterdam, Netherlands.
   [Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98115 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Div Epidemiol, Houston, TX 77030 USA.
   [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
   [Hengstenberg, Christian] Univ Regensburg, Med Ctr, Innere Med 2, D-93053 Regensburg, Germany.
   [Lathrop, G. Mark] Ctr Natl Genotypage, F-91057 Paris, France.
   [Schreiber, Stefan] Univ Kiel, Univ Hosp Schleswig Holstein, Clin Mol Biol, D-24105 Kiel, Germany.
   [Schreiber, Stefan] Dept Internal Med 1, D-24105 Kiel, Germany.
   [Waterworth, Dawn; Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA 19406 USA.
   [Barroso, Ines] Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 OQQ, England.
   [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA 01702 USA.
   [Hayes, Richard B.] NYU, Med Ctr, New York, NY 10016 USA.
   [Jarvelin, Marjo-Ritta] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland.
   [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, NL-2300 RC Leiden, Netherlands.
   [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands.
   [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
   [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA.
   [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
   [Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London SW17 0RE, England.
   [Schadt, H. -Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
   [Eriksson, Johan G.] Pacific Biosci, Menlo Pk, CA 94025 USA.
   Sage Bionetworks, Seattle, WA 98109 USA.
   [Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki 00014, Finland.
   [McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England.
   [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 University of Plymouth; University of Exeter; Erasmus University Rotterdam; Erasmus University Rotterdam - Excl Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Universite de Montreal; Universite de Montreal; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Michigan System; University of Michigan; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Oxford; Wellcome Centre for Human Genetics; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Wellcome Trust Sanger Institute; University of London; King's College London; QIMR Berghofer Medical Research Institute; Decode Genetics; Boston University; Harvard University; Harvard T.H. 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Chan School of Public Health; University of Oxford; Universitat Greifswald; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Edinburgh; Vrije Universiteit Amsterdam; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Stanford University; University of North Carolina; University of North Carolina Chapel Hill; University of Zagreb; University of Lubeck; University of Cambridge; Karolinska Institutet; Wake Forest University; QIMR Berghofer Medical Research Institute; University of Helsinki; Finland National Institute for Health & Welfare; University of Washington; University of Washington Seattle; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard T.H. Chan School of Public Health; Imperial College London; University of Western Australia; University of Bath; Royal National Hospital for Rheumatic Diseases (RNHRD); University System of Maryland; University of Maryland Baltimore; Merck & Company; University of Oulu; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Stanford University; University of Gothenburg; University of Washington; University of Washington Seattle; University of Munich; University of Munich; Boston University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University of Milan; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University of Leicester; University of Lubeck; Lund University; University of Leeds; University of Edinburgh; Vita-Salute San Raffaele University; European Academy of Bozen-Bolzano; University of Lubeck; University of Glasgow; NorthShore University Health System; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; University of Helsinki; Finland National Institute for Health & Welfare; University of Helsinki; Helsinki University Central Hospital; Folkhalsan Research Center; Vaasa Central Hospital; University of California System; University of California Los Angeles; University of Sassari; University of Oulu; Finland National Institute for Health & Welfare; Queen Elizabeth II Medical Centre; University of Western Australia; University of Western Australia; Sir Charles Gairdner Hospital; Finland National Institute for Health & Welfare; University of Oulu; Leipzig University; Finnish Institute of Occupational Health; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of Helsinki; University of Split; Technical University of Munich; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; McMaster University; Amgen; University of Oxford; Universitat Greifswald; Universitat Greifswald; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; Finland National Institute for Health & Welfare; Lund University; University of Cambridge; University of Helsinki; Helsinki University Central Hospital; Vrije Universiteit Amsterdam; University of Oxford; Wellcome Centre for Human Genetics; University of Bristol; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Western Australia; University of Southern California; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Radboud University Nijmegen; Karolinska Institutet; Karolinska University Hospital; Kaiser Permanente; University of California System; University of California San Francisco; Tampere University; Tampere University; Tampere University Hospital; Finland National Institute for Health & Welfare; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Boston University; Framingham Heart Study; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Harvard University; Harvard Medical School; Radboud University Nijmegen; Radboud University Nijmegen; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Tampere University; Tampere University; Tampere University Hospital; University of Mississippi Medical Center; University of Mississippi; University of Western Australia; National Institutes of Health (NIH) - USA; Erasmus University Rotterdam; Erasmus MC; University of Turku; University of Turku; University of Lubeck; Geriatric Research Education & Clinical Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Leipzig University; Leipzig University; Leipzig University; Finland National Institute for Health & Welfare; University of Helsinki; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Turku; University of Turku; Washington University (WUSTL); QIMR Berghofer Medical Research Institute; QIMR Berghofer Medical Research Institute; Washington University (WUSTL); Erasmus University Rotterdam; Erasmus MC; University of Texas System; University of Texas Health Science Center Houston; University of Texas System; University of Texas Health Science Center Houston; University of Texas System; University of Texas Health Science Center Houston; University of Regensburg; University of Regensburg; CEA; University of Kiel; Schleswig Holstein University Hospital; GlaxoSmithKline; Glaxosmithkline USA; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); New York University; University of Oulu; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Groningen; Krankenhaus Bozen; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); City St Georges, University of London; University of Munich; University of Iceland; University of Helsinki; University of Oxford; Harvard University; Harvard Medical School
RP Allen, HL (corresponding author), Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
FU Academy of Finland [104781, 117797, 120315, 121584, 126925, 129269, 129494, 129680, 213506]; Affymetrix for genotyping services [N02-HL-6-4278]; Agency for Science, Technology and Research of Singapore; ALF/LUA Gothenburg; Althingi (the Icelandic Parliament); Amgen; AstraZeneca AB; Australian National Health and Medical Research Council [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672]; Australian Research Council [DP0770096]; Biocentrum Helsinki; Boston Obesity Nutrition Research Center [DK46200]; British Diabetes Association; British Heart Foundation [PG/02/128]; British Heart Foundation Centre for Research Excellence, Oxford; CamStrad; Cancer Research UK; Centre for Neurogenomics and Cognitive Research; Chief Scientist Office of the Scottish Government [CZB/4/279]; Council of Health of the Academy of Finland; German Network of Diabetes; Diabetes UK; Donald W. Reynolds Foundation; Emil and Vera Cornell Foundation; Erasmus MC; Estonian Government [SF0180142s08]; European Commission [201413, ECOGENE:205419, BBMRI:212111, OPENGENE:245536, ENGAGE:HEALTH-F4-2007-201413, EURODIA:LSHG-CT-2004-518153, EU/WLRT-2001-01254, HEALTH-F2-2008-ENGAGE, HEALTH-F4-2007-201550, LSH-2006-037593, LSHG-CT-2006-018947, LSHG-CT-2006-01947, Procardis:LSHM-CT-2007-037273, POLYGENE:LSHC-CT-2005, QLG1-CT-2000-01643, QLG2-CT-2002-01254]; Eve Appeal; Finnish Ministry of Education; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Medical Society; Finska Lakaresallskapet; Folkhalsan Research Foundation; Fondation LeDucq; Foundation for Life and Health in Finland; Foundation for Strategic Research; GEN-AU; Genetic Association Information Network; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; German Federal Ministry of Education and Research [01GS0831]; German Ministry for Health, Welfare and Sports; German Ministry of Cultural Affairs; German Ministry of Education, Culture and Science; German National Genome Research Net [01GS0823, 01ZZ0103, 01ZZ0403, 01ZZ9603, 03ZIK012]; German Research Council [KFO-152]; GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Helmholtz Center Munich; Juvenile Diabetes Research Foundation International [U01 DK062418]; Karolinska Institute; Knut and Alice Wallenberg Foundation; Lundberg Foundation; March of Dimes [6-FY-09-507]; MC Health; Medical Research Council UK [G0000649, G0000934, G0500539, G0600331, G0601261, G9521010D]; Microarray Core Facility of the Interdisciplinary Centre for Clinical Research [B27]; Mid-Atlantic Nutrition and Obesity Research Center of Maryland [P30 DK072488]; Ministry of Health and Department of Educational Assistance (South Tyrol, Italy); Ministry of Science, Education and Sport of the Republic of Croatia [216-1080315-0302]; Montreal Heart Institute Foundation; Narpes Health Care Foundation; National Cancer Institute; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre; National Institute for Health Research Comprehensive Biomedical Research Centre; National Institutes of Health [263-MA-410953, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, CA047988, CA49449, CA50385, CA65725, CA67262, CA87969, DA12854, DK062370, DK063491, DK072193, DK079466, DK080145, DK58845, HG002651, HG005214, HG005581, HL043851, HL084729, HL69757, HL71981, K08-AR055688]; ADA; Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]; Netherlands Organisation for Scientific Research [175.010.2005.011, 911-03-012]; Netherlands Organization for the Health Research and Development [10-000-1002]; Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419]; NIA; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Queensland Institute of Medical Research; Radboud University Nijmegen Medical Centre; Research Institute for Diseases in the Elderly [014-93-015]; Royal Swedish Academy of Science; Sahlgrenska Center for Cardiovascular and Metabolic Research [A305:188]; Siemens Healthcare, Erlangen, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; Social Ministry of the Federal State of Mecklenburg-West Pomerania; South Tyrolean Sparkasse Foundation; Stockholm County Council; Support for Science Funding programme; Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council; Swedish National Cancer Institute; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation; Torsten and Ragnar Soderberg's Foundation; Vandervell Foundation; Vastra Gotaland Foundation; Wellcome Trust [072960, 075491, 079557, 079895, 083270, 068545/Z/02, 076113/B/04/Z, 076113/C/04/Z, 077016/Z/05/Z, 081682/Z/06/Z, 084183/Z/07/Z, 085301/Z/08/Z, 086596/Z/08/Z, 091746/Z/10/Z]; Wellcome Trust; Western Australian Genetic Epidemiology Resource; Western Australian DNA Bank;  [560183];  [K2007-66X-20270-01-3];  [8691];  [33CSCO-122661]; MRC [MC_U106188470, G0701863, MC_qA137934, G9521010, G0601261, G0600331, MC_U127561128, G0000934] Funding Source: UKRI; Chief Scientist Office [CZB/4/710] Funding Source: researchfish; Medical Research Council [G9521010, MC_U106179471, MC_U106188470, MC_U127561128, G0600331, G0000934, G0701863, G0601261, MC_qA137934] Funding Source: researchfish; National Heart Lung and Blood Institute [R01HL059367, R01HL086694] Funding Source: NIH RePORTER; National Human Genome Research Institute [T32HG000040, ZIAHG000024] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK075787, R01DK091718, R01DK062370, P30DK046200, R01DK072193, U01DK062370, P30DK063491] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000675, ZIAAG007380] Funding Source: NIH RePORTER
NR 28
TC 1509
Z9 1732
U1 1
U2 298
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 832
EP 838
DI 10.1038/nature09410
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700065
PM 20881960
DA 2026-03-09
ER

PT J
AU Neeley, M
   Bialczak, RC
   Lenander, M
   Lucero, E
   Mariantoni, M
   O'Connell, AD
   Sank, D
   Wang, H
   Weides, M
   Wenner, J
   Yin, Y
   Yamamoto, T
   Cleland, AN
   Martinis, JM
AF Neeley, Matthew
   Bialczak, Radoslaw C.
   Lenander, M.
   Lucero, E.
   Mariantoni, Matteo
   O'Connell, A. D.
   Sank, D.
   Wang, H.
   Weides, M.
   Wenner, J.
   Yin, Y.
   Yamamoto, T.
   Cleland, A. N.
   Martinis, John M.
TI Generation of three-qubit entangled states using superconducting phase qubits
SO NATURE
LA English
DT Article
AB Entanglement is one of the key resources required for quantum computation(1), so the experimental creation and measurement of entangled states is of crucial importance for various physical implementations of quantum computers(2). In superconducting devices(3), two-qubit entangled states have been demonstrated and used to show violations of Bell's inequality(4) and to implement simple quantum algorithms(5). Unlike the two-qubit case, where all maximally entangled two-qubit states are equivalent up to local changes of basis, three qubits can be entangled in two fundamentally different ways(6). These are typified by the states vertical bar GHZ > = (vertical bar 000 > vertical bar 111 >)/root 2 and vertical bar W > = (vertical bar 001 > + vertical bar 010 > + vertical bar 100 >)/root 3. Here we demonstrate the operation of three coupled superconducting phase qubits(7) and use them to create and measure vertical bar GHZ > and vertical bar W > states. The states are fully characterized using quantum state tomography(8) and are shown to satisfy entanglement witnesses(9), confirming that they are indeed examples of three-qubit entanglement and are not separable into mixtures of two-qubit entanglement.
C1 [Neeley, Matthew; Bialczak, Radoslaw C.; Lenander, M.; Lucero, E.; Mariantoni, Matteo; O'Connell, A. D.; Sank, D.; Wang, H.; Weides, M.; Wenner, J.; Yin, Y.; Yamamoto, T.; Cleland, A. N.; Martinis, John M.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Yamamoto, T.] NEC Corp Ltd, Green Innovat Res Labs, Tsukuba, Ibaraki 3058501, Japan.
C3 University of California System; University of California Santa Barbara; NEC Corporation
RP Martinis, JM (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM martinis@physics.ucsb.edu
FU NSF; IARPA [W911NF-04-1-0204]; Elings Fellowship
NR 23
TC 365
Z9 409
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 SEP 15
PY 2010
VL 467
IS 7315
BP 570
EP 573
DI 10.1038/nature09418
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100034
PM 20882012
DA 2026-03-09
ER

PT J
AU Soderberg, AM
   Chakraborti, S
   Pignata, G
   Chevalier, RA
   Chandra, P
   Ray, A
   Wieringa, MH
   Copete, A
   Chaplin, V
   Connaughton, V
   Barthelmy, SD
   Bietenholz, MF
   Chugai, N
   Stritzinger, MD
   Hamuy, M
   Fransson, C
   Fox, O
   Levesque, EM
   Grindlay, JE
   Challis, P
   Foley, RJ
   Kirshner, RP
   Milne, PA
   Torres, MAP
AF Soderberg, A. M.
   Chakraborti, S.
   Pignata, G.
   Chevalier, R. A.
   Chandra, P.
   Ray, A.
   Wieringa, M. H.
   Copete, A.
   Chaplin, V.
   Connaughton, V.
   Barthelmy, S. D.
   Bietenholz, M. F.
   Chugai, N.
   Stritzinger, M. D.
   Hamuy, M.
   Fransson, C.
   Fox, O.
   Levesque, E. M.
   Grindlay, J. E.
   Challis, P.
   Foley, R. J.
   Kirshner, R. P.
   Milne, P. A.
   Torres, M. A. P.
TI A relativistic type Ibc supernova without a detected γ-ray burst
SO NATURE
LA English
DT Article
ID ic supernovae; emission; 1998bw
AB Long duration gamma-ray bursts (GRBs) mark(1) the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered(2) by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested(3) in the pulse of gamma-rays and a long-lived radio afterglow. Until now, central-engine driven supernovae have been discovered exclusively through their gamma-ray emission, yet it is expected(4) that a larger population goes undetected because of limited satellite sensitivity or beaming of the collimated emission away from our line of sight. In this framework, the recovery of undetected GRBs may be possible through radio searches(5,6) for type Ibc supernovae with relativistic outflows. Here we report the discovery of luminous radio emission from the seemingly ordinary type Ibc SN 2009bb, which requires a substantial relativistic outflow powered by a central engine. A comparison with our radio survey of type Ibc supernovae reveals that the fraction harbouring central engines is low, about one per cent, measured independently from, but consistent with, the inferred(7) rate of nearby GRBs. Independently, a second mildly relativistic supernova has been reported(8).
C1 [Soderberg, A. M.; Copete, A.; Levesque, E. M.; Grindlay, J. E.; Challis, P.; Foley, R. J.; Kirshner, R. P.; Torres, M. A. P.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Chakraborti, S.; Ray, A.] Tata Inst Fundamental Res, Mumbai 400005, Maharashtra, India.
   [Pignata, G.; Hamuy, M.] Univ Chile, Dept Astron, Santiago, Chile.
   [Chevalier, R. A.; Fox, O.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Chandra, P.] Royal Mil Coll Canada, Kingston, ON K7K 7B4, Canada.
   [Wieringa, M. H.] CSIRO, Australia Telescope Natl Facil, Epping, NSW 2121, Australia.
   [Chaplin, V.; Connaughton, V.] Univ Alabama, Huntsville, AL 35899 USA.
   [Barthelmy, S. D.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Bietenholz, M. F.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Bietenholz, M. F.] Hartebeestehoek Radio Observ, ZA-1740 Krugersdorp, South Africa.
   [Chugai, N.] RAS, Inst Astron, Moscow 119017, Russia.
   [Stritzinger, M. D.] Carnegie Observ, Las Campanas Observ, La Serena, Chile.
   [Stritzinger, M. D.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
   [Fransson, C.] Stockholm Univ, Dept Astron, SE-10691 Stockholm, Sweden.
   [Levesque, E. M.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Milne, P. A.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
C3 Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University; Tata Institute of Fundamental Research (TIFR); Tata Institute of Fundamental Research (TIFR), Mumbai; Universidad de Chile; University of Virginia; Royal Military College - Canada; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility; University of Alabama System; University of Alabama Huntsville; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; York University - Canada; National Research Foundation - South Africa; Hartebeesthoek Radio Astronomy Observatory; Russian Academy of Sciences; Institute of Astronomy of the Russian Academy of Sciences; Carnegie Institution for Science; University of Copenhagen; Niels Bohr Institute; Stockholm University; University of Hawaii System; University of Arizona
RP Soderberg, AM (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St,MS-51, Cambridge, MA 02138 USA.
EM asoderberg@cfa.harvard.edu
FU NASA; Ford Foundation; NSF; FONDECYT; Iniciativa Cientifica Milenio; FONDAP; CONICYT; 11th Five Year Plan Project; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0907903] Funding Source: National Science Foundation
NR 28
TC 276
Z9 295
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 JAN 28
PY 2010
VL 463
IS 7280
BP 513
EP 515
DI 10.1038/nature08714
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100044
PM 20110995
DA 2026-03-09
ER

PT J
AU McPherron, SP
   Alemseged, Z
   Marean, CW
   Wynn, JG
   Reed, D
   Geraads, D
   Bobe, R
   Béarat, HA
AF McPherron, Shannon P.
   Alemseged, Zeresenay
   Marean, Curtis W.
   Wynn, Jonathan G.
   Reed, Denne
   Geraads, Denis
   Bobe, Rene
   Bearat, Hamdallah A.
TI Evidence for stone-tool-assisted consumption of animal tissues before 3.39 million years ago at Dikika, Ethiopia
SO NATURE
LA English
DT Article
ID hammerstone percussion; hadar formation; bone surfaces; cut marks; hominin; behavior; pleistocene; hypothesis; diagnosis; turkana
AB The oldest direct evidence of stone tool manufacture comes from Gona (Ethiopia) and dates to between 2.6 and 2.5 million years (Myr) ago(1). At the nearby Bouri site several cut-marked bones also show stone tool use approximately 2.5 Myr ago(2). Here we report stone-tool-inflicted marks on bones found during recent survey work in Dikika, Ethiopia, a research area close to Gona and Bouri. On the basis of low-power microscopic and environmental scanning electron microscope observations, these bones show unambiguous stone-tool cut marks for flesh removal and percussion marks for marrow access. The bones derive from the Sidi Hakoma Member of the Hadar Formation. Established (40)Ar-(39)Ar dates on the tuffs that bracket this member constrain the finds to between 3.42 and 3.24 Myr ago, and stratigraphic scaling between these units and other geological evidence indicate that they are older than 3.39 Myr ago. Our discovery extends by approximately 800,000 years the antiquity of stone tools and of stone-tool-assisted consumption of ungulates by hominins; furthermore, this behaviour can now be attributed to Australopithecus afarensis.
C1 [McPherron, Shannon P.] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Alemseged, Zeresenay] Calif Acad Sci, Dept Anthropol, San Francisco, CA 94118 USA.
   [Marean, Curtis W.] Arizona State Univ, Inst Human Origins, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
   [Wynn, Jonathan G.] Univ S Florida, Dept Geol, Tampa, FL 33620 USA.
   [Reed, Denne] Univ Texas Austin, Dept Anthropol, Austin, TX 78712 USA.
   [Geraads, Denis] CNRS, UPR 2147, F-75014 Paris, France.
   [Bobe, Rene] Univ Georgia, Dept Anthropol, Athens, GA 30602 USA.
   [Bearat, Hamdallah A.] Arizona State Univ, Sch Engn Matter Transport & Energy, Ira A Fulton Sch Engn, Tempe, AZ 85287 USA.
C3 Max Planck Society; California Academy of Sciences; Arizona State University; Arizona State University-Tempe; State University System of Florida; University of South Florida; University of Texas System; University of Texas Austin; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University System of Georgia; University of Georgia; Arizona State University; Arizona State University-Tempe
RP McPherron, SP (corresponding author), Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, DeutscherPl 6, D-04103 Leipzig, Germany.
EM mcpherron@eva.mpg.de
FU Authority for Research and Conservation of Cultural Heritage; National Museum of Ethiopia; Ministry of Tourism and Culture; Afar regional government; California Academy of Sciences
NR 30
TC 474
Z9 585
U1 1
U2 140
PU 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 12
PY 2010
VL 466
IS 7308
BP 857
EP 860
DI 10.1038/nature09248
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100034
PM 20703305
DA 2026-03-09
ER

PT J
AU London, M
   Roth, A
   Beeren, L
   Häusser, M
   Latham, PE
AF London, Michael
   Roth, Arnd
   Beeren, Lisa
   Haeusser, Michael
   Latham, Peter E.
TI Sensitivity to perturbations in vivo implies high noise and suggests rate coding in cortex
SO NATURE
LA English
DT Article
ID pyramidal neurons; visual-cortex; networks; precision; model; computation; dendrites; neocortex; patterns; systems
AB It is well known that neural activity exhibits variability, in the sense that identical sensory stimuli produce different responses(1-3), but it has been difficult to determine what this variability means. Is it noise, or does it carry important information-about, for example, the internal state of the organism? Here we address this issue from the bottom up, by asking whether small perturbations to activity in cortical networks are amplified. Based on in vivo whole-cell patch-clamp recordings in rat barrel cortex, we find that a perturbation consisting of a single extra spike in one neuron produces approximately 28 additional spikes in its postsynaptic targets. We also show, using simultaneous intra-and extracellular recordings, that a single spike in a neuron produces a detectable increase in firing rate in the local network. Theoretical analysis indicates that this amplification leads to intrinsic, stimulus-independent variations in membrane potential of the order of +/- 2.2-4.5 mV-variations that are pure noise, and so carry no information at all. Therefore, for the brain to perform reliable computations, it must either use a rate code, or generate very large, fast depolarizing events, such as those proposed by the theory of synfire chains(4,5). However, in our in vivo recordings, we found that such events were very rare. Our findings are thus consistent with the idea that cortex is likely to use primarily a rate code.
C1 [Latham, Peter E.] UCL, Gatsby Computat Neurosci Unit, London WC1N 3AR, England.
   [London, Michael; Roth, Arnd; Beeren, Lisa; Haeusser, Michael] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England.
   [London, Michael; Roth, Arnd; Beeren, Lisa; Haeusser, Michael] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
C3 University of London; University College London; University of London; University College London; University of London; University College London
RP Latham, PE (corresponding author), UCL, Gatsby Computat Neurosci Unit, Queen Sq, London WC1N 3AR, England.
EM pel@gatsby.ucl.ac.uk
FU Gatsby Charitable Foundation; US National Institute of Mental Health [R01 MH62447]; Wellcome Trust; Engineering and Physical Sciences Research Council; Medical Research Council; Engineering and Physical Sciences Research Council [EP/C010841/1] Funding Source: researchfish; Medical Research Council [G0500244] Funding Source: researchfish; MRC [G0500244] Funding Source: UKRI
NR 35
TC 323
Z9 366
U1 2
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 JUL 1
PY 2010
VL 466
IS 7302
BP 123
EP U142
DI 10.1038/nature09086
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800047
PM 20596024
DA 2026-03-09
ER

PT J
AU Bird, JC
   de Ruiter, R
   Courbin, L
   Stone, HA
AF Bird, James C.
   de Ruiter, Rielle
   Courbin, Laurent
   Stone, Howard A.
TI Daughter bubble cascades produced by folding of ruptured thin films
SO NATURE
LA English
DT Article
ID free-surface; air; instability; mechanism; dynamics; fluid; water
AB Thin liquid films, such as soap bubbles, have been studied extensively for over a century because they are easily formed and mediate a wide range of transport processes in physics, chemistry and engineering(1-3). When a bubble on a liquid-gas or solid-gas interface (referred to herein as an interfacial bubble) ruptures, the general expectation is that the bubble vanishes. More precisely, the ruptured thin film is expected to retract rapidly until it becomes part of the interface, an event that typically occurs within milliseconds(4-6). The assumption that ruptured bubbles vanish is central to theories on foam evolution(7) and relevant to health(8) and climate(9) because bubble rupture is a source for aerosol droplets(10,11). Here we show that for a large range of fluid parameters, interfacial bubbles can create numerous small bubbles when they rupture, rather than vanishing. We demonstrate, both experimentally and numerically, that the curved film of the ruptured bubble can fold and entrap air as it retracts. The resulting toroidal geometry of the trapped air is unstable, leading to the creation of a ring of smaller bubbles. The higher pressure associated with the higher curvature of the smaller bubbles increases the absorption of gas into the liquid, and increases the efficiency of rupture-induced aerosol dispersal.
C1 [Bird, James C.; de Ruiter, Rielle; Stone, Howard A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Courbin, Laurent] Univ Rennes 1, CNRS, UMR 6251, Inst Phys Rennes, F-35042 Rennes, France.
   [Stone, Howard A.] Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA.
C3 Harvard University; Universite de Rennes; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Princeton University
RP Bird, JC (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM jbird@fas.harvard.edu; hastone@princeton.edu
FU NSF via the Harvard MRSEC; Direct For Mathematical & Physical Scien; Division Of Materials Research [0820484] Funding Source: National Science Foundation
NR 30
TC 195
Z9 215
U1 2
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 JUN 10
PY 2010
VL 465
IS 7299
BP 759
EP 762
DI 10.1038/nature09069
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800040
PM 20535206
DA 2026-03-09
ER

PT J
AU Niedzwiedzki, G
   Szrek, P
   Narkiewicz, K
   Narkiewicz, M
   Ahlberg, PE
AF Niedzwiedzki, Grzegorz
   Szrek, Piotr
   Narkiewicz, Katarzyna
   Narkiewicz, Marek
   Ahlberg, Per E.
TI Tetrapod trackways from the early Middle Devonian period of Poland
SO NATURE
LA English
DT Article
ID near-tetrapod; pectoral fin; origin; panderichthys; evolution; fossils; fish; jaws
AB The fossil record of the earliest tetrapods (vertebrates with limbs rather than paired fins) consists of body fossils and trackways. The earliest body fossils of tetrapods date to the Late Devonian period (late Frasnian stage) and are preceded by transitional elpistostegids such as Panderichthys and Tiktaalik that still have paired fins. Claims of tetrapod trackways predating these body fossils have remained controversial with regard to both age and the identity of the track makers. Here we present well-preserved and securely dated tetrapod tracks from Polish marine tidal flat sediments of early Middle Devonian (Eifelian stage) age that are approximately 18 million years older than the earliest tetrapod body fossils and 10 million years earlier than the oldest elpistostegids. They force a radical reassessment of the timing, ecology and environmental setting of the fish-tetrapod transition, as well as the completeness of the body fossil record.
C1 [Ahlberg, Per E.] Uppsala Univ, Dept Physiol & Dev Biol, Subdept Evolutionary Organismal Biol, S-75236 Uppsala, Sweden.
   [Niedzwiedzki, Grzegorz] Warsaw Univ, Fac Biol, Dept Paleobiol & Evolut, PL-02097 Warsaw, Poland.
   [Szrek, Piotr] Warsaw Univ, Fac Geol, Dept Paleontol, PL-02089 Warsaw, Poland.
   [Szrek, Piotr; Narkiewicz, Katarzyna; Narkiewicz, Marek] Polish Geol Inst, PL-00975 Warsaw, Poland.
C3 Uppsala University; University of Warsaw; University of Warsaw; Polish Geological Institute - National Research Institute
RP Ahlberg, PE (corresponding author), Uppsala Univ, Dept Physiol & Dev Biol, Subdept Evolutionary Organismal Biol, Norbyvagen 18A, S-75236 Uppsala, Sweden.
EM per.ahlberg@ebc.uu.se
FU Faculty of Biology, Warsaw University; Polish Geological Institute; Swedish Research Council
NR 50
TC 205
Z9 234
U1 3
U2 192
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 43
EP 48
DI 10.1038/nature08623
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900026
PM 20054388
DA 2026-03-09
ER

PT J
AU Grünwald, D
   Singer, RH
AF Grunwald, David
   Singer, Robert H.
TI In vivo imaging of labelled endogenous β-actin mRNA during nucleocytoplasmic transport
SO NATURE
LA English
DT Article
ID nuclear-pore complex; cryoelectron tomography; amphibian oocytes; single-molecule; myosin-v; export; translocation; architecture; envelope; protein
AB Export of messenger RNA occurs via nuclear pores, which are large nanomachines with diameters of roughly 120 nm that are the only link between the nucleus and cytoplasm(1). Hence, mRNA export occurs over distances smaller than the optical resolution of conventional light microscopes. There is extensive knowledge on the physical structure and composition of the nuclear pore complex(2-7), but transport selectivity and the dynamics of mRNA export at nuclear pores remain unknown(8). Here we developed a super-registration approach using fluorescence microscopy that can overcome the current limitations of co-localization by means of measuring intermolecular distances of chromatically different fluorescent molecules with nanometre precision. With this method we achieve 20-ms time-precision and at least 26-nm spatial precision, enabling the capture of highly transient interactions in living cells. Using this approach we were able to spatially resolve the kinetics of mRNA transport in mammalian cells and present a three-step model consisting of docking (80 ms), transport (5-20 ms) and release (80 ms), totalling 180 +/- 10 ms. Notably, the translocation through the channel was not the rate-limiting step, mRNAs can move bi-directionally in the pore complex and not all pores are equally active.
C1 [Grunwald, David; Singer, Robert H.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
   [Grunwald, David; Singer, Robert H.] Gruss Lipper Biophoton Ctr, Bronx, NY 10461 USA.
   [Grunwald, David] Delft Univ Technol, Dept BioNanoSci, Kavli Inst NanoSci, NL-2628 CJ Delft, Netherlands.
C3 Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Delft University of Technology
RP Singer, RH (corresponding author), Albert Einstein Coll Med, Dept Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM Robert.Singer@einstein.yu.edu
FU DFG [3388/1]; NIH [EB2060, GM86217]
NR 31
TC 252
Z9 292
U1 0
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 SEP 15
PY 2010
VL 467
IS 7315
BP 604
EP U128
DI 10.1038/nature09438
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100042
PM 20844488
DA 2026-03-09
ER

PT J
AU Niu, HY
   Chung, WH
   Zhu, Z
   Kwon, Y
   Zhao, WX
   Chi, P
   Prakash, R
   Seong, CH
   Liu, DQ
   Lu, L
   Ira, G
   Sung, P
AF Niu, Hengyao
   Chung, Woo-Hyun
   Zhu, Zhu
   Kwon, Youngho
   Zhao, Weixing
   Chi, Peter
   Prakash, Rohit
   Seong, Changhyun
   Liu, Dongqing
   Lu, Lucy
   Ira, Grzegorz
   Sung, Patrick
TI Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae
SO NATURE
LA English
DT Article
ID replication-protein-a; homologous recombination; break repair; in-vitro; yeast; helicase; mre11; sgs1; recognition; maintenance
AB If not properly processed and repaired, DNA double-strand breaks (DSBs) can give rise to deleterious chromosome rearrangements, which could ultimately lead to the tumour phenotype(1,2). DSB ends are resected in a 5' to 3' fashion in cells, to yield single-stranded DNA (ssDNA) for the recruitment of factors critical for DNA damage checkpoint activation and repair by homologous recombination 2. The resection process involves redundant pathways consisting of nucleases, DNA helicases and associated proteins(3). Being guided by recent genetic studies(4-6), we have reconstituted the first eukaryotic ATP-dependent DNA end-resection machinery comprising the Saccharomyces cerevisiae Mre11-Rad50-Xrs2 (MRX) complex, the Sgs1-Top3-Rmi1 complex, Dna2 protein and the heterotrimeric ssDNA-binding protein RPA. Here we show that DNA strand separation during end resection is mediated by the Sgs1 helicase function, in a manner that is enhanced by Top3-Rmi1 and MRX. In congruence with genetic observations(6), although the Dna2 nuclease activity is critical for resection, the Mre11 nuclease activity is dispensable. By examining the top3 Y356F allele and its encoded protein, we provide evidence that the topoisomerase activity of Top3, although critical for the suppression of crossover recombination(2,7), is not needed for resection either in cells or in the reconstituted system. Our results also unveil a multifaceted role of RPA, in the sequestration of ssDNA generated by DNA unwinding, enhancement of 5' strand incision, and protection of the 3' strand. Our reconstituted system should serve as a useful model for delineating the mechanistic intricacy of the DNA break resection process in eukaryotes.
C1 [Chung, Woo-Hyun; Zhu, Zhu; Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Niu, Hengyao; Kwon, Youngho; Zhao, Weixing; Chi, Peter; Prakash, Rohit; Seong, Changhyun; Liu, Dongqing; Lu, Lucy; Sung, Patrick] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
C3 Baylor College of Medicine; Yale University
RP Ira, G (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA.
EM gira@bcm.edu; patrick.sung@yale.edu
FU US National Institutes of Health; Susan G. Komen for the Cure Foundation; National Cancer Institute [P01CA092584] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [R01ES007061] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM080600] Funding Source: NIH RePORTER
NR 29
TC 313
Z9 384
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 SEP 2
PY 2010
VL 467
IS 7311
BP 108
EP U143
DI 10.1038/nature09318
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200045
PM 20811460
DA 2026-03-09
ER

PT J
AU Elliott, MR
   Zheng, SQ
   Park, D
   Woodson, RI
   Reardon, MA
   Juncadella, IJ
   Kinchen, JM
   Zhang, J
   Lysiak, JJ
   Ravichandran, KS
AF Elliott, Michael R.
   Zheng, Shuqiu
   Park, Daeho
   Woodson, Robin I.
   Reardon, Michael A.
   Juncadella, Ignacio J.
   Kinchen, Jason M.
   Zhang, Jun
   Lysiak, Jeffrey J.
   Ravichandran, Kodi S.
TI Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo
SO NATURE
LA English
DT Article
ID crkii/dock180/rac pathway; scavenger receptor; sertoli-cells; ph domain; phagocytosis; elegans; corpse; ischemia/reperfusion; activation; engulfment
AB Apoptosis and the subsequent clearance of dying cells occurs throughout development and adult life in many tissues. Failure to promptly clear apoptotic cells has been linked to many diseases(1-3). ELMO1 is an evolutionarily conserved cytoplasmic engulfment protein that functions downstream of the phosphatidylserine receptor BAI1, and, along with DOCK1 and the GTPase RAC1, promotes internalization of the dying cells(4-7). Here we report the generation of ELMO1-deficient mice, which we found to be unexpectedly viable and grossly normal. However, they had a striking testicular pathology, with disrupted seminiferous epithelium, multinucleated giant cells, uncleared apoptotic germ cells and decreased sperm output. Subsequent in vitro and in vivo analyses revealed a crucial role for ELMO1 in the phagocytic clearance of apoptotic germ cells by Sertoli cells lining the seminiferous epithelium. The engulfment receptor BAI1 and RAC1 (upstream and downstream of ELMO1, respectively) were also important for Sertoli-cell-mediated engulfment. Collectively, these findings uncover a selective requirement for ELMO1 in Sertoli-cell-mediated removal of apoptotic germ cells and make a compelling case for a relationship between engulfment and tissue homeostasis in vivo.
C1 [Elliott, Michael R.; Park, Daeho; Juncadella, Ignacio J.; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Elliott, Michael R.; Park, Daeho; Juncadella, Ignacio J.; Kinchen, Jason M.; Lysiak, Jeffrey J.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Zheng, Shuqiu; Woodson, Robin I.; Reardon, Michael A.; Zhang, Jun; Lysiak, Jeffrey J.] Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA.
   [Kinchen, Jason M.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
EM jl6n@virginia.edu; ravi@virginia.edu
FU National Institutes of Health; American Cancer Society; National Institute of Allergy and Infectious Diseases [T32AI055432] Funding Source: NIH RePORTER
NR 37
TC 139
Z9 168
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 333
EP U114
DI 10.1038/nature09356
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900040
PM 20844538
DA 2026-03-09
ER

PT J
AU Sotillo, R
   Schvartzman, JM
   Socci, ND
   Benezra, R
AF Sotillo, Rocio
   Schvartzman, Juan-Manuel
   Socci, Nicholas D.
   Benezra, Robert
TI Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal
SO NATURE
LA English
DT Article
ID mitotic checkpoint; clonal evolution; cancer; mice; adenocarcinomas; tumorigenesis; mechanisms; resistance; missegregation; regression
AB Inhibition of an initiating oncogene often leads to extensive tumour cell death, a phenomenon known as oncogene addiction(1). This has led to the search for compounds that specifically target and inhibit oncogenes as anticancer agents. However, there has been no systematic exploration of whether chromosomal instability generated as a result of deregulation of the mitotic checkpoint pathway(2,3), a frequent characteristic of solid tumours, has any effect on oncogene addiction. Here we show that induction of chromosome instability by overexpression of the mitotic checkpoint gene Mad2 in mice does not affect the regression of Kras-driven lung tumours when Kras is inhibited. However, tumours that experience transient Mad2 overexpression and consequent chromosome instability recur at markedly elevated rates. The recurrent tumours are highly aneuploid and have varied activation of pro-proliferative pathways. Thus, early chromosomal instability may be responsible for tumour relapse after seemingly effective anticancer treatments.
C1 [Sotillo, Rocio; Schvartzman, Juan-Manuel; Benezra, Robert] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
   [Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Benezra, R (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
EM r-benezra@ski.mskcc.org
FU Charles H. Revson Foundation; US Department of Defense; National Institutes of Health
NR 28
TC 220
Z9 247
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 MAR 18
PY 2010
VL 464
IS 7287
BP 436
EP U138
DI 10.1038/nature08803
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100052
PM 20173739
DA 2026-03-09
ER

PT J
AU Krishnan, M
   Mojarad, N
   Kukura, P
   Sandoghdar, V
AF Krishnan, Madhavi
   Mojarad, Nassiredin
   Kukura, Philipp
   Sandoghdar, Vahid
TI Geometry-induced electrostatic trapping of nanometric objects in a fluid
SO NATURE
LA English
DT Article
ID optical manipulation; brownian-motion; nanoparticles; nanoslit; dna; biomolecules; pressure; dynamics; force
AB The ability to trap an object-whether a single atom or a macroscopic entity-affects fields as diverse as quantum optics(1), soft condensed-matter physics, biophysics and clinical medicine(2). Many sophisticated methodologies have been developed to counter the randomizing effect of Brownian motion in solution(3-10), but stable trapping of nanometre-sized objects remains challenging(8-10). Optical tweezers are widely used traps, but require sufficiently polarizable objects and thus are unable to manipulate small macromolecules. Confinement of single molecules has been achieved using electrokinetic feedback guided by tracking of a fluorescent label, but photophysical constraints limit the trap stiffness and lifetime(8). Here we show that a fluidic slit with appropriately tailored topography has a spatially modulated electrostatic potential that can trap and levitate charged objects in solution for up to several hours. We illustrate this principle with gold particles, polymer beads and lipid vesicles with diameters of tens of nanometres, which are all trapped without external intervention and independently of their mass and dielectric function. The stiffness and stability of our electrostatic trap is easily tuned by adjusting the system geometry and the ionic strength of the solution, and it lends itself to integration with other manipulation mechanisms. We anticipate that these features will allow its use for contact-free confinement of single proteins and macromolecules, and the sorting and fractionation of nanometre-sized objects or their assembly into high-density arrays.
C1 [Krishnan, Madhavi; Mojarad, Nassiredin; Kukura, Philipp; Sandoghdar, Vahid] ETH, Phys Chem Lab, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Krishnan, M (corresponding author), ETH, Phys Chem Lab, CH-8093 Zurich, Switzerland.
EM mkrishnan@ethz.ch
FU European Commission
NR 32
TC 206
Z9 232
U1 4
U2 207
PU 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 7
PY 2010
VL 467
IS 7316
BP 692
EP U75
DI 10.1038/nature09404
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500034
PM 20930840
DA 2026-03-09
ER

PT J
AU Bid, A
   Ofek, N
   Inoue, H
   Heiblum, M
   Kane, CL
   Umansky, V
   Mahalu, D
AF Bid, Aveek
   Ofek, N.
   Inoue, H.
   Heiblum, M.
   Kane, C. L.
   Umansky, V.
   Mahalu, D.
TI Observation of neutral modes in the fractional quantum Hall regime
SO NATURE
LA English
DT Article
ID edge states; noise; transport; excitations; scattering; charge
AB The quantum Hall effect takes place in a two-dimensional electron gas under a strong magnetic field and involves current flow along the edges of the sample. For some particle-hole conjugate states of the fractional regime (for example, with fillings between 1/2 and 1 of the lowest Landau level), early predictions suggested the presence of counter-propagating edge currents in addition to the expected ones. When this did not agree with the measured conductance, it was suggested that disorder and interactions will lead to counter-propagating modes that carry only energy-the so called neutral modes. In addition, a neutral upstream mode (the Majorana mode) was expected for selected wavefunctions proposed for the even-denominator filling 5/2. Here we report the direct observation of counter-propagating neutral modes for fillings of 2/3, 3/5 and 5/2. The basis of our approach is that, if such modes impinge on a narrow constriction, the neutral quasiparticles will be partly reflected and fragmented into charge carriers, which can be detected through shot noise measurements. We find that the resultant shot noise is proportional to the injected current. Moreover, when we simultaneously inject a charge mode, the presence of the neutral mode was found to significantly affect the Fano factor and the temperature of the backscattered charge mode. In particular, such observations for filling 5/2 may single out the non-Abelian wavefunctions for the state.
C1 [Bid, Aveek; Ofek, N.; Inoue, H.; Heiblum, M.; Umansky, V.; Mahalu, D.] Weizmann Inst Sci, Dept Condensed Matter Phys, Braun Ctr Submicron Res, IL-76100 Rehovot, Israel.
   [Kane, C. L.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
C3 Weizmann Institute of Science; University of Pennsylvania
RP Heiblum, M (corresponding author), Weizmann Inst Sci, Dept Condensed Matter Phys, Braun Ctr Submicron Res, IL-76100 Rehovot, Israel.
EM moty.heiblum@weizmann.ac.il
FU Israeli Science Foundation (ISF); Minerva Foundation; German Israeli Foundation (GIF); German Israeli Project Cooperation (DIP); European Research Council under the European Community [FP7/2007-2013, 227716]; US-Israel Bi-National Science Foundation; Israeli Ministry of Science and Technology; NSF [DMR 0906175]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0906175] Funding Source: National Science Foundation; European Research Council (ERC) [227716] Funding Source: European Research Council (ERC)
NR 28
TC 189
Z9 222
U1 0
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 JUL 29
PY 2010
VL 466
IS 7306
BP 585
EP 590
DI 10.1038/nature09277
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100045
PM 20671702
DA 2026-03-09
ER

PT J
AU Kim, K
   Chang, MS
   Korenblit, S
   Islam, R
   Edwards, EE
   Freericks, JK
   Lin, GD
   Duan, LM
   Monroe, C
AF Kim, K.
   Chang, M. -S.
   Korenblit, S.
   Islam, R.
   Edwards, E. E.
   Freericks, J. K.
   Lin, G. -D.
   Duan, L. -M.
   Monroe, C.
TI Quantum simulation of frustrated Ising spins with trapped ions
SO NATURE
LA English
DT Article
ID entanglement; systems; computation; glasses; state
AB A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. This compromise is central to the behaviour of many complex systems, from social(1) and neural(2) networks to protein folding(3) and magnetism(4,5). Frustrated networks have highly degenerate ground states, with excess entropy and disorder even at zero temperature. In the case of quantum networks, frustration can lead to massively entangled ground states, underpinning exotic materials such as quantum spin liquids and spin glasses(6-9). Here we realize a quantum simulation of frustrated Ising spins in a system of three trapped atomic ions(10-12), whose interactions are precisely controlled using optical forces(13). We study the ground state of this system as it adiabatically evolves from a transverse polarized state, and observe that frustration induces extra degeneracy. We also measure the entanglement in the system, finding a link between frustration and ground-state entanglement. This experimental system can be scaled to simulate larger numbers of spins, the ground states of which (for frustrated interactions) cannot be simulated on a classical computer.
C1 [Kim, K.; Chang, M. -S.; Korenblit, S.; Islam, R.; Edwards, E. E.; Monroe, C.] Univ Maryland, Dept Phys, Joint Quantum Inst, College Pk, MD 20742 USA.
   [Kim, K.; Chang, M. -S.; Korenblit, S.; Islam, R.; Edwards, E. E.; Monroe, C.] NIST, College Pk, MD 20742 USA.
   [Freericks, J. K.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
   [Lin, G. -D.; Duan, L. -M.] Univ Michigan, MCTP, Ann Arbor, MI 48109 USA.
   [Lin, G. -D.; Duan, L. -M.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
C3 University System of Maryland; University of Maryland College Park; National Institute of Standards & Technology (NIST) - USA; Georgetown University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Kim, K (corresponding author), Univ Maryland, Dept Phys, Joint Quantum Inst, College Pk, MD 20742 USA.
EM khkim@umd.edu
FU US Army Research Office (ARO) [W911NF0710576, W911NF0410234]; US National Science Foundation (NSF); NSF Physics Frontier Center at the Joint Quantum Institute
NR 29
TC 651
Z9 737
U1 2
U2 168
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 590
EP U81
DI 10.1038/nature09071
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000035
PM 20520708
DA 2026-03-09
ER

PT J
AU Jennings, MD
   Pavitt, GD
AF Jennings, Martin D.
   Pavitt, Graham D.
TI eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation
SO NATURE
LA English
DT Article
ID guanine-nucleotide exchange; c-terminal domain; eukaryotic translation; ribosomal-subunit; gtpase activation; gcn4 translation; initiation; yeast; complex; binding
AB In protein synthesis initiation, the eukaryotic translation initiation factor (eIF) 2 (a G protein) functions in its GTP-bound state to deliver initiator methionyl-tRNA (tRNA(i)(Met)) to the small ribosomal subunit and is necessary for protein synthesis in all cells(1,2). Phosphorylation of eIF2 [eIF2(alpha P)] is critical for translational control in diverse settings including nutrient deprivation, viral infection and memory formation(3-5). eIF5 functions in start site selection as a GTPase accelerating protein (GAP) for the eIF2.GTP.tRNA(i)(Met) ternary complex within the ribosome-bound pre-initiation complex(6-8). Here we define new regulatory functions of eIF5 in the recycling of eIF2 from its inactive eIF2.GDP state between successive rounds of translation initiation. First we show that eIF5 stabilizes the binding of GDP to eIF2 and is therefore a bi-functional protein that acts as a GDP dissociation inhibitor (GDI). We find that this activity is independent of the GAP function and identify conserved residues within eIF5 that are necessary for this role. Second we show that eIF5 is a critical component of the eIF2(alpha P) regulatory complex that inhibits the activity of the guanine-nucleotide exchange factor (GEF) eIF2B. Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls.
C1 [Jennings, Martin D.; Pavitt, Graham D.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
C3 University of Manchester
RP Pavitt, GD (corresponding author), Univ Manchester, Fac Life Sci, Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
EM graham.pavitt@manchester.ac.uk
FU BBSRC [BB/E002005/1, BB/H010599/1]; Biotechnology and Biological Sciences Research Council [BB/H010599/1, BB/E002005/1] Funding Source: researchfish; BBSRC [BB/E002005/1, BB/H010599/1] Funding Source: UKRI
NR 29
TC 89
Z9 115
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 MAY 20
PY 2010
VL 465
IS 7296
BP 378
EP U142
DI 10.1038/nature09003
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200047
PM 20485439
DA 2026-03-09
ER

PT J
AU Iannacone, M
   Moseman, EA
   Tonti, E
   Bosurgi, L
   Junt, T
   Henrickson, SE
   Whelan, SP
   Guidotti, LG
   von Andrian, UH
AF Iannacone, Matteo
   Moseman, E. Ashley
   Tonti, Elena
   Bosurgi, Lidia
   Junt, Tobias
   Henrickson, Sarah E.
   Whelan, Sean P.
   Guidotti, Luca G.
   von Andrian, Ulrich H.
TI Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus
SO NATURE
LA English
DT Article
ID liposome-mediated depletion; vesicular stomatitis-virus; in-vivo depletion; cd8(+) t-cells; lymph-nodes; b-cells; dendritic cells; mice; activation; antigen
AB Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens(1). Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses(2-4). Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.
C1 [Iannacone, Matteo; Moseman, E. Ashley; Tonti, Elena; Bosurgi, Lidia; Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
   [Iannacone, Matteo; Moseman, E. Ashley; Tonti, Elena; Bosurgi, Lidia; Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Iannacone, Matteo; Guidotti, Luca G.] Ist Sci San Raffaele, Dept Immunol Infect Dis & Transplantat, I-20132 Milan, Italy.
   [Junt, Tobias] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland.
   [Whelan, Sean P.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard Medical School; Harvard University; Harvard Medical School; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Novartis; Harvard University; Harvard Medical School
RP von Andrian, UH (corresponding author), Harvard Univ, Sch Med, Immune Dis Inst, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM Matteo_Iannacone@hms.harvard.edu; uva@hms.harvard.edu
FU National Institutes of Health (NIH) [AI069259, AI072252, AI078897, AR42689]; Giovanni Armenise-Harvard Foundation; NIH; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 26
TC 276
Z9 326
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 JUN 24
PY 2010
VL 465
IS 7301
BP 1079
EP U143
DI 10.1038/nature09118
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900053
PM 20577213
DA 2026-03-09
ER

PT J
AU Li, RQ
   Fan, W
   Tian, G
   Zhu, HM
   He, L
   Cai, J
   Huang, QF
   Cai, QL
   Li, B
   Bai, YQ
   Zhang, ZH
   Zhang, YP
   Wang, W
   Li, J
   Wei, FW
   Li, H
   Jian, M
   Li, JW
   Zhang, ZL
   Nielsen, R
   Li, DW
   Gu, WJ
   Yang, ZT
   Xuan, ZL
   Ryder, OA
   Leung, FCC
   Zhou, Y
   Cao, JJ
   Sun, X
   Fu, YG
   Fang, XD
   Guo, XS
   Wang, B
   Hou, R
   Shen, FJ
   Mu, B
   Ni, PX
   Lin, RM
   Qian, WB
   Wang, GD
   Yu, C
   Nie, WH
   Wang, JH
   Wu, ZG
   Liang, HQ
   Min, JM
   Wu, Q
   Cheng, SF
   Ruan, J
   Wang, MW
   Shi, ZB
   Wen, M
   Liu, BH
   Ren, XL
   Zheng, HS
   Dong, D
   Cook, K
   Shan, G
   Zhang, H
   Kosiol, C
   Xie, XY
   Lu, ZH
   Zheng, HC
   Li, YR
   Steiner, CC
   Lam, TTY
   Lin, SY
   Zhang, QH
   Li, GQ
   Tian, J
   Gong, TM
   Liu, HD
   Zhang, DJ
   Fang, L
   Ye, C
   Zhang, JB
   Hu, WB
   Xu, AL
   Ren, YY
   Zhang, GJ
   Bruford, MW
   Li, QB
   Ma, LJ
   Guo, YR
   An, N
   Hu, YJ
   Zheng, Y
   Shi, YY
   Li, ZQ
   Liu, Q
   Chen, YL
   Zhao, J
   Qu, N
   Zhao, SC
   Tian, F
   Wang, XL
   Wang, HY
   Xu, LZ
   Liu, X
   Vinar, T
   Wang, YJ
   Lam, TW
   Yiu, SM
   Liu, SP
   Zhang, HM
   Li, DS
   Huang, Y
   Wang, X
   Yang, GH
   Jiang, Z
   Wang, JY
   Qin, N
   Li, L
   Li, JX
   Bolund, L
   Kristiansen, K
   Wong, GKS
   Olson, M
   Zhang, XQ
   Li, SG
   Yang, HM
   Wang, J
   Wang, J
AF Li, Ruiqiang
   Fan, Wei
   Tian, Geng
   Zhu, Hongmei
   He, Lin
   Cai, Jing
   Huang, Quanfei
   Cai, Qingle
   Li, Bo
   Bai, Yinqi
   Zhang, Zhihe
   Zhang, Yaping
   Wang, Wen
   Li, Jun
   Wei, Fuwen
   Li, Heng
   Jian, Min
   Li, Jianwen
   Zhang, Zhaolei
   Nielsen, Rasmus
   Li, Dawei
   Gu, Wanjun
   Yang, Zhentao
   Xuan, Zhaoling
   Ryder, Oliver A.
   Leung, Frederick Chi-Ching
   Zhou, Yan
   Cao, Jianjun
   Sun, Xiao
   Fu, Yonggui
   Fang, Xiaodong
   Guo, Xiaosen
   Wang, Bo
   Hou, Rong
   Shen, Fujun
   Mu, Bo
   Ni, Peixiang
   Lin, Runmao
   Qian, Wubin
   Wang, Guodong
   Yu, Chang
   Nie, Wenhui
   Wang, Jinhuan
   Wu, Zhigang
   Liang, Huiqing
   Min, Jiumeng
   Wu, Qi
   Cheng, Shifeng
   Ruan, Jue
   Wang, Mingwei
   Shi, Zhongbin
   Wen, Ming
   Liu, Binghang
   Ren, Xiaoli
   Zheng, Huisong
   Dong, Dong
   Cook, Kathleen
   Shan, Gao
   Zhang, Hao
   Kosiol, Carolin
   Xie, Xueying
   Lu, Zuhong
   Zheng, Hancheng
   Li, Yingrui
   Steiner, Cynthia C.
   Lam, Tommy Tsan-Yuk
   Lin, Siyuan
   Zhang, Qinghui
   Li, Guoqing
   Tian, Jing
   Gong, Timing
   Liu, Hongde
   Zhang, Dejin
   Fang, Lin
   Ye, Chen
   Zhang, Juanbin
   Hu, Wenbo
   Xu, Anlong
   Ren, Yuanyuan
   Zhang, Guojie
   Bruford, Michael W.
   Li, Qibin
   Ma, Lijia
   Guo, Yiran
   An, Na
   Hu, Yujie
   Zheng, Yang
   Shi, Yongyong
   Li, Zhiqiang
   Liu, Qing
   Chen, Yanling
   Zhao, Jing
   Qu, Ning
   Zhao, Shancen
   Tian, Feng
   Wang, Xiaoling
   Wang, Haiyin
   Xu, Lizhi
   Liu, Xiao
   Vinar, Tomas
   Wang, Yajun
   Lam, Tak-Wah
   Yiu, Siu-Ming
   Liu, Shiping
   Zhang, Hemin
   Li, Desheng
   Huang, Yan
   Wang, Xia
   Yang, Guohua
   Jiang, Zhi
   Wang, Junyi
   Qin, Nan
   Li, Li
   Li, Jingxiang
   Bolund, Lars
   Kristiansen, Karsten
   Wong, Gane Ka-Shu
   Olson, Maynard
   Zhang, Xiuqing
   Li, Songgang
   Yang, Huanming
   Wang, Jian
   Wang, Jun
TI The sequence and de novo assembly of the giant panda genome
SO NATURE
LA English
DT Article
ID taste receptor; evolution; family; dna
AB Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
C1 [Li, Ruiqiang; Fan, Wei; Tian, Geng; Zhu, Hongmei; Huang, Quanfei; Cai, Qingle; Li, Bo; Bai, Yinqi; Li, Jun; Jian, Min; Li, Jianwen; Li, Dawei; Yang, Zhentao; Xuan, Zhaoling; Zhou, Yan; Cao, Jianjun; Fang, Xiaodong; Guo, Xiaosen; Wang, Bo; Mu, Bo; Ni, Peixiang; Lin, Runmao; Qian, Wubin; Yu, Chang; Wu, Zhigang; Liang, Huiqing; Min, Jiumeng; Cheng, Shifeng; Ruan, Jue; Wang, Mingwei; Shi, Zhongbin; Wen, Ming; Liu, Binghang; Ren, Xiaoli; Zheng, Huisong; Shan, Gao; Zhang, Hao; Zheng, Hancheng; Li, Yingrui; Lin, Siyuan; Zhang, Qinghui; Li, Guoqing; Tian, Jing; Gong, Timing; Fang, Lin; Ye, Chen; Zhang, Juanbin; Ren, Yuanyuan; Zhang, Guojie; Li, Qibin; Ma, Lijia; Guo, Yiran; An, Na; Hu, Yujie; Zheng, Yang; Liu, Qing; Chen, Yanling; Zhao, Jing; Qu, Ning; Zhao, Shancen; Tian, Feng; Wang, Xiaoling; Wang, Haiyin; Xu, Lizhi; Liu, Xiao; Wang, Xia; Yang, Guohua; Jiang, Zhi; Wang, Junyi; Qin, Nan; Li, Li; Li, Jingxiang; Bolund, Lars; Kristiansen, Karsten; Wong, Gane Ka-Shu; Zhang, Xiuqing; Li, Songgang; Yang, Huanming; Wang, Jian; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Li, Ruiqiang; Kristiansen, Karsten; Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Tian, Geng; Cai, Jing; Wang, Guodong; Ruan, Jue; Li, Yingrui; Zhang, Guojie; Li, Qibin; Ma, Lijia; Guo, Yiran; Hu, Yujie; Zheng, Yang] Chinese Acad Sci, Grad Univ, Beijing 100062, Peoples R China.
   [He, Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.
   [He, Lin; Shi, Yongyong; Li, Zhiqiang] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, BioX Ctr, Shanghai 200030, Peoples R China.
   [Cai, Jing; Zhang, Yaping; Wang, Wen; Wang, Guodong; Nie, Wenhui; Wang, Jinhuan; Zhang, Guojie] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China.
   [Cai, Qingle; Min, Jiumeng; Cheng, Shifeng; Qu, Ning] Shenzhen Univ, Sch Med, Genome Res Inst, Shenzhen 518000, Peoples R China.
   [Zhang, Zhihe; Hou, Rong; Shen, Fujun] Chengdu Res Base Giant Panda Breeding, Chengdu 610081, Peoples R China.
   [Wei, Fuwen; Wu, Qi] Chinese Acad Sci, Inst Zool, Key Lab Anim Ecol & Conservat Biol, Beijing 100101, Peoples R China.
   [Li, Heng] Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
   [Zhang, Zhaolei; Dong, Dong; Cook, Kathleen] Univ Toronto, Dept Mol Genet, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Gu, Wanjun; Xie, Xueying; Lu, Zuhong] Southeast Univ, Minist Educ, Key Lab Child Dev & Learning Sci, Nanjing 210096, Peoples R China.
   [Ryder, Oliver A.; Steiner, Cynthia C.] San Diego Zoos Inst Conservat Res, Escondido, CA 92027 USA.
   [Leung, Frederick Chi-Ching; Lam, Tommy Tsan-Yuk] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China.
   [Sun, Xiao; Liu, Hongde; Zhang, Dejin] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Peoples R China.
   [Fu, Yonggui; Hu, Wenbo; Xu, Anlong] Sun Yat Sen Univ, Coll Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China.
   [Kosiol, Carolin] Vet Med Univ Wien, Inst Populat Genet, A-1210 Vienna, Austria.
   [Bruford, Michael W.] Cardiff Univ, Cardiff Sch Biosci, Biodivers & Ecol Proc Grp, Cardiff CF10 3AX, Wales.
   [Vinar, Tomas] Comenius Univ, Dept Appl Informat, Fac Math Phys & Informat, Bratislava 84248, Slovakia.
   [Wang, Yajun] Sichuan Univ, Sch Life Sci, Chengdu 610064, Peoples R China.
   [Lam, Tak-Wah; Yiu, Siu-Ming] Univ Hong Kong, Dept Comp Sci, Hong Kong, Hong Kong, Peoples R China.
   [Liu, Shiping] S China Univ Technol, Guangzhou 510641, Peoples R China.
   [Zhang, Hemin; Li, Desheng; Huang, Yan] China Conservat & Res Ctr Giant Panda, Wolong Nat Reserve 623006, Peoples R China.
   [Wong, Gane Ka-Shu] Univ Alberta, Dept Med, Edmonton, AB T6G 2E9, Canada.
   [Wong, Gane Ka-Shu] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
   [Olson, Maynard] Univ Washington, Genome Ctr, Seattle, WA USA.
C3 Beijing Genomics Institute (BGI); University of Copenhagen; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Fudan University; Shanghai Jiao Tong University; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Shenzhen University; Chinese Academy of Sciences; Institute of Zoology, CAS; Wellcome Trust Sanger Institute; University of Toronto; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Southeast University - China; Zoological Society of San Diego; University of Hong Kong; Southeast University - China; Sun Yat Sen University; University of Veterinary Medicine Vienna; Cardiff University; Comenius University Bratislava; Sichuan University; University of Hong Kong; South China University of Technology; University of Alberta; University of Alberta; University of Washington; University of Washington Seattle
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM wangjian@genomics.org.cn; wangj@genomics.org.cn
FU Shenzhen Municipal Government; Yantian District local government of Shenzhen; National Natural Science Foundation of China [30725008]; Danish Natural Science Research Council; Solexa project [272-07-0196]; Danish Strategic Research Council [2106-07-0021]
NR 30
TC 877
Z9 1108
U1 10
U2 616
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 311
EP 317
DI 10.1038/nature08696
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100035
PM 20010809
DA 2026-03-09
ER

PT J
AU Lee, CTA
   Luffi, P
   Le Roux, V
   Dasgupta, R
   Albaréde, F
   Leeman, WP
AF Lee, Cin-Ty A.
   Luffi, Peter
   Le Roux, Veronique
   Dasgupta, Rajdeep
   Albarede, Francis
   Leeman, William P.
TI The redox state of arc mantle using Zn/Fe systematics
SO NATURE
LA English
DT Article
ID oxidation-state; oxygen fugacity; source regions; earths mantle; differentiation; peridotites; insights; basalts; magmas; metasomatism
AB Many arc lavas are more oxidized than mid-ocean-ridge basalts and subduction introduces oxidized components into the mantle(1-4). As a consequence, the sub-arc mantle wedge is widely believed to be oxidized(3,5). The Fe oxidation state of sub-arc mantle is, however, difficult to determine directly, and debate persists as to whether this oxidation is intrinsic to the mantle source(6,7). Here we show that Zn/Fe(T) (where Fe(T) = Fe(2+) + Fe(3+)) is redox-sensitive and retains a memory of the valence state of Fe in primary arc basalts and their mantle sources. During melting of mantle peridotite, Fe(2+) and Zn behave similarly, but because Fe(3+) is more incompatible than Fe(2+), melts generated in oxidized environments have low Zn/Fe(T). Primitive arc magmas have identical Zn/Fe(T) to mid-ocean-ridge basalts, suggesting that primary mantle melts in arcs and ridges have similar Fe oxidation states. The constancy of Zn/Fe(T) during early differentiation involving olivine requires that Fe(3+)/Fe(T) remains low in the magma. Only after progressive fractionation does Fe(3+)/Fe(T) increase and stabilize magnetite as a fractionating phase. These results suggest that subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. Thus, the higher oxidation states of arc lavas must be in part a consequence of shallow-level differentiation processes, though such processes remain poorly understood.
C1 [Lee, Cin-Ty A.; Luffi, Peter; Le Roux, Veronique; Dasgupta, Rajdeep; Albarede, Francis; Leeman, William P.] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Albarede, Francis] Univ Lyon 1, Ecole Normale Super Lyon, F-69007 Lyon, France.
   [Albarede, Francis] CNRS, F-69007 Lyon, France.
   [Leeman, William P.] Natl Sci Fdn, Div Earth Sci, Arlington, VA 22230 USA.
C3 Rice University; Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); National Science Foundation (NSF); NSF - Directorate for Geosciences (GEO); NSF - Division of Earth Sciences (EAR)
RP Lee, CTA (corresponding author), Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
EM ctlee@rice.edu
FU Geological Society of America
NR 31
TC 243
Z9 285
U1 1
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 DEC 2
PY 2010
VL 468
IS 7324
BP 681
EP 685
DI 10.1038/nature09617
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700038
PM 21124454
DA 2026-03-09
ER

PT J
AU Bignell, GR
   Greenman, CD
   Davies, H
   Butler, AP
   Edkins, S
   Andrews, JM
   Buck, G
   Chen, LN
   Beare, D
   Latimer, C
   Widaa, S
   Hinton, J
   Fahey, C
   Fu, BY
   Swamy, S
   Dalgliesh, GL
   Teh, BT
   Deloukas, P
   Yang, FT
   Campbell, PJ
   Futreal, PA
   Stratton, MR
AF Bignell, Graham R.
   Greenman, Chris D.
   Davies, Helen
   Butler, Adam P.
   Edkins, Sarah
   Andrews, Jenny M.
   Buck, Gemma
   Chen, Lina
   Beare, David
   Latimer, Calli
   Widaa, Sara
   Hinton, Jonathon
   Fahey, Ciara
   Fu, Beiyuan
   Swamy, Sajani
   Dalgliesh, Gillian L.
   Teh, Bin T.
   Deloukas, Panos
   Yang, Fengtang
   Campbell, Peter J.
   Futreal, P. Andrew
   Stratton, Michael R.
TI Signatures of mutation and selection in the cancer genome
SO NATURE
LA English
DT Article
ID somatic frameshift mutations; candidate tumor-suppressor; fragile site stability; copy number variation; glioblastoma-multiforme; chromosome fragility; lung adenocarcinoma; colorectal cancers; colon cancers; gene
AB The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery.
C1 [Bignell, Graham R.; Greenman, Chris D.; Davies, Helen; Butler, Adam P.; Edkins, Sarah; Andrews, Jenny M.; Buck, Gemma; Chen, Lina; Beare, David; Latimer, Calli; Widaa, Sara; Hinton, Jonathon; Fahey, Ciara; Fu, Beiyuan; Swamy, Sajani; Dalgliesh, Gillian L.; Deloukas, Panos; Yang, Fengtang; Campbell, Peter J.; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Teh, Bin T.] Van Andel Inst, Grand Rapids, MI 49503 USA.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
C3 Wellcome Trust Sanger Institute; Van Andel Institute; University of London; Institute of Cancer Research - UK
RP Stratton, MR (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM paf@sanger.ac.uk; mrs@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; National Cancer Institute [P01CA155258] Funding Source: NIH RePORTER
NR 40
TC 571
Z9 667
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 893
EP U61
DI 10.1038/nature08768
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700035
PM 20164919
DA 2026-03-09
ER

PT J
AU Sacanna, S
   Irvine, WTM
   Chaikin, PM
   Pine, DJ
AF Sacanna, S.
   Irvine, W. T. M.
   Chaikin, P. M.
   Pine, D. J.
TI Lock and key colloids
SO NATURE
LA English
DT Article
ID dna; crystallization
AB New functional materials can in principle be created using colloids that self-assemble into a desired structure by means of a programmable recognition and binding scheme. This idea has been explored by attaching 'programmed' DNA strands to nanometre-(1-3) and micrometre-(4,5) sized particles and then using DNA hybridization to direct the placement of the particles in the final assembly. Here we demonstrate an alternative recognition mechanism for directing the assembly of composite structures, based on particles with complementary shapes. Our system, which uses Fischer's lock-and-key principle(6), employs colloidal spheres as keys and monodisperse colloidal particles with a spherical cavity as locks that bind spontaneously and reversibly via the depletion interaction. The lock-and-key binding is specific because it is controlled by how closely the size of a spherical colloidal key particle matches the radius of the spherical cavity of the lock particle. The strength of the binding can be further tuned by adjusting the solution composition or temperature. The composite assemblies have the unique feature of having flexible bonds, allowing us to produce flexible dimeric, trimeric and tetrameric colloidal molecules as well as more complex colloidal polymers. We expect that this lock-and-key recognition mechanism will find wider use as a means of programming and directing colloidal self-assembly.
C1 [Sacanna, S.; Irvine, W. T. M.; Chaikin, P. M.; Pine, D. J.] New York Univ, Dept Phys, New York, NY 10003 USA.
C3 New York University
RP Sacanna, S (corresponding author), New York Univ, Dept Phys, 4 Washington Pl, New York, NY 10003 USA.
EM s.sacanna@nyu.edu; pine@nyu.edu
FU National Science Foundation [DMR 0706453]; Keck Foundation; Netherlands Organization for Scientific Research (NWO) through a Rubicon fellowship; English Speaking Union through a Lindemann Fellowship and Rhodia
NR 15
TC 688
Z9 838
U1 7
U2 462
PU 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 25
PY 2010
VL 464
IS 7288
BP 575
EP 578
DI 10.1038/nature08906
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200044
PM 20336142
DA 2026-03-09
ER

PT J
AU Kapranov, P
   Ozsolak, F
   Kim, SW
   Foissac, S
   Lipson, D
   Hart, C
   Roels, S
   Borel, C
   Antonarakis, SE
   Monaghan, AP
   John, B
   Milos, PM
AF Kapranov, Philipp
   Ozsolak, Fatih
   Kim, Sang Woo
   Foissac, Sylvain
   Lipson, Doron
   Hart, Chris
   Roels, Steve
   Borel, Christelle
   Antonarakis, Stylianos E.
   Monaghan, A. Paula
   John, Bino
   Milos, Patrice M.
TI New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism
SO NATURE
LA English
DT Article
ID polymerase-ii; transcription
AB Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with hundreds of thousands of sRNA species present(1-4). Genetic and in vitro studies show that these RNAs are not merely degradation products of longer transcripts but could indeed have a function(1,2,5). Furthermore, profiling of RNAs, including the sRNAs, can reveal not only novel transcripts, but also make clear predictions about the existence and properties of novel biochemical pathways operating in a cell. For example, sRNA profiling in human cells indicated the existence of an unknown capping mechanism operating on cleaved RNA(2), a biochemical component of which was later identified(6). Here we show that human cells contain a novel type of sRNA that has non-genomically encoded 5' poly(U) tails. The presence of these RNAs at the termini of genes, specifically at the very 3' ends of known mRNAs, strongly argues for the presence of a yet uncharacterized endogenous biochemical pathway in cells that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcript-encoding components of the translational machinery. Finally, we show that genes are also flanked by sense, 3' polyadenylated sRNAs that are likely to be capped.
C1 [Kapranov, Philipp; Ozsolak, Fatih; Lipson, Doron; Hart, Chris; Roels, Steve; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA.
   [Kim, Sang Woo; John, Bino] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
   [Foissac, Sylvain] Integromics SL, Madrid 28760, Spain.
   [Borel, Christelle; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Monaghan, A. Paula] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15260 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Geneva; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Kapranov, P (corresponding author), Helicos BioSci Corp, 1 Kendall Sq,Ste B7301, Cambridge, MA 02139 USA.
EM philippk08@gmail.com; pmilos@helicosbio.com
FU Swiss National Science Foundation; NIH [GM079756, MH60774]; American Cancer Society [RSG0905401]; Comunidad de Madrid; European Union [Exp. 11/2009]
NR 19
TC 65
Z9 85
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 642
EP 646
DI 10.1038/nature09190
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100057
PM 20671709
DA 2026-03-09
ER

PT J
AU Guo, HL
   Ingolia, NT
   Weissman, JS
   Bartel, DP
AF Guo, Huili
   Ingolia, Nicholas T.
   Weissman, Jonathan S.
   Bartel, David P.
TI Mammalian microRNAs predominantly act to decrease target mRNA levels
SO NATURE
LA English
DT Article
ID genome-wide analysis; posttranscriptional regulation; protein-synthesis; in-vivo; translation; initiation; deadenylation; degradation; elegans; mirnas
AB MicroRNAs (miRNAs) are endogenous similar to 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>= 84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
C1 [Guo, Huili; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Guo, Huili; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Guo, Huili; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.] Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Bartel, DP (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dbartel@wi.mit.edu
FU NIH; Agency for Science, Technology and Research, Singapore; Ruth L. Kirschstein National Research Service Award [GM080853]
NR 34
TC 3212
Z9 3814
U1 0
U2 372
PU NATURE PUBLISHING 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 12
PY 2010
VL 466
IS 7308
BP 835
EP U66
DI 10.1038/nature09267
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100029
PM 20703300
DA 2026-03-09
ER

PT J
AU Boyce, JW
   Liu, Y
   Rossman, GR
   Guan, YB
   Eiler, JM
   Stolper, EM
   Taylor, LA
AF Boyce, Jeremy W.
   Liu, Yang
   Rossman, George R.
   Guan, Yunbin
   Eiler, John M.
   Stolper, Edward M.
   Taylor, Lawrence A.
TI Lunar apatite with terrestrial volatile abundances
SO NATURE
LA English
DT Article
ID microphenocrystic apatite; so3 contents; basalt; metallogenesis; philippines; evolution; fluorine; interior; chlorine; glasses
AB The Moon is thought to be depleted relative to the Earth in volatile elements such as H, Cl and the alkalis(1-3). Nevertheless, evidence for lunar explosive volcanism(4,5) has been used to infer that some lunar magmas exsolved a CO-rich and CO(2)-rich vapour phase before or during eruption(6-8). Although there is also evidence for other volatile species on glass spherules(9), until recently(10) there had been no unambiguous reports of indigenous H in lunar rocks. Here we report quantitative ion microprobe measurements of late-stage apatite from lunar basalt 14053 that document concentrations of H, Cl and S that are indistinguishable from apatites in common terrestrial igneous rocks. These volatile contents could reflect post-magmatic metamorphic volatile addition or growth from a late-stage, interstitial, sulphide-saturated melt that contained similar to 1,600 parts per million H(2)O and similar to 3,500 parts per million Cl. Both metamorphic and igneous models of apatite formation suggest a volatile inventory for at least some lunar materials that is similar to comparable terrestrial materials. One possible implication is that portions of the lunar mantle or crust are more volatile-rich than previously thought.
C1 [Boyce, Jeremy W.; Rossman, George R.; Guan, Yunbin; Eiler, John M.; Stolper, Edward M.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Boyce, Jeremy W.] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Liu, Yang; Taylor, Lawrence A.] Univ Tennessee, Dept Earth & Planetary Sci, Planetary Geosci Inst, Knoxville, TN 37996 USA.
C3 California Institute of Technology; University of California System; University of California Los Angeles; University of Tennessee System; University of Tennessee Knoxville
RP Boyce, JW (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM jwboyce@alum.mit.edu
FU NASA Cosmochemistry [NNX08AG54G, NNX09AG40G]; NSF [OCE-0840983]; Moore foundation; NASA [NNX09AG40G, 100416, NNX08AG54G, 118479] Funding Source: Federal RePORTER; Directorate For Geosciences [0840983] Funding Source: National Science Foundation; Division Of Ocean Sciences [0840983] Funding Source: National Science Foundation
NR 31
TC 270
Z9 311
U1 2
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 JUL 22
PY 2010
VL 466
IS 7305
BP 466
EP U2
DI 10.1038/nature09274
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200030
PM 20651686
DA 2026-03-09
ER

PT J
AU Dong, AG
   Chen, J
   Vora, PM
   Kikkawa, JM
   Murray, CB
AF Dong, Angang
   Chen, Jun
   Vora, Patrick M.
   Kikkawa, James M.
   Murray, Christopher B.
TI Binary nanocrystal superlattice membranes self-assembled at the liquid-air interface
SO NATURE
LA English
DT Article
ID nanoparticle superlattices; structural-characterization; monodisperse nanocrystals; electron tomography; arrays; crystals; phase; cdse; dna
AB The spontaneous organization of multicomponent micrometresized colloids(1) or nanocrystals(2) into superlattices is of scientific importance for understanding the assembly process on the nanometre scale and is of great interest for bottom-up fabrication of functional devices. In particular, co-assembly of two types of nanocrystal into binary nanocrystal superlattices (BNSLs) has recently attracted significant attention(2-8), as this provides a lowcost, programmable way to design metamaterials(4) with precisely controlled properties that arise from the organization and interactions of the constituent nanocrystal components(9). Although challenging, the ability to grow and manipulate large-scale BNSLs is critical for extensive exploration of this new class of material. Here we report a general method of growing centimetre-scale, uniform membranes of BNSLs that can readily be transferred to arbitrary substrates. Our method is based on the liquid-air interfacial assembly of multicomponent nanocrystals and circumvents the limitations associated with the current assembly strategies, allowing integration of BNSLs on any substrate for the fabrication of nanocrystal-based devices(10). We demonstrate the construction of magnetoresistive devices by incorporating large-area (1.5 mm x 32.5 mm) BNSL membranes; their magnetotransport measurements clearly show that device magnetoresistance is dependent onthe structure (stoichiometry) of the BNSLs. The ability to transfer BNSLs also allows the construction of free-standing membranes and other complex architectures that have not been accessible previously.
C1 [Dong, Angang; Murray, Christopher B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
   [Chen, Jun; Murray, Christopher B.] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
   [Vora, Patrick M.; Kikkawa, James M.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania
RP Dong, AG (corresponding author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
EM angang@sas.upenn.edu; cbmurray@sas.upenn.edu
FU US Army Research Office (ARO) [MURI W911NF-08-1-0364]; NSF [DMR-0520020]
NR 30
TC 792
Z9 916
U1 13
U2 995
PU 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 22
PY 2010
VL 466
IS 7305
BP 474
EP 477
DI 10.1038/nature09188
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200032
PM 20651688
DA 2026-03-09
ER

PT J
AU Liu, CM
   Young, AL
   Starling-Windhof, A
   Bracher, A
   Saschenbrecker, S
   Rao, BV
   Rao, KV
   Berninghausen, O
   Mielke, T
   Hartl, FU
   Beckmann, R
   Hayer-Hartl, M
AF Liu, Cuimin
   Young, Anna L.
   Starling-Windhof, Amanda
   Bracher, Andreas
   Saschenbrecker, Sandra
   Rao, Bharathi Vasudeva
   Rao, Karnam Vasudeva
   Berninghausen, Otto
   Mielke, Thorsten
   Hartl, F. Ulrich
   Beckmann, Roland
   Hayer-Hartl, Manajit
TI Coupled chaperone action in folding and assembly of hexadecameric Rubisco
SO NATURE
LA English
DT Article
ID ribulose-bisphosphate carboxylase; photo-cross-linking; escherichia-coli; ribulose-1,5-bisphosphate carboxylase/oxygenase; 1,5-bisphosphate carboxylase/oxygenase; small subunits; amino-acid; rbcx gene; in-vivo; protein
AB Form I Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase), a complex of eight large (RbcL) and eight small (RbcS) subunits, catalyses the fixation of atmospheric CO2 in photosynthesis. The limited catalytic efficiency of Rubisco has sparked extensive efforts to re-engineer the enzyme with the goal of enhancing agricultural productivity. To facilitate such efforts we analysed the formation of cyanobacterial form I Rubisco by in vitro reconstitution and cryo-electron microscopy. We show that RbcL subunit folding by the GroEL/GroES chaperonin is tightly coupled with assembly mediated by the chaperone RbcX(2). RbcL monomers remain partially unstable and retain high affinity for GroEL until captured by RbcX(2). As revealed by the structure of a RbcL(8)-(RbcX2)(8) assembly intermediate, RbcX(2) acts as a molecular staple in stabilizing the RbcL subunits as dimers and facilitates RbcL(8) core assembly. Finally, addition of RbcS results in RbcX(2) release and holoenzyme formation. Specific assembly chaperones may be required more generally in the formation of complex oligomeric structures when folding is closely coupled to assembly.
C1 [Liu, Cuimin; Starling-Windhof, Amanda; Bracher, Andreas; Saschenbrecker, Sandra; Rao, Bharathi Vasudeva; Rao, Karnam Vasudeva; Hartl, F. Ulrich; Hayer-Hartl, Manajit] Max Planck Inst Biochem, Dept Cellular Biochem, D-82152 Martinsried, Germany.
   [Young, Anna L.; Berninghausen, Otto; Beckmann, Roland] Univ Munich, Dept Chem & Biochem, Ctr Integrated Prot Sci CIPSM, D-81377 Munich, Germany.
   [Young, Anna L.; Berninghausen, Otto; Beckmann, Roland] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Mielke, Thorsten] Max Planck Inst Mol Genet, USN, D-14195 Berlin, Germany.
   [Mielke, Thorsten] Charite, Inst Med Phys & Biophys, D-10098 Berlin, Germany.
C3 Max Planck Society; University of Munich; University of Munich; Max Planck Society; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Hayer-Hartl, M (corresponding author), Max Planck Inst Biochem, Dept Cellular Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM uhartl@biochem.mpg.de; beckmann@lmb.uni-muenchen.de; mhartl@biochem.mpg.de
FU Deutsche Forschungsgemeinschaft [SFB 594]; Ernst-Jung Foundation; Korber Foundation; European Union and the Center for Integrated Protein Science Munich (CIPSM)
NR 50
TC 152
Z9 189
U1 1
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 197
EP U81
DI 10.1038/nature08651
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700028
PM 20075914
DA 2026-03-09
ER

PT J
AU Falconer, E
   Chavez, EA
   Henderson, A
   Poon, SSS
   McKinney, S
   Brown, L
   Huntsman, DG
   Lansdorp, PM
AF Falconer, Ester
   Chavez, Elizabeth A.
   Henderson, Alexander
   Poon, Steven S. S.
   McKinney, Steven
   Brown, Lindsay
   Huntsman, David G.
   Lansdorp, Peter M.
TI Identification of sister chromatids by DNA template strand sequences
SO NATURE
LA English
DT Article
ID adenomatous polyposis-coli; in-situ hybridization; apc tumor-suppressor; embryonic stem-cells; satellite dna; segregation; chromosm; centrosome; protein; orientation
AB It is generally assumed that sister chromatids are genetically and functionally identical and that segregation to daughter cells is a random process. However, functional differences between sister chromatids regulate daughter cell fate in yeast(1) and sister chromatid segregation is not random in Escherichia coli(2). Differentiated sister chromatids, coupled with non-random segregation, have been proposed to regulate cell fate during the development of multicellular organisms(3). This hypothesis has not been tested because molecular features to reliably distinguish between sister chromatids are not obvious. Here we show that parental 'Watson' and 'Crick' DNA template strands can be identified in sister chromatids of murine metaphase chromosomes using CO-FISH(chromosome orientation fluorescence in situ hybridization(4)) with unidirectional probes specific for centromeric and telomeric repeats. All chromosomes were found to have a uniform orientation with the 5' end of the short arm on the same strand as T-rich major satellite repeats. The invariable orientation of repetitive DNA was used to differentially label sister chromatids and directly study mitotic segregation patterns in different cell types. Whereas sister chromatids appeared to be randomly distributed between daughter cells in cultured lung fibroblasts and embryonic stem cells, significant non-random sister chromatid segregation was observed in a subset of colon crypt epithelial cells, including cells outside positions reported for colon stem cells(5). Our results establish that DNA template sequences can be used to distinguish sister chromatids and follow their mitotic segregation in vivo.
C1 [Falconer, Ester; Chavez, Elizabeth A.; Henderson, Alexander; Poon, Steven S. S.; Lansdorp, Peter M.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
   [Poon, Steven S. S.; McKinney, Steven] British Columbia Canc Agcy, Mol Oncol & Breast Canc Program, Vancouver, BC V5Z 1L3, Canada.
   [Brown, Lindsay; Huntsman, David G.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V6H 3Z6, Canada.
   [Lansdorp, Peter M.] Univ British Columbia, Dept Med, Div Hematol, Vancouver, BC V5Z 1L3, Canada.
C3 British Columbia Cancer Agency; British Columbia Cancer Agency; British Columbia Cancer Agency; University of British Columbia
RP Lansdorp, PM (corresponding author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM plansdor@bccrc.ca
FU Canadian Institutes of Health Research [RMF-92093]; Michael Smith Foundation for Health Research; Canadian Cancer Society Research Institute; Terry Fox Foundation; British Columbia Cancer Agency; Canada Foundation for Innovation; British Columbia Knowledge Development Fund; British Columbia Cancer Foundation; Blossom Fund of the University of British Columbia; Mahon family
NR 35
TC 79
Z9 84
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 JAN 7
PY 2010
VL 463
IS 7277
BP 93
EP U103
DI 10.1038/nature08644
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900037
PM 20016487
DA 2026-03-09
ER

PT J
AU Ranero, CR
   Pérez-Gussinyé, M
AF Ranero, Cesar R.
   Perez-Gussinye, Marta
TI Sequential faulting explains the asymmetry and extension discrepancy of conjugate margins
SO NATURE
LA English
DT Article
ID nonvolcanic rifted margins; continental extension; flemish cap; evolution; iberia; sea; models; basin; west; newfoundland
AB During early extension, cold continental lithosphere thins and subsides, creating rift basins. If extension continues to final break-up, the split and greatly thinned plates subside deep below sea level to form a conjugate pair of rifted margins. Although basins and margins are ubiquitous structures, the deformation processes leading from moderately extended basins to highly stretched margins are unclear, as studies consistently report that crustal thinning is greater than extension caused by brittle faulting(1-4). This extension discrepancy might arise from differential stretching of brittle and ductile crustal layers(2), but that does not readily explain the typical asymmetric structure of conjugate margins(5,6)-in cross-section, one margin displays gradual thinning accompanied by large faults, and the conjugate margin displays abrupt thinning but smaller-scale faulting(5). Whole-crust detachments, active from early in the rifting, could in theory create both thinning and asymmetry(1), but are mechanically problematical. Furthermore, the extension discrepancy occurs at both conjugate margins, leading to the apparent contradiction that both seem to be upper plates to a detachment fault(7,8). Alternative models propose that much brittle extension is undetected because of seismic imaging limitations caused either by subseismic-resolution faulting(9), invisible deformation along top-basement 100-km-scale detachments(8) or the structural complexity of cross-cutting arrays of faults(3). Here we use depth-migrated seismic images to accurately measure fault extension and compare it with crustal thinning. The observations are used to create a balanced kinematic model of rifting that resolves the extension discrepancy by producing both fault-controlled crustal thinning which progresses from a rift basin to the asymmetric structure, and extreme thinning of conjugate rifted margins. Contrary to current wisdom, the observations support the idea that thinning is to a first degree explained by simple Andersonian faulting that is unambiguously visible in seismic data.
C1 [Ranero, Cesar R.] CSIC, Inst Ciencias Mar, Barcelona Ctr Subsurface Imaging, ICREA, E-08003 Barcelona, Spain.
   [Perez-Gussinye, Marta] Univ London, Dept Earth Sci, Egham TW20 0BD, Surrey, England.
C3 ICREA; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); University of London; Royal Holloway University London
RP Ranero, CR (corresponding author), CSIC, Inst Ciencias Mar, Barcelona Ctr Subsurface Imaging, ICREA, Passeig Maritim Barcelona 37-49, E-08003 Barcelona, Spain.
EM cranero@icm.csic.es; m.perez@es.rhul.ac.uk
FU Repsol; Ministry of Science and Innovation; ICREA Funding Source: Custom
NR 44
TC 199
Z9 225
U1 4
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 NOV 11
PY 2010
VL 468
IS 7321
BP 294
EP U180
DI 10.1038/nature09520
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000049
PM 21048712
DA 2026-03-09
ER

PT J
AU Bowman, JD
   Rogers, AEE
AF Bowman, Judd D.
   Rogers, Alan E. E.
TI A lower limit of Δz &gt; 0.06 for the duration of the reionization epoch
SO NATURE
LA English
DT Article
ID high redshifts; fluctuations
AB Observations of the 21-centimetre line of atomic hydrogen in the early Universe directly probe the history of the reionization of the gas between galaxies(1). The observations are challenging, though, because of the low expected signal strength (similar to 10 mK), and contamination by strong (>100 K) foreground synchrotron emission in the Milky Way and extragalactic continuum sources(2). If reionization happened rapidly, there should be a characteristic signature(2-4) visible against the smooth foreground in an all-sky spectrum. Here we report an all-sky spectrum between 100 and 200 MHz, corresponding to the redshift range 6 < z < 13 for the 21-centimetre line. The data exclude a rapid reionization timescale of Delta z<0.06 at the 95% confidence level.
C1 [Bowman, Judd D.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Rogers, Alan E. E.] MIT, Haystack Observ, Westford, MA 01886 USA.
C3 Arizona State University; Arizona State University-Tempe; Massachusetts Institute of Technology (MIT)
RP Bowman, JD (corresponding author), Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
EM judd.bowman@asu.edu
FU NSF; NASA; Space Telescope Science Institute; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0905990] Funding Source: National Science Foundation
NR 13
TC 184
Z9 209
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 DEC 9
PY 2010
VL 468
IS 7325
BP 796
EP 798
DI 10.1038/nature09601
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700039
PM 21150993
DA 2026-03-09
ER

PT J
AU Liu, H
   Takeda, S
   Kumar, R
   Westergard, TD
   Brown, EJ
   Pandita, TK
   Cheng, EHY
   Hsieh, JJD
AF Liu, Han
   Takeda, Shugaku
   Kumar, Rakesh
   Westergard, Todd D.
   Brown, Eric J.
   Pandita, Tej K.
   Cheng, Emily H. -Y.
   Hsieh, James J. -D.
TI Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint
SO NATURE
LA English
DT Article
ID cell-cycle; dna-damage; fusion gene; maintenance; proteins; complex; association; activation; expression; stability
AB Cell cycle checkpoints are implemented to safeguard the genome, avoiding the accumulation of genetic errors(1,2). Checkpoint loss results in genomic instability and contributes to the evolution of cancer. Among G1-, S-, G2- and M-phase checkpoints, genetic studies indicate the role of an intact S-phase checkpoint in maintaining genome integrity(3,4). Although the basic framework of the S-phase checkpoint in multicellular organisms has been outlined, the mechanistic details remain to be elucidated. Human chromosome-11 band-q23 translocations disrupting the MLL gene lead to poor prognostic leukaemias(5-9). Here we assign MLL as a novel effector in the mammalian S-phase checkpoint network and identify checkpoint dysfunction as an underlying mechanism of MLL leukaemias. MLL is phosphorylated at serine 516 by ATR in response to genotoxic stress in the S phase, which disrupts its interaction with, and hence its degradation by, the SCFSkp2 E3 ligase, leading to its accumulation. Stabilized MLL protein accumulates on chromatin, methylates histone H3 lysine 4 at late replication origins and inhibits the loading of CDC45 to delay DNA replication. Cells deficient in MLL showed radioresistant DNA synthesis and chromatid-type genomic abnormalities, indicative of S-phase checkpoint dysfunction. Reconstitution of Mll(-/-) (Mll also known as Mll1) mouse embryonic fibroblasts with wild-type but not S516A or Delta SET mutant MLL rescues the S-phase checkpoint defects. Moreover, murine myeloid progenitor cells carrying an Mll-CBP knock-in allele that mimics human t(11;16) leukaemia show a severe radioresistant DNA synthesis phenotype. MLL fusions function as dominant negative mutants that abrogate the ATR-mediated phosphorylation/stabilization of wild-type MLL on damage to DNA, and thus compromise the S-phase checkpoint. Together, our results identify MLL as a key constituent of the mammalian DNA damage response pathway and show that deregulation of the S-phase checkpoint incurred by MLL translocations probably contributes to the pathogenesis of human MLL leukaemias.
C1 [Liu, Han; Takeda, Shugaku; Westergard, Todd D.; Cheng, Emily H. -Y.; Hsieh, James J. -D.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Kumar, Rakesh; Pandita, Tej K.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
   [Brown, Eric J.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
C3 Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; University of Pennsylvania
RP Hsieh, JJD (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM jhsieh@dom.wustl.edu
FU American Society of Hematology [CA119008, CA129537/CA123232]
NR 38
TC 117
Z9 147
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 343
EP U126
DI 10.1038/nature09350
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900042
PM 20818375
DA 2026-03-09
ER

PT J
AU Dierolf, M
   Menzel, A
   Thibault, P
   Schneider, P
   Kewish, CM
   Wepf, R
   Bunk, O
   Pfeiffer, F
AF Dierolf, Martin
   Menzel, Andreas
   Thibault, Pierre
   Schneider, Philipp
   Kewish, Cameron M.
   Wepf, Roger
   Bunk, Oliver
   Pfeiffer, Franz
TI Ptychographic X-ray computed tomography at the nanoscale
SO NATURE
LA English
DT Article
ID diffraction microscopy; phase retrieval
AB X-ray tomography is an invaluable tool in biomedical imaging. It can deliver the three-dimensional internal structure of entire organisms as well as that of single cells, and even gives access to quantitative information, crucially important both for medical applications and for basic research(1-4). Most frequently such information is based on X-ray attenuation. Phase contrast is sometimes used for improved visibility but remains significantly harder to quantify(5,6). Here we describe an X-ray computed tomography technique that generates quantitative high-contrast three-dimensional electron density maps from phase contrast information without reverting to assumptions of a weak phase object or negligible absorption. This method uses a ptychographic coherent imaging approach to record tomographic data sets, exploiting both the high penetration power of hard X-rays and the high sensitivity of lensless imaging(7-9). As an example, we present images of a bone sample in which structures on the 100 nm length scale such as the osteocyte lacunae and the interconnective canalicular network are clearly resolved. The recovered electron density map provides a contrast high enough to estimate nanoscale bone density variations of less than one per cent. We expect this high-resolution tomography technique to provide invaluable information for both the life and materials sciences.
C1 [Dierolf, Martin; Thibault, Pierre; Pfeiffer, Franz] Tech Univ Munich, Dept Phys E17, D-85748 Garching, Germany.
   [Menzel, Andreas; Kewish, Cameron M.; Bunk, Oliver] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Schneider, Philipp] ETH, Inst Biomech, CH-8093 Zurich, Switzerland.
   [Wepf, Roger] EMEZ, CH-8093 Zurich, Switzerland.
C3 Technical University of Munich; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Thibault, P (corresponding author), Tech Univ Munich, Dept Phys E17, D-85748 Garching, Germany.
EM pierre.thibault@tum.de
FU DFG Cluster of Excellence "Munich-Centre for Advanced Photonics"
NR 30
TC 746
Z9 853
U1 4
U2 314
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 436
EP U82
DI 10.1038/nature09419
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200037
PM 20864997
DA 2026-03-09
ER

PT J
AU Li, J
   Liu, ZY
   Tan, C
   Guo, XM
   Wang, LJ
   Sancar, A
   Zhong, DP
AF Li, Jiang
   Liu, Zheyun
   Tan, Chuang
   Guo, Xunmin
   Wang, Lijuan
   Sancar, Aziz
   Zhong, Dongping
TI Dynamics and mechanism of repair of ultraviolet-induced (6-4) photoproduct by photolyase
SO NATURE
LA English
DT Article
ID dna photolyase; electron-transfer; crystal-structure; cofactor; enzyme; cryptochrome; histidines; binding
AB One of the detrimental effects of ultraviolet radiation on DNA is the formation of the (6-4) photoproduct, 6-4PP, between two adjacent pyrimidine rings(1). This lesion interferes with replication and transcription, and may result in mutation and cell death(2). In many organisms, a flavoenzyme called photolyase uses blue light energy to repair the 6-4PP (ref. 3). The molecular mechanism of the repair reaction is poorly understood. Here, we use ultrafast spectroscopy to show that the key step in the repair photocycle is a cyclic proton transfer between the enzyme and the substrate. By femtosecond synchronization of the enzymatic dynamics with the repair function, we followed the function evolution and observed direct electron transfer from the excited flavin cofactor to the 6-4PP in 225 picoseconds, but surprisingly fast back electron transfer in 50 picoseconds without repair. We found that the catalytic proton transfer between a histidine residue in the active site and the 6-4PP, induced by the initial photoinduced electron transfer from the excited flavin cofactor to 6-4PP, occurs in 425 picoseconds and leads to 6-4PP repair in tens of nanoseconds. These key dynamics define the repair photocycle and explain the underlying molecular mechanism of the enzyme's modest efficiency.
C1 [Li, Jiang; Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Li, Jiang; Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA.
   [Li, Jiang; Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping] Ohio State Univ, Dept Biochem, Program Biophys, Columbus, OH 43210 USA.
   [Li, Jiang; Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping] Ohio State Univ, Chem Phys Program, Columbus, OH 43210 USA.
   [Li, Jiang; Liu, Zheyun; Tan, Chuang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping] Ohio State Univ, Program Biochem, Columbus, OH 43210 USA.
   [Sancar, Aziz] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
C3 University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
RP Zhong, DP (corresponding author), Ohio State Univ, Dept Phys, 191 W Woodruff Ave, Columbus, OH 43210 USA.
EM dongping@mps.ohio-state.edu
FU National Institutes of Health [GM074813]; Packard fellowship; National Institute of Environmental Health Sciences [P30ES010126] Funding Source: NIH RePORTER
NR 26
TC 192
Z9 207
U1 1
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 887
EP U124
DI 10.1038/nature09192
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100041
PM 20657578
DA 2026-03-09
ER

PT J
AU Nogi, T
   Yasui, N
   Mihara, E
   Matsunaga, Y
   Noda, M
   Yamashita, N
   Toyofuku, T
   Uchiyama, S
   Goshima, Y
   Kumanogoh, A
   Takagi, J
AF Nogi, Terukazu
   Yasui, Norihisa
   Mihara, Emiko
   Matsunaga, Yukiko
   Noda, Masanori
   Yamashita, Naoya
   Toyofuku, Toshihiko
   Uchiyama, Susumu
   Goshima, Yoshio
   Kumanogoh, Atsushi
   Takagi, Junichi
TI Structural basis for semaphorin signalling through the plexin receptor
SO NATURE
LA English
DT Article
ID crystal-structure; protein; binding; ligand; resolution; complex; domain; met
AB Semaphorins and their receptor plexins constitute a pleiotropic cell-signalling system that is used in a wide variety of biological processes, and both protein families have been implicated in numerous human diseases(1-4). The binding of soluble or membrane-anchored semaphorins to the membrane-distal region of the plexin ecto-domain activates plexin's intrinsic GTPase-activating protein (GAP) at the cytoplasmic region, ultimately modulating cellular adhesion behaviour(5). However, the structural mechanism underlying the receptor activation remains largely unknown. Here we report the crystal structures of the semaphorin 6A (Sema6A) receptor-binding fragment and the plexin A2 (PlxnA2) ligand-binding fragment in both their pre-signalling (that is, before binding) and signalling (after complex formation) states. Before binding, the Sema6A ectodomain was in the expected 'face-to-face' homodimer arrangement, similar to that adopted by Sema3A and Sema4D, whereas PlxnA2 was in an unexpected 'head-on' homodimer arrangement. In contrast, the structure of the Sema6A-PlxnA2 signalling complex revealed a 2:2 heterotetramer in which the two PlxnA2 monomers dissociated from one another and docked onto the top face of the Sema6A homodimer using the same interface as the head-on homodimer, indicating that plexins undergo 'partner exchange'. Cell-based activity measurements using mutant ligands/receptors confirmed that the Sema6A face-to-face dimer arrangement is physiologically relevant and is maintained throughout signalling events. Thus, homodimer-to-heterodimer transitions of cell-surface plexin that result in a specific orientation of its molecular axis relative to the membrane may constitute the structural mechanism by which the ligand-binding 'signal' is transmitted to the cytoplasmic region, inducing GAP domain rearrangements and activation.
C1 [Nogi, Terukazu; Yasui, Norihisa; Mihara, Emiko; Matsunaga, Yukiko; Takagi, Junichi] Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, Suita, Osaka 5650871, Japan.
   [Noda, Masanori; Uchiyama, Susumu] Osaka Univ, Grad Sch Engn, Dept Biotechnol, Suita, Osaka 5650871, Japan.
   [Yamashita, Naoya; Goshima, Yoshio] Yokohama City Univ, Grad Sch Med, Dept Mol Pharmacol & Neurobiol, Yokohama, Kanagawa 2360004, Japan.
   [Toyofuku, Toshihiko; Kumanogoh, Atsushi] Osaka Univ, Microbial Dis Res Inst, Immunol Frontier Res Ctr, Dept Immunopathol, Suita, Osaka 5650871, Japan.
C3 University of Osaka; University of Osaka; Yokohama City University; University of Osaka
RP Takagi, J (corresponding author), Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, 3-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM takagi@protein.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Grants-in-Aid for Scientific Research [21700411, 22247010, 22370039] Funding Source: KAKEN
NR 42
TC 128
Z9 158
U1 0
U2 30
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1123
EP U138
DI 10.1038/nature09473
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600051
PM 20881961
DA 2026-03-09
ER

PT J
AU Kraus, S
   Hofmann, KH
   Menten, KM
   Schertl, D
   Weigelt, G
   Wyrowski, F
   Meilland, A
   Perraut, K
   Petrov, R
   Robbe-Dubois, S
   Schilke, P
   Testi, L
AF Kraus, Stefan
   Hofmann, Karl-Heinz
   Menten, Karl M.
   Schertl, Dieter
   Weigelt, Gerd
   Wyrowski, Friedrich
   Meilland, Anthony
   Perraut, Karine
   Petrov, Romain
   Robbe-Dubois, Sylvie
   Schilke, Peter
   Testi, Leonardo
TI A hot compact dust disk around a massive young stellar object
SO NATURE
LA English
DT Article
ID spectral energy-distributions; t-tauri stars; southern-hemisphere; radiative-transfer; accretion; candidates; emission; outflows; glimpse; systems
AB Circumstellar disks are an essential ingredient of the formation(1) of low-mass stars. It is unclear, however, whether the accretion-disk paradigm can also account for the formation of stars more massive than about 10 solar masses(2), in which strong radiation pressure might halt mass infall(3,4). Massive stars may form by stellar merging(5), although more recent theoretical investigations suggest that the radiative-pressure limit may be overcome by considering more complex, non-spherical infall geometries(6,7). Clear observational evidence, such as the detection of compact dusty disks(8) around massive young stellar objects, is needed to identify unambiguously the formation mode of the most massive stars. Here we report near-infrared interferometric observations that spatially resolve the astronomical-unit-scale distribution of hot material around a high-mass (similar to 20 solar masses) young stellar object. The image shows an elongated structure with a size of similar to 13 x 19 astronomical units, consistent with a disk seen at an inclination angle of similar to 45 degrees. Using geometric and detailed physical models, we found a radial temperature gradient in the disk, with a dust-free region less than 9.5 astronomical units from the star, qualitatively and quantitatively similar to the disks observed in low-mass star formation. Perpendicular to the disk plane we observed a molecular outflow and two bow shocks, indicating that a bipolar outflow emanates from the inner regions of the system.
C1 [Kraus, Stefan] Univ Michigan, Dept Astron, Ann Arbor, MI 48103 USA.
   [Hofmann, Karl-Heinz; Menten, Karl M.; Schertl, Dieter; Weigelt, Gerd; Wyrowski, Friedrich; Meilland, Anthony] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Meilland, Anthony; Petrov, Romain; Robbe-Dubois, Sylvie] Univ Nice Sophia Antipolis, CNRS, Observ Cote Azur, Lab Hippolyte Fizeau,UMR 6525, F-06108 Nice 2, France.
   [Perraut, Karine] Univ Grenoble 1, CNRS, UMR 5571, Lab Astrophys Grenoble, F-38041 Grenoble 9, France.
   [Schilke, Peter] Univ Cologne, Inst Phys 1, D-50937 Cologne, Germany.
   [Testi, Leonardo] INAF Osservatorio Astrofis Arcetri, I-50125 Florence, Italy.
C3 University of Michigan System; University of Michigan; Max Planck Society; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); University of Cologne; Istituto Nazionale Astrofisica (INAF)
RP Kraus, S (corresponding author), Univ Michigan, Dept Astron, 500 Church St, Ann Arbor, MI 48103 USA.
EM stefankr@umich.edu
FU NASA
NR 30
TC 126
Z9 139
U1 0
U2 18
PU 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 15
PY 2010
VL 466
IS 7304
BP 339
EP 342
DI 10.1038/nature09174
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100042
PM 20631793
DA 2026-03-09
ER

PT J
AU Krivanek, OL
   Chisholm, MF
   Nicolosi, V
   Pennycook, TJ
   Corbin, GJ
   Dellby, N
   Murfitt, MF
   Own, CS
   Szilagyi, ZS
   Oxley, MP
   Pantelides, ST
   Pennycook, SJ
AF Krivanek, Ondrej L.
   Chisholm, Matthew F.
   Nicolosi, Valeria
   Pennycook, Timothy J.
   Corbin, George J.
   Dellby, Niklas
   Murfitt, Matthew F.
   Own, Christopher S.
   Szilagyi, Zoltan S.
   Oxley, Mark P.
   Pantelides, Sokrates T.
   Pennycook, Stephen J.
TI Atom-by-atom structural and chemical analysis by annular dark-field electron microscopy
SO NATURE
LA English
DT Article
ID sub-angstrom resolution; single atoms; graphite; nitrogen; graphene; carbon; oxygen; boron
AB Direct imaging and chemical identification of all the atoms in a material with unknown three-dimensional structure would constitute a very powerful general analysis tool. Transmission electron microscopy should in principle be able to fulfil this role, as many scientists including Feynman realized early on(1). It images matter with electrons that scatter strongly from individual atoms and whose wavelengths are about 50 times smaller than an atom. Recently the technique has advanced greatly owing to the introduction of aberration-corrected optics(2-8). However, neither electron microscopy nor any other experimental technique has yet been able to resolve and identify all the atoms in a non-periodic material consisting of several atomic species. Here we show that annular dark-field imaging in an aberration-corrected scanning transmission electron microscope optimized for low voltage operation can resolve and identify the chemical type of every atom in monolayer hexagonal boron nitride that contains substitutional defects. Three types of atomic substitutions were found and identified: carbon substituting for boron, carbon substituting for nitrogen, and oxygen substituting for nitrogen. The substitutions caused in-plane distortions in the boron nitride monolayer of about 0.1 angstrom magnitude, which were directly resolved, and verified by density functional theory calculations. The results demonstrate that atom-by-atom structural and chemical analysis of all radiation-damage-resistant atoms present in, and on top of, ultrathin sheets has now become possible.
C1 [Krivanek, Ondrej L.; Corbin, George J.; Dellby, Niklas; Murfitt, Matthew F.; Own, Christopher S.; Szilagyi, Zoltan S.] Nion Co, Kirkland, WA 98033 USA.
   [Chisholm, Matthew F.; Pennycook, Timothy J.; Oxley, Mark P.; Pantelides, Sokrates T.; Pennycook, Stephen J.] Oak Ridge Natl Lab, Div Mat Sci & Technol, Oak Ridge, TN 37831 USA.
   [Nicolosi, Valeria] Univ Oxford, Dept Mat, Oxford OX1 3PH, England.
   [Pennycook, Timothy J.; Oxley, Mark P.; Pantelides, Sokrates T.; Pennycook, Stephen J.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA.
C3 United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Oxford; Vanderbilt University
RP Krivanek, OL (corresponding author), Nion Co, 1102 8th St, Kirkland, WA 98033 USA.
EM krivanek@nion.com
FU Division of Materials Sciences and Engineering of the US Department of Energy [DE-FG02-09ER46554]; McMinn Endowment
NR 28
TC 1172
Z9 1322
U1 25
U2 788
PU 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 25
PY 2010
VL 464
IS 7288
BP 571
EP 574
DI 10.1038/nature08879
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200043
PM 20336141
DA 2026-03-09
ER

PT J
AU Alushin, GM
   Ramey, VH
   Pasqualato, S
   Ball, DA
   Grigorieff, N
   Musacchio, A
   Nogales, E
AF Alushin, Gregory M.
   Ramey, Vincent H.
   Pasqualato, Sebastiano
   Ball, David A.
   Grigorieff, Nikolaus
   Musacchio, Andrea
   Nogales, Eva
TI The Ndc80 kinetochore complex forms oligomeric arrays along microtubules
SO NATURE
LA English
DT Article
ID chromosome bi-orientation; electron-microscopy; attachment site; molecular architecture; outer kinetochore; structural basis; spindle pole; resolution; hec1; visualization
AB The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment (a process required for cell division), but the molecular mechanism underlying its function remains unknown. Here we present a subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules, sufficient for precise docking of crystal structures of the component proteins. We find that the Ndc80 complex binds the microtubule with a tubulin monomer repeat, recognizing alpha- and beta-tubulin at both intra-and inter-tubulin dimer interfaces in a manner that is sensitive to tubulin conformation. Furthermore, Ndc80 complexes self-associate along protofilaments through interactions mediated by the amino-terminal tail of the NDC80 protein, which is the site of phospho-regulation by Aurora B kinase. The complex's mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing kinetochore-microtubule attachments.
C1 [Ball, David A.; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Alushin, Gregory M.; Ramey, Vincent H.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
   [Pasqualato, Sebastiano; Musacchio, Andrea] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy.
   [Grigorieff, Nikolaus] Brandeis Univ, Rosenstiel Basic Med Res Ctr, Howard Hughes Med Inst, Waltham, MA 02453 USA.
   [Musacchio, Andrea] Italian Inst Technol, Res Unit, I-20139 Milan, Italy.
   [Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, Howard Hughes Med Inst, 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; IRCCS European Institute of Oncology (IEO); Brandeis University; Howard Hughes Medical Institute; Istituto Italiano di Tecnologia - IIT; Howard Hughes Medical Institute; University of California System; University of California Berkeley
RP Nogales, E (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
EM enogales@lbl.gov
FU National Institute of General Medical Sciences
NR 57
TC 253
Z9 287
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 OCT 14
PY 2010
VL 467
IS 7317
BP 805
EP U68
DI 10.1038/nature09423
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700058
PM 20944740
DA 2026-03-09
ER

PT J
AU D'Angiolella, V
   Donato, V
   Vijayakumar, S
   Saraf, A
   Florens, L
   Washburn, MP
   Dynlacht, B
   Pagano, M
AF D'Angiolella, Vincenzo
   Donato, Valerio
   Vijayakumar, Sangeetha
   Saraf, Anita
   Florens, Laurence
   Washburn, Michael P.
   Dynlacht, Brian
   Pagano, Michele
TI SCFCyclin F controls centrosome homeostasis and mitotic fidelity through CP110 degradation
SO NATURE
LA English
DT Article
ID proteomic analysis; ubiquitin ligase; cyclin-f; identification; biogenesis; mechanisms; substrate
AB Generally, F-box proteins are the substrate recognition subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes, which mediate the timely proteolysis of important eukaryotic regulatory proteins(1,2). Mammalian genomes encode roughly 70 F-box proteins, but only a handful have established functions(3,4). The F-box protein family obtained its name from Cyclin F (also called Fbxo1), in which the F-box motif (the similar to 40-amino-acid domain required for binding to Skp1) was first described(5). Cyclin F, which is encoded by an essential gene, also contains a cyclin box domain, but in contrast to most cyclins, it does not bind or activate any cyclin-dependent kinases (CDKs)(5-7). However, like other cyclins, Cyclin F oscillates during the cell cycle, with protein levels peaking in G2. Despite its essential nature and status as the founding member of the F-box protein family, Cyclin F remains an orphan protein, whose functions are unknown. Starting from an unbiased screen, we identified CP110, a protein that is essential for centrosome duplication, as an interactor and substrate of Cyclin F. Using a mode of substrate binding distinct from other F-box protein-substrate pairs, CP110 and Cyclin F physically associate on the centrioles during the G2 phase of the cell cycle, and CP110 is ubiquitylated by the SCFCyclin F ubiquitin ligase complex, leading to its degradation. siRNA-mediated depletion of Cyclin F in G2 induces centrosomal and mitotic abnormalities, such as multipolar spindles and asymmetric, bipolar spindles with lagging chromosomes. These phenotypes were reverted by co-silencing CP110 and were recapitulated by expressing a stable mutant of CP110 that cannot bind Cyclin F. Finally, expression of a stable CP110 mutant in cultured cells also promotes the formation of micronuclei, a hallmark of chromosome instability. We propose that SCFCyclin F-mediated degradation of CP110 is required for the fidelity of mitosis and genome integrity.
C1 [D'Angiolella, Vincenzo; Donato, Valerio; Vijayakumar, Sangeetha; Dynlacht, Brian; Pagano, Michele] NYU, Sch Med, Inst Canc, Dept Pathol, New York, NY 10016 USA.
   [Saraf, Anita; Florens, Laurence; Washburn, Michael P.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Washburn, Michael P.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA.
   [Pagano, Michele] Howard Hughes Med Inst, Chevy Chase, MD USA.
C3 New York University; Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center; Howard Hughes Medical Institute
RP Pagano, M (corresponding author), NYU, Sch Med, Inst Canc, Dept Pathol, 522 1st Ave,SRB 1107, New York, NY 10016 USA.
EM michele.pagano@nyumc.org
FU American Italian Cancer Foundation; March of Dimes [1-FY08-372]; National Institutes of Health [R01-GM057587, R37-CA076584, R21-AG032560]; Stowers Institute for Medical Research
NR 34
TC 224
Z9 268
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 JUL 1
PY 2010
VL 466
IS 7302
BP 138
EP U161
DI 10.1038/nature09140
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800050
PM 20596027
DA 2026-03-09
ER

PT J
AU Gilbert, C
   Schaack, S
   Pace, JK
   Brindley, PJ
   Feschotte, C
AF Gilbert, Clement
   Schaack, Sarah
   Pace, John K., II
   Brindley, Paul J.
   Feschotte, Cedric
TI A role for host-parasite interactions in the horizontal transfer of transposons across phyla
SO NATURE
LA English
DT Article
ID gene-transfer; dna transposon; trypanosoma-rangeli; lymnaea-stagnalis; divergence times; phylogeny; mitochondrial; rodents; model; phylogeography
AB Horizontal transfer (HT), or the passage of genetic material between non-mating species, is increasingly recognized as an important force in the evolution of eukaryotic genomes(1,2). Transposons, with their inherent ability to mobilize and amplify within genomes, may be especially prone to HT3-7. However, the means by which transposons can spread across widely diverged species remain elusive. Here we present evidence that host-parasite interactions have promoted the HT of four transposon families between invertebrates and vertebrates. We found that Rhodnius prolixus, a triatomine bug feeding on the blood of various tetrapods and vector of Chagas' disease in humans, carries in its genome four distinct transposon families that also invaded the genomes of a diverse, but overlapping, set of tetrapods. The bug transposons are similar to 98% identical and cluster phylogenetically with those of the opossum and squirrel monkey, two of its preferred mammalian hosts in South America. We also identified one of these transposon families in the pond snail Lymnaea stagnalis, a cosmopolitan vector of trematodes infecting diverse vertebrates, whose ancestral sequence is nearly identical and clusters with those found in Old World mammals. Together these data provide evidence for a previously hypothesized role of host-parasite interactions in facilitating HT among animals(3,7). Furthermore, the large amount of DNA generated by the amplification of the horizontally transferred transposons supports the idea that the exchange of genetic material between hosts and parasites influences their genomic evolution.
C1 [Gilbert, Clement; Schaack, Sarah; Pace, John K., II; Feschotte, Cedric] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
   [Brindley, Paul J.] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
C3 University of Texas System; University of Texas Arlington; George Washington University
RP Feschotte, C (corresponding author), Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
EM cedric@uta.edu
FU National Institutes of Health; National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0805546] Funding Source: National Science Foundation
NR 62
TC 198
Z9 231
U1 0
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1347
EP U4
DI 10.1038/nature08939
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000046
PM 20428170
DA 2026-03-09
ER

PT J
AU Walters, RG
   Jacquemont, S
   Valsesia, A
   de Smith, AJ
   Martinet, D
   Andersson, J
   Falchi, M
   Chen, F
   Andrieux, J
   Lobbens, S
   Delobel, B
   Stutzmann, F
   Moustafa, JSES
   Chèvre, JC
   Lecoeur, C
   Vatin, V
   Bouquillon, S
   Buxton, JL
   Boute, O
   Holder-Espinasse, M
   Cuisset, JM
   Lemaitre, MP
   Ambresin, AE
   Brioschi, A
   Gaillard, M
   Giusti, V
   Fellmann, F
   Ferrarini, A
   Hadjikhani, N
   Campion, D
   Guilmatre, A
   Goldenberg, A
   Calmels, N
   Mandel, JL
   Le Caignec, C
   David, A
   Isidor, B
   Cordier, MP
   Dupuis-Girod, S
   Labalme, A
   Sanlaville, D
   Béri-Dexheimer, M
   Jonveaux, P
   Leheup, B
   Ounap, K
   Bochukova, EG
   Henning, E
   Keogh, J
   Ellis, RJ
   MacDermot, KD
   van Haelst, MM
   Vincent-Delorme, C
   Plessis, G
   Touraine, R
   Philippe, A
   Malan, V
   Mathieu-Dramard, M
   Chiesa, J
   Blaumeiser, B
   Kooy, RF
   Caiazzo, R
   Pigeyre, M
   Balkau, B
   Sladek, R
   Bergmann, S
   Mooser, V
   Waterworth, D
   Reymond, A
   Vollenweider, P
   Waeber, G
   Kurg, A
   Palta, P
   Esko, T
   Metspalu, A
   Nelis, M
   Elliott, P
   Hartikainen, AL
   McCarthy, MI
   Peltonen, L
   Carlsson, L
   Jacobson, P
   Sjöström, L
   Huang, N
   Hurles, ME
   O'Rahilly, S
   Farooqi, IS
   Männik, K
   Jarvelin, MR
   Pattou, F
   Meyre, D
   Walley, AJ
   Coin, LJM
   Blakemore, AIF
   Froguel, P
   Beckmann, JS
AF Walters, R. G.
   Jacquemont, S.
   Valsesia, A.
   de Smith, A. J.
   Martinet, D.
   Andersson, J.
   Falchi, M.
   Chen, F.
   Andrieux, J.
   Lobbens, S.
   Delobel, B.
   Stutzmann, F.
   Moustafa, J. S. El-Sayed
   Chevre, J. -C.
   Lecoeur, C.
   Vatin, V.
   Bouquillon, S.
   Buxton, J. L.
   Boute, O.
   Holder-Espinasse, M.
   Cuisset, J. -M.
   Lemaitre, M. -P.
   Ambresin, A. -E.
   Brioschi, A.
   Gaillard, M.
   Giusti, V.
   Fellmann, F.
   Ferrarini, A.
   Hadjikhani, N.
   Campion, D.
   Guilmatre, A.
   Goldenberg, A.
   Calmels, N.
   Mandel, J. -L.
   Le Caignec, C.
   David, A.
   Isidor, B.
   Cordier, M. -P.
   Dupuis-Girod, S.
   Labalme, A.
   Sanlaville, D.
   Beri-Dexheimer, M.
   Jonveaux, P.
   Leheup, B.
   Ounap, K.
   Bochukova, E. G.
   Henning, E.
   Keogh, J.
   Ellis, R. J.
   MacDermot, K. D.
   van Haelst, M. M.
   Vincent-Delorme, C.
   Plessis, G.
   Touraine, R.
   Philippe, A.
   Malan, V.
   Mathieu-Dramard, M.
   Chiesa, J.
   Blaumeiser, B.
   Kooy, R. F.
   Caiazzo, R.
   Pigeyre, M.
   Balkau, B.
   Sladek, R.
   Bergmann, S.
   Mooser, V.
   Waterworth, D.
   Reymond, A.
   Vollenweider, P.
   Waeber, G.
   Kurg, A.
   Palta, P.
   Esko, T.
   Metspalu, A.
   Nelis, M.
   Elliott, P.
   Hartikainen, A. -L.
   McCarthy, M. I.
   Peltonen, L.
   Carlsson, L.
   Jacobson, P.
   Sjostrom, L.
   Huang, N.
   Hurles, M. E.
   O'Rahilly, S.
   Farooqi, I. S.
   Maennik, K.
   Jarvelin, M. -R.
   Pattou, F.
   Meyre, D.
   Walley, A. J.
   Coin, L. J. M.
   Blakemore, A. I. F.
   Froguel, P.
   Beckmann, J. S.
TI A new highly penetrant form of obesity due to deletions on chromosome 16p11.2
SO NATURE
LA English
DT Article
ID genome-wide association; circular binary segmentation; copy number variation; frameshift mutation; risk loci; microdeletion; autism; sample; birth; mc4r
AB Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution(1). Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component(1). Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge(2). Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >= 40 kg m(-2) or BMI standard deviation score >= 4; P = 6.43 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme'(4) in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
C1 [Walters, R. G.; de Smith, A. J.; Andersson, J.; Falchi, M.; Moustafa, J. S. El-Sayed; Buxton, J. L.; Walley, A. J.; Blakemore, A. I. F.; Froguel, P.] Univ London Imperial Coll Sci Technol & Med, Sect Genom Med, London W12 0NN, England.
   [Walters, R. G.; Elliott, P.; Jarvelin, M. -R.; Coin, L. J. M.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
   [Jacquemont, S.; Martinet, D.; Gaillard, M.; Fellmann, F.; Ferrarini, A.; Beckmann, J. S.] CHU Vaudois, Serv Genet Med, CH-1011 Lausanne, Switzerland.
   [Valsesia, A.; Bergmann, S.; Beckmann, J. S.] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland.
   [Valsesia, A.] Univ Lausanne, Ludwig Inst Canc Res, CH-1015 Lausanne, Switzerland.
   [Valsesia, A.; Bergmann, S.] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Chen, F.; Hadjikhani, N.] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland.
   [Andrieux, J.; Bouquillon, S.] Ctr Hosp Reg Univ, Med Genet Lab, F-59000 Lille, France.
   [Lobbens, S.; Stutzmann, F.; Chevre, J. -C.; Lecoeur, C.; Vatin, V.; Meyre, D.; Froguel, P.] Inst Pasteur, Inst Biol 8090, CNRS, F-59800 Lille, France.
   [Delobel, B.] Hop St Vincent de Paul, Ctr Genet Chromosom, GHICL, F-59020 Lille, France.
   [Boute, O.; Holder-Espinasse, M.] CHU Lille, Serv Genet Clin, Hop Jeanne Flandre, F-59000 Lille, France.
   [Cuisset, J. -M.; Lemaitre, M. -P.] Ctr Hosp Reg Univ, Serv Neuropediat, F-59000 Lille, France.
   [Ambresin, A. -E.] CHU Vaudois, Unite Multidisciplinaire Sante Adolescents, CH-1011 Lausanne, Switzerland.
   [Brioschi, A.] CHU Vaudois, Serv Neuropsychol & Neurorehabil, CH-1011 Lausanne, Switzerland.
   [Giusti, V.] CHU Vaudois, Serv Endocrinol, CH-1011 Lausanne, Switzerland.
   [Hadjikhani, N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
   [Campion, D.; Guilmatre, A.] Fac Med, INSERM, U614, F-76183 Rouen, France.
   [Goldenberg, A.] CHU Rouen, Serv Genet, F-76031 Rouen, France.
   [Calmels, N.; Mandel, J. -L.] Nouvel Hop Civil, Lab Diagnost Genet, F-67091 Strasbourg, France.
   [Le Caignec, C.; David, A.; Isidor, B.] CHU Nantes, Serv Genet Med, F-44093 Nantes, France.
   [Le Caignec, C.] Inst Thorax, UMR915, INSERM, F-44007 Nantes, France.
   [Cordier, M. -P.; Dupuis-Girod, S.; Labalme, A.; Sanlaville, D.] Hop Hotel Dieu, Hosp Civils Lyon, Serv Genet, F-69288 Lyon, France.
   [Sanlaville, D.] Univ Lyon 1, EA 4171, F-69622 Villeurbanne, France.
   [Beri-Dexheimer, M.; Jonveaux, P.; Leheup, B.] Nancy Univ, Ctr Hosp Univ, Genet Lab, F-54511 Vandoeuvre Les Nancy, France.
   [Leheup, B.] Univ Henri Poincare, Med Sch Nancy EA4368, F-54003 Nancy, France.
   [Ounap, K.] Univ Tartu, Childrens Hosp, United Labs, Dept Genet, EE-50406 Tartu, Estonia.
   [Bochukova, E. G.; Henning, E.; Keogh, J.; O'Rahilly, S.; Farooqi, I. S.] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
   [Ellis, R. J.; MacDermot, K. D.; van Haelst, M. M.] Northwick Pk & St Marks Hosp, NW Thames Reg Genet Serv, Harrow HA1 3UJ, Middx, England.
   [Vincent-Delorme, C.] Ctr Hosp Arras, F-62000 Arras, France.
   [Plessis, G.] Ctr Hosp Univ Clemenceau, Serv Genet Med, F-14033 Caen, France.
   [Touraine, R.] Ctr Hosp Univ Hop Nord, Serv Genet, F-42055 St Etienne, France.
   [Philippe, A.; Malan, V.] Univ Paris 05, Hop Necker Enfants Malad, Dept Genet, F-75015 Paris, France.
   [Philippe, A.; Malan, V.] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U781, F-75015 Paris, France.
   [Mathieu-Dramard, M.] Ctr Hosp Univ, Serv Genet Clin, F-80054 Amiens, France.
   [Chiesa, J.] Ctr Hosp Univ Caremeau, Lab Cytogenet, F-30029 Nimes, France.
   [Blaumeiser, B.; Kooy, R. F.] Univ Hosp & Univ Antwerp, Dept Med Genet, B-2650 Edegem, Belgium.
   [Caiazzo, R.; Pattou, F.] INSERM, U859, F-59045 Lille, France.
   [Caiazzo, R.; Pigeyre, M.; Pattou, F.] Univ Lille Nord France, CHU Lille, F-59037 Lille, France.
   [Balkau, B.] INSERM, U780, IFR69, F-94807 Villejuif, France.
   [Sladek, R.] McGill Univ, Montreal, PQ H3A 1A4, Canada.
   [Sladek, R.] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada.
   [Sladek, R.] McGill Univ, Dept Med & Human Genet, Montreal, PQ H3A 1B1, Canada.
   [Mooser, V.; Waterworth, D.] GlaxoSmithKline, Div Genet, Philadelphia, PA 19101 USA.
   [Reymond, A.] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
   [Vollenweider, P.; Waeber, G.] CHU Vaudois, Dept Med, CH-1011 Lausanne, Switzerland.
   [Kurg, A.; Palta, P.; Maennik, K.] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
   [Esko, T.; Metspalu, A.; Nelis, M.] Univ Tartu, Estonian Genome Project, EE-50410 Tartu, Estonia.
   [Esko, T.; Metspalu, A.; Nelis, M.] Estonian Bioctr, EE-51010 Tartu, Estonia.
   [Hartikainen, A. -L.] Univ Oulu, Dept Obstet & Gynaecol, SF-90220 Oulu, Finland.
   [McCarthy, M. I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [McCarthy, M. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Peltonen, L.; Huang, N.; Hurles, M. E.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Peltonen, L.] Biomedicum, Inst Mol Med, Helsinki 00290, Finland.
   [Peltonen, L.] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Carlsson, L.; Jacobson, P.; Sjostrom, L.] Sahlgrens Acad, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden.
   [Carlsson, L.; Jacobson, P.; Sjostrom, L.] Sahlgrens Acad, Ctr Cardiovasc & Metab Res, S-41345 Gothenburg, Sweden.
   [Jarvelin, M. -R.] Natl Publ Hlth Inst, Dept Child & Adolescent Hlth, Oulu 90101, Finland.
   [Jarvelin, M. -R.] Univ Oulu, Inst Hlth Sci, SF-90220 Oulu, Finland.
   [Jarvelin, M. -R.] Univ Oulu, Bioctr Oulu, SF-90220 Oulu, Finland.
C3 Imperial College London; Imperial College London; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Lausanne; Ludwig Institute for Cancer Research; Swiss Institute of Bioinformatics; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Universite de Lille; CHU Lille; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite de Lille; Institut Pasteur Lille; Universite de Lille; CHU Lille; Universite de Lille; CHU Lille; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Universite de Rouen Normandie; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Rouen Normandie; CHU de Rouen; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Strasbourg; Nantes Universite; CHU de Nantes; Nantes Universite; CHU de Nantes; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Lyon; Universite Lyon 1; CHU de Nancy; Universite de Lorraine; Universite de Lorraine; University of Tartu; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; Imperial College London; CHU de Caen NORMANDIE; CHU de St Etienne; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite de Picardie Jules Verne (UPJV); CHU Amiens; Universite de Montpellier; CHU de Nimes; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Lille; Universite de Lille; CHU Lille; Institut National de la Sante et de la Recherche Medicale (Inserm); McGill University; McGill University; GlaxoSmithKline; Glaxosmithkline USA; University of Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Tartu; University of Tartu; Estonian Biocentre; University of Oulu; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; Wellcome Trust Sanger Institute; University of Helsinki; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Gothenburg; University of Gothenburg; Finland National Institute for Health & Welfare; University of Oulu; University of Oulu
RP Froguel, P (corresponding author), Univ London Imperial Coll Sci Technol & Med, Sect Genom Med, London W12 0NN, England.
EM p.froguel@imperial.ac.uk; jacques.beckmann@chuv.ch
FU Wellcome Trust; Medical Research Council (MRC) [G0500539]; Swiss National Foundation [310000-112552, 33CSCO-122661]; RCUK; Swiss National Fund [320030_122674]; Synapsis Foundation; University of Lausanne; Ludwig Institute for Cancer Research; Swiss Institute of Bioinformatics; le Conseil Regional Nord Pas de Calais/FEDER; GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne; Estonian Government [SF0180142s08]; EU; FP7 [201413 ENGAGE, 212111 BBMRI]; ECOGENE [205419]; Genome Canada; Genome Quebec; Swedish Research Council [K2008-65X-20753-01-4, K2007-55X-11285-13, 529-2002-6671]; Swedish Foundation for Strategic Research; Swedish Diabetes Foundation; Ake Wiberg Foundation; Foundations of the National Board of Health and Welfare; Jeansson Foundations; Magn Bergvall Foundation; Tore Nilson Foundation; Royal Physiographic Society; INNOVA-VINNMER; Swedish federal government; INSERM; CNAMTS; Lilly; Novartis Pharma; Sanofi-Aventis; Association Diabete Risque Vasculaire; Federation Francaise de Cardiologie; La Fondation de France; ALFEDIAM; ONIVINS; Ardix Medical, Bayer Diagnostics; Becton Dickinson; Cardionics; Merck Sante; Novo Nordisk; Pierre Fabre; Roche and Topcon; Academy of Finland [104781, 120315]; University Hospital Oulu; Biocenter, University of Oulu, Finland; European Commission [QLG1-CT-2000-01643]; NHLBI [5R01HL087679-02, 1RL1MH083268-01]; NIH/NIMH [5R01MH63706: 02]; ENGAGE [HEALTH-F4-2007-201413];  [SF0180026s09]; Medical Research Council [G0600331, G0900554] Funding Source: researchfish; Swiss National Science Foundation (SNF) [320030_122674] Funding Source: Swiss National Science Foundation (SNF); MRC [G0600331, G0900554] Funding Source: UKRI
NR 41
TC 398
Z9 464
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 FEB 4
PY 2010
VL 463
IS 7281
BP 671
EP U104
DI 10.1038/nature08727
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900038
PM 20130649
DA 2026-03-09
ER

PT J
AU Krause, J
   Fu, QM
   Good, JM
   Viola, B
   Shunkov, MV
   Derevianko, AP
   Pääbo, S
AF Krause, Johannes
   Fu, Qiaomei
   Good, Jeffrey M.
   Viola, Bence
   Shunkov, Michael V.
   Derevianko, Anatoli P.
   Paeaebo, Svante
TI The complete mitochondrial DNA genome of an unknown hominin from southern Siberia
SO NATURE
LA English
DT Article
ID sequence; origin; flores; age
AB With the exception of Neanderthals, from which DNA sequences of numerous individuals have now been determined(1), the number and genetic relationships of other hominin lineages are largely unknown. Here we report a complete mitochondrial (mt) DNA sequence retrieved from a bone excavated in 2008 in Denisova Cave in the Altai Mountains in southern Siberia. It represents a hitherto unknown type of hominin mtDNA that shares a common ancestor with anatomically modern human and Neanderthal mtDNAs about 1.0 million years ago. This indicates that it derives from a hominin migration out of Africa distinct from that of the ancestors of Neanderthals and of modern humans. The stratigraphy of the cave where the bone was found suggests that the Denisova hominin lived close in time and space with Neanderthals as well as with modern humans(2-4).
C1 [Krause, Johannes; Fu, Qiaomei; Viola, Bence; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
   [Good, Jeffrey M.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Viola, Bence] Univ Vienna, Dept Anthropol, A-1090 Vienna, Austria.
   [Shunkov, Michael V.; Derevianko, Anatoli P.] Russian Acad Sci, Siberian Branch, Inst Archaeol & Ethnog, Paleolith Dept, RU-630090 Novosibirsk 17, Russia.
C3 Max Planck Society; University of Montana System; University of Montana; University of Vienna; Russian Academy of Sciences
RP Krause, J (corresponding author), Max Planck Inst Evolutionary Anthropol, Deutsch Pl 6, D-04103 Leipzig, Germany.
EM krause@eva.mpg.de
FU Max Planck Society; NSF [OISE-0754461]
NR 29
TC 534
Z9 636
U1 2
U2 251
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 894
EP 897
DI 10.1038/nature08976
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300038
PM 20336068
DA 2026-03-09
ER

PT J
AU Panáková, D
   Werdich, AA
   MacRae, CA
AF Panakova, Daniela
   Werdich, Andreas A.
   MacRae, Calum A.
TI Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca2+ channel
SO NATURE
LA English
DT Article
ID voltage-sensitive dyes; cardiac tissue; cell-cultures; conduction; gastrulation; activation; movements; differentiation; morphogenesis; mechanisms
AB Electrical gradients are critical for many biological processes, including the normal function of excitable tissues, left-right patterning, organogenesis and wound healing(1-4). The fundamental mechanisms that regulate the establishment and maintenance of such electrical polarities are poorly understood. Here we identify a gradient of electrical coupling across the developing ventricular myocardium using high-speed optical mapping of transmembrane potentials and calcium concentrations in the zebrafish heart. We excluded a role for differences in cellular excitability, connexin localization, tissue geometry and mechanical inputs, but in contrast we were able to demonstrate that non-canonical Wnt11 signals are required for the genesis of this myocardial electrical gradient. Although the traditional planar cell polarity pathway is not involved, we obtained evidence that Wnt11 acts to set up this gradient of electrical coupling through effects on transmembrane Ca2+ conductance mediated by the L-type calcium channel. These data reveal a previously unrecognized role for Wnt/Ca2+ signalling in establishing an electrical gradient in the plane of the developing cardiac epithelium through modulation of ion-channel function. The regulation of cellular coupling through such mechanisms may be a general property of non-canonical Wnt signals.
C1 [Panakova, Daniela; Werdich, Andreas A.; MacRae, Calum A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP MacRae, CA (corresponding author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, 75 Francis St,Thorn 11, Boston, MA 02115 USA.
EM camacrae@bics.bwh.harvard.edu
FU HFSP; NIH; March of Dimes
NR 42
TC 120
Z9 145
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 874
EP U109
DI 10.1038/nature09249
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100038
PM 20657579
DA 2026-03-09
ER

PT J
AU Moschetti, MP
   Ritzwoller, MH
   Lin, F
   Yang, Y
AF Moschetti, M. P.
   Ritzwoller, M. H.
   Lin, F.
   Yang, Y.
TI Seismic evidence for widespread western-US deep-crustal deformation caused by extension
SO NATURE
LA English
DT Article
ID surface-wave tomography; phase-velocity; united-states; mantle flow; anisotropy; inversion; beneath; noise; model
AB Laboratory experiments have established that many of the materials comprising the Earth are strongly anisotropic in terms of seismic-wave speeds(1). Observations of azimuthal(2,3) and radial(4,5) anisotropy in the upper mantle are attributed to the lattice-preferred orientation of olivine caused by the shear strains associated with deformation, and provide some of the most direct evidence for deformation and flow within the Earth's interior. Although observations of crustal radial anisotropy would improve our understanding of crustal deformation and flow patterns resulting from tectonic processes, large-scale observations have been limited to regions of particularly thick crust(6). Here we show that observations from ambient noise tomography in the western United States reveal strong deep (middle to lower)-crustal radial anisotropy that is confined mainly to the geological provinces that have undergone significant extension during the Cenozoic Era (since similar to 65 Myr ago)(7,8). The coincidence of crustal radial anisotropy with the extensional provinces of the western United States suggests that the radial anisotropy results from the lattice-preferred orientation of anisotropic crustal minerals caused by extensional deformation. These observations also provide support for the hypothesis that the deep crust within these regions has undergone widespread and relatively uniform strain in response to crustal thinning and extension(9-11).
C1 [Moschetti, M. P.; Ritzwoller, M. H.; Lin, F.; Yang, Y.] Univ Colorado, Dept Phys, Ctr Imaging Earths Interior, Boulder, CO 80309 USA.
C3 University of Colorado System; University of Colorado Boulder
RP Moschetti, MP (corresponding author), US Geol Survey, Geol Hazards Sci Ctr, Box 25046, Denver, CO 80225 USA.
EM mmoschetti@usgs.gov
FU US National Science Foundation, Division of Earth Sciences; US National Defense; American Society for Engineering Education
NR 33
TC 194
Z9 222
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 885
EP U94
DI 10.1038/nature08951
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300036
PM 20376148
DA 2026-03-09
ER

PT J
AU Clarkson, AN
   Huang, BS
   MacIsaac, SE
   Mody, I
   Carmichael, ST
AF Clarkson, Andrew N.
   Huang, Ben S.
   MacIsaac, Sarah E.
   Mody, Istvan
   Carmichael, S. Thomas
TI Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
SO NATURE
LA English
DT Article
ID receptor subunits; alpha-5 subunit; plasticity; brain; mechanisms; rats; mice; reorganization; conductances; activation
AB Stroke is a leading cause of disability, but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage-the peri-infarct zone-is critical for rehabilitation, as it shows heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas(1-3). Thus, understanding the neuronal properties constraining this plasticity is important for the development of new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA(A) receptors and is caused by an impairment in GABA (gamma-aminobutyric acid) transporter (GAT-3/GAT-4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for alpha 5-subunit-containing extrasynaptic GABA(A) receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of alpha 5- or delta-subunit-containing GABA(A) receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA(A) receptor function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.
C1 [Clarkson, Andrew N.; Huang, Ben S.; MacIsaac, Sarah E.; Mody, Istvan; Carmichael, S. Thomas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [Huang, Ben S.; Mody, Istvan] Univ Calif Los Angeles, David Geffen Sch Med, Interdept PhD Program Neurosci, Los Angeles, CA 90095 USA.
   [Mody, Istvan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, 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 California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Carmichael, ST (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 635 Charles Young Dr S, Los Angeles, CA 90095 USA.
EM scarmichael@mednet.ucla.edu
FU Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Larry L. Hillblom Foundation; Coelho Endowment; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS30549]; American Heart Association; New Zealand Neurological Foundation; Health Research Council of New Zealand
NR 38
TC 704
Z9 815
U1 3
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 305
EP U193
DI 10.1038/nature09511
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000051
PM 21048709
DA 2026-03-09
ER

PT J
AU Musunuru, K
   Strong, A
   Frank-Kamenetsky, M
   Lee, NE
   Ahfeldt, T
   Sachs, KV
   Li, XY
   Li, H
   Kuperwasser, N
   Ruda, VM
   Pirruccello, JP
   Muchmore, B
   Prokunina-Olsson, L
   Hall, JL
   Schadt, EE
   Morales, CR
   Lund-Katz, S
   Phillips, MC
   Wong, J
   Cantley, W
   Racie, T
   Ejebe, KG
   Orho-Melander, M
   Melander, O
   Koteliansky, V
   Fitzgerald, K
   Krauss, RM
   Cowan, CA
   Kathiresan, S
   Rader, DJ
AF Musunuru, Kiran
   Strong, Alanna
   Frank-Kamenetsky, Maria
   Lee, Noemi E.
   Ahfeldt, Tim
   Sachs, Katherine V.
   Li, Xiaoyu
   Li, Hui
   Kuperwasser, Nicolas
   Ruda, Vera M.
   Pirruccello, James P.
   Muchmore, Brian
   Prokunina-Olsson, Ludmila
   Hall, Jennifer L.
   Schadt, Eric E.
   Morales, Carlos R.
   Lund-Katz, Sissel
   Phillips, Michael C.
   Wong, Jamie
   Cantley, William
   Racie, Timothy
   Ejebe, Kenechi G.
   Orho-Melander, Marju
   Melander, Olle
   Koteliansky, Victor
   Fitzgerald, Kevin
   Krauss, Ronald M.
   Cowan, Chad A.
   Kathiresan, Sekar
   Rader, Daniel J.
TI From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus
SO NATURE
LA English
DT Article
ID density-lipoprotein cholesterol; genome-wide association; protein; gene; sortilin; transcription; disease; design; risk; mice
AB Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.
C1 [Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
   [Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Musunuru, Kiran; Lee, Noemi E.; Ahfeldt, Tim; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Musunuru, Kiran; Lee, Noemi E.; Ahfeldt, Tim; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Musunuru, Kiran; Lee, Noemi E.; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Musunuru, Kiran; Pirruccello, James P.; Hall, Jennifer L.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Broad Inst, Cambridge, MA 02142 USA.
   [Musunuru, Kiran] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21287 USA.
   [Frank-Kamenetsky, Maria; Wong, Jamie; Cantley, William; Racie, Timothy; Koteliansky, Victor; Fitzgerald, Kevin] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA.
   [Ahfeldt, Tim] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany.
   [Muchmore, Brian; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Hall, Jennifer L.] Univ Minnesota, Program Cardiovasc Translat Genom, Lillehei Heart Inst, Minneapolis, MN 55455 USA.
   [Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
   [Morales, Carlos R.] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada.
   [Lund-Katz, Sissel; Phillips, Michael C.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
   [Orho-Melander, Marju; Melander, Olle] Lund Univ, Skania Univ Hosp, Dept Clin Sci, SE-20502 Malmo, Sweden.
   [Krauss, Ronald M.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Johns Hopkins University; Alnylam Pharmaceuticals; University of Hamburg; University Medical Center Hamburg-Eppendorf; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; University of Minnesota System; University of Minnesota Twin Cities; McGill University; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Lund University; Children's Hospital Los Angeles; Children's Hospital Oakland Research Institute
RP Rader, DJ (corresponding author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
EM skathiresan@partners.org; rader@mail.med.upenn.edu
FU United States National Institutes of Health (NIH); NIH [K99-HL098364, U01-HL069757, RC2-HL101864, P01-HL059407]; Harvard Stem Cell Institute; Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH; Swedish Medical Research Council; Heart-Lung Foundation; Pahlsson Foundation; Quest Diagnostics, Inc.; Bristol-Myers Squibb
NR 35
TC 879
Z9 1077
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 AUG 5
PY 2010
VL 466
IS 7307
BP 714
EP U2
DI 10.1038/nature09266
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500030
PM 20686566
DA 2026-03-09
ER

PT J
AU Sengupta, S
   Peterson, TR
   Laplante, M
   Oh, S
   Sabatini, DM
AF Sengupta, Shomit
   Peterson, Timothy R.
   Laplante, Mathieu
   Oh, Stephanie
   Sabatini, David M.
TI mTORC1 controls fasting-induced ketogenesis and its modulation by ageing
SO NATURE
LA English
DT Article
ID proliferator-activated receptor; fatty-acid oxidation; rat-liver; mice; identification; genes
AB The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors(1). Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor(1), leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component(1), has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPAR alpha (peroxisome proliferator activated receptor alpha), the master transcriptional activator of ketogenic genes(2), and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPAR alpha(3), reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis(4,5), which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPAR alpha activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPAR alpha function and hepatic ketogenesis and suggest a role for mTORC1 activity in promoting the ageing of the liver.
C1 [Sengupta, Shomit; Peterson, Timothy R.; Laplante, Mathieu; Oh, Stephanie; Sabatini, David M.] Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Sengupta, Shomit; Peterson, Timothy R.; Laplante, Mathieu; Oh, Stephanie; Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
   [Sengupta, Shomit; Peterson, Timothy R.; Laplante, Mathieu; Oh, Stephanie; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, 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)
RP Sabatini, DM (corresponding author), Nine Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU American Diabetes Association; Ludwig Cancer Fund; Canadian Institutes of Health Research; NIH [CA103866, CA129105]; National Cancer Institute [R01CA129105, R01CA103866] Funding Source: NIH RePORTER
NR 30
TC 546
Z9 645
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1100
EP U502
DI 10.1038/nature09584
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800058
PM 21179166
DA 2026-03-09
ER

PT J
AU Jaeger, JJ
   Beard, KC
   Chaimanee, Y
   Salem, M
   Benammi, M
   Hlal, O
   Coster, P
   Bilal, AA
   Duringer, P
   Schuster, M
   Valentin, X
   Marandat, B
   Marivaux, L
   Métais, E
   Hammuda, O
   Brunet, M
AF Jaeger, Jean-Jacques
   Beard, K. Christopher
   Chaimanee, Yaowalak
   Salem, Mustafa
   Benammi, Mouloud
   Hlal, Osama
   Coster, Pauline
   Bilal, Awad A.
   Duringer, Philippe
   Schuster, Mathieu
   Valentin, Xavier
   Marandat, Bernard
   Marivaux, Laurent
   Metais, Eddy
   Hammuda, Omar
   Brunet, Michel
TI Late middle Eocene epoch of Libya yields earliest known radiation of African anthropoids
SO NATURE
LA English
DT Article
ID primate; mammalia; myanmar; origins; china; tarsiidae; algeria; shanxi
AB Reconstructing the early evolutionary history of anthropoid primates is hindered by a lack of consensus on both the timing and biogeography of anthropoid origins(1-3). Some prefer an ancient (Cretaceous) origin for anthropoids in Africa or some other Gondwanan landmass(4), whereas others advocate a more recent (early Cenozoic) origin for anthropoids in Asia(1,2,5), with subsequent dispersal of one or more early anthropoid taxa to Africa. The oldest undoubted African anthropoid primates described so far are three species of the parapithecid Biretia from the late middle Eocene Bir El Ater locality of Algeria(6) and the late Eocene BQ-2 site in the Fayum region of northern Egypt(7). Here we report the discovery of the oldest known diverse assemblage of African anthropoids from the late middle Eocene Dur At-Talah escarpment in central Libya. The primate assemblage from Dur At-Talah includes diminutive species pertaining to three higher-level anthropoid clades (Afrotarsiidae, Parapithecidae and Oligopithecidae) as well as a small species of the early strepsirhine primate Karanisia. The high taxonomic diversity of anthropoids at Dur At-Talah indicates either a much longer interval of anthropoid evolution in Africa than is currently documented in the fossil record or the nearly synchronous colonization of Africa by multiple anthropoid clades at some time during the middle Eocene epoch.
C1 [Jaeger, Jean-Jacques; Benammi, Mouloud; Coster, Pauline; Schuster, Mathieu; Valentin, Xavier; Brunet, Michel] Univ Poitiers, Inst Int Paleoprimatol & Paleontol Humaine, CNRS, UMR 6046, F-86022 Poitiers, France.
   [Beard, K. Christopher] Carnegie Museum Nat Hist, Sect Vertebrate Paleontol, Pittsburgh, PA 15213 USA.
   [Chaimanee, Yaowalak] Dept Mineral Resources, Paleontol Sect, Bangkok 10400, Thailand.
   [Salem, Mustafa; Hlal, Osama; Hammuda, Omar] Al Fateh Univ, Dept Geol, Tripoli, Libya.
   [Bilal, Awad A.] Garyounis Univ, Dept Geol, Benghazi, Libya.
   [Duringer, Philippe] Univ Strasbourg, Inst Phys Globe Strasbourg, Inst Geol, CNRS,UMR 7516, F-67084 Strasbourg, France.
   [Marandat, Bernard; Marivaux, Laurent] Univ Montpellier 2, Inst Sci Evolut, UMR 5554, CNRS, F-34095 Montpellier, France.
   [Metais, Eddy] Grp TOTAL, F-92400 Courbevoie, France.
   [Brunet, Michel] Coll France, Chaire Paleontol Humaine, F-75005 Paris, France.
C3 Universite de Poitiers; Centre National de la Recherche Scientifique (CNRS); Department of Mineral Resources - Thailand; University of Tripoli; University of Benghazi; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; Universite PSL; College de France
RP Jaeger, JJ (corresponding author), Univ Poitiers, Inst Int Paleoprimatol & Paleontol Humaine, CNRS, UMR 6046, 40 Ave Recteur Pineau, F-86022 Poitiers, France.
EM jean-jacques.jaeger@univ-poitiers.fr
FU University of Poitiers; CNRS [ANR-05-BLAN-0235, ANR-09-BLAN-0238-02-EVAH]; Groupe 'TOTAL'; National Science Foundation
NR 29
TC 68
Z9 75
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1096
EP U103
DI 10.1038/nature09425
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600045
PM 20981098
DA 2026-03-09
ER

PT J
AU Medina, PP
   Nolde, M
   Slack, FJ
AF Medina, Pedro P.
   Nolde, Mona
   Slack, Frank J.
TI OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma
SO NATURE
LA English
DT Article
ID oncogene addiction; expression; cancer; micrornas; prognosis; invasion; mir-21; myc
AB MicroRNAs (miRNAs) belong to a recently discovered class of small RNA molecules that regulate gene expression at the post-transcriptional level. miRNAs have crucial functions in the development and establishment of cell identity, and aberrant metabolism or expression of miRNAs has been linked to human diseases, including cancer(1). Components of the miRNA machinery and miRNAs themselves are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. Some miRNAs, referred to as oncomiRs(2), show differential expression levels in cancer and are able to affect cellular transformation, carcinogenesis and metastasis, acting either as oncogenes or tumour suppressors. The phenomenon of 'oncogene addiction' reveals that despite the multistep nature of tumorigenesis, targeting of certain single oncogenes can have therapeutic value(3,4), and the possibility of oncomiR addiction has been proposed but never demonstrated(3). MicroRNA-21 (miR-21) is a unique miRNA in that it is overexpressed in most tumour types analysed so far. Despite great interest in miR-21, most of the data implicating it in cancer have been obtained through miRNA profiling and limited in vitro functional assays. To explore the role of miR-21 in cancer in vivo, we used Cre and Tet-off technologies to generate mice conditionally expressing miR-21. Here we show that overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype, demonstrating that mir-21 is a genuine oncogene. When miR-21 was inactivated, the tumours regressed completely in a few days, partly as a result of apoptosis. These results demonstrate that tumours can become addicted to oncomiRs and support efforts to treat human cancers through pharmacological inactivation of miRNAs such as miR-21.
C1 [Medina, Pedro P.; Nolde, Mona; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
C3 Yale University
RP Slack, FJ (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, POB 208103, New Haven, CT 06520 USA.
EM frank.slack@yale.edu
FU Hope Funds for Cancer Research; James McDonnell Foundation; Yale Comprehensive Cancer Center
NR 30
TC 801
Z9 993
U1 0
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 86
EP U119
DI 10.1038/nature09284
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200040
PM 20693987
DA 2026-03-09
ER

PT J
AU Calais, E
   Freed, AM
   Van Arsdale, R
   Stein, S
AF Calais, E.
   Freed, A. M.
   Van Arsdale, R.
   Stein, S.
TI Triggering of New Madrid seismicity by late-Pleistocene erosion
SO NATURE
LA English
DT Article
ID intraplate seismicity; earthquakes; stress; fault; deformation; evolution; hazard; crust
AB The spatiotemporal behaviour of earthquakes within continental plate interiors is different from that at plate boundaries. At plate margins, tectonic motions quickly reload earthquake ruptures, making the location of recent earthquakes and the average time between them consistent with the faults' geological, palaeoseismic and seismic histories. In contrast, what determines the activation of a particular mid-continental fault and controls the duration of its seismic activity remains poorly understood(1). Here we argue that the concentration of magnitude-7 or larger earthquakes in the New Madrid seismic zone of the central United States(2,3) since the end of the last ice age results from the recent, climate-controlled, erosional history of the northern Mississippi embayment. We show that the upward flexure of the lithosphere caused by unloading from river incision between 16,000 and 10,000 years ago caused a reduction of normal stresses in the upper crust sufficient to unclamp preexisting faults close to failure equilibrium. Models indicate that fault segments that have already ruptured are unlikely to fail again soon, but stress changes from sediment unloading and previous earthquakes may eventually be sufficient to bring to failure other nearby segments that have not yet ruptured.
C1 [Calais, E.; Freed, A. M.] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
   [Van Arsdale, R.] Univ Memphis, Dept Earth Sci, Memphis, TN 38152 USA.
   [Stein, S.] Northwestern Univ, Dept Earth & Planetary Sci, Evanston, IL 60208 USA.
C3 Purdue University System; Purdue University; University of Memphis; Northwestern University
RP Calais, E (corresponding author), Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
EM ecalais@purdue.edu
FU US Geological Survey through the Department of the Interior [07HQGR0049]
NR 30
TC 135
Z9 164
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 JUL 29
PY 2010
VL 466
IS 7306
BP 608
EP U2
DI 10.1038/nature09258
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100050
PM 20671707
DA 2026-03-09
ER

PT J
AU Gudasz, C
   Bastviken, D
   Steger, K
   Premke, K
   Sobek, S
   Tranvik, LJ
AF Gudasz, Cristian
   Bastviken, David
   Steger, Kristin
   Premke, Katrin
   Sobek, Sebastian
   Tranvik, Lars J.
TI Temperature-controlled organic carbon mineralization in lake sediments
SO NATURE
LA English
DT Article
ID terrestrial carbon; climate-change; boreal forest; soil carbon; burial; cycle; accumulation; respiration; reservoirs; dynamics
AB Peatlands, soils and the ocean floor are well-recognized as sites of organic carbonaccumulation andrepresentimportant global carbon sinks(1,2). Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments(3), these inland waters are components of the global carbon cycle that receive only limited attention(4-6). Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input froma compilation of published data from awide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change(7) could result in a 4-27 per cent (0.9-6.4 Tg Cyr(-1)) decrease in annual organic carbon burial in boreal lakes.
C1 [Gudasz, Cristian; Steger, Kristin; Premke, Katrin; Sobek, Sebastian; Tranvik, Lars J.] Uppsala Univ, Dept Ecol & Evolut, SE-75236 Uppsala, Sweden.
   [Bastviken, David] Linkoping Univ, Dept Themat Studies Water & Environm Studies, SE-58662 Linkoping, Sweden.
C3 Uppsala University; Linkoping University
RP Gudasz, C (corresponding author), Uppsala Univ, Dept Ecol & Evolut, Norbyvagen 18D, SE-75236 Uppsala, Sweden.
EM cristian.gudasz@ebc.uu.se
FU FORMAS (the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning); VR (the Swedish Research Council)
NR 35
TC 516
Z9 613
U1 16
U2 603
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 478
EP U3
DI 10.1038/nature09186
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200033
PM 20651689
DA 2026-03-09
ER

PT J
AU Frebel, A
   Kirby, EN
   Simon, JD
AF Frebel, Anna
   Kirby, Evan N.
   Simon, Joshua D.
TI Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor
SO NATURE
LA English
DT Article
ID spheroidal galaxy; milky-way; chemical-composition; galactic halo; dark-matter; abundances; spectroscopy; satellites; signatures; giant
AB Current cosmological models(1,2) indicate that the Milky Way's stellar halo was assembled from many smaller systems. On the basis of the apparent absence of the most metal-poor stars in present-day dwarf galaxies, recent studies(3) claimed that the true Galactic building blocks must have been vastly different from the surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in the Sculptor dwarf galaxy based on a medium-resolution spectrum(4) cast some doubt on this conclusion. Verification of the iron-deficiency, however, and measurements of additional elements, such as the a-element Mg, are necessary to demonstrate that the same type of stars produced the metals found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars be conclusively linked to early stellar halo assembly. Here we report high-resolution spectroscopic abundances for 11 elements in S1020549, confirming its iron abundance of less than 1/4,000th that of the Sun, and showing that the overall abundance pattern follows that seen in low-metallicity halo stars, including the a-elements. Such chemical similarity indicates that the systems destroyed to form the halo billions of years ago were not fundamentally different from the progenitors of present-day dwarfs, and suggests that the early chemical enrichment of all galaxies may be nearly identical.
C1 [Frebel, Anna] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Kirby, Evan N.] CALTECH, Pasadena, CA 91125 USA.
   [Simon, Joshua D.] Observ Carnegie Inst Washington, Pasadena, CA 91101 USA.
C3 Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; California Institute of Technology; Carnegie Institution for Science
RP Frebel, A (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM afrebel@cfa.harvard.edu
FU NASA; Space Telescope Science Institute; Carnegie Institution of Washington
NR 30
TC 148
Z9 156
U1 0
U2 1
PU 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 4
PY 2010
VL 464
IS 7285
BP 72
EP 75
DI 10.1038/nature08772
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500035
PM 20203604
DA 2026-03-09
ER

PT J
AU Maeda, K
   Benetti, S
   Stritzinger, M
   Röpke, FK
   Folatelli, G
   Sollerman, J
   Taubenberger, S
   Nomoto, K
   Leloudas, G
   Hamuy, M
   Tanaka, M
   Mazzali, PA
   Elias-Rosa, N
AF Maeda, K.
   Benetti, S.
   Stritzinger, M.
   Roepke, F. K.
   Folatelli, G.
   Sollerman, J.
   Taubenberger, S.
   Nomoto, K.
   Leloudas, G.
   Hamuy, M.
   Tanaka, M.
   Mazzali, P. A.
   Elias-Rosa, N.
TI An asymmetric explosion as the origin of spectral evolution diversity in type Ia supernovae
SO NATURE
LA English
DT Article
ID detonation model; nucleosynthesis; ignition; decline; 1991bg
AB Type Ia supernovae form an observationally uniform class of stellar explosions, in that more luminous objects have smaller decline-rates(1). This one-parameter behaviour allows type Ia supernovae to be calibrated as cosmological 'standard candles', and led to the discovery of an accelerating Universe(2,3). Recent investigations, however, have revealed that the true nature of type Ia supernovae is more complicated. Theoretically, it has been suggested(4-8) that the initial thermonuclear sparks are ignited at an offset from the centre of the white-dwarf progenitor, possibly as a result of convection before the explosion(4). Observationally, the diversity seen in the spectral evolution of type Ia supernovae beyond the luminosity-decline-rate relation is an unresolved issue(9,10). Here we report that the spectral diversity is a consequence of random directions from which an asymmetric explosion is viewed. Our findings suggest that the spectral evolution diversity is no longer a concern when using type Ia supernovae as cosmological standard candles. Furthermore, this indicates that ignition at an offset from the centre is a generic feature of type Ia supernovae.
C1 [Maeda, K.; Nomoto, K.; Tanaka, M.] Univ Tokyo, IPMU, Chiba 2778583, Japan.
   [Benetti, S.] INAF Osservatorio Astron Padova, I-35122 Padua, Italy.
   [Stritzinger, M.] Las Campanas Observ, Carnegie Inst Sci, La Serena, Chile.
   [Stritzinger, M.; Sollerman, J.; Leloudas, G.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen O, Denmark.
   [Roepke, F. K.; Taubenberger, S.; Mazzali, P. A.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Folatelli, G.; Hamuy, M.] Univ Chile, Dept Astron, Santiago, Chile.
   [Sollerman, J.] Stockholm Univ, Dept Astron, Oskar Klein Ctr, S-10691 Stockholm, Sweden.
   [Mazzali, P. A.] Scuola Normale Super Pisa, I-56127 Pisa, Italy.
   [Elias-Rosa, N.] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
C3 University of Tokyo; Istituto Nazionale Astrofisica (INAF); Carnegie Institution for Science; University of Copenhagen; Niels Bohr Institute; Max Planck Society; Universidad de Chile; Oskar Klein Centre; Stockholm University; Scuola Normale Superiore di Pisa; California Institute of Technology
RP Maeda, K (corresponding author), Univ Tokyo, IPMU, 5-1-5 Kashiwanoha, Chiba 2778583, Japan.
EM keiichi.maeda@ipmu.jp
FU World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan; JSPS; ASI; National Science Foundation; German Research Foundation; Cluster of Excellence 'Origin and Structure of the Universe'; Iniciativa Cientifica Milenio; CONICYT; Knut and Alice Wallenberg Foundation; Transregional Collaborative Research Centre; Danish National Research Foundation
NR 30
TC 219
Z9 248
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 1
PY 2010
VL 466
IS 7302
BP 82
EP 85
DI 10.1038/nature09122
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800038
PM 20596015
DA 2026-03-09
ER

PT J
AU Screen, JA
   Simmonds, I
AF Screen, James A.
   Simmonds, Ian
TI The central role of diminishing sea ice in recent Arctic temperature amplification
SO NATURE
LA English
DT Article
ID polar amplification; vertical structure
AB The rise in Arctic near-surface air temperatures has been almost twice as large as the global average in recent decades(1-3)-a feature known as 'Arctic amplification'. Increased concentrations of atmospheric greenhouse gases have driven Arctic and global average warming(1,4); however, the underlying causes of Arctic amplification remain uncertain. The roles of reductions in snow and sea ice cover(5-7) and changes in atmospheric and oceanic circulation(8-10), cloud cover and water vapour(11,12) are still matters of debate. A better understanding of the processes responsible for the recent amplified warming is essential for assessing the likelihood, and impacts, of future rapid Arctic warming and sea ice loss(13,14). Here we show that the Arctic warming is strongest at the surface during most of the year and is primarily consistent with reductions in sea ice cover. Changes in cloud cover, in contrast, have not contributed strongly to recent warming. Increases in atmospheric water vapour content, partly in response to reduced sea ice cover, may have enhanced warming in the lower part of the atmosphere during summer and early autumn. We conclude that diminishing sea ice has had a leading role in recent Arctic temperature amplification. The findings reinforce suggestions that strong positive ice-temperature feedbacks have emerged in the Arctic(15), increasing the chances of further rapid warming and sea ice loss, and will probably affect polar ecosystems, ice-sheet mass balance and human activities in the Arctic(2).
C1 [Screen, James A.; Simmonds, Ian] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
C3 University of Melbourne
RP Screen, JA (corresponding author), Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
EM screenj@unimelb.edu.au
FU Australian Research Council
NR 30
TC 1897
Z9 2271
U1 26
U2 816
PU NATURE PUBLISHING 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 29
PY 2010
VL 464
IS 7293
BP 1334
EP 1337
DI 10.1038/nature09051
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000043
PM 20428168
DA 2026-03-09
ER

PT J
AU Li, Y
   Balédent, V
   Yu, G
   Barisic, N
   Hradil, K
   Mole, RA
   Sidis, Y
   Steffens, P
   Zhao, X
   Bourges, P
   Greven, M
AF Li, Yuan
   Baledent, V.
   Yu, G.
   Barisic, N.
   Hradil, K.
   Mole, R. A.
   Sidis, Y.
   Steffens, P.
   Zhao, X.
   Bourges, P.
   Greven, M.
TI Hidden magnetic excitation in the pseudogap phase of a high-Tc superconductor
SO NATURE
LA English
DT Article
ID high-temperature superconductor; spin excitations; hgba2cuo4+delta; states; model
AB The elucidation of the pseudogap phenomenon of the high-transition-temperature (high-T-c) copper oxides-a set of anomalous physical properties below the characteristic temperature T* and above T-c-has been a major challenge in condensed matter physics for the past two decades(1). Following initial indications of broken time-reversal symmetry in photoemission experiments(2), recent polarized neutron diffraction work demonstrated the universal existence of an unusual magnetic order below T* (refs 3, 4). These findings have the profound implication that the pseudogap regime constitutes a genuine new phase of matter rather than a mere crossover phenomenon. They are furthermore consistent with a particular type of order involving circulating orbital currents, and with the notion that the phase diagram is controlled by a quantum critical point(5). Here we report inelastic neutron scattering results for HgBa2CuO4+delta that reveal a fundamental collective magnetic mode associated with the unusual order, and which further support this picture. The mode's intensity rises below the same temperature T* and its dispersion is weak, as expected for an Ising-like order parameter(6). Its energy of 52-56 meV renders it a new candidate for the hitherto unexplained ubiquitous electron-boson coupling features observed in spectroscopic studies(7-10).
C1 [Yu, G.; Greven, M.] Univ Minnesota, Sch Phys & Astron, Minneapolis, MN 55455 USA.
   [Li, Yuan] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Baledent, V.; Sidis, Y.; Bourges, P.] CEA Saclay, CEA, CNRS, Lab Leon Brillouin, F-91191 Gif Sur Yvette, France.
   [Barisic, N.; Zhao, X.] Stanford Univ, TH Geballe Lab Adv Mat, Stanford, CA 94305 USA.
   [Barisic, N.] Univ Stuttgart, Inst Phys 1, D-70550 Stuttgart, Germany.
   [Hradil, K.] Univ Gottingen, Inst Phys Chem, D-37077 Gottingen, Germany.
   [Mole, R. A.] Forsch Neutronenquelle Heinz Maier Leibnitz, D-85747 Garching, Germany.
   [Steffens, P.] Inst Laue Langevin, F-38042 Grenoble 9, France.
   [Zhao, X.] Jilin Univ, Coll Chem, State Key Lab Inorgan Synth & Preparat Chem, Changchun 130012, Peoples R China.
C3 University of Minnesota System; University of Minnesota Twin Cities; Stanford University; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Stanford University; University of Stuttgart; University of Gottingen; Institut Laue-Langevin (ILL); Jilin University
RP Greven, M (corresponding author), Univ Minnesota, Sch Phys & Astron, Minneapolis, MN 55455 USA.
EM greven@physics.umn.edu
FU US Department of Energy; US National Science Foundation; National Natural Science Foundation, China; Alexander von Humboldt Foundation
NR 29
TC 108
Z9 124
U1 1
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 283
EP 285
DI 10.1038/nature09477
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000046
PM 21068838
DA 2026-03-09
ER

PT J
AU Sigurdsson, T
   Stark, KL
   Karayiorgou, M
   Gogos, JA
   Gordon, JA
AF Sigurdsson, Torfi
   Stark, Kimberly L.
   Karayiorgou, Maria
   Gogos, Joseph A.
   Gordon, Joshua A.
TI Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia
SO NATURE
LA English
DT Article
ID 22q11 deletion syndrome; functional connectivity; working-memory; deficits; contributes; mechanisms; children; cortex; risk
AB Abnormalities in functional connectivity between brain areas have been postulated as an important pathophysiological mechanism underlying schizophrenia(1,2). In particular, macroscopic measurements of brain activity in patients suggest that functional connectivity between the frontal and temporal lobes may be altered(3,4). However, it remains unclear whether such dysconnectivity relates to the aetiology of the illness, and how it is manifested in the activity of neural circuits. Because schizophrenia has a strong genetic component(5), animal models of genetic risk factors are likely to aid our understanding of the pathogenesis and pathophysiology of the disease. Here we study Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22 (22q11.2) that constitutes one of the largest known genetic risk factors for schizophrenia(6). To examine functional connectivity in these mice, we measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wild-type mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats(7). Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. These data suggest how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level. Our findings further suggest that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia.
C1 [Sigurdsson, Torfi; Stark, Kimberly L.; Karayiorgou, Maria; Gordon, Joshua A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Stark, Kimberly L.; Gogos, Joseph A.] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Gogos, Joseph A.] Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
   [Karayiorgou, Maria; Gordon, Joshua A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute
RP Gordon, JA (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
EM jag90@columbia.edu; jg343@columbia.edu
FU Simons Foundation; US National Institute of Mental Health [MH67068, MH081968]; Lieber Center for Schizophrenia Research and Treatment
NR 30
TC 540
Z9 661
U1 0
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 763
EP U139
DI 10.1038/nature08855
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000046
PM 20360742
DA 2026-03-09
ER

PT J
AU Ni, KK
   Ospelkaus, S
   Wang, D
   Quéméner, G
   Neyenhuis, B
   de Miranda, MHG
   Bohn, JL
   Ye, J
   Jin, DS
AF Ni, K. -K.
   Ospelkaus, S.
   Wang, D.
   Quemener, G.
   Neyenhuis, B.
   de Miranda, M. H. G.
   Bohn, J. L.
   Ye, J.
   Jin, D. S.
TI Dipolar collisions of polar molecules in the quantum regime
SO NATURE
LA English
DT Article
AB Ultracold polar molecules offer the possibility of exploring quantum gases with interparticle interactions that are strong, long-range and spatially anisotropic. This is in stark contrast to the much studied dilute gases of ultracold atoms, which have isotropic and extremely short-range (or 'contact') interactions. Furthermore, the large electric dipole moment of polar molecules can be tuned using an external electric field; this has a range of applications such as the control of ultracold chemical reactions(1), the design of a platform for quantum information processing(2-4) and the realization of novel quantum many-body systems(5-8). Despite intense experimental efforts aimed at observing the influence of dipoles on ultracold molecules(9), only recently have sufficiently high densities been achieved(10). Here we report the experimental observation of dipolar collisions in an ultracold molecular gas prepared close to quantum degeneracy. For modest values of an applied electric field, we observe a pronounced increase in the loss rate of fermionic potassium-rubidium molecules due to ultracold chemical reactions. We find that the loss rate has a steep power-law dependence on the induced electric dipole moment, and we show that this dependence can be understood in a relatively simple model based on quantum threshold laws for the scattering of fermionic polar molecules. In addition, we directly observe the spatial anisotropy of the dipolar interaction through measurements of the thermodynamics of the dipolar gas. These results demonstrate how the long-range dipolar interaction can be used for electric-field control of chemical reaction rates in an ultracold gas of polar molecules. Furthermore, the large loss rates in an applied electric field suggest that creating a long-lived ensemble of ultracold polar molecules may require confinement in a two-dimensional trap geometry to suppress the influence of the attractive, 'head-to-tail', dipolar interactions(11-14).
C1 [Ni, K. -K.; Ospelkaus, S.; Wang, D.; Quemener, G.; Neyenhuis, B.; de Miranda, M. H. G.; Bohn, J. L.; Ye, J.; Jin, D. S.] Univ Colorado, NIST, JILA, Boulder, CO 80309 USA.
   [Ni, K. -K.; Ospelkaus, S.; Wang, D.; Quemener, G.; Neyenhuis, B.; de Miranda, M. H. G.; Bohn, J. L.; Ye, J.; Jin, D. S.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder
RP Ye, J (corresponding author), Univ Colorado, NIST, JILA, Boulder, CO 80309 USA.
EM ye@jila.colorado.edu; jin@jilau1.colorado.edu
FU US National Institute of Standards and Technology; US National Science Foundation (NSF) Physics Frontier Center at JILA; US Department of Energy, Air Force Office of Scientific Research Multidisciplinary Research Initiative on Ultracold Molecules
NR 30
TC 459
Z9 522
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 APR 29
PY 2010
VL 464
IS 7293
BP 1324
EP 1328
DI 10.1038/nature08953
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000041
PM 20428166
DA 2026-03-09
ER

PT J
AU Lieberman, DE
   Venkadesan, M
   Werbel, WA
   Daoud, AI
   D'Andrea, S
   Davis, IS
   Mang'Eni, RO
   Pitsiladis, Y
AF Lieberman, Daniel E.
   Venkadesan, Madhusudhan
   Werbel, William A.
   Daoud, Adam I.
   D'Andrea, Susan
   Davis, Irene S.
   Mang'Eni, Robert Ojiambo
   Pitsiladis, Yannis
TI Foot strike patterns and collision forces in habitually barefoot versus shod runners
SO NATURE
LA English
DT Article
ID running injury; female runners; stance phase; evolution; walking; homo; mass
AB Humans have engaged in endurance running for millions of years(1), but the modern running shoe was not invented until the 1970s. For most of human evolutionary history, runners were either barefoot or wore minimal footwear such as sandals or moccasins with smaller heels and little cushioning relative to modern running shoes. We wondered how runners coped with the impact caused by the foot colliding with the ground before the invention of the modern shoe. Here we show that habitually barefoot endurance runners often land on the fore-foot (fore-foot strike) before bringing down the heel, but they sometimes land with a flat foot (mid-foot strike) or, less often, on the heel (rear-foot strike). In contrast, habitually shod runners mostly rear-foot strike, facilitated by the elevated and cushioned heel of the modern running shoe. Kinematic and kinetic analyses show that even on hard surfaces, barefoot runners who fore-foot strike generate smaller collision forces than shod rear-foot strikers. This difference results primarily from a more plantarflexed foot at landing and more ankle compliance during impact, decreasing the effective mass of the body that collides with the ground. Fore-foot-and mid-foot-strike gaits were probably more common when humans ran barefoot or in minimal shoes, and may protect the feet and lower limbs from some of the impact-related injuries now experienced by a high percentage of runners.
C1 [Lieberman, Daniel E.; Venkadesan, Madhusudhan; Daoud, Adam I.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Venkadesan, Madhusudhan] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Werbel, William A.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
   [D'Andrea, Susan] Providence Vet Affairs Med Ctr, Ctr Restorat & Regenerat Med, Providence, RI 02906 USA.
   [Davis, Irene S.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
   [Mang'Eni, Robert Ojiambo; Pitsiladis, Yannis] Moi Univ, Sch Med, Dept Med Physiol, Eldoret 30100, Kenya.
   [Mang'Eni, Robert Ojiambo; Pitsiladis, Yannis] Univ Glasgow, Fac Biomed Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
C3 Harvard University; Harvard University; University of Michigan System; University of Michigan; US Department of Veterans Affairs; Veterans Health Administration (VHA); Providence VA Medical Center; University of Delaware; Moi University; University of Glasgow
RP Lieberman, DE (corresponding author), Harvard Univ, Dept Human Evolutionary Biol, 11 Divin Ave, Cambridge, MA 02138 USA.
EM danlieb@fas.harvard.edu
FU US National Science Foundation; American School of Prehistoric Research; Goelet Fund; Harvard University; Vibram USA
NR 30
TC 991
Z9 1245
U1 5
U2 720
PU 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 28
PY 2010
VL 463
IS 7280
BP 531
EP U149
DI 10.1038/nature08723
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100049
PM 20111000
DA 2026-03-09
ER

PT J
AU Lambert, O
   Bianucci, G
   Post, K
   de Muizon, C
   Salas-Gismondi, R
   Urbina, M
   Reumer, J
AF Lambert, Olivier
   Bianucci, Giovanni
   Post, Klaas
   de Muizon, Christian
   Salas-Gismondi, Rodolfo
   Urbina, Mario
   Reumer, Jelle
TI The giant bite of a new raptorial sperm whale from the Miocene epoch of Peru
SO NATURE
LA English
DT Article
ID marine mammals; cetacea
AB The modern giant sperm whale Physeter macrocephalus, one of the largest known predators, preys upon cephalopods at great depths(1,2). Lacking a functional upper dentition, it relies on suction for catching its prey(3); in contrast, several smaller Miocene sperm whales (Physeteroidea) have been interpreted as raptorial (versus suction) feeders(4,5), analogous to the modern killer whale Orcinus orca. Whereas very large physeteroid teeth have been discovered in various Miocene localities, associated diagnostic cranial remains have not been found so far(6-8). Here we report the discovery of a new giant sperm whale from the Middle Miocene of Peru (approximately 12-13 million years ago), Leviathan melvillei, described on the basis of a skull with teeth and mandible. With a 3-m-long head, very large upper and lower teeth (maximum diameter and length of 12 cm and greater than 36 cm, respectively), robust jaws and a temporal fossa considerably larger than in Physeter, this stem physeteroid represents one of the largest raptorial predators and, to our knowledge, the biggest tetrapod bite ever found. The appearance of gigantic raptorial sperm whales in the fossil record coincides with a phase of diversification and size-range increase of the baleen-bearing mysticetes in the Miocene. We propose that Leviathan fed mostly on high-energy content medium-size baleen whales. As a top predator, together with the contemporaneous giant shark Carcharocles megalodon, it probably had a profound impact on the structuring of Miocene marine communities. The development of a vast supracranial basin in Leviathan, extending on the rostrum as in Physeter, might indicate the presence of an enlarged spermaceti organ in the former that is not associated with deep diving or obligatory suction feeding.
C1 [Lambert, Olivier] Inst Royal Sci Nat Belgique, Dept Paleontol, B-1000 Brussels, Belgium.
   [Bianucci, Giovanni] Univ Pisa, Dipartimento Sci Terra, I-56126 Pisa, Italy.
   [Post, Klaas; Reumer, Jelle] Nat Hist Museum Rotterdam, NL-3001 KL Rotterdam, Netherlands.
   [de Muizon, Christian] Museum Natl Hist Nat, Dept Hist Terre, F-75005 Paris, France.
   [Salas-Gismondi, Rodolfo; Urbina, Mario] Univ Nacl Mayor San Marcos, Museo Hist Nat, Lima 14, Peru.
   [Reumer, Jelle] Univ Utrecht, Dept Geosci, NL-3508 TA Utrecht, Netherlands.
C3 University of Pisa; Museum National d'Histoire Naturelle (MNHN); Universidad Nacional Mayor de San Marcos; Utrecht University
RP Lambert, O (corresponding author), Museum Natl Hist Nat, Dept Hist Terre, F-75005 Paris, France.
EM olambert@mnhn.fr; bianucci@dst.unipi.it
FU Board of the Natuurhistorisch Museum Rotterdam Foundation; Belgian Federal Science Policy Office
NR 30
TC 174
Z9 192
U1 0
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 1
PY 2010
VL 466
IS 7302
BP 105
EP 108
DI 10.1038/nature09067
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800043
PM 20596020
DA 2026-03-09
ER

PT J
AU Alboussière, T
   Deguen, R
   Melzani, M
AF Alboussiere, Thierry
   Deguen, Renaud
   Melzani, Mickael
TI Melting-induced stratification above the Earth's inner core due to convective translation
SO NATURE
LA English
DT Article
ID seismic velocity; anisotropy; heterogeneity; boundary; iron; constraints; model; base
AB In addition to its global North-South anisotropy(1), there are two other enigmatic seismological observations related to the Earth's inner core: asymmetry between its eastern and western hemispheres(2-6) and the presence of a layer of reduced seismic velocity at the base of the outer core(6-12). This 250-km-thick layer has been interpreted as a stably stratified region of reduced composition in light elements(13). Here we show that this layer can be generated by simultaneous crystallization and melting at the surface of the inner core, and that a translational mode of thermal convection in the inner core can produce enough melting and crystallization on each hemisphere respectively for the dense layer to develop. The dynamical model we propose introduces a clear asymmetry between a melting and a crystallizing hemisphere which forms a basis for also explaining the East-West asymmetry. The present translation rate is found to be typically 100 million years for the inner core to be entirely renewed, which is one to two orders of magnitude faster than the growth rate of the inner core's radius. The resulting strong asymmetry of buoyancy flux caused by light elements is anticipated to have an impact on the dynamics of the outer core and on the geodynamo.
C1 [Alboussiere, Thierry; Deguen, Renaud; Melzani, Mickael] Univ Grenoble 1, CNRS, Observ Grenoble, Lab Geophys Interne & Tectonophys, F-38041 Grenoble 9, France.
   [Alboussiere, Thierry] UCB Lyon 1, UMR5570, CNRS, F-69622 Villeurbanne, France.
   [Alboussiere, Thierry] Univ Lyon 1, ENS Lyon, F-69622 Villeurbanne, France.
   [Deguen, Renaud] Johns Hopkins Univ, Dept Earth & Planetary Sci, Baltimore, MD 21218 USA.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Johns Hopkins University
RP Alboussière, T (corresponding author), Univ Grenoble 1, CNRS, Observ Grenoble, Lab Geophys Interne & Tectonophys, BP 53, F-38041 Grenoble 9, France.
EM thierry.alboussiere@ens-lyon.fr
FU LGIT; ANR (Agence Nationale de la Recherche) [ANR-08-BLAN-0234-01]; Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0234] Funding Source: Agence Nationale de la Recherche (ANR)
NR 35
TC 195
Z9 214
U1 0
U2 61
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 744
EP U9
DI 10.1038/nature09257
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500036
PM 20686572
DA 2026-03-09
ER

PT J
AU David, CJ
   Chen, M
   Assanah, M
   Canoll, P
   Manley, JL
AF David, Charles J.
   Chen, Mo
   Assanah, Marcela
   Canoll, Peter
   Manley, James L.
TI HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
SO NATURE
LA English
DT Article
ID tract-binding-protein; expression; growth; a1; cells; gene; ptb; differentiation; specificity; repression
AB When oxygen is abundant, quiescent cells efficiently extract energy from glucose primarily by oxidative phosphorylation, whereas under the same conditions tumour cells consume glucose more avidly, converting it to lactate. This long-observed phenomenon is known as aerobic glycolysis(1), and is important for cell growth(2,3). Because aerobic glycolysis is only useful to growing cells, it is tightly regulated in a proliferation-linked manner(4). In mammals, this is partly achieved through control of pyruvate kinase isoform expression. The embryonic pyruvate kinase isoform, PKM2, is almost universally re-expressed in cancer(2), and promotes aerobic glycolysis, whereas the adult isoform, PKM1, promotes oxidative phosphorylation(2). These two isoforms result from mutually exclusive alternative splicing of the PKM pre-mRNA, reflecting inclusion of either exon 9 (PKM1) or exon 10 (PKM2). Here we show that three heterogeneous nuclear ribonucleoprotein (hnRNP) proteins, polypyrimidine tract binding protein (PTB, also known as hnRNPI), hnRNPA1 and hnRNPA2, bind repressively to sequences flanking exon 9, resulting in exon 10 inclusion. We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, ensuring a high PKM2/PKM1 ratio. Establishing a relevance to cancer, we show that human gliomas overexpress c-Myc, PTB, hnRNPA1 and hnRNPA2 in a manner that correlates with PKM2 expression. Our results thus define a pathway that regulates an alternative splicing event required for tumour cell proliferation.
C1 [David, Charles J.; Chen, Mo; Manley, James L.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Assanah, Marcela; Canoll, Peter] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University
RP Manley, JL (corresponding author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
EM jlm2@columbia.edu
FU Avon Foundation; NIH
NR 31
TC 937
Z9 1094
U1 1
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 364
EP U114
DI 10.1038/nature08697
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100046
PM 20010808
DA 2026-03-09
ER

PT J
AU Gao, X
   Zhou, LJ
   Jiao, XY
   Lu, FR
   Yan, CY
   Zeng, X
   Wang, JW
   Shi, YG
AF Gao, Xiang
   Zhou, Lijun
   Jiao, Xuyao
   Lu, Feiran
   Yan, Chuangye
   Zeng, Xin
   Wang, Jiawei
   Shi, Yigong
TI Mechanism of substrate recognition and transport by an amino acid antiporter
SO NATURE
LA English
DT Article
ID agmatine antiporter; bacterial homolog; crystal-structure; resistance; putrescine; excretion; arginine; site; identification; cadaverine
AB In extremely acidic environments, enteric bacteria such as Escherichia coli rely on the amino acid antiporter AdiC to expel protons by exchanging intracellular agmatine (Agm(2+)) for extracellular arginine (Arg(+))(1-3). AdiC is a representative member of the amino acid-polyamine-organocation (APC) superfamily of membrane transporters(4,5). The structure of substrate-free AdiC revealed a homodimeric assembly, with each protomer containing 12 transmembrane segments and existing in an outward-open conformation(6,7). The overall folding of AdiC is similar to that of the Na+-coupled symporters(8-11). Despite these advances, it remains unclear how the substrate (arginine or agmatine) is recognized and transported by AdiC. Here we report the crystal structure of an E. coli AdiC variant bound to Arg at 3.0 angstrom resolution. The positively charged Arg is enclosed in an acidic binding chamber, with the head groups of Arg hydrogen-bonded to main chain atoms of AdiC and the aliphatic portion of Arg stacked by hydrophobic side chains of highly conserved residues. Arg binding induces pronounced structural rearrangement in transmembrane helix 6 (TM6) and, to a lesser extent, TM2 and TM10, resulting in an occluded conformation. Structural analysis identified three potential gates, involving four aromatic residues and Glu 208, which may work in concert to differentially regulate the upload and release of Arg and Agm.
C1 [Gao, Xiang; Zeng, Xin; Shi, Yigong] Tsinghua Univ, Minist Educ, Prot Sci Lab, Beijing 100084, Peoples R China.
   [Zhou, Lijun; Jiao, Xuyao; Lu, Feiran; Yan, Chuangye; Wang, Jiawei] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Zhou, Lijun; Jiao, Xuyao; Lu, Feiran; Yan, Chuangye; Wang, Jiawei] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Jiao, Xuyao] Shandong Univ, Sch Life Sci, Jinan 250100, Shandong, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Shandong University
RP Shi, YG (corresponding author), Tsinghua Univ, Minist Educ, Prot Sci Lab, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918801]; Tsinghua University; National Natural Science Foundation; Beijing Municipal Commissions of Education and Science and Technology
NR 31
TC 173
Z9 195
U1 0
U2 145
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 828
EP U143
DI 10.1038/nature08741
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300044
PM 20090677
DA 2026-03-09
ER

PT J
AU Insel, TR
AF Insel, Thomas R.
TI Rethinking schizophrenia
SO NATURE
LA English
DT Article
ID childhood-onset schizophrenia; ultra-high risk; follow-up; obstetric complications; adult schizophrenia; psychotic disorders; prenatal exposure; brain-development; deficits; genes
AB How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.
C1 NIMH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
RP Insel, TR (corresponding author), NIMH, Bethesda, MD 20892 USA.
EM tinsel@mail.nih.gov
NR 99
TC 1390
Z9 1676
U1 1
U2 276
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 187
EP 193
DI 10.1038/nature09552
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000034
PM 21068826
DA 2026-03-09
ER

PT J
AU Tricomi, E
   Rangel, A
   Camerer, CF
   O'Doherty, JP
AF Tricomi, Elizabeth
   Rangel, Antonio
   Camerer, Colin F.
   O'Doherty, John P.
TI Neural evidence for inequality-averse social preferences
SO NATURE
LA English
DT Article
ID orbitofrontal cortex; decision-making; fairness; responses; brain; prediction; punishment; motives
AB A popular hypothesis in the social sciences is that humans have social preferences to reduce inequality in outcome distributions because it has a negative impact on their experienced reward(1-3). Although there is a large body of behavioural and anthropological evidence consistent with the predictions of these theories(1,4-6), there is no direct neural evidence for the existence of inequality-averse preferences. Such evidence would be especially useful because some behaviours that are consistent with a dislike for unequal outcomes could also be explained by concerns for social image(7) or reciprocity(8,9), which do not require a direct aversion towards inequality. Here we use functional MRI to test directly for the existence of inequality-averse social preferences in the human brain. Inequality was created by recruiting pairs of subjects and giving one of them a large monetary endowment. While both subjects evaluated further monetary transfers from the experimenter to themselves and to the other participant, we measured neural responses in the ventral striatum and ventromedial prefrontal cortex, two areas that have been shown to be involved in the valuation of monetary and primary rewards in both social and non-social contexts(10-14). Consistent with inequality-averse models of social preferences, we find that activity in these areas was more responsive to transfers to others than to self in the 'high-pay' subject, whereas the activity of the 'low-pay' subject showed the opposite pattern. These results provide direct evidence for the validity of this class of models, and also show that the brain's reward circuitry is sensitive to both advantageous and disadvantageous inequality.
C1 [Rangel, Antonio; Camerer, Colin F.; O'Doherty, John P.] CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA.
   [Tricomi, Elizabeth] Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA.
   [O'Doherty, John P.] Trinity Coll Dublin, Sch Psychol, Dublin 2, Ireland.
   [O'Doherty, John P.] Trinity Coll Dublin, Inst Neurosci, Dublin 2, Ireland.
C3 California Institute of Technology; Rutgers University System; Rutgers University Newark; Rutgers University New Brunswick; Trinity College Dublin; Trinity College Dublin
RP O'Doherty, JP (corresponding author), CALTECH, Div Humanities & Social Sci, Pasadena, CA 91125 USA.
EM johnpodoherty@gmail.com
FU US National Science Foundation [0617174]; Human Frontiers of Science Program; Gordon and Betty Moore Foundation; Caltech Brain Imaging Center; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [0617174] Funding Source: National Science Foundation
NR 39
TC 318
Z9 362
U1 3
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1089
EP U109
DI 10.1038/nature08785
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400038
PM 20182511
DA 2026-03-09
ER

PT J
AU Peslier, AH
   Woodland, AB
   Bell, DR
   Lazarov, M
AF Peslier, Anne H.
   Woodland, Alan B.
   Bell, David R.
   Lazarov, Marina
TI Olivine water contents in the continental lithosphere and the longevity of cratons
SO NATURE
LA English
DT Article
ID upper-mantle beneath; thermal evolution; oxygen fugacity; viscosity; hydrogen; garnet; vatnajokull; calibration; kimberlite; solubility
AB Cratons, the ancient cores of continents, contain the oldest crust and mantle on the Earth (>2 Gyr old)(1). They extend laterally for hundreds of kilometres, and are underlain to depths of 180-250 km by mantle roots that are chemically and physically distinct from the surrounding mantle(2-4). Forming the thickest lithosphere on our planet, they act as rigid keels isolated from the flowing asthenosphere(5); however, it has remained an open question how these large portions of the mantle can stay isolated for so long from mantle convection. Key physical properties thought to contribute to this longevity include chemical buoyancy due to high degrees of melt-depletion and the stiffness imparted by the low temperatures of a conductive thermal gradient(2,6,7). Geodynamic calculations, however, suggest that these characteristics are not sufficient to prevent the lithospheric mantle from being entrained during mantle convection over billions of years(6,7). Differences in water content are a potential source of additional viscosity contrast between cratonic roots and ambient mantle owing to the well-established hydrolytic weakening effect in olivine(8-10), the most abundant mineral of the upper mantle. However, the water contents of cratonic mantle roots have to date been poorly constrained. Here we show that olivine in peridotite xenoliths from the lithosphere-asthenosphere boundary region of the Kaapvaal craton mantle root are water-poor and provide sufficient viscosity contrast with underlying asthenosphere to satisfy the stability criteria required by geodynamic calculations(9). Our results provide a solution to a puzzling mystery of plate tectonics, namely why the oldest continents, in contrast to short-lived oceanic plates, have resisted recycling into the interior of our tectonically dynamic planet.
C1 [Peslier, Anne H.] ESCG, Houston, TX 77058 USA.
   [Peslier, Anne H.] NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [Woodland, Alan B.; Lazarov, Marina] Goethe Univ Frankfurt, Inst Geosci, D-60438 Frankfurt, Germany.
   [Bell, David R.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; Goethe University Frankfurt; Arizona State University; Arizona State University-Tempe
RP Peslier, AH (corresponding author), ESCG, Mail Code JE23,2224 Bay Area Blvd, Houston, TX 77058 USA.
EM anne.h.peslier@nasa.gov
FU NSF [EAR0802652]
NR 49
TC 253
Z9 294
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 78
EP U108
DI 10.1038/nature09317
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200038
PM 20811455
DA 2026-03-09
ER

PT J
AU Yooseph, S
   Nealson, KH
   Rusch, DB
   McCrow, JP
   Dupont, CL
   Kim, M
   Johnson, J
   Montgomery, R
   Ferriera, S
   Beeson, K
   Williamson, SJ
   Tovchigrechko, A
   Allen, AE
   Zeigler, LA
   Sutton, G
   Eisenstadt, E
   Rogers, YH
   Friedman, R
   Frazier, M
   Venter, JC
AF Yooseph, Shibu
   Nealson, Kenneth H.
   Rusch, Douglas B.
   McCrow, John P.
   Dupont, Christopher L.
   Kim, Maria
   Johnson, Justin
   Montgomery, Robert
   Ferriera, Steve
   Beeson, Karen
   Williamson, Shannon J.
   Tovchigrechko, Andrey
   Allen, Andrew E.
   Zeigler, Lisa A.
   Sutton, Granger
   Eisenstadt, Eric
   Rogers, Yu-Hui
   Friedman, Robert
   Frazier, Marvin
   Venter, J. Craig
TI Genomic and functional adaptation in surface ocean planktonic prokaryotes
SO NATURE
LA English
DT Article
ID protein; diversity; database; alignment; family; iron
AB The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0 mu m size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass.
C1 [Yooseph, Shibu; Nealson, Kenneth H.; Rusch, Douglas B.; McCrow, John P.; Dupont, Christopher L.; Kim, Maria; Johnson, Justin; Montgomery, Robert; Ferriera, Steve; Beeson, Karen; Williamson, Shannon J.; Tovchigrechko, Andrey; Allen, Andrew E.; Zeigler, Lisa A.; Sutton, Granger; Eisenstadt, Eric; Rogers, Yu-Hui; Friedman, Robert; Frazier, Marvin; Venter, J. Craig] J Craig Venter Inst, Rockville, MD 20850 USA.
C3 J. Craig Venter Institute
RP Nealson, KH (corresponding author), J Craig Venter Inst, Rockville, MD 20850 USA.
EM knealson@usc.edu
FU Gordon and Betty Moore Foundation [521]; Department of Energy, Office of Science, Office of Biological and Environmental Research [DE-FC02-02ER63453]; JCVI; US National Science Foundation [0850256]; Div Of Biological Infrastructure; Direct For Biological Sciences [0850256] Funding Source: National Science Foundation
NR 44
TC 231
Z9 261
U1 6
U2 132
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 60
EP +
DI 10.1038/nature09530
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900035
PM 21048761
DA 2026-03-09
ER

PT J
AU Kim, YJ
   Lee, HS
   Kim, ES
   Bae, SS
   Lim, JK
   Matsumi, R
   Lebedinsky, AV
   Sokolova, TG
   Kozhevnikova, DA
   Cha, SS
   Kim, SJ
   Kwon, KK
   Imanaka, T
   Atomi, H
   Bonch-Osmolovskaya, EA
   Lee, JH
   Kang, SG
AF Kim, Yun Jae
   Lee, Hyun Sook
   Kim, Eun Sook
   Bae, Seung Seob
   Lim, Jae Kyu
   Matsumi, Rie
   Lebedinsky, Alexander V.
   Sokolova, Tatyana G.
   Kozhevnikova, Darya A.
   Cha, Sun-Shin
   Kim, Sang-Jin
   Kwon, Kae Kyoung
   Imanaka, Tadayuki
   Atomi, Haruyuki
   Bonch-Osmolovskaya, Elizaveta A.
   Lee, Jung-Hyun
   Kang, Sung Gyun
TI Formate-driven growth coupled with H2 production
SO NATURE
LA English
DT Article
ID sea hydrothermal vent; hyperthermophilic archaeon; escherichia-coli; methanobacterium-formicicum; methanococcus-maripaludis; hydrogenlyase system; operon; hydrogenase-3; metabolism; prediction
AB Although a common reaction in anaerobic environments, the conversion of formate and water to bicarbonate and H-2 (with a change in Gibbs free energy of Delta G degrees = + 1.3 kJ mol(-1)) has not been considered energetic enough to support growth of microorganisms. Recently, experimental evidence for growth on formate was reported for syntrophic communities of Moorella sp. strain AMP and a hydrogen-consuming Methanothermobacter species and of Desulfovibrio sp. strain G11 and Methanobrevibacter arboriphilus strain AZ(1). The basis of the sustainable growth of the formate-users is explained by H-2 consumption by the methanogens, which lowers the H-2 partial pressure, thus making the pathway exergonic(2). However, it has not been shown that a single strain can grow on formate by catalysing its conversion to bicarbonate and H-2. Here we report that several hyperthermophilic archaea belonging to the Thermococcus genus are capable of formate-oxidizing, H-2-producing growth. The actual Delta G values for the formate metabolism are calculated to range between -8 and -20 kJ mol(-1) under the physiological conditions where Thermococcus onnurineus strain NA1 are grown. Furthermore, we detected ATP synthesis in the presence of formate as a sole energy source. Gene expression profiling and disruption identified the gene cluster encoding formate hydrogen lyase, cation/proton antiporter and formate transporter, which were responsible for the growth of T. onnurineus NA1 on formate. This work shows formate-driven growth by a single microorganism with protons as the electron acceptor, and reports the biochemical basis of this ability.
C1 [Kim, Yun Jae; Lee, Hyun Sook; Kim, Eun Sook; Bae, Seung Seob; Lim, Jae Kyu; Cha, Sun-Shin; Kim, Sang-Jin; Kwon, Kae Kyoung; Lee, Jung-Hyun; Kang, Sung Gyun] Korea Ocean Res & Dev Inst, Ansan 425600, South Korea.
   [Lee, Hyun Sook; Bae, Seung Seob; Lim, Jae Kyu; Cha, Sun-Shin; Kim, Sang-Jin; Kwon, Kae Kyoung; Lee, Jung-Hyun; Kang, Sung Gyun] Univ Sci & Technol, Dept Marine Biotechnol, Taejon 305333, South Korea.
   [Matsumi, Rie; Imanaka, Tadayuki; Atomi, Haruyuki] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Nishikyo Ku, Kyoto 6158510, Japan.
   [Lebedinsky, Alexander V.; Sokolova, Tatyana G.; Kozhevnikova, Darya A.; Bonch-Osmolovskaya, Elizaveta A.] Russian Acad Sci, Winogradsky Inst Microbiol, Moscow 117312, Russia.
C3 Korea Institute of Ocean Science & Technology (KIOST); Kyoto University; Research Center of Biotechnology RAS; Russian Academy of Sciences
RP Lee, JH (corresponding author), Korea Ocean Res & Dev Inst, POB 29, Ansan 425600, South Korea.
EM jlee@kordi.re.kr; sgkang@kordi.re.kr
FU KORDI [PE98513]; Marine and Extreme Genome Research Center; Ministry of Land, Transport, and Maritime Affairs, Korea; RAS; Russian Foundation of Basic Research [10-04-01180]
NR 27
TC 195
Z9 219
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 16
PY 2010
VL 467
IS 7313
BP 352
EP U137
DI 10.1038/nature09375
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900044
PM 20844539
DA 2026-03-09
ER

PT J
AU Hehemann, JH
   Correc, G
   Barbeyron, T
   Helbert, W
   Czjzek, M
   Michel, G
AF Hehemann, Jan-Hendrik
   Correc, Gaelle
   Barbeyron, Tristan
   Helbert, William
   Czjzek, Mirjam
   Michel, Gurvan
TI Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota
SO NATURE
LA English
DT Article
ID glycoside hydrolases; maximum-likelihood; kappa-carrageenase; sequence alignment; diffraction data; beta-agarases; sp-nov; polysaccharide; evolution; classification
AB Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes(1), which are absent in the human genome. These enzymes target polysaccharides from terrestrial plants that dominated diet throughout human evolution(2). The array of CAZymes in gut microbes is highly diverse, exemplified by the human gut symbiont Bacteroides thetaiotaomicron(3), which contains 261 glycoside hydrolases and polysaccharide lyases, as well as 208 homologues of susC and susD-genes coding for two outer membrane proteins involved in starch utilization(1,4). A fundamental question that, to our knowledge, has yet to be addressed is how this diversity evolved by acquiring new genes from microbes living outside the gut. Here we characterize the first porphyranases from a member of the marine Bacteroidetes, Zobellia galactanivorans, active on the sulphated polysaccharide porphyran from marine red algae of the genus Porphyra. Furthermore, we show that genes coding for these porphyranases, agarases and associated proteins have been transferred to the gut bacterium Bacteroides plebeius isolated from Japanese individuals(5). Our comparative gut metagenome analyses show that porphyranases and agarases are frequent in the Japanese population(6) and that they are absent in metagenome data(7) from North American individuals. Seaweeds make an important contribution to the daily diet in Japan (14.2 g per person per day)(8), and Porphyra spp. (nori) is the most important nutritional seaweed, traditionally used to prepare sushi(9,10). This indicates that seaweeds with associated marine bacteria may have been the route by which these novel CAZymes were acquired in human gut bacteria, and that contact with non-sterile food may be a general factor in CAZyme diversity in human gut microbes.
C1 [Hehemann, Jan-Hendrik; Correc, Gaelle; Barbeyron, Tristan; Helbert, William; Czjzek, Mirjam; Michel, Gurvan] Univ Paris 06, F-29682 Roscoff, France.
   [Hehemann, Jan-Hendrik; Correc, Gaelle; Barbeyron, Tristan; Helbert, William; Czjzek, Mirjam; Michel, Gurvan] CNRS, Stn Biol Roscoff, Vegetaux Marins & Biomol UMR 7139, F-29682 Roscoff, France.
C3 Sorbonne Universite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Czjzek, M (corresponding author), Univ Paris 06, F-29682 Roscoff, France.
EM czjzek@sb-roscoff.fr; gurvan@sb-roscoff.fr
FU French national research centre (Centre National de la Recherche Scientifique); University Marie Curie; European Marie Curie PhD grant; Region Bretagne; GIS 'Genomique Marine'; French Research Ministry
NR 41
TC 847
Z9 988
U1 4
U2 515
PU NATURE PUBLISHING 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 8
PY 2010
VL 464
IS 7290
BP 908
EP U123
DI 10.1038/nature08937
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300041
PM 20376150
DA 2026-03-09
ER

PT J
AU Rose, KA
   Sikes, EL
   Guilderson, TP
   Shane, P
   Hill, TM
   Zahn, R
   Spero, HJ
AF Rose, Kathryn A.
   Sikes, Elisabeth L.
   Guilderson, Thomas P.
   Shane, Phil
   Hill, Tessa M.
   Zahn, Rainer
   Spero, Howard J.
TI Upper-ocean-to-atmosphere radiocarbon offsets imply fast deglacial carbon dioxide release
SO NATURE
LA English
DT Article
ID pacific-ocean; north-atlantic; new-zealand; co2; ventilation; calibration; westerly; record; ages; beds
AB Radiocarbon in the atmosphere is regulated largely by ocean circulation, which controls the sequestration of carbon dioxide (CO2) in the deep sea through atmosphere-ocean carbon exchange. During the last glaciation, lower atmospheric CO2 levels were accompanied by increased atmospheric radiocarbon concentrations that have been attributed to greater storage of CO2 in a poorly ventilated abyssal ocean(1,2). The end of the ice age was marked by a rapid increase in atmospheric CO2 concentrations(2) that coincided with reduced C-14/C-12 ratios (Delta C-14) in the atmosphere(3), suggesting the release of very 'old' (C-14-depleted) CO2 from the deep ocean to the atmosphere(3). Here we present radiocarbon records of surface and intermediate-depth waters from two sediment cores in the southwest Pacific and Southern oceans. We find a steady 170 per mil decrease in Delta C-14 that precedes and roughly equals in magnitude the decrease in the atmospheric radiocarbon signal during the early stages of the glacial-interglacial climatic transition. The atmospheric decrease in the radiocarbon signal coincides with regionally intensified upwelling and marine biological productivity(4), suggesting that CO2 released by means of deep water upwelling in the Southern Ocean lost most of its original depleted-C-14 imprint as a result of exchange and isotopic equilibration with the atmosphere. Our data imply that the deglacial C-14 depletion previously identified in the eastern tropical North Pacific(5) must have involved contributions from sources other than the previously suggested carbon release by way of a deep Southern Ocean pathway(5), and may reflect the expanded influence of the C-14-depleted North Pacific carbon reservoir across this interval. Accordingly, shallow water masses advecting north across the South Pacific in the early deglaciation had little or no residual C-14-depleted signals owing to degassing of CO2 and biological uptake in the Southern Ocean.
C1 [Sikes, Elisabeth L.] Rutgers State Univ, Inst Marine & Coastal Sci, New Brunswick, NJ 08901 USA.
   [Rose, Kathryn A.; Hill, Tessa M.; Spero, Howard J.] Univ Calif Davis, Dept Geol, Davis, CA 95616 USA.
   [Guilderson, Thomas P.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Guilderson, Thomas P.] Univ Calif Santa Cruz, Inst Marine Sci, Santa Cruz, CA 95064 USA.
   [Shane, Phil] Univ Auckland, Sch Environm, Auckland 1142, New Zealand.
   [Zahn, Rainer] Univ Autonoma Barcelona, Inst Ciencia & Tecnol Ambientals, Dept Geol, Inst Catalana Recerca & Estudis Avancats,ICREA, Bellaterra 08193, Spain.
C3 Rutgers University System; Rutgers University New Brunswick; University of California System; University of California Davis; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California Santa Cruz; University of Auckland; Autonomous University of Barcelona; ICREA
RP Sikes, EL (corresponding author), Rutgers State Univ, Inst Marine & Coastal Sci, 71 Dudley Rd, New Brunswick, NJ 08901 USA.
EM sikes@marine.rutgers.edu
FU National Science Foundation (NSF) [RR0503]; Evolving Earth Foundation; Geological Society of America; MICINN, Spain; US Department of Energy; Division Of Ocean Sciences; Directorate For Geosciences [0823487, 0823549] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [0962077] Funding Source: National Science Foundation; ICREA Funding Source: Custom
NR 32
TC 66
Z9 83
U1 2
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 26
PY 2010
VL 466
IS 7310
BP 1093
EP 1097
DI 10.1038/nature09288
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600037
PM 20740012
DA 2026-03-09
ER

PT J
AU Schröder, GF
   Levitt, M
   Brunger, AT
AF Schroeder, Gunnar F.
   Levitt, Michael
   Brunger, Axel T.
TI Super-resolution biomolecular crystallography with low-resolution data
SO NATURE
LA English
DT Article
ID structure refinement; energy minimization; phase determination; normal-modes; protein; likelihood; ribonuclease; dynamics
AB X-ray diffraction plays a pivotal role in the understanding of biological systems by revealing atomic structures of proteins, nucleic acids and their complexes, with much recent interest in very large assemblies like the ribosome. As crystals of such large assemblies often diffract weakly (resolution worse than 4 angstrom), we need methods that work at such low resolution. In macromolecular assemblies, some of the components may be known at high resolution, whereas others are unknown: current refinement methods fail as they require a high-resolution starting structure for the entire complex(1). Determining the structure of such complexes, which are often of key biological importance, should be possible in principle as the number of independent diffraction intensities at a resolution better than 5 angstrom generally exceeds the number of degrees of freedom. Here we introduce a method that adds specific information from known homologous structures but allows global and local deformations of these homology models. Our approach uses the observation that local protein structure tends to be conserved as sequence and function evolve. Cross-validation with R-free ( the free R-factor) determines the optimum deformation and influence of the homology model. For test cases at 3.5-5 angstrom resolution with known structures at high resolution, our method gives significant improvements over conventional refinement in the model as monitored by coordinate accuracy, the definition of secondary structure and the quality of electron density maps. For re-refinements of a representative set of 19 low-resolution crystal structures from the Protein Data Bank, we find similar improvements. Thus, a structure derived from low-resolution diffraction data can have quality similar to a high-resolution structure. Our method is applicable to the study of weakly diffracting crystals using X-ray micro-diffraction(2) as well as data from new X-ray light sources(3). Use of homology information is not restricted to X-ray crystallography and cryo-electron microscopy: as optical imaging advances to subnanometre resolution(4,5), it can use similar tools.
C1 [Schroeder, Gunnar F.] Forschungszentrum Julich, Inst Strukturbiol & Biophys ISB 3, D-52425 Julich, Germany.
   [Schroeder, Gunnar F.; Levitt, Michael; Brunger, Axel T.] Stanford Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Brunger, Axel T.] Stanford Univ, Howard Hughes Med Inst, James H Clark Ctr E300, Stanford, CA 94305 USA.
   [Brunger, Axel T.] Stanford Univ, Dept Mol & Cellular Physiol, James H Clark Ctr E300, Stanford, CA 94305 USA.
   [Brunger, Axel T.] Stanford Univ, Dept Neurol & Neurol Sci, James H Clark Ctr E300, Stanford, CA 94305 USA.
   [Brunger, Axel T.] Stanford Univ, Dept Photon Sci, James H Clark Ctr E300, Stanford, CA 94305 USA.
C3 Helmholtz Association; Julich Research Centre; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University; Stanford University
RP Schröder, GF (corresponding author), Forschungszentrum Julich, Inst Strukturbiol & Biophys ISB 3, D-52425 Julich, Germany.
EM gu.schroeder@fz-juelich.de; brunger@stanford.edu
FU National Science Foundation [CNS-0619926]; National Institutes of Health [PN2 (EY016525), GM63718]; Deutsche Forschungsgemeinschaft (DFG)
NR 39
TC 236
Z9 261
U1 0
U2 47
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1218
EP U146
DI 10.1038/nature08892
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100043
PM 20376006
DA 2026-03-09
ER

PT J
AU Ng, SF
   Lin, RCY
   Laybutt, DR
   Barres, R
   Owens, JA
   Morris, MJ
AF Ng, Sheau-Fang
   Lin, Ruby C. Y.
   Laybutt, D. Ross
   Barres, Romain
   Owens, Julie A.
   Morris, Margaret J.
TI Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring
SO NATURE
LA English
DT Article
ID low-birth-weight; body-mass index; childhood; obesity; undernutrition; transmission; association; protein; plasma; islets
AB The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic(1,2). Having either parent obese is an independent risk factor for childhood obesity(3). Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established(4), the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs beta-cell 'dysfunction' in rat F-1 female offspring. Chronic HFD consumption in Sprague-Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642 pancreatic islet genes in adult female offspring (P < 0.01); genes belonged to 13 functional clusters, including cation and ATP binding, cytoskeleton and intracellular transport. Broader pathway analysis of 2,492 genes differentially expressed (P < 0.05) demonstrated involvement of calcium-, MAPK- and Wnt-signalling pathways, apoptosis and the cell cycle. Hypomethylation of the Il13ra2 gene, which showed the highest fold difference in expression (1.76-fold increase), was demonstrated. This is the first report in mammals of non-genetic, intergenerational transmission of metabolic sequelae of a HFD from father to offspring.
C1 [Ng, Sheau-Fang; Morris, Margaret J.] Univ New S Wales, Dept Pharmacol, Sch Med Sci, Sydney, NSW 2052, Australia.
   [Lin, Ruby C. Y.] Univ New S Wales, Ramaciotti Ctr Gene Funct Anal, Sydney, NSW 2052, Australia.
   [Lin, Ruby C. Y.] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia.
   [Laybutt, D. Ross] Garvan Inst Med Res, Sydney, NSW 2010, Australia.
   [Barres, Romain] Univ New S Wales, Sch Med Sci, Dept Anat, Sydney, NSW 2052, Australia.
   [Owens, Julie A.] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA 5005, Australia.
C3 University of New South Wales Sydney; University of New South Wales Sydney; University of New South Wales Sydney; Garvan Institute of Medical Research; University of New South Wales Sydney; Adelaide University; University of Adelaide
RP Morris, MJ (corresponding author), Univ New S Wales, Dept Pharmacol, Sch Med Sci, Sydney, NSW 2052, Australia.
EM m.morris@unsw.edu.au
FU National Health and Medical Research Council (NHMRC) of Australia; Ministry of Higher Education; National University of Malaysia; NHMRC
NR 42
TC 1067
Z9 1228
U1 3
U2 203
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 21
PY 2010
VL 467
IS 7318
BP 963
EP U103
DI 10.1038/nature09491
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700038
PM 20962845
DA 2026-03-09
ER

PT J
AU Akella, JS
   Wloga, D
   Kim, J
   Starostina, NG
   Lyons-Abbott, S
   Morrissette, NS
   Dougan, ST
   Kipreos, ET
   Gaertig, J
AF Akella, Jyothi S.
   Wloga, Dorota
   Kim, Jihyun
   Starostina, Natalia G.
   Lyons-Abbott, Sally
   Morrissette, Naomi S.
   Dougan, Scott T.
   Kipreos, Edward T.
   Gaertig, Jacek
TI MEC-17 is an α-tubulin acetyltransferase
SO NATURE
LA English
DT Article
ID touch receptor neurons; tetrahymena-thermophila; caenorhabditis-elegans; c-elegans; acetylation; microtubule; cilia; transport; domain; identification
AB In most eukaryotic cells, subsets of microtubules are adapted for specific functions by post-translational modifications (PTMs) of tubulin subunits. Acetylation of the epsilon-amino group of K40 on alpha-tubulin is a conserved PTM on the luminal side of microtubules(1) that was discovered in the flagella of Chlamydomonas reinhardtii(2,3). Studies on the significance of microtubule acetylation have been limited by the undefined status of the alpha-tubulin acetyltransferase. Here we show that MEC-17, a protein related to the Gcn5 histone acetyltransferases(4) and required for the function of touch receptor neurons in Caenorhabditis elegans(5,6), acts as a K40-specific acetyltransferase for alpha-tubulin. In vitro, MEC-17 exclusively acetylates K40 of alpha-tubulin. Disruption of the Tetrahymena MEC-17 gene phenocopies the K40R alpha-tubulin mutation and makes microtubules more labile. Depletion of MEC-17 in zebrafish produces phenotypes consistent with neuromuscular defects. In C. elegans, MEC-17 and its paralogue W06B11.1 are redundantly required for acetylation of MEC-12 alpha-tubulin, and contribute to the function of touch receptor neurons partly via MEC-12 acetylation and partly via another function, possibly by acetylating another protein. In summary, we identify MEC-17 as an enzyme that acetylates the K40 residue of alpha-tubulin, the only PTM known to occur on the luminal surface of microtubules.
C1 [Akella, Jyothi S.; Wloga, Dorota; Kim, Jihyun; Starostina, Natalia G.; Dougan, Scott T.; Kipreos, Edward T.; Gaertig, Jacek] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA.
   [Lyons-Abbott, Sally; Morrissette, Naomi S.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
C3 University System of Georgia; University of Georgia; University of California System; University of California Irvine
RP Gaertig, J (corresponding author), Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA.
EM jgaertig@cb.uga.edu
FU National Science Foundation [MBC-033965]; American Cancer Society [RSG DDC-112979]; National Institutes of Health [R01GM074212, R01AI067981, R01GM089912]
NR 44
TC 391
Z9 487
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 218
EP U111
DI 10.1038/nature09324
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300037
PM 20829795
DA 2026-03-09
ER

PT J
AU Park, H
   Pontius, W
   Guet, CC
   Marko, JF
   Emonet, T
   Cluzel, P
AF Park, Heungwon
   Pontius, William
   Guet, Calin C.
   Marko, John F.
   Emonet, Thierry
   Cluzel, Philippe
TI Interdependence of behavioural variability and response to small stimuli in bacteria
SO NATURE
LA English
DT Article
ID signal-transduction; escherichia-coli; chemotaxis; noise; sensitivity; robustness; networks; systems; gene
AB The chemotaxis signalling network in Escherichia coli that controls the locomotion of bacteria is a classic model system for signal transduction(1,2). This pathway modulates the behaviour of flagellar motors to propel bacteria towards sources of chemical attractants. Although this system relaxes to a steady state in response to environmental changes, the signalling events within the chemotaxis network are noisy and cause large temporal variations of the motor behaviour even in the absence of stimulus(3). That the same signalling network governs both behavioural variability and cellular response raises the question of whether these two traits are independent. Here, we experimentally establish a fluctuation-response relationship in the chemotaxis system of living bacteria. Using this relationship, we demonstrate the possibility of inferring the cellular response from the behavioural variability measured before stimulus. In monitoring the pre- and post-stimulus switching behaviour of individual bacterial motors, we found that variability scales linearly with the response time for different functioning states of the cell. This study highlights that the fundamental relationship between fluctuation and response is not constrained to physical systems at thermodynamic equilibrium(4) but is extensible to living cells(5). Such a relationship not only implies that behavioural variability and cellular response can be coupled traits, but it also provides a general framework within which we can examine how the selection of a network design shapes this interdependence.
C1 [Guet, Calin C.; Cluzel, Philippe] Harvard Univ, FAS Ctr Syst Biol, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Guet, Calin C.; Cluzel, Philippe] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Park, Heungwon] Univ Chicago, James Franck Inst, Inst Biophys Dynam, Chicago, IL 60637 USA.
   [Park, Heungwon] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
   [Pontius, William; Emonet, Thierry] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Pontius, William; Emonet, Thierry] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Marko, John F.] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
   [Marko, John F.] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA.
C3 Harvard University; Harvard University; University of Chicago; University of Chicago; Yale University; Yale University; Northwestern University; Northwestern University
RP Cluzel, P (corresponding author), Harvard Univ, FAS Ctr Syst Biol, Dept Mol & Cellular Biol, 52 Oxford St, Cambridge, MA 02138 USA.
EM cluzel@mcb.harvard.edu
FU NSF DMR [0213745]; NIH [R01AI059195-03, 1U54CA143869-01]; NSF [CCF0829836, PHY-0852130, DMR-0715099]; Alfred P. Sloan Research Fellowship; National Academies Keck Futures Initiative; Chicago Biomedical Consortium; Chicago Community Trust; Direct For Mathematical & Physical Scien; Division Of Materials Research [0213745] Funding Source: National Science Foundation
NR 35
TC 60
Z9 74
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 DEC 9
PY 2010
VL 468
IS 7325
BP 819
EP U114
DI 10.1038/nature09551
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700045
PM 21076396
DA 2026-03-09
ER

PT J
AU Shelly, DR
AF Shelly, David R.
TI Migrating tremors illuminate complex deformation beneath the seismogenic San Andreas fault
SO NATURE
LA English
DT Article
ID non-volcanic tremor; episodic tremor; parkfield; california; subduction; slip
AB The San Andreas fault is one of the most extensively studied faults in the world, yet its physical character and deformation mode beneath the relatively shallow earthquake-generating portion remain largely unconstrained. Tectonic 'non-volcanic' tremor, a recently discovered seismic signal(1) probably generated by shear slip on the deep extension of some major faults(2-4), can provide new insight into the deep fate of such faults, including that of the San Andreas fault near Parkfield, California(5). Here I examine continuous seismic data from mid-2001 to 2008, identifying tremor and decomposing the signal into different families of activity based on the shape and timing of the waveforms at multiple stations(6). This approach allows differentiation between activities from nearby patches of the deep fault and begins to unveil rich and complex patterns of tremor occurrence. I find that tremor exhibits nearly continuous migration, with the most extensive episodes propagating more than 20 kilometres along fault strike at rates of 15-80 kilometres per hour. This suggests that the San Andreas fault remains a localized through-going structure, at least to the base of the crust, in this area. Tremor rates and recurrence behaviour changed markedly in the wake of the 2004 magnitude-6.0 Parkfield earthquake(6,7), but these changes were far from uniform within the tremor zone, probably reflecting heterogeneous fault properties and static and dynamic stresses decaying away from the rupture. The systematic recurrence of tremor demonstrated here suggests the potential to monitor detailed time-varying deformation on this portion of the deep San Andreas fault, deformation which unsteadily loads the shallower zone that last ruptured in the 1857 magnitude-7.9 Fort Tejon earthquake(8).
C1 US Geol Survey, Menlo Pk, CA 94025 USA.
C3 United States Department of the Interior; United States Geological Survey
RP Shelly, DR (corresponding author), US Geol Survey, 345 Middlefield Rd,MS 977, Menlo Pk, CA 94025 USA.
EM dshelly@usgs.gov
NR 30
TC 133
Z9 149
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 4
PY 2010
VL 463
IS 7281
BP 648
EP U75
DI 10.1038/nature08755
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900033
PM 20130648
DA 2026-03-09
ER

PT J
AU Tooley, CES
   Petkowski, JJ
   Muratore-Schroeder, TL
   Balsbaugh, JL
   Shabanowitz, J
   Sabat, M
   Minor, W
   Hunt, DF
   Macara, IG
AF Tooley, Christine E. Schaner
   Petkowski, Janusz J.
   Muratore-Schroeder, Tara L.
   Balsbaugh, Jeremy L.
   Shabanowitz, Jeffrey
   Sabat, Michal
   Minor, Wladek
   Hunt, Donald F.
   Macara, Ian G.
TI NRMT is an α-N-methyltransferase that methylates RCC1 and retinoblastoma protein
SO NATURE
LA English
DT Article
ID amino-acid; ribosome; dimethylproline; subunit; h2b
AB The post-translational methylation of alpha-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function or enzymology of this modification. Several other bacterial and eukaryotic proteins have since been shown to be alpha-N-methylated(3-10). However, the Ran guanine nucleotide-exchange factor, RCC1, is the only protein for which any biological function of alpha-N-methylation has been identified(3,11). Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects(3,11), but further characterization of this modification has been hindered by ignorance of the responsible methyltransferase. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)Pro-Lys, indicating that they may be targets of the same, unknown enzyme(3,12). The initiating Met is cleaved, and the exposed alpha-amino group is mono-, di- or trimethylated. Here we report the discovery of the first alpha-N-methyltransferase, which we named N-terminal RCC1 methyltransferase (NRMT). Substrate docking and mutational analysis of RCC1 defined the NRMT recognition sequence and enabled the identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB. Knockdown of NRMT recapitulates the multi-spindle phenotype seen with methylation-defective RCC1 mutants(3), demonstrating the importance of alpha-N-methylation for normal bipolar spindle formation and chromosome segregation.
C1 [Tooley, Christine E. Schaner; Petkowski, Janusz J.; Macara, Ian G.] Univ Virginia, Sch Med, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA.
   [Petkowski, Janusz J.; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
   [Muratore-Schroeder, Tara L.; Balsbaugh, Jeremy L.; Shabanowitz, Jeffrey; Sabat, Michal; Hunt, Donald F.] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA.
   [Hunt, Donald F.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Tooley, CES (corresponding author), Univ Virginia, Sch Med, Dept Microbiol, Ctr Cell Signaling, Charlottesville, VA 22908 USA.
EM ces5g@virginia.edu
FU National Institutes of Health; National Institute of General Medical Sciences [R01GM037537] Funding Source: NIH RePORTER
NR 23
TC 109
Z9 147
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 26
PY 2010
VL 466
IS 7310
BP 1125
EP 1128
DI 10.1038/nature09343
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600044
PM 20668449
DA 2026-03-09
ER

PT J
AU Richardson, CE
   Kooistra, T
   Kim, DH
AF Richardson, Claire E.
   Kooistra, Tristan
   Kim, Dennis H.
TI An essential role for XBP-1 in host protection against immune activation in C. elegans
SO NATURE
LA English
DT Article
ID unfolded protein-response; plasma-cell differentiation; caenorhabditis-elegans; transcription factor; endoplasmic-reticulum; er stress; bacteria; pathway; induce; kinase
AB The detection and compensatory response to the accumulation of unfolded proteins in the endoplasmic reticulum (ER), termed the unfolded protein response (UPR), represents a conserved cellular homeostatic mechanism with important roles in normal development and in the pathogenesis of disease(1). The IRE1-XBP1/Hac1 pathway is a major branch of the UPR that has been conserved from yeast to human(2-6). X-box binding protein 1 (XBP1) is required for the differentiation of the highly secretory plasma cells of the mammalian adaptive immune system(7,8), but recent work also points to reciprocal interactions between the UPR and other aspects of immunity and inflammation(9-11). We have been studying innate immunity in the nematode Caenorhabditis elegans, having established a principal role for a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway in mediating resistance to microbial pathogens(12). Here we show that during C. elegans development, XBP-1 has an essential role in protecting the host during activation of innate immunity. Activation of the PMK-1-mediated response to infection with Pseudomonas aeruginosa induces the XBP-1-dependent UPR. Whereas a loss-of-function xbp-1 mutant develops normally in the presence of relatively non-pathogenic bacteria, infection of the xbp-1 mutant with P. aeruginosa leads to disruption of ER morphology and larval lethality. Unexpectedly, the larval lethality phenotype on pathogenic P. aeruginosa is suppressed by loss of PMK-1-mediated immunity. Furthermore, hyperactivation of PMK-1 causes larval lethality in the xbp-1 mutant even in the absence of pathogenic bacteria. Our data establish innate immunity as a physiologically relevant inducer of ER stress during C. elegans development and indicate that an ancient, conserved role for XBP-1 may be to protect the host organism from the detrimental effects of mounting an innate immune response to microbes.
C1 [Richardson, Claire E.; Kooistra, Tristan; 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 [DK43351, DK57521, R01-GM084477]; Howard Hughes Medical Institute; Burroughs Wellcome Fund; Ellison Medical Foundation
NR 35
TC 247
Z9 289
U1 0
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1092
EP U114
DI 10.1038/nature08762
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400039
PM 20182512
DA 2026-03-09
ER

PT J
AU Pickrell, JK
   Marioni, JC
   Pai, AA
   Degner, JF
   Engelhardt, BE
   Nkadori, E
   Veyrieras, JB
   Stephens, M
   Gilad, Y
   Pritchard, JK
AF Pickrell, Joseph K.
   Marioni, John C.
   Pai, Athma A.
   Degner, Jacob F.
   Engelhardt, Barbara E.
   Nkadori, Everlyne
   Veyrieras, Jean-Baptiste
   Stephens, Matthew
   Gilad, Yoav
   Pritchard, Jonathan K.
TI Understanding mechanisms underlying human gene expression variation with RNA sequencing
SO NATURE
LA English
DT Article
ID genome; cells; seq; contribute; discovery; variants
AB Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal(1). Although all eQTL studies so far have assayed messenger RNA levels using expression microarrays, recent advances in RNA sequencing enable the analysis of transcript variation at unprecedented resolution. We sequenced RNA from 69 lymphoblastoid cell lines derived from unrelated Nigerian individuals that have been extensively genotyped by the International HapMap Project(2). By pooling data from all individuals, we generated a map of the transcriptional landscape of these cells, identifying extensive use of unannotated untranslated regions and more than 100 new putative protein-coding exons. Using the genotypes from the HapMap project, we identified more than a thousand genes at which genetic variation influences overall expression levels or splicing. We demonstrate that eQTLs near genes generally act by a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within and near the consensus splice sites. Our results illustrate the power of high-throughput sequencing for the joint analysis of variation in transcription, splicing and allele-specific expression across individuals.
C1 [Pickrell, Joseph K.; Marioni, John C.; Pai, Athma A.; Degner, Jacob F.; Nkadori, Everlyne; Veyrieras, Jean-Baptiste; Stephens, Matthew; Gilad, Yoav; Pritchard, Jonathan K.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Engelhardt, Barbara E.] Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA.
   [Nkadori, Everlyne; Pritchard, Jonathan K.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
   [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago; Howard Hughes Medical Institute; University of Chicago
RP Pickrell, JK (corresponding author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
EM pickrell@uchicago.edu; gilad@uchicago.edu; pritch@uchicago.edu
FU HHMI; NIH [MH084703-01, GM077959]
NR 29
TC 968
Z9 1211
U1 0
U2 181
PU 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 1
PY 2010
VL 464
IS 7289
BP 768
EP 772
DI 10.1038/nature08872
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000047
PM 20220758
DA 2026-03-09
ER

PT J
AU Bento, G
   Ogawa, A
   Sommer, RJ
AF Bento, Gilberto
   Ogawa, Akira
   Sommer, Ralf J.
TI Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution
SO NATURE
LA English
DT Article
ID phenotypic plasticity; nuclear receptor; dauer formation; daf-12; identification; origins
AB Morphological novelties are lineage-specific traits that serve new functions(1,2). Developmental polyphenisms have been proposed to be facilitators of phenotypic evolution, but little is known about the interplay between the associated genetic and environmental factors(3-11). Here, we study two alternative morphologies in the mouth of the nematode Pristionchus pacificus and the formation of teeth-like structures that are associated with bacteriovorous feeding and predatory behaviour on fungi and other worms(12-16). These teeth-like denticles represent an evolutionary novelty, which is restricted to some members of the nematode family Diplogastridae but is absent from Caenorhabditis elegans and related nematodes(14). We show that the mouth dimorphism is a polyphenism that is controlled by starvation and the co-option of an endocrine switch mechanism. Mutations in the nuclear hormone receptor DAF-12 and application of its ligand, the sterol hormone dafachronic acid, strongly influence this switch mechanism. The dafachronic acid-DAF-12 module has been shown to control the formation of arrested dauer larvae in both C. elegans and P. pacificus, as well as related life-history decisions in distantly related nematodes(17-20). The comparison of dauer formation and mouth morphology switch reveals that different thresholds of dafachronic acid signalling provide specificity. This study shows how hormonal signalling acts by coupling environmental change and genetic regulation and identifies dafachronic acid as a key hormone in nematode evolution.
C1 [Bento, Gilberto; Ogawa, Akira; Sommer, Ralf J.] Max Planck Inst Dev Biol, Dept Evolutionary Biol, D-72076 Tubingen, Germany.
C3 Max Planck Society
RP Sommer, RJ (corresponding author), Max Planck Inst Dev Biol, Dept Evolutionary Biol, Spemannstr 37, D-72076 Tubingen, Germany.
EM ralf.sommer@tuebingen.mpg.de
NR 31
TC 177
Z9 199
U1 3
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 494
EP U9
DI 10.1038/nature09164
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200037
PM 20592728
DA 2026-03-09
ER

PT J
AU Papai, G
   Tripathi, MK
   Ruhlmann, C
   Layer, JH
   Weil, PA
   Schultz, P
AF Papai, Gabor
   Tripathi, Manish K.
   Ruhlmann, Christine
   Layer, Justin H.
   Weil, P. Anthony
   Schultz, Patrick
TI TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation
SO NATURE
LA English
DT Article
ID yeast tfiia/tbp/dna complex; dna-binding; saccharomyces-cerevisiae; electron-microscopy; crystal-structure; promoter; activation; protein; tafs; distinct
AB Transcription of eukaryotic messenger RNA (mRNA) encoding genes by RNA polymerase II (Pol II) is triggered by the binding of transactivating proteins to enhancer DNA, which stimulates the recruitment of general transcription factors (TFIIA, B, D, E, F, H) and Pol II on the cis-linked promoter, leading to pre-initiation complex formation and transcription(1). In TFIID-dependent activation pathways, this general transcription factor containing TATA-box-binding protein is first recruited on the promoter through interaction with activators(1-3) and cooperates with TFIIA to form a committed pre-initiation complex(4). However, neither the mechanisms by which activation signals are communicated between these factors nor the structural organization of the activated pre-initiation complex are known. Here we used cryo-electron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID, TFIIA, the transcriptional activator Rap1 and yeast enhancer-promoter DNA. These structures revealed the mode of binding of Rap1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by its interaction with Rap1. We propose that this change in position increases the exposure of TATA-box-binding protein within TFIID, consequently enhancing its ability to interact with the promoter. A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region. This loop is topologically locked by a TFIIA-Rap1 protein bridge that folds over the DNA. These results highlight the role of TFIIA in transcriptional activation, define a molecular mechanism for enhancer-promoter communication and provide structural insights into the pathways of intramolecular communication that convey transcription activation signals through the TFIID complex.
C1 [Papai, Gabor; Ruhlmann, Christine; Schultz, Patrick] IGBMC, Dept Struct Biol & Genom, F-67404 Illkirch Graffenstaden, France.
   [Papai, Gabor; Ruhlmann, Christine; Schultz, Patrick] CNRS, UMR7104, F-67400 Illkirch Graffenstaden, France.
   [Papai, Gabor; Ruhlmann, Christine; Schultz, Patrick] INSERM, U964, F-67400 Illkirch Graffenstaden, France.
   [Papai, Gabor; Ruhlmann, Christine; Schultz, Patrick] Univ Strasbourg, F-67000 Strasbourg, France.
   [Tripathi, Manish K.; Layer, Justin H.; Weil, P. Anthony] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Vanderbilt University
RP Schultz, P (corresponding author), IGBMC, Dept Struct Biol & Genom, 1 Rue Laurent Fries,BP10142, F-67404 Illkirch Graffenstaden, France.
EM tony.weil@vanderbilt.edu; patrick.schultz@igbmc.fr
FU Institut National de la Sante et de la Recherche Medicale; Centre National pour la Recherche Scientifique; Association pour la Recherche sur le Cancer; Fondation pour la Recherche Medicale; Agence Nationale pour le Recherche; EU [QLG2-CT-00988]; National Institutes of Health [GM52461]
NR 38
TC 58
Z9 80
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 956
EP U14
DI 10.1038/nature09080
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500044
PM 20559389
DA 2026-03-09
ER

PT J
AU Reches, Z
   Lockner, DA
AF Reches, Ze'ev
   Lockner, David A.
TI Fault weakening and earthquake instability by powder lubrication
SO NATURE
LA English
DT Article
ID high-speed; friction; wear; mechanism; zones; gouge
AB Earthquake instability has long been attributed to fault weakening during accelerated slip(1), and a central question of earthquake physics is identifying the mechanisms that control this weakening(2). Even with much experimental effort(2-12), the weakening mechanisms have remained enigmatic. Here we present evidence for dynamic weakening of experimental faults that are sheared at velocities approaching earthquake slip rates. The experimental faults, which were made of room-dry, solid granite blocks, quickly wore to form a fine-grain rock powder known as gouge. At modest slip velocities of 10-60 mm s(-1), this newly formed gouge organized itself into a thin deforming layer that reduced the fault's strength by a factor of 2-3. After slip, the gouge rapidly 'aged' and the fault regained its strength in a matter of hours to days. Therefore, only newly formed gouge can weaken the experimental faults. Dynamic gouge formation is expected to be a common and effective mechanism of earthquake instability in the brittle crust as (1) gouge always forms during fault slip(5,10,12-20); (2) fault-gouge behaves similarly to industrial powder lubricants(21); (3) dynamic gouge formation explains various significant earthquake properties; and (4) gouge lubricant can form for a wide range of fault configurations, compositions and temperatures(15).
C1 [Reches, Ze'ev] Univ Oklahoma, Sch Geol & Geophys, Norman, OK 73019 USA.
   [Lockner, David A.] US Geol Survey, Menlo Pk, CA 94025 USA.
C3 University of Oklahoma System; University of Oklahoma - Norman; United States Department of the Interior; United States Geological Survey
RP Reches, Z (corresponding author), Univ Oklahoma, Sch Geol & Geophys, 100 E Boyd St, Norman, OK 73019 USA.
EM reches@ou.edu; lockner@usgs.gov
FU National Science Foundation [0732715]; Division Of Earth Sciences; Directorate For Geosciences [0732715] Funding Source: National Science Foundation
NR 31
TC 261
Z9 296
U1 9
U2 108
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 452
EP U102
DI 10.1038/nature09348
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200041
PM 20865001
DA 2026-03-09
ER

PT J
AU Huppa, JB
   Axmann, M
   Mörtelmaier, MA
   Lillemeier, BF
   Newell, EW
   Brameshuber, M
   Klein, LO
   Schütz, GJ
   Davis, MM
AF Huppa, Johannes B.
   Axmann, Markus
   Moertelmaier, Manuel A.
   Lillemeier, Bjoern F.
   Newell, Evan W.
   Brameshuber, Mario
   Klein, Lawrence O.
   Schuetz, Gerhard J.
   Davis, Mark M.
TI TCR-peptide-MHC interactions in situ show accelerated kinetics and increased affinity
SO NATURE
LA English
DT Article
ID t-cell-receptor; 2-dimensional dissociation-constant; immunological synapse; adhesion molecules; recognition; activation; complex; binding; sensitivity; antigen
AB The recognition of foreign antigens by T lymphocytes is essential to most adaptive immune responses. It is driven by specific T-cell antigen receptors (TCRs) binding to antigenic peptide-major histocompatibility complex (pMHC) molecules on other cells(1). If productive, these interactions promote the formation of an immunological synapse(2,3). Here we show that synaptic TCR-pMHC binding dynamics differ significantly from TCR-pMHC binding in solution. We used single-molecule microscopy and fluorescence resonance energy transfer (FRET) between fluorescently tagged TCRs and their cognate pMHC ligands to measure the kinetics of TCR-pMHC binding in situ. When compared with solution measurements, the dissociation of this complex was increased significantly (4-12-fold). Disruption of actin polymers reversed this effect, indicating that cytoskeletal dynamics destabilize this interaction directly or indirectly. Nevertheless, TCR affinity for pMHC was significantly elevated as the result of a large (about 100-fold) increase in the association rate, a likely consequence of complementary molecular orientation and clustering. In helper T cells, the CD4 molecule has been proposed to bind cooperatively with the TCR to the same pMHC complex. However, CD4 blockade had no effect on the synaptic TCR affinity, nor did it destabilize TCR-pMHC complexes, indicating that the TCR binds pMHC independently of CD4.
C1 [Huppa, Johannes B.; Moertelmaier, Manuel A.; Lillemeier, Bjoern F.; Newell, Evan W.; Klein, Lawrence O.; Davis, Mark M.] Stanford Univ, Dept Microbiol & Immunol, Stanford Sch Med, Stanford, CA 94305 USA.
   [Davis, Mark M.] Beckman Ctr B221, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Axmann, Markus; Moertelmaier, Manuel A.; Brameshuber, Mario; Schuetz, Gerhard J.] Johannes Kepler Univ Linz, Inst Biophys, A-4040 Linz, Austria.
C3 Stanford University; Howard Hughes Medical Institute; Johannes Kepler University Linz
RP Davis, MM (corresponding author), Stanford Univ, Dept Microbiol & Immunol, Stanford Sch Med, Stanford, CA 94305 USA.
EM mmdavis@stanford.edu
FU National Institutes of Health [RO1 AI52211]; Howard Hughes Medical Institute; Frontier Research Center (iFREC); Wilhelm Macke Stiftung; American Cancer Society; National Science Foundation; Austrian Science Fund [Y250-B10]; Austrian Ministry for Science and Research; Austrian Science Fund (FWF) [Y250] Funding Source: Austrian Science Fund (FWF); National Institute of Allergy and Infectious Diseases [T32AI007290] Funding Source: NIH RePORTER; Austrian Science Fund (FWF) [Y 250] Funding Source: researchfish
NR 30
TC 399
Z9 471
U1 0
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 963
EP U143
DI 10.1038/nature08746
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700049
PM 20164930
DA 2026-03-09
ER

PT J
AU Moss, RH
   Edmonds, JA
   Hibbard, KA
   Manning, MR
   Rose, SK
   van Vuuren, DP
   Carter, TR
   Emori, S
   Kainuma, M
   Kram, T
   Meehl, GA
   Mitchell, JFB
   Nakicenovic, N
   Riahi, K
   Smith, SJ
   Stouffer, RJ
   Thomson, AM
   Weyant, JP
   Wilbanks, TJ
AF Moss, Richard H.
   Edmonds, Jae A.
   Hibbard, Kathy A.
   Manning, Martin R.
   Rose, Steven K.
   van Vuuren, Detlef P.
   Carter, Timothy R.
   Emori, Seita
   Kainuma, Mikiko
   Kram, Tom
   Meehl, Gerald A.
   Mitchell, John F. B.
   Nakicenovic, Nebojsa
   Riahi, Keywan
   Smith, Steven J.
   Stouffer, Ronald J.
   Thomson, Allison M.
   Weyant, John P.
   Wilbanks, Thomas J.
TI The next generation of scenarios for climate change research and assessment
SO NATURE
LA English
DT Article
ID model; atmosphere
AB Advances in the science and observation of climate change are providing a clearer understanding of the inherent variability of Earth's climate system and its likely response to human and natural influences. The implications of climate change for the environment and society will depend not only on the response of the Earth system to changes in radiative forcings, but also on how humankind responds through changes in technology, economies, lifestyle and policy. Extensive uncertainties exist in future forcings of and responses to climate change, necessitating the use of scenarios of the future to explore the potential consequences of different response options. To date, such scenarios have not adequately examined crucial possibilities, such as climate change mitigation and adaptation, and have relied on research processes that slowed the exchange of information among physical, biological and social scientists. Here we describe a new process for creating plausible scenarios to investigate some of the most challenging and important questions about climate change confronting the global community.
C1 [Moss, Richard H.; Edmonds, Jae A.; Smith, Steven J.; Thomson, Allison M.] Univ Maryland, Pacific NW Natl Lab, Joint Global Change Res Inst, College Pk, MD 20740 USA.
   [Hibbard, Kathy A.; Meehl, Gerald A.] Natl Ctr Atmospher Res, Climate & Global Dynam Div, Boulder, CO 80305 USA.
   [Manning, Martin R.] Victoria Univ Wellington, New Zealand Climate Change Res Inst, Wellington, New Zealand.
   [Rose, Steven K.] Elect Power Res Inst, Washington, DC 20036 USA.
   [van Vuuren, Detlef P.; Kram, Tom] Netherlands Environm Assessment Agcy, NL-3720 AH Bilthoven, Netherlands.
   [Carter, Timothy R.] Finnish Environm Inst, Helsinki 00251, Finland.
   [Emori, Seita; Kainuma, Mikiko] Natl Inst Environm Studies, Tsukuba, Ibaraki 3058506, Japan.
   [Mitchell, John F. B.] Met Off, Exeter EX1 3PB, Devon, England.
   [Nakicenovic, Nebojsa; Riahi, Keywan] Int Inst Appl Syst Anal, A-2361 Laxenburg, Austria.
   [Nakicenovic, Nebojsa] Vienna Univ Technol, A-1040 Vienna, Austria.
   [Stouffer, Ronald J.] NOAA, Geophys Fluid Dynam Lab, Princeton, NJ 08542 USA.
   [Weyant, John P.] Stanford Univ, Stanford, CA 94305 USA.
   [Wilbanks, Thomas J.] Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA.
C3 University System of Maryland; University of Maryland College Park; United States Department of Energy (DOE); Pacific Northwest National Laboratory; National Center Atmospheric Research (NCAR) - USA; Victoria University Wellington; Electric Power Research Institute (EPRI); Netherlands National Institute for Public Health & the Environment; Finnish Environment Institute; National Institute for Environmental Studies - Japan; Met Office - UK; International Institute for Applied Systems Analysis (IIASA); Technische Universitat Wien; National Oceanic Atmospheric Admin (NOAA) - USA; Stanford University; United States Department of Energy (DOE); Oak Ridge National Laboratory
RP Moss, RH (corresponding author), Univ Maryland, Pacific NW Natl Lab, Joint Global Change Res Inst, 5825 Univ Res Court,Suite 3500, College Pk, MD 20740 USA.
EM rhm@pnl.gov
NR 87
TC 4999
Z9 5771
U1 35
U2 2479
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 747
EP 756
DI 10.1038/nature08823
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300028
PM 20148028
DA 2026-03-09
ER

PT J
AU Kim, K
   Doi, A
   Wen, B
   Ng, K
   Zhao, R
   Cahan, P
   Kim, J
   Aryee, MJ
   Ji, H
   Ehrlich, LIR
   Yabuuchi, A
   Takeuchi, A
   Cunniff, KC
   Hongguang, H
   Mckinney-Freeman, S
   Naveiras, O
   Yoon, TJ
   Irizarry, RA
   Jung, N
   Seita, J
   Hanna, J
   Murakami, P
   Jaenisch, R
   Weissleder, R
   Orkin, SH
   Weissman, IL
   Feinberg, AP
   Daley, GQ
AF Kim, K.
   Doi, A.
   Wen, B.
   Ng, K.
   Zhao, R.
   Cahan, P.
   Kim, J.
   Aryee, M. J.
   Ji, H.
   Ehrlich, L. I. R.
   Yabuuchi, A.
   Takeuchi, A.
   Cunniff, K. C.
   Hongguang, H.
   Mckinney-Freeman, S.
   Naveiras, O.
   Yoon, T. J.
   Irizarry, R. A.
   Jung, N.
   Seita, J.
   Hanna, J.
   Murakami, P.
   Jaenisch, R.
   Weissleder, R.
   Orkin, S. H.
   Weissman, I. L.
   Feinberg, A. P.
   Daley, G. Q.
TI Epigenetic memory in induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID mammalian-cells; dna methylation; ips cells; differentiation; tissue; generation; mice; activation; microarray; system
AB Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer more readily establishes the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
C1 [Doi, A.; Wen, B.; Ji, H.; Irizarry, R. A.; Jung, N.; Murakami, P.; Feinberg, A. P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA.
   [Doi, A.; Wen, B.; Ji, H.; Irizarry, R. A.; Jung, N.; Murakami, P.; Feinberg, A. P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA.
   [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Kim, J.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Orkin, S. H.; Daley, G. Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Kim, J.; Orkin, S. H.] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Aryee, M. J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
   [Ehrlich, L. I. R.; Seita, J.; Weissman, I. L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Yoon, T. J.; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
   [Hanna, J.; Jaenisch, R.] MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
C3 Johns Hopkins University; Johns Hopkins University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins Medicine; Stanford University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Massachusetts Institute of Technology (MIT); Whitehead Institute
RP Feinberg, AP (corresponding author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA.
EM afeinberg@jhu.edu; george.daley@childrens.harvard.edu
FU NIH [RO1-DK70055, RO1-DK59279, K99HL093212-01, R37CA054358, P50HG003233, R01AI047457, R01AI047458, CA86065, HL099999]; American Recovery and Reinvestment Act [RC2-HL102815]; LLS [3567-07]; Cooley's Anemia Foundation; Thomas and Stacey Siebel Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine [T1-00001]
NR 54
TC 1755
Z9 2079
U1 2
U2 524
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 285
EP U60
DI 10.1038/nature09342
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900030
PM 20644535
DA 2026-03-09
ER

PT J
AU Schaller, V
   Weber, C
   Semmrich, C
   Frey, E
   Bausch, AR
AF Schaller, Volker
   Weber, Christoph
   Semmrich, Christine
   Frey, Erwin
   Bausch, Andreas R.
TI Polar patterns of driven filaments
SO NATURE
LA English
DT Article
ID self-organization; active gels; motors; hydrodynamics; microtubules; vortices; dynamics
AB The emergence of collective motion exhibited by systems ranging from flocks of animals to self-propelled microorganisms to the cytoskeleton is a ubiquitous and fascinating self-organization phenomenon(1-12). Similarities between these systems, such as the inherent polarity of the constituents, a density-dependent transition to ordered phases or the existence of very large density fluctuations(13-16), suggest universal principles underlying pattern formation. This idea is followed by theoretical models at all levels of description: micro-or mesoscopic models directly map local forces and interactions using only a few, preferably simple, interaction rules(12,17-21), and more macroscopic approaches in the hydrodynamic limit rely on the systems' generic symmetries(8,22,23). All these models characteristically have a broad parameter space with a manifold of possible patterns, most of which have not yet been experimentally verified. The complexity of interactions and the limited parameter control of existing experimental systems are major obstacles to our understanding of the underlying ordering principles(13). Here we demonstrate the emergence of collective motion in a high-density motility assay that consists of highly concentrated actin filaments propelled by immobilized molecular motors in a planar geometry. Above a critical density, the filaments self-organize to form coherently moving structures with persistent density modulations, such as clusters, swirls and interconnected bands. These polar nematic structures are long lived and can span length scales orders of magnitudes larger than their constituents. Our experimental approach, which offers control of all relevant system parameters, complemented by agent-based simulations, allows backtracking of the assembly and disassembly pathways to the underlying local interactions. We identify weak and local alignment interactions to be essential for the observed formation of patterns and their dynamics. The presented minimal polar-pattern-forming system may thus provide new insight into emerging order in the broad class of active fluids(8,23,24) and self-propelled particles(17,25)
C1 [Schaller, Volker; Semmrich, Christine; Bausch, Andreas R.] Tech Univ Munich, Lehrstuhl Biophy E27, D-85748 Garching, Germany.
   [Weber, Christoph; Frey, Erwin] Univ Munich, Dept Phys, Arnold Sommerfeld Ctr Theoret Phys, D-80333 Munich, Germany.
   [Weber, Christoph; Frey, Erwin] Univ Munich, Dept Phys, CENS, D-80333 Munich, Germany.
C3 Technical University of Munich; University of Munich; University of Munich
RP Bausch, AR (corresponding author), Tech Univ Munich, Lehrstuhl Biophy E27, D-85748 Garching, Germany.
EM abausch@ph.tum.de
FU DFG [SFB 863]; German Excellence Initiatives via the 'Nano-Initiative Munich (NIM)'; Technische Universitat Munchen - Institute for Advanced Study; Elite Network of Bavaria
NR 28
TC 707
Z9 801
U1 3
U2 221
PU 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 2
PY 2010
VL 467
IS 7311
BP 73
EP 77
DI 10.1038/nature09312
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200037
PM 20811454
DA 2026-03-09
ER

PT J
AU Kalinka, AT
   Varga, KM
   Gerrard, DT
   Preibisch, S
   Corcoran, DL
   Jarrells, J
   Ohler, U
   Bergman, CM
   Tomancak, P
AF Kalinka, Alex T.
   Varga, Karolina M.
   Gerrard, Dave T.
   Preibisch, Stephan
   Corcoran, David L.
   Jarrells, Julia
   Ohler, Uwe
   Bergman, Casey M.
   Tomancak, Pavel
TI Gene expression divergence recapitulates the developmental hourglass model
SO NATURE
LA English
DT Article
ID conserved embryonic stage; phylotypic stage; evolution; patterns; variability; sequence; level
AB The observation that animal morphology tends to be conserved during the embryonic phylotypic period (a period of maximal similarity between the species within each animal phylum) led to the proposition that embryogenesis diverges more extensively early and late than in the middle, known as the hourglass model(1,2). This pattern of conservation is thought to reflect a major constraint on the evolution of animal body plans(3). Despite a wealth of morphological data confirming that there is often remarkable divergence in the early and late embryos of species from the same phylum(4-7), it is not yet known to what extent gene expression evolution, which has a central role in the elaboration of different animal forms(8,9), underpins the morphological hourglass pattern. Here we address this question using species-specific microarrays designed from six sequenced Drosophila species separated by up to 40 million years. We quantify divergence at different times during embryogenesis, and show that expression is maximally conserved during the arthropod phylotypic period. By fitting different evolutionary models to each gene, we show that at each time point more than 80% of genes fit best to models incorporating stabilizing selection, and that for genes whose evolutionarily optimal expression level is the same across all species, selective constraint is maximized during the phylotypic period. The genes that conform most to the hourglass pattern are involved in key developmental processes. These results indicate that natural selection acts to conserve patterns of gene expression during mid-embryogenesis, and provide a genome-wide insight into the molecular basis of the hourglass pattern of developmental evolution.
C1 [Kalinka, Alex T.; Varga, Karolina M.; Preibisch, Stephan; Jarrells, Julia; Tomancak, Pavel] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Gerrard, Dave T.; Bergman, Casey M.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [Corcoran, David L.; Ohler, Uwe] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
C3 Max Planck Society; University of Manchester; Duke University
RP Tomancak, P (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
EM tomancak@mpi-cbg.de
FU Human Frontier Science Program (HFSP) [RGY0084]
NR 50
TC 317
Z9 368
U1 0
U2 101
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 811
EP U102
DI 10.1038/nature09634
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700043
PM 21150996
DA 2026-03-09
ER

PT J
AU Wood, BJ
   Halliday, AN
AF Wood, Bernard J.
   Halliday, Alex N.
TI The lead isotopic age of the Earth can be explained by core formation alone
SO NATURE
LA English
DT Article
ID oxidation-state; giant impact; moon; pb; constraints; driven; origin; cr
AB The meaning of the age of the Earth defined by lead isotopes has long been unclear. Recently it has been proposed(1) that the age of the Earth deduced from lead isotopes reflects volatile loss to space at the time of the Moon-forming giant impact rather than partitioning into metallic liquids during protracted core formation. Here we show that lead partitioning into liquid iron depends strongly on carbon content and that, given a content of similar to 0.2% carbon(2,3), experimental and isotopic data both provide evidence of strong partitioning of lead into the core throughout the Earth's accretion. Earlier conclusions that lead is weakly partitioned into iron arose from the use of carbon-saturated (about 5% C) iron alloys. The lead isotopic age of the Earth is therefore consistent with partitioning into the core and with no significant late losses of moderately volatile elements to space during the giant impact.
C1 [Wood, Bernard J.; Halliday, Alex N.] Univ Oxford, Dept Earth Sci, Oxford OX1 3PR, England.
   [Wood, Bernard J.] Macquarie Univ, Dept Earth & Planetary Sci, N Ryde, NSW 2109, Australia.
C3 University of Oxford; Macquarie University
RP Wood, BJ (corresponding author), Univ Oxford, Dept Earth Sci, Parks Rd, Oxford OX1 3PR, England.
EM berniew@earth.ox.ac.uk
FU Australian Research Council [FF 0456999]; NERC (UK) [NE/F018266/1]; STFC; EU [505320]; NERC [NE/F018266/1] Funding Source: UKRI; STFC [PP/D001250/1, ST/F001940/1, ST/G00272X/1] Funding Source: UKRI; Natural Environment Research Council [NE/F018266/1] Funding Source: researchfish; Science and Technology Facilities Council [ST/G00272X/1, PP/D001250/1, ST/F001940/1] Funding Source: researchfish
NR 36
TC 78
Z9 84
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 JUN 10
PY 2010
VL 465
IS 7299
BP 767
EP U4
DI 10.1038/nature09072
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800042
PM 20535208
DA 2026-03-09
ER

PT J
AU Huang, CS
   Sadre-Bazzaz, K
   Shen, Y
   Deng, BB
   Zhou, ZH
   Tong, LA
AF Huang, Christine S.
   Sadre-Bazzaz, Kianoush
   Shen, Yang
   Deng, Binbin
   Zhou, Z. Hong
   Tong, Liang
TI Crystal structure of the α6β6 holoenzyme of propionyl-coenzyme A carboxylase
SO NATURE
LA English
DT Article
ID acetyl-coa carboxylase; biotin carboxylase; carboxyltransferase domain; pyruvate-carboxylase; functional-analysis; catalytic-activity; mccb mutations; a carboxylase; acidemia; subunit
AB Propionyl-coenzyme A carboxylase (PCC), a mitochondrial biotin-dependent enzyme, is essential for the catabolism of the amino acids Thr, Val, Ile and Met, cholesterol and fatty acids with an odd number of carbon atoms. Deficiencies in PCC activity in humans are linked to the disease propionic acidaemia, an autosomal recessive disorder that can be fatal in infants(1-4). The holoenzyme of PCC is an alpha(6)beta(6) dodecamer, with a molecular mass of 750 kDa. The alpha-subunit contains the biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains, whereas the beta-subunit supplies the carboxyltransferase (CT) activity. Here we report the crystal structure at 3.2-angstrom resolution of a bacterial PCC alpha(6)beta(6) holoenzyme as well as cryo-electron microscopy (cryo-EM) reconstruction at 15-angstrom resolution demonstrating a similar structure for human PCC. The structure defines the overall architecture of PCC and reveals unexpectedly that the alpha-subunits are arranged as monomers in the holoenzyme, decorating a central beta(6) hexamer. A hitherto unrecognized domain in the alpha-subunit, formed by residues between the BC and BCCP domains, is crucial for interactions with the beta-subunit. We have named it the BT domain. The structure reveals for the first time the relative positions of the BC and CT active sites in the holoenzyme. They are separated by approximately 55 angstrom, indicating that the entire BCCP domain must translocate during catalysis. The BCCP domain is located in the active site of the beta-subunit in the current structure, providing insight for its involvement in the CT reaction. The structural information establishes a molecular basis for understanding the large collection of disease-causing mutations in PCC and is relevant for the holoenzymes of other biotin-dependent carboxylases, including 3-methylcrotonyl-CoA carboxylase (MCC)(5-7) and eukaryotic acetyl-CoA carboxylase (ACC)(8,9).
C1 [Huang, Christine S.; Sadre-Bazzaz, Kianoush; Shen, Yang; Tong, Liang] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Deng, Binbin; Zhou, Z. Hong] Univ Texas Houston, Sch Med, Dept Pathol & Lab Med, Houston, TX 77030 USA.
   [Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA.
C3 Columbia University; University of Texas System; University of Texas Health Science Center Houston; University of California System; University of California Los Angeles
RP Tong, LA (corresponding author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
EM ltong@columbia.edu
FU National Institutes of Health [DK067238, GM071940, AI069015, GM08281]; National Institute of General Medical Sciences [R01GM071940] Funding Source: NIH RePORTER
NR 39
TC 78
Z9 106
U1 2
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 1001
EP U135
DI 10.1038/nature09302
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300040
PM 20725044
DA 2026-03-09
ER

PT J
AU Will, S
   Best, T
   Schneider, U
   Hackermüller, L
   Lühmann, DS
   Bloch, I
AF Will, Sebastian
   Best, Thorsten
   Schneider, Ulrich
   Hackermueller, Lucia
   Luehmann, Dirk-Soeren
   Bloch, Immanuel
TI Time-resolved observation of coherent multi-body interactions in quantum phase revivals
SO NATURE
LA English
DT Article
ID bose-einstein condensate; optical lattices; states; field; atom
AB Interactions lie at the heart of correlated many-body quantum phases(1-3). Typically, the interactions between microscopic particles are described as two-body interactions. However, it has been shown that higher-order multi-body interactions could give rise to novel quantum phases with intriguing properties. So far, multi-body interactions have been observed as inelastic loss resonances in three-and four-body recombinations of atom-atom and atom-molecule collisions(4-6). Here we demonstrate the presence of effective multi-body interactions(7) in a system of ultracold bosonic atoms in a three-dimensional optical lattice, emerging through virtual transitions of particles from the lowest energy band to higher energy bands. We observe such interactions up to the six-body case in time-resolved traces of quantum phase revivals(8-11), using an atom interferometric technique that allows us to precisely measure the absolute energies of atom number states at a lattice site. In addition, we show that the spectral content of these time traces can reveal the atom number statistics at a lattice site, similar to foundational experiments in cavity quantum electrodynamics that yield the statistics of a cavity photon field(12). Our precision measurement of multi-body interaction energies provides crucial input for the comparison of optical-lattice quantum simulators with many-body quantum theory.
C1 [Will, Sebastian; Best, Thorsten; Schneider, Ulrich; Hackermueller, Lucia; Bloch, Immanuel] Johannes Gutenberg Univ Mainz, Inst Phys, D-55099 Mainz, Germany.
   [Will, Sebastian; Schneider, Ulrich; Bloch, Immanuel] Univ Munich, Fac Phys, D-80799 Munich, Germany.
   [Luehmann, Dirk-Soeren] Univ Hamburg, Inst Theoret Phys, D-20355 Hamburg, Germany.
   [Bloch, Immanuel] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Johannes Gutenberg University of Mainz; University of Munich; University of Hamburg; Max Planck Society
RP Will, S (corresponding author), Johannes Gutenberg Univ Mainz, Inst Phys, D-55099 Mainz, Germany.
EM sebastian.will@lmu.de
FU Deutsche Forschungsgemeinschaft; European Union, EuroQUAM; Defense Advanced Research Projects Agency; US Air Force Office of Scientific Research, MATCOR; Gutenberg Akademie; Engineering and Physical Sciences Research Council [EP/E036473/1] Funding Source: researchfish; EPSRC [EP/E036473/1] Funding Source: UKRI
NR 33
TC 253
Z9 286
U1 1
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 197
EP 201
DI 10.1038/nature09036
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500030
PM 20463733
DA 2026-03-09
ER

PT J
AU Bevilacqua, L
   Doly, S
   Kaprio, J
   Yuan, QP
   Tikkanen, R
   Paunio, T
   Zhou, ZF
   Wedenoja, J
   Maroteaux, L
   Diaz, S
   Belmer, A
   Hodgkinson, CA
   Dell'Osso, L
   Suvisaari, J
   Coccaro, E
   Rose, RJ
   Peltonen, L
   Virkkunen, M
   Goldman, D
AF Bevilacqua, Laura
   Doly, Stephane
   Kaprio, Jaakko
   Yuan, Qiaoping
   Tikkanen, Roope
   Paunio, Tiina
   Zhou, Zhifeng
   Wedenoja, Juho
   Maroteaux, Luc
   Diaz, Silvina
   Belmer, Arnaud
   Hodgkinson, Colin A.
   Dell'Osso, Liliana
   Suvisaari, Jaana
   Coccaro, Emil
   Rose, Richard J.
   Peltonen, Leena
   Virkkunen, Matti
   Goldman, David
TI A population-specific HTR2B stop codon predisposes to severe impulsivity
SO NATURE
LA English
DT Article
ID monoamine-oxidase; molecular-genetics; serotonin; vulnerability; dopamine; mutation; polymorphism; aggression; mechanisms; receptors
AB Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency >1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.
C1 [Bevilacqua, Laura; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
   [Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] INSERM, UMR S 839, F-75654 Paris, France.
   [Doly, Stephane; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud] Univ Paris 06, Inst du Fer Moulin, F-75654 Paris, France.
   [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.
   [Kaprio, Jaakko] Inst Mol Med, FI-00014 Helsinki, Finland.
   [Kaprio, Jaakko] Natl Inst Hlth & Welf, Unit Child & Adolescent Psychiat, FI-00271 Helsinki, Finland.
   [Tikkanen, Roope; Virkkunen, Matti] Univ Helsinki, Inst Clin Med, Dept Psychiat, FI-00014 Helsinki, Finland.
   [Paunio, Tiina; Suvisaari, Jaana] Univ Helsinki, Dept Psychiat, Cent Hosp, FI-00014 Helsinki, Finland.
   [Wedenoja, Juho] Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland.
   [Wedenoja, Juho] Univ Helsinki, Inst Mol Med Finland, FI-00014 Helsinki, Finland.
   [Wedenoja, Juho] Natl Inst Hlth & Welf, FI-00014 Helsinki, Finland.
   [Dell'Osso, Liliana] Univ Pisa, Dept Psychiat, I-56100 Pisa, Italy.
   [Coccaro, Emil] Univ Chicago, Pritzker Sch Med, Dept Psychiat, Chicago, IL 60637 USA.
   [Rose, Richard J.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
   [Virkkunen, Matti] Kellokoski Psychiat Hosp, FI-04500 Kellokoski, Finland.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Sorbonne Universite; University of Helsinki; Finland National Institute for Health & Welfare; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; University of Helsinki; University of Helsinki; Finland National Institute for Health & Welfare; University of Pisa; University of Chicago; Indiana University System; Indiana University Bloomington
RP Goldman, D (corresponding author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
EM davidgoldman@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, NIH; Academy of Finland Centre of Excellence in Complex Disease Genetics; National Institute on Alcohol Abuse and Alcoholism [AA-12502, AA-09203]; Academy of Finland [100499, 205585, 118555]; Centre National de la Recherche Scientifique; Institut National de la Sante et de la Recherche Medicale; Universite Pierre et Marie Curie; Fondation de France; Fondation pour la Recherche Medicale; French Ministry of Research (Agence Nationale pour la Recherche); European Union; IBRO; Region Ile de France DIM STEM; National Institute on Alcohol Abuse and Alcoholism [ZIAAA000301] Funding Source: NIH RePORTER; Academy of Finland (AKA) [118555, 205585] Funding Source: Academy of Finland (AKA)
NR 39
TC 198
Z9 234
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 DEC 23
PY 2010
VL 468
IS 7327
BP 1061
EP U460
DI 10.1038/nature09629
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800050
PM 21179162
DA 2026-03-09
ER

PT J
AU Sozzani, R
   Cui, H
   Moreno-Risueno, MA
   Busch, W
   Van Norman, JM
   Vernoux, T
   Brady, SM
   Dewitte, W
   Murray, JAH
   Benfey, PN
AF Sozzani, R.
   Cui, H.
   Moreno-Risueno, M. A.
   Busch, W.
   Van Norman, J. M.
   Vernoux, T.
   Brady, S. M.
   Dewitte, W.
   Murray, J. A. H.
   Benfey, P. N.
TI Spatiotemporal regulation of cell-cycle genes by SHORTROOT links patterning and growth
SO NATURE
LA English
DT Article
ID arabidopsis root; expression; scarecrow; progression; endodermis; mechanism; movement; division; pathway; shr
AB The development of multicellular organisms relies on the coordinated control of cell divisions leading to proper patterning and growth(1-3). The molecular mechanisms underlying pattern formation, particularly the regulation of formative cell divisions, remain poorly understood. In Arabidopsis, formative divisions generating the root ground tissue are controlled by SHORTROOT (SHR) and SCARECROW (SCR)(4-6). Here we show, using cell-type-specific transcriptional effects of SHR and SCR combined with data from chromatin immunoprecipitation-based microarray experiments, that SHR regulates the spatiotemporal activation of specific genes involved in cell division. Coincident with the onset of a specific formative division, SHR and SCR directly activate a D-type cyclin; furthermore, altering the expression of this cyclin resulted in formative division defects. Our results indicate that proper pattern formation is achieved through transcriptional regulation of specific cell-cycle genes in a cell-type-and developmental-stage-specific context. Taken together, we provide evidence for a direct link between developmental regulators, specific components of the cell-cycle machinery and organ patterning.
C1 [Sozzani, R.; Cui, H.; Moreno-Risueno, M. A.; Busch, W.; Van Norman, J. M.; Vernoux, T.; Brady, S. M.; Benfey, P. N.] Duke Univ, Dept Biol, Durham, NC 27708 USA.
   [Sozzani, R.; Cui, H.; Moreno-Risueno, M. A.; Busch, W.; Van Norman, J. M.; Vernoux, T.; Brady, S. M.; Benfey, P. N.] Duke Univ, IGSP Ctr Syst Biol, Durham, NC 27708 USA.
   [Dewitte, W.; Murray, J. A. H.] Cardiff Sch Biosci, Cardiff CF10 3AX, Wales.
C3 Duke University; Duke University; Cardiff University
RP Benfey, PN (corresponding author), Duke Univ, Dept Biol, Durham, NC 27708 USA.
EM philip.benfey@duke.edu
FU Ministerio de Ciencia y Innovacion (Spain); Biotechnology and Biological Sciences Research Council [BB/E022383]; European Research Area in Plant Genomics network on Plant Stem Cells [BB/E024858]; NIH [RO1-GM043778, P50-GM081883]; NSF [AT2010 0618304]; BBSRC [BB/E022383/2, BB/E024858/1, BB/E022383/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E022383/2, BB/E022383/1, BB/E024858/1] Funding Source: researchfish
NR 38
TC 348
Z9 391
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 1
PY 2010
VL 466
IS 7302
BP 128
EP U149
DI 10.1038/nature09143
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800048
PM 20596025
DA 2026-03-09
ER

PT J
AU Nowacki, A
   Wookey, J
   Kendall, JM
AF Nowacki, Andy
   Wookey, James
   Kendall, J-Michael
TI Deformation of the lowermost mantle from seismic anisotropy
SO NATURE
LA English
DT Article
ID post-perovskite phase; d'' layer; azimuthal anisotropy; lateral variations; shear deformation; beneath; flow; constraints; (mg,fe)o; pacific
AB The lowermost part of the Earth's mantle-known as D ''-shows significant seismic anisotropy, the variation of seismic wave speed with direction(1-5). This is probably due to deformation-induced alignment of MgSiO3-post-perovskite (ppv), which is believed to be the main mineral phase present in the region. If this is the case, then previous measurements of D '' anisotropy, which are generally made in one direction only, are insufficient to distinguish candidate mechanisms of slip in ppv because the mineral is orthorhombic. Here we measure anisotropy in D '' beneath North and Central America, where material from subducting oceanic slabs impinges(6) on the core-mantle boundary, using shallow as well as deep earthquakes to increase the azimuthal coverage in D ''. We make more than 700 individual measurements of shear wave splitting in D '' in three regions from two different azimuths in each case. We show that the previously assumed(2,3,7) case of vertical transverse isotropy (where wave speed shows no azimuthal variation) is not possible, and that more complicated mechanisms must be involved. We test the fit of different MgSiO3-ppv deformation mechanisms to our results and find that shear on (001) is most consistent with observations and the expected shear above the core-mantle boundary beneath subduction zones. With new models of mantle flow, or improved experimental determination of the dominant ppv slip systems, this method will allow us to map deformation at the core-mantle boundary and link processes in D '', such as plume initiation, to the rest of the mantle.
C1 [Nowacki, Andy; Wookey, James; Kendall, J-Michael] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
C3 University of Bristol
RP Nowacki, A (corresponding author), Univ Bristol, Dept Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM andy.nowacki@bristol.ac.uk
FU NERC
NR 37
TC 83
Z9 93
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1091
EP 1095
DI 10.1038/nature09507
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600044
PM 20981097
DA 2026-03-09
ER

PT J
AU Smith, SB
   Qu, HQ
   Taleb, N
   Kishimoto, NY
   Scheel, DW
   Lu, Y
   Patch, AM
   Grabs, R
   Wang, JH
   Lynn, FC
   Miyatsuka, T
   Mitchell, J
   Seerke, R
   Désir, J
   Eijnden, SV
   Abramowicz, M
   Kacet, N
   Weill, J
   Renard, ME
   Gentile, M
   Hansen, I
   Dewar, K
   Hattersley, AT
   Wang, R
   Wilson, ME
   Johnson, JD
   Polychronakos, C
   German, MS
AF Smith, Stuart B.
   Qu, Hui-Qi
   Taleb, Nadine
   Kishimoto, Nina Y.
   Scheel, David W.
   Lu, Yang
   Patch, Ann-Marie
   Grabs, Rosemary
   Wang, Juehu
   Lynn, Francis C.
   Miyatsuka, Takeshi
   Mitchell, John
   Seerke, Rina
   Desir, Julie
   Eijnden, Serge Vanden
   Abramowicz, Marc
   Kacet, Nadine
   Weill, Jacques
   Renard, Marie-Eve
   Gentile, Mattia
   Hansen, Inger
   Dewar, Ken
   Hattersley, Andrew T.
   Wang, Rennian
   Wilson, Maria E.
   Johnson, Jeffrey D.
   Polychronakos, Constantin
   German, Michael S.
TI Rfx6 directs islet formation and insulin production in mice and humans
SO NATURE
LA English
DT Article
ID genome-wide association; congenital malabsorptive diarrhea; autosomal recessive syndrome; cell-differentiation; dna-binding; mutant neurogenin-3; endocrine pancreas; primary cilia; expression; reveals
AB Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.
C1 [Qu, Hui-Qi; Taleb, Nadine; Lu, Yang; Grabs, Rosemary; Mitchell, John; Polychronakos, Constantin] McGill Univ, Dept Paediat, Montreal, PQ H3H 1P3, Canada.
   [Qu, Hui-Qi; Taleb, Nadine; Lu, Yang; Grabs, Rosemary; Mitchell, John; Polychronakos, Constantin] McGill Univ, Dept Human Genet, Montreal, PQ H3H 1P3, Canada.
   [Smith, Stuart B.; Kishimoto, Nina Y.; Scheel, David W.; Wang, Juehu; Lynn, Francis C.; Miyatsuka, Takeshi; Seerke, Rina; German, Michael S.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
   [Patch, Ann-Marie; Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England.
   [Desir, Julie; Eijnden, Serge Vanden; Abramowicz, Marc] ULB, Hop Erasme, Dept Neonatol, B-1070 Brussels, Belgium.
   [Hansen, Inger] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
   [Kacet, Nadine; Weill, Jacques; Renard, Marie-Eve] Hop Calmette, Dept Neonatol, F-59037 Lille, France.
   [Gentile, Mattia] Di Venere Gen Hosp, Med Genet Unit, I-70012 Bari, Italy.
   [Dewar, Ken] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.
   [Dewar, Ken] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3A 1B1, Canada.
   [Wang, Rennian] Univ Western Ontario, Child Hlth Res Inst, Dept Physiol, London, ON N6C 2V5, Canada.
   [Wang, Rennian] Univ Western Ontario, Child Hlth Res Inst, Dept Med & Pharmacol, London, ON N6C 2V5, Canada.
   [Wilson, Maria E.; Johnson, Jeffrey D.] Metabolex Inc, Hayward, CA 94545 USA.
   [German, Michael S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
C3 McGill University; McGill University; University of California System; University of California San Francisco; University of Exeter; Universite Libre de Bruxelles; Emory University; Universite de Lille; CHU Lille; McGill University; McGill University; Western University (University of Western Ontario); Western University (University of Western Ontario); Metabolex, Inc.; University of California System; University of California San Francisco
RP Polychronakos, C (corresponding author), McGill Univ, Dept Paediat, Montreal, PQ H3H 1P3, Canada.
EM constantin.polychronakos@mcgill.ca; mgerman@diabetes.ucsf.edu
FU Larry L. Hillblom Foundation; Juvenile Diabetes Research Foundation; American Diabetes Association; Nora Eccles Treadwell Foundation; Canadian Institutes of Health Research; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases
NR 42
TC 275
Z9 339
U1 0
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 FEB 11
PY 2010
VL 463
IS 7282
BP 775
EP 780
DI 10.1038/nature08748
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300032
PM 20148032
DA 2026-03-09
ER

PT J
AU Behrends, C
   Sowa, ME
   Gygi, SP
   Harper, JW
AF Behrends, Christian
   Sowa, Mathew E.
   Gygi, Steven P.
   Harper, J. Wade
TI Network organization of the human autophagy system
SO NATURE
LA English
DT Article
ID protein; ubiquitin; accumulation; complexes; rubicon; atg14l; lc3
AB Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.
C1 [Behrends, Christian; Sowa, Mathew E.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Harper, JW (corresponding author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM wade_harper@hms.harvard.edu
FU Millennium Pharmaceuticals; National Institutes of Health; Paul F. Glenn Foundation on Aging; National Institute on Aging [R01AG011085] Funding Source: NIH RePORTER
NR 38
TC 1294
Z9 1536
U1 3
U2 231
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 1
PY 2010
VL 466
IS 7302
BP 68
EP U84
DI 10.1038/nature09204
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800036
PM 20562859
DA 2026-03-09
ER

PT J
AU McPhee, CK
   Logan, MA
   Freeman, MR
   Baehrecke, EH
AF McPhee, Christina K.
   Logan, Mary A.
   Freeman, Marc R.
   Baehrecke, Eric H.
TI Activation of autophagy during cell death requires the engulfment receptor Draper
SO NATURE
LA English
DT Article
ID starvation-induced autophagy; drosophila fat-body; gene-expression; growth arrest; phagocytosis; degradation; induction; oogenesis; pathway
AB Autophagy degrades cytoplasmic components that are required for cell survival in response to starvation(1). Autophagy has also been associated with cell death, but it is unclear how this is distinguished from autophagy during cell survival. Drosophila salivary glands undergo programmed cell death that requires autophagy genes(2), and engulfment of salivary gland cells by phagocytes does not appear to occur(3). Here we show that Draper (Drpr), the Drosophila melanogaster orthologue of the Caenorhabditis elegans engulfment receptor CED-1, is required for autophagy during cell death. Null mutations in, and salivary gland-specific knockdown of, drpr inhibit salivary gland degradation. Knockdown of drpr prevents the induction of autophagy in dying salivary glands, and expression of the Atg1 autophagy regulator in drpr mutants suppresses the failure in degradation of salivary glands. Surprisingly, drpr is required in the same dying salivary gland cells in which it regulates autophagy induction, but drpr knockdown does not prevent starvation-induced autophagy in the fat body, which is associated with survival. In addition, components of the conserved engulfment pathway are required for clearance of dying salivary glands. To our knowledge, this is the first example of an engulfment factor that is required for self-clearance of cells. Further, Drpr is the first factor that distinguishes autophagy that is associated with cell death from autophagy associated with cell survival.
C1 [McPhee, Christina K.; Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
   [McPhee, Christina K.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
   [Logan, Mary A.; Freeman, Marc R.] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
   [Freeman, Marc R.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; University System of Maryland; University of Maryland College Park; University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester
RP Baehrecke, EH (corresponding author), Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
EM Eric.Baehrecke@umassmed.edu
FU American Cancer Society [PF-07-258-01-CSM]; NIH [NS053538, GM079431]; Merck and Co. Inc.; National Institute of Neurological Disorders and Stroke [R01NS053538, R37NS053538] Funding Source: NIH RePORTER
NR 29
TC 111
Z9 126
U1 0
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 24
PY 2010
VL 465
IS 7301
BP 1093
EP U159
DI 10.1038/nature09127
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900056
PM 20577216
DA 2026-03-09
ER

PT J
AU Nakada, D
   Saunders, TL
   Morrison, SJ
AF Nakada, Daisuke
   Saunders, Thomas L.
   Morrison, Sean J.
TI Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
SO NATURE
LA English
DT Article
ID peutz-jeghers-syndrome; drosophila lkb1; gene; kinase; deficiency; pathway; maintenance; mice; embryogenesis; progenitors
AB Little is known about metabolic regulation in stem cells and how this modulates tissue regeneration or tumour suppression. We studied the Lkb1 tumour suppressor and its substrate AMP-activated protein kinase (AMPK), kinases that coordinate metabolism with cell growth. Deletion of the Lkb1 (also called Stk11) gene in mice caused increased haematopoietic stem cell (HSC) division, rapid HSC depletion and pancytopenia. HSCs depended more acutely on Lkb1 for cell-cycle regulation and survival than many other haematopoietic cells. HSC depletion did not depend on mTOR activation or oxidative stress. Lkb1-deficient HSCs, but not myeloid progenitors, had reduced mitochondrial membrane potential and ATP levels. HSCs deficient for two catalytic alpha-subunits of AMPK (AMPK-deficient HSCs) showed similar changes in mitochondrial function but remained able to reconstitute irradiated mice. Lkb1-deficient HSCs, but not AMPK-deficient HSCs, exhibited defects in centrosomes and mitotic spindles in culture, and became aneuploid. Lkb1 is therefore required for HSC maintenance through AMPK-dependent and AMPK-independent mechanisms, revealing differences in metabolic and cell-cycle regulation between HSCs and some other haematopoietic progenitors.
C1 [Nakada, Daisuke; Morrison, Sean J.] Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
   [Nakada, Daisuke; Saunders, Thomas L.; Morrison, Sean J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Michigan System; University of Michigan
RP Morrison, SJ (corresponding author), Univ Michigan, Howard Hughes Med Inst, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
EM seanjm@umich.edu
FU Howard Hughes Medical Institute; University of Michigan (UM) Comprehensive Cancer National Institutes of Health (NIH) [CA46592]; Japan Society for the Promotion of Science; National Cancer Institute [P30CA046592] Funding Source: NIH RePORTER
NR 45
TC 425
Z9 500
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 DEC 2
PY 2010
VL 468
IS 7324
BP 653
EP U69
DI 10.1038/nature09571
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700032
PM 21124450
DA 2026-03-09
ER

PT J
AU Hang, CT
   Yang, J
   Han, P
   Cheng, HL
   Shang, C
   Ashley, E
   Zhou, B
   Chang, CP
AF Hang, Calvin T.
   Yang, Jin
   Han, Pei
   Cheng, Hsiu-Ling
   Shang, Ching
   Ashley, Euan
   Zhou, Bin
   Chang, Ching-Pin
TI Chromatin regulation by Brg1 underlies heart muscle development and disease
SO NATURE
LA English
DT Article
ID myosin heavy-chain; gene-expression; dilated cardiomyopathy; isoform expression; cardiac growth; poly(adp-ribose); hypertrophy; inhibition; ventricle
AB Cardiac hypertrophy and failure are characterized by transcriptional reprogramming of gene expression. Adult cardiomyocytes in mice primarily express alpha-myosin heavy chain (alpha-MHC, also known as Myh6), whereas embryonic cardiomyocytes express beta-MHC (also known as Myh7). Cardiac stress triggers adult hearts to undergo hypertrophy and a shift from alpha-MHC to fetal beta-MHC expression. Here we show that Brg1, a chromatin-remodelling protein, has a critical role in regulating cardiac growth, differentiation and gene expression. In embryos, Brg1 promotes myocyte proliferation by maintaining Bmp10 and suppressing p57(kip2) expression. It preserves fetal cardiac differentiation by interacting with histone deacetylase (HDAC) and poly (ADP ribose) polymerase (PARP) to repress alpha-MHC and activate beta-MHC. In adults, Brg1 (also known as Smarca4) is turned off in cardiomyocytes. It is reactivated by cardiac stresses and forms a complex with its embryonic partners, HDAC and PARP, to induce a pathological alpha-MHC to beta-MHC shift. Preventing Brg1 re-expression decreases hypertrophy and reverses this MHC switch. BRG1 is activated in certain patients with hypertrophic cardiomyopathy, its level correlating with disease severity and MHC changes. Our studies show that Brg1 maintains cardiomyocytes in an embryonic state, and demonstrate an epigenetic mechanism by which three classes of chromatin-modifying factors-Brg1, HDAC and PARP-cooperate to control developmental and pathological gene expression.
C1 [Hang, Calvin T.; Yang, Jin; Han, Pei; Cheng, Hsiu-Ling; Shang, Ching; Ashley, Euan; Chang, Ching-Pin] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
   [Zhou, Bin] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA.
   [Zhou, Bin] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
   [Zhou, Bin] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
C3 Stanford University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Chang, CP (corresponding author), Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
EM chingpin@stanford.edu
FU NIH; American Heart Association (AHA); Children's Heart Foundation; March of Dimes Foundation; Office of the University of California; California Institute of Regenerative Medicine; Kaiser Foundation; Baxter Foundation; Oak Foundation; Stanford Cardiovascular Institute; Kirschstein-NRSA Postdoctoral Fellowship; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER
NR 39
TC 381
Z9 467
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 1
PY 2010
VL 466
IS 7302
BP 62
EP U74
DI 10.1038/nature09130
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800035
PM 20596014
DA 2026-03-09
ER

PT J
AU Lourido, S
   Shuman, J
   Zhang, C
   Shokat, KM
   Hui, R
   Sibley, LD
AF Lourido, Sebastian
   Shuman, Joel
   Zhang, Chao
   Shokat, Kevan M.
   Hui, Raymond
   Sibley, L. David
TI Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma
SO NATURE
LA English
DT Article
ID host-cells; apicomplexan parasites; microneme discharge; gondii; invasion; secretion; transformation; genetics; motility; reveals
AB Calcium-regulated exocytosis is a ubiquitous process in eukaryotes, whereby secretory vesicles fuse with the plasma membrane and release their contents in response to an intracellular calcium surge(1). This process regulates various cellular functions such as plasma membrane repair in plants and animals(2,3), the discharge of defensive spikes in Paramecium 4, and the secretion of insulin from pancreatic cells, immune modulators from lymphocytes, and chemical transmitters from neurons(5). In animal cells, serine/threonine kinases including cAMP-dependent protein kinase, protein kinase C and calmodulin kinases have been implicated in calcium-signal transduction leading to regulated secretion(1,6,7). Although plants and protozoa also regulate secretion by means of intracellular calcium, the method by which these signals are relayed has not been explained. Here we show that the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) is an essential regulator of calcium-dependent exocytosis in this opportunistic human pathogen. Conditional suppression of TgCDPK1 revealed that it controls calcium-dependent secretion of specialized organelles called micronemes, resulting in a block of essential phenotypes including parasite motility, host-cell invasion, and egress. These phenotypes were recapitulated by using a chemical biology approach in which pyrazolopyrimidine-derived compounds specifically inhibited TgCDPK1 and disrupted the parasite's life cycle at stages dependent on microneme secretion. Inhibition was specific to TgCDPK1, because expression of a resistant mutant kinase reversed sensitivity to the inhibitor. TgCDPK1 is conserved among apicomplexans and belongs to a family of kinases shared with plants and ciliates(8), suggesting that related CDPKs may have a function in calcium-regulated secretion in other organisms. Because this kinase family is absent from mammalian hosts, it represents a validated target that may be exploitable for chemotherapy against T. gondii and related apicomplexans.
C1 [Lourido, Sebastian; Shuman, Joel; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Zhang, Chao; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Hui, Raymond] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
C3 Washington University (WUSTL); Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of Toronto; Structural Genomics Consortium
RP Sibley, LD (corresponding author), Washington Univ, Sch Med, Dept Mol Microbiol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM sibley@borcim.wustl.edu
FU American Heart Association; National Institutes of Health
NR 33
TC 290
Z9 334
U1 3
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 MAY 20
PY 2010
VL 465
IS 7296
BP 359
EP U118
DI 10.1038/nature09022
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200043
PM 20485436
DA 2026-03-09
ER

PT J
AU Boos, WR
   Kuang, ZM
AF Boos, William R.
   Kuang, Zhiming
TI Dominant control of the South Asian monsoon by orographic insulation versus plateau heating
SO NATURE
LA English
DT Article
ID summer monsoon; quasi-equilibrium; indian monsoon; uplift; variability; simulation; mountains; evolution; climate; onset
AB The Tibetan plateau, like any landmass, emits energy into the atmosphere in the form of dry heat and water vapour, but its mean surface elevation is more than 5km above sea level. This elevation is widely held to cause the plateau to serve as a heat source that drives the South Asian summer monsoon, potentially coupling uplift of the plateau to climate changes on geologic timescales(1-5). Observations of the present climate, however, do not clearly establish the Tibetan plateau as the dominant thermal forcing in the region: peak upper-tropospheric temperatures during boreal summer are located over continental India, south of the plateau. Here we show that, although Tibetan plateau heating locally enhances rainfall along its southern edge in an atmospheric model, the large-scale South Asian summer monsoon circulation is otherwise unaffected by removal of the plateau, provided that the narrow orography of the Himalayas and adjacent mountain ranges is preserved. Additional observational and model results suggest that these mountains produce a strong monsoon by insulating warm, moist air over continental India from the cold and dry extratropics. These results call for both a reinterpretation of how South Asian climate may have responded to orographic uplift, and a re-evaluation of how this climate may respond to modified land surface and radiative forcings in coming decades.
C1 [Boos, William R.; Kuang, Zhiming] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Kuang, Zhiming] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Boos, WR (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM billboos@alum.mit.edu
FU Department of Earth and Planetary Sciences at Harvard University; Harvard University Center for the Environment; NSF [ATM-0754332]; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [0754332] Funding Source: National Science Foundation
NR 32
TC 788
Z9 911
U1 16
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 JAN 14
PY 2010
VL 463
IS 7278
BP 218
EP U102
DI 10.1038/nature08707
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700033
PM 20075917
DA 2026-03-09
ER

PT J
AU Seo, J
   Roushan, P
   Beidenkopf, H
   Hor, YS
   Cava, RJ
   Yazdani, A
AF Seo, Jungpil
   Roushan, Pedram
   Beidenkopf, Haim
   Hor, Y. S.
   Cava, R. J.
   Yazdani, Ali
TI Transmission of topological surface states through surface barriers
SO NATURE
LA English
DT Article
ID hgte quantum-wells; insulator; confinement; corrals; bi2te3; waves; phase
AB Topological surface states are a class of novel electronic states that are of potential interest in quantum computing or spintronic applications(1-7). Unlike conventional two-dimensional electron states, these surface states are expected to be immune to localization and to overcome barriers caused by material imperfection(8-14). Previous experiments have demonstrated that topological surface states do not backscatter between equal and opposite momentum states, owing to their chiral spin texture(15-18). However, so far there is no evidence that these states in fact transmit through naturally occurring surface defects. Here we use a scanning tunnelling microscope to measure the transmission and reflection probabilities of topological surface states of antimony through naturally occurring crystalline steps separating atomic terraces. In contrast to nontopological surface states of common metals (copper, silver and gold)(19-23), which are either reflected or absorbed by atomic steps, we show that topological surface states of antimony penetrate such barriers with high probability. This demonstration of the extended nature of antimony's topological surface states suggests that such states may be useful for high current transmission even in the presence of atomic-scale irregularities-an electronic feature sought to efficiently interconnect nanoscale devices.
C1 [Seo, Jungpil; Roushan, Pedram; Beidenkopf, Haim; Yazdani, Ali] Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
   [Seo, Jungpil; Roushan, Pedram; Beidenkopf, Haim; Yazdani, Ali] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Hor, Y. S.; Cava, R. J.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Yazdani, A (corresponding author), Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
EM yazdani@princeton.edu
FU NSF-MRSEC through the Princeton Center for Complex Materials; ARO; DOE; NSF-DMR; W. M. Keck Foundation; NSF; Direct For Mathematical & Physical Scien; Division Of Materials Research [0819860] Funding Source: National Science Foundation
NR 27
TC 191
Z9 211
U1 2
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 JUL 15
PY 2010
VL 466
IS 7304
BP 343
EP 346
DI 10.1038/nature09189
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100043
PM 20631794
DA 2026-03-09
ER

PT J
AU Jensen, RB
   Carreira, A
   Kowalczykowski, SC
AF Jensen, Ryan B.
   Carreira, Aura
   Kowalczykowski, Stephen C.
TI Purified human BRCA2 stimulates RAD51-mediated recombination
SO NATURE
LA English
DT Article
ID replication protein-a; dna strand exchange; human rad51 protein; susceptibility gene brca2; homology-directed repair; radiation hypersensitivity; nucleoprotein filaments; binding selectivity; complex-formation; reca protein
AB Mutation of the breast cancer susceptibility gene, BRCA2, leads to breast and ovarian cancers. Mechanistic insight into the functions of human BRCA2 has been limited by the difficulty of isolating this large protein (3,418 amino acids). Here we report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). BRCA2 acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not anneal ssDNA complexed with RPA, implying it does not directly function in repair processes that involve ssDNA annealing. Our findings show that BRCA2 is a key mediator of homologous recombination, and they provide a molecular basis for understanding how this DNA repair process is disrupted by BRCA2 mutations, which lead to chromosomal instability and cancer.
C1 [Jensen, Ryan B.; Carreira, Aura; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Jensen, Ryan B.; Carreira, Aura; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis
RP Kowalczykowski, SC (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM sckowalczykowski@ucdavis.edu
FU NIH [NIH GM 62653]; DOD [BC085223]; American Cancer Society [PF-05-225-01-GMC]; Ministerio de Educacion y Ciencia (Spain); American Cancer Society
NR 53
TC 549
Z9 699
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 7
PY 2010
VL 467
IS 7316
BP 678
EP U62
DI 10.1038/nature09399
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500031
PM 20729832
DA 2026-03-09
ER

PT J
AU Helffrich, G
   Kaneshima, S
AF Helffrich, George
   Kaneshima, Satoshi
TI Outer-core compositional stratification from observed core wave speed profiles
SO NATURE
LA English
DT Article
ID fe-fes; phase-relations; high-pressure; travel-times; earths core; p-wave; velocity; constraints; resolution; system
AB Light elements must be present in the nearly pure iron core of the Earth to match the remotely observed properties of the outer and inner cores(1,2). Crystallization of the inner core excludes light elements from the solid, concentrating them in liquid near the inner-core boundary that potentially rises and collects at the top of the core(3), and this may have a seismically observable signal. Here we present array-based observations of seismic waves sensitive to this part of the core whose wave speeds require there to be radial compositional variation in the topmost 300 km of the outer core. The velocity profile significantly departs from that of compression of a homogeneous liquid. Total light-element enrichment is up to five weight per cent at the top of the core if modelled in the Fe-O-S system. The stratification suggests the existence of a subadiabatic temperature gradient at the top of the outer core.
C1 [Helffrich, George] Univ Tokyo, Earthquake Res Inst, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kaneshima, Satoshi] Kyushu Univ, Higashi Ku, Fukuoka 8128581, Japan.
C3 University of Tokyo; Kyushu University
RP Helffrich, G (corresponding author), Univ Bristol, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM george.helffrich@bris.ac.uk
FU ERI
NR 40
TC 163
Z9 177
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 807
EP U96
DI 10.1038/nature09636
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700042
PM 21150995
DA 2026-03-09
ER

PT J
AU Raines, KS
   Salha, S
   Sandberg, RL
   Jiang, HD
   Rodríguez, JA
   Fahimian, BP
   Kapteyn, HC
   Du, JC
   Miao, JW
AF Raines, Kevin S.
   Salha, Sara
   Sandberg, Richard L.
   Jiang, Huaidong
   Rodriguez, Jose A.
   Fahimian, Benjamin P.
   Kapteyn, Henry C.
   Du, Jincheng
   Miao, Jianwei
TI Three-dimensional structure determination from a single view
SO NATURE
LA English
DT Article
ID x-ray-diffraction; resolution; microscopy
AB The ability to determine the structure of matter in three dimensions has profoundly advanced our understanding of nature. Traditionally, the most widely used schemes for three-dimensional (3D) structure determination of an object are implemented by acquiring multiple measurements over various sample orientations, as in the case of crystallography and tomography(1,2), or by scanning a series of thin sections through the sample, as in confocal microscopy(3). Here we present a 3D imaging modality, termed ankylography (derived from the Greek words ankylos meaning 'curved' and graphein meaning 'writing'), which under certain circumstances enables complete 3D structure determination from a single exposure using a monochromatic incident beam. We demonstrate that when the diffraction pattern of a finite object is sampled at a sufficiently fine scale on the Ewald sphere, the 3D structure of the object is in principle determined by the 2D spherical pattern. We confirm the theoretical analysis by performing 3D numerical reconstructions of a sodium silicate glass structure at 2 angstrom resolution, and a single poliovirus at 2-3nm resolution, from 2D spherical diffraction patterns alone. Using diffraction data from a soft X-ray laser, we also provide a preliminary demonstration that ankylography is experimentally feasible by obtaining a 3D image of a test object from a single 2D diffraction pattern. With further development, this approach of obtaining complete 3D structure information from a single view could find broad applications in the physical and life sciences.
C1 [Raines, Kevin S.; Salha, Sara; Jiang, Huaidong; Fahimian, Benjamin P.; Miao, Jianwei] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Raines, Kevin S.; Salha, Sara; Jiang, Huaidong; Fahimian, Benjamin P.; Miao, Jianwei] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
   [Rodriguez, Jose A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
   [Sandberg, Richard L.; Kapteyn, Henry C.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Sandberg, Richard L.; Kapteyn, Henry C.] Univ Colorado, JILA, Boulder, CO 80309 USA.
   [Du, Jincheng] Univ N Texas, Dept Mat Sci & Engn, Denton, TX 76203 USA.
   [Du, Jincheng] Univ N Texas, Ctr Adv Sci Comp & Modeling, Denton, TX 76203 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of North Texas System; University of North Texas Denton; University of North Texas System; University of North Texas Denton
RP Miao, JW (corresponding author), Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
EM miao@physics.ucla.edu
FU US DOE, Office of Basic Energy Sciences; US NSF, Division of Materials Research and Engineering Research Center; UCLA MBI Whitcome; NSF Center in EUV Science and Technology
NR 31
TC 141
Z9 167
U1 4
U2 141
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 214
EP 217
DI 10.1038/nature08705
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700032
PM 20016484
DA 2026-03-09
ER

PT J
AU Biertümpfel, C
   Zhao, Y
   Kondo, Y
   Ramón-Maiques, S
   Gregory, M
   Lee, JY
   Masutani, C
   Lehmann, AR
   Hanaoka, F
   Yang, W
AF Biertuempfel, Christian
   Zhao, Ye
   Kondo, Yuji
   Ramon-Maiques, Santiago
   Gregory, Mark
   Lee, Jae Young
   Masutani, Chikahide
   Lehmann, Alan R.
   Hanaoka, Fumio
   Yang, Wei
TI Structure and mechanism of human DNA polymerase η
SO NATURE
LA English
DT Article
ID syn thymine dimer; translesion synthesis; crystal-structure; molecular analysis; bypass; lesion; recognition; replication; mutations; cisplatin
AB The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites.
C1 [Biertuempfel, Christian; Zhao, Ye; Ramon-Maiques, Santiago; Gregory, Mark; Lee, Jae Young; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Zhao, Ye] Zhejiang Univ, Inst Nucl Agr Sci, Hangzhou 310029, Zhejiang, Peoples R China.
   [Kondo, Yuji; Masutani, Chikahide; Hanaoka, Fumio] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Lehmann, Alan R.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
   [Hanaoka, Fumio] Gakushuin Univ, Fac Sci, Toshima Ku, Tokyo 1718588, Japan.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Zhejiang University; University of Osaka; University of Sussex; Gakushuin University
RP Yang, W (corresponding author), NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B103, Bethesda, MD 20892 USA.
EM fumio.hanaoka@gakushuin.ac.jp; wei.yang@nih.gov
FU NIDDK, NIH; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Chinese Ministry of Education; NIH-Zhejiang University; Human Frontiers Science Program; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK036119, ZIADK036146] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [22249005] Funding Source: KAKEN; Medical Research Council [G0801130B, G0501450] Funding Source: researchfish; MRC [G0501450] Funding Source: UKRI
NR 58
TC 291
Z9 368
U1 1
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1044
EP U102
DI 10.1038/nature09196
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900045
PM 20577208
DA 2026-03-09
ER

PT J
AU Schmutz, J
   Cannon, SB
   Schlueter, J
   Ma, JX
   Mitros, T
   Nelson, W
   Hyten, DL
   Song, QJ
   Thelen, JJ
   Cheng, JL
   Xu, D
   Hellsten, U
   May, GD
   Yu, Y
   Sakurai, T
   Umezawa, T
   Bhattacharyya, MK
   Sandhu, D
   Valliyodan, B
   Lindquist, E
   Peto, M
   Grant, D
   Shu, SQ
   Goodstein, D
   Barry, K
   Futrell-Griggs, M
   Abernathy, B
   Du, JC
   Tian, ZX
   Zhu, LC
   Gill, N
   Joshi, T
   Libault, M
   Sethuraman, A
   Zhang, XC
   Shinozaki, K
   Nguyen, HT
   Wing, RA
   Cregan, P
   Specht, J
   Grimwood, J
   Rokhsar, D
   Stacey, G
   Shoemaker, RC
   Jackson, SA
AF Schmutz, Jeremy
   Cannon, Steven B.
   Schlueter, Jessica
   Ma, Jianxin
   Mitros, Therese
   Nelson, William
   Hyten, David L.
   Song, Qijian
   Thelen, Jay J.
   Cheng, Jianlin
   Xu, Dong
   Hellsten, Uffe
   May, Gregory D.
   Yu, Yeisoo
   Sakurai, Tetsuya
   Umezawa, Taishi
   Bhattacharyya, Madan K.
   Sandhu, Devinder
   Valliyodan, Babu
   Lindquist, Erika
   Peto, Myron
   Grant, David
   Shu, Shengqiang
   Goodstein, David
   Barry, Kerrie
   Futrell-Griggs, Montona
   Abernathy, Brian
   Du, Jianchang
   Tian, Zhixi
   Zhu, Liucun
   Gill, Navdeep
   Joshi, Trupti
   Libault, Marc
   Sethuraman, Anand
   Zhang, Xue-Cheng
   Shinozaki, Kazuo
   Nguyen, Henry T.
   Wing, Rod A.
   Cregan, Perry
   Specht, James
   Grimwood, Jane
   Rokhsar, Dan
   Stacey, Gary
   Shoemaker, Randy C.
   Jackson, Scott A.
TI Genome sequence of the palaeopolyploid soybean
SO NATURE
LA English
DT Article
ID phylogenetic analysis; glycine-max; genes; evolution; identification; protein; plants; dna; diversification; resistance
AB Soybean (Glycine max) is one of the most important crop plants for seed protein and oil content, and for its capacity to fix atmospheric nitrogen through symbioses with soil-borne microorganisms. We sequenced the 1.1-gigabase genome by a whole-genome shotgun approach and integrated it with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly. We predict 46,430 protein-coding genes, 70% more than Arabidopsis and similar to the poplar genome which, like soybean, is an ancient polyploid (palaeopolyploid). About 78% of the predicted genes occur in chromosome ends, which comprise less than one-half of the genome but account for nearly all of the genetic recombination. Genome duplications occurred at approximately 59 and 13 million years ago, resulting in a highly duplicated genome with nearly 75% of the genes present in multiple copies. The two duplication events were followed by gene diversification and loss, and numerous chromosome rearrangements. An accurate soybean genome sequence will facilitate the identification of the genetic basis of many soybean traits, and accelerate the creation of improved soybean varieties.
C1 [Schlueter, Jessica; Ma, Jianxin; Futrell-Griggs, Montona; Abernathy, Brian; Du, Jianchang; Tian, Zhixi; Zhu, Liucun; Gill, Navdeep; Jackson, Scott A.] Purdue Univ, Dept Agron, W Lafayette, IN 47906 USA.
   [Schmutz, Jeremy; Sethuraman, Anand; Grimwood, Jane] HudsonAlpha Genome Sequencing Ctr, Huntsville, AL 35806 USA.
   [Schmutz, Jeremy; Hellsten, Uffe; Lindquist, Erika; Shu, Shengqiang; Goodstein, David; Barry, Kerrie; Grimwood, Jane; Rokhsar, Dan] Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Cannon, Steven B.; Peto, Myron; Grant, David; Shoemaker, Randy C.] ARS, USDA, Corn Insects & Crop Genet Res Unit, Ames, IA 50011 USA.
   [Schlueter, Jessica] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA.
   [Mitros, Therese] Univ Calif Berkeley, Ctr Integrat Genom, Berkeley, CA 94720 USA.
   [Nelson, William] Univ Arizona, Inst BIO5, Arizona Genom Computat Lab, Tucson, AZ 85721 USA.
   [Hyten, David L.; Song, Qijian; Cregan, Perry] ARS, USDA, Soybean Genom & Improvement Lab, Beltsville, MD 20705 USA.
   [Song, Qijian] Univ Maryland, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA.
   [Thelen, Jay J.; Stacey, Gary] Univ Missouri, Christopher S Bond Life Sci Ctr 109, Div Biochem, Columbia, MO 65211 USA.
   [Thelen, Jay J.; Stacey, Gary] Univ Missouri, Christopher S Bond Life Sci Ctr 109, Interdisciplinary Plant Grp, Columbia, MO 65211 USA.
   [Cheng, Jianlin; Xu, Dong; Joshi, Trupti] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA.
   [May, Gregory D.] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
   [Yu, Yeisoo; Wing, Rod A.] Univ Arizona, Sch Plant Sci, Arizona Genom Inst, Tucson, AZ 85721 USA.
   [Sakurai, Tetsuya; Umezawa, Taishi; Shinozaki, Kazuo] RIKEN, Plant Sci Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Bhattacharyya, Madan K.] Iowa State Univ, Dept Agron, Ames, IA 50011 USA.
   [Sandhu, Devinder] Univ Wisconsin, Dept Biol, Stevens Point, WI 54481 USA.
   [Valliyodan, Babu; Libault, Marc; Zhang, Xue-Cheng; Nguyen, Henry T.; Stacey, Gary] Univ Missouri, Div Plant Sci, Natl Ctr Soybean Biotechnol, Columbia, MO 65211 USA.
   [Specht, James] Univ Nebraska, Dept Agron & Hort, Lincoln, NE 68583 USA.
C3 Purdue University System; Purdue University; HudsonAlpha Institute for Biotechnology; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; United States Department of Agriculture (USDA); USDA Agricultural Research Service; University of North Carolina; University of North Carolina Charlotte; University of California System; University of California Berkeley; University of Arizona; United States Department of Agriculture (USDA); University System of Maryland; University of Maryland College Park; University of Missouri System; University of Missouri Columbia; University of Missouri System; University of Missouri Columbia; University of Missouri System; University of Missouri Columbia; National Center for Genome Resources (NCGR); University of Arizona; RIKEN; Iowa State University; University of Wisconsin System; University of Wisconsin Stevens Point; University of Missouri System; University of Missouri Columbia; University of Nebraska System; University of Nebraska Lincoln
RP Jackson, SA (corresponding author), Purdue Univ, Dept Agron, 915 W State St, W Lafayette, IN 47906 USA.
EM sjackson@purdue.edu
FU National Science Foundation [DBI-0421620, DBI-0501877, 082225]; United Soybean Board
NR 44
TC 3472
Z9 4236
U1 29
U2 753
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 178
EP 183
DI 10.1038/nature08670
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700025
PM 20075913
DA 2026-03-09
ER

PT J
AU Thornton, JA
   Kercher, JP
   Riedel, TP
   Wagner, NL
   Cozic, J
   Holloway, JS
   Dubé, WP
   Wolfe, GM
   Quinn, PK
   Middlebrook, AM
   Alexander, B
   Brown, SS
AF Thornton, Joel A.
   Kercher, James P.
   Riedel, Theran P.
   Wagner, Nicholas L.
   Cozic, Julie
   Holloway, John S.
   Dube, William P.
   Wolfe, Glenn M.
   Quinn, Patricia K.
   Middlebrook, Ann M.
   Alexander, Becky
   Brown, Steven S.
TI A large atomic chlorine source inferred from mid-continental reactive nitrogen chemistry
SO NATURE
LA English
DT Article
ID sea-salt aerosol; gaseous n2o5; clno2; cl; photochemistry; emissions; nitrate; model
AB Halogen atoms and oxides are highly reactive and can profoundly affect atmospheric composition. Chlorine atoms can decrease the lifetimes of gaseous elemental mercury(1) and hydrocarbons such as the greenhouse gas methane(2). Chlorine atoms also influence cycles that catalytically destroy or produce tropospheric ozone(3), a greenhouse gas potentially toxic to plant and animal life. Conversion of inorganic chloride into gaseous chlorine atom precursors within the troposphere is generally considered a coastal or marine air phenomenon(4). Here we report mid-continental observations of the chlorine atom precursor nitryl chloride at a distance of 1,400km from the nearest coastline. We observe persistent and significant nitryl chloride production relative to the consumption of its nitrogen oxide precursors. Comparison of these findings to model predictions based on aerosol and precipitation composition data from long-term monitoring networks suggests nitryl chloride production in the contiguous USA alone is at a level similar to previous global estimates for coastal and marine regions(5). We also suggest that a significant fraction of tropospheric chlorine atoms(6) may arise directly from anthropogenic pollutants.
C1 [Thornton, Joel A.; Kercher, James P.; Riedel, Theran P.; Wolfe, Glenn M.; Alexander, Becky] Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
   [Riedel, Theran P.; Wolfe, Glenn M.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   [Wagner, Nicholas L.; Cozic, Julie; Holloway, John S.; Dube, William P.; Middlebrook, Ann M.; Brown, Steven S.] NOAA, Earth Syst Res Lab, Boulder, CO 80305 USA.
   [Cozic, Julie; Holloway, John S.; Dube, William P.] Cooperat Inst Res Environm Studies, Boulder, CO 80309 USA.
   [Quinn, Patricia K.] NOAA, Pacific Marine Environm Lab, Seattle, WA 98115 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; National Oceanic Atmospheric Admin (NOAA) - USA; National Oceanic Atmospheric Admin (NOAA) - USA
RP Thornton, JA (corresponding author), Univ Washington, Dept Atmospher Sci, Seattle, WA 98195 USA.
EM thornton@atmos.washington.edu
FU NSF [ATM-0633897, ATM-0846183]; NOAA Atmospheric Chemistry and Climate Program; Camille and Henry Dreyfus Foundation; National Research Council; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0846183] Funding Source: National Science Foundation
NR 30
TC 526
Z9 604
U1 13
U2 381
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 271
EP 274
DI 10.1038/nature08905
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100045
PM 20220847
DA 2026-03-09
ER

PT J
AU Gan, BY
   Hu, JA
   Jiang, S
   Liu, YC
   Sahin, E
   Zhuang, L
   Fletcher-Sananikone, E
   Colla, S
   Wang, YA
   Chin, L
   DePinho, RA
AF Gan, Boyi
   Hu, Jian
   Jiang, Shan
   Liu, Yingchun
   Sahin, Erguen
   Zhuang, Li
   Fletcher-Sananikone, Eliot
   Colla, Simona
   Wang, Y. Alan
   Chin, Lynda
   DePinho, Ronald A.
TI Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells
SO NATURE
LA English
DT Article
ID mitochondrial biogenesis; energy; resistance; pathway; biology; stress; kinase; foxos
AB The capacity to fine-tune cellular bioenergetics with the demands of stem-cell maintenance and regeneration is central to normal development and ageing, and to organismal survival during periods of acute stress. How energy metabolism and stem-cell homeostatic processes are coordinated is not well understood. Lkb1 acts as an evolutionarily conserved regulator of cellular energy metabolism in eukaryotic cells and functions as the major upstream kinase to phosphorylate AMP-activated protein kinase (AMPK) and 12 other AMPK-related kinases(1-3). Whether Lkb1 regulates stem-cell maintenance remains unknown. Here we show that Lkb1 has an essential role in haematopoietic stem cell (HSC) homeostasis. We demonstrate that ablation of Lkb1 in adult mice results in severe pancytopenia and subsequent lethality. Loss of Lkb1 leads to impaired survival and escape from quiescence of HSCs, resulting in exhaustion of the HSC pool and a marked reduction of HSC repopulating potential in vivo. Lkb1 deletion has an impact on cell proliferation in HSCs, but not on more committed compartments, pointing to context-specific functions for Lkb1 in haematopoiesis. The adverse impact of Lkb1 deletion on haematopoiesis was predominantly cell-autonomous and mTOR complex 1 (mTORC1)-independent, and involves multiple mechanisms converging on mitochondrial apoptosis and possibly downregulation of PGC-1 coactivators and their transcriptional network, which have critical roles in mitochondrial biogenesis and function. Thus, Lkb1 serves as an essential regulator of HSCs and haematopoiesis, and more generally, points to the critical importance of coupling energy metabolism and stem-cell homeostasis.
C1 [Gan, Boyi; Hu, Jian; Jiang, Shan; Liu, Yingchun; Sahin, Erguen; Zhuang, Li; Fletcher-Sananikone, Eliot; Colla, Simona; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Gan, Boyi; Hu, Jian; Jiang, Shan; Liu, Yingchun; Sahin, Erguen; Zhuang, Li; Fletcher-Sananikone, Eliot; Colla, Simona; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Gan, Boyi; Hu, Jian; Jiang, Shan; Liu, Yingchun; Sahin, Erguen; Zhuang, Li; Fletcher-Sananikone, Eliot; Colla, Simona; Wang, Y. Alan; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA.
   [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, 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
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 DOD [TS093049]; Multiple Myeloma Research Foundation; Robert A. and Renee E. Belfer Foundation;  [U01CA141508];  [R21CA135057]
NR 24
TC 347
Z9 401
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 701
EP U125
DI 10.1038/nature09595
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700042
PM 21124456
DA 2026-03-09
ER

PT J
AU Liao, L
   Lin, YC
   Bao, MQ
   Cheng, R
   Bai, JW
   Liu, YA
   Qu, YQ
   Wang, KL
   Huang, Y
   Duan, XF
AF Liao, Lei
   Lin, Yung-Chen
   Bao, Mingqiang
   Cheng, Rui
   Bai, Jingwei
   Liu, Yuan
   Qu, Yongquan
   Wang, Kang L.
   Huang, Yu
   Duan, Xiangfeng
TI High-speed graphene transistors with a self-aligned nanowire gate
SO NATURE
LA English
DT Article
ID epitaxial graphene; dielectrics; mobility; phase
AB Graphene has attracted considerable interest as a potential new electronic material(1-11). With its high carrier mobility, graphene is of particular interest for ultrahigh-speed radio-frequency electronics(12-18). However, conventional device fabrication processes cannot readily be applied to produce high-speed graphene transistors because they often introduce significant defects into the monolayer of carbon lattices and severely degrade the device performance(19-21). Here we report an approach to the fabrication of high-speed graphene transistors with a self-aligned nanowire gate to prevent such degradation. A Co(2)Si-Al(2)O(3) core-shell nanowire is used as the gate, with the source and drain electrodes defined through a self-alignment process and the channel length defined by the nanowire diameter. The physical assembly of the nanowire gate preserves the high carrier mobility in graphene, and the self-alignment process ensures that the edges of the source, drain and gate electrodes are automatically and precisely positioned so that no overlapping or significant gaps exist between these electrodes, thus minimizing access resistance. It therefore allows for transistor performance not previously possible. Graphene transistors with a channel length as low as 140 nm have been fabricated with the highest scaled on-current (3.32 mA mu m(-1)) and transconductance (1.27 mS mu m(-1)) reported so far. Significantly, on-chip microwave measurements demonstrate that the self-aligned devices have a high intrinsic cut-off (transit) frequency of f(T) = 100-300 GHz, with the extrinsic f(T) (in the range of a few gigahertz) largely limited by parasitic pad capacitance. The reported intrinsic f(T) of the graphene transistors is comparable to that of the very best high-electron-mobility transistors with similar gate lengths(10).
C1 [Liao, Lei; Qu, Yongquan; Duan, Xiangfeng] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Lin, Yung-Chen; Cheng, Rui; Bai, Jingwei; Liu, Yuan; Huang, Yu] Univ Calif Los Angeles, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA.
   [Bao, Mingqiang; Wang, Kang L.] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA.
   [Wang, Kang L.; Huang, Yu] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Duan, XF (corresponding author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
EM xduan@chem.ucla.edu
FU NSF [0956171]; NIH [1DP2OD004342-01]
NR 30
TC 1149
Z9 1366
U1 5
U2 879
PU 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 16
PY 2010
VL 467
IS 7313
BP 305
EP 308
DI 10.1038/nature09405
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900034
PM 20811365
DA 2026-03-09
ER

PT J
AU Wensley, BG
   Batey, S
   Bone, FAC
   Chan, ZM
   Tumelty, NR
   Steward, A
   Kwa, LG
   Borgia, A
   Clarke, J
AF Wensley, Beth G.
   Batey, Sarah
   Bone, Fleur A. C.
   Chan, Zheng Ming
   Tumelty, Nuala R.
   Steward, Annette
   Kwa, Lee Gyan
   Borgia, Alessandro
   Clarke, Jane
TI Experimental evidence for a frustrated energy landscape in a three-helix-bundle protein family
SO NATURE
LA English
DT Article
ID internal-friction; transition-state; contact order; diffusion; barrier; stability; kinetics; model; viscosity; dynamics
AB Energy landscape theory is a powerful tool for understanding the structure and dynamics of complex molecular systems, in particular biological macromolecules(1). The primary sequence of a protein defines its free-energy landscape and thus determines the folding pathway and the rate constants of folding and unfolding, as well as the protein's native structure. Theory has shown that roughness in the energy landscape will lead to slower folding(1), but derivation of detailed experimental descriptions of this landscape is challenging. Simple folding models(2,3) show that folding is significantly influenced by chain entropy; proteins in which the contacts are local fold quickly, owing to the low entropy cost of forming stabilizing, native contacts during folding(4,5). For some protein families, stability is also a determinant of folding rate constants(6). Where these simple metrics fail to predict folding behaviour, it is probable that there are features in the energy landscape that are unusual. Such general observations cannot explain the folding behaviour of the R15, R16 and R17 domains of alpha-spectrin. R15 folds similar to 3,000 times faster than its homologues, although they have similar structures, stabilities and, as far as can be determined, transition-state stabilities(7-10). Here we show that landscape roughness (internal friction) is responsible for the slower folding and unfolding of R16 and R17. We use chimaeric domains to demonstrate that this internal friction is a property of the core, and suggest that frustration in the landscape of the slow-folding spectrin domains may be due to misdocking of the long helices during folding. Theoretical studies have suggested that rugged landscapes will result in slower folding; here we show experimentally that such a phenomenon directly influences the folding kinetics of a 'normal' protein, that is, one with a significant energy barrier that folds on a relatively slow, millisecond-second, timescale.
C1 [Wensley, Beth G.; Batey, Sarah; Bone, Fleur A. C.; Chan, Zheng Ming; Tumelty, Nuala R.; Steward, Annette; Kwa, Lee Gyan; Borgia, Alessandro; Clarke, Jane] Univ Cambridge, Dept Chem, MRC, Ctr Prot Engn, Cambridge CB2 1EW, England.
C3 University of Cambridge
RP Clarke, J (corresponding author), Univ Cambridge, Dept Chem, MRC, Ctr Prot Engn, Lensfield Rd, Cambridge CB2 1EW, England.
EM jc162@cam.ac.uk
FU Wellcome Trust [064417/Z/01/A]; UK Medical Research Council; MRC [MC_U105485808] Funding Source: UKRI; Medical Research Council [MC_U105485808] Funding Source: researchfish; Wellcome Trust [064417/Z/01/A] Funding Source: Wellcome Trust
NR 44
TC 139
Z9 153
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 4
PY 2010
VL 463
IS 7281
BP 685
EP U122
DI 10.1038/nature08743
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900041
PM 20130652
DA 2026-03-09
ER

PT J
AU Ito, T
   Yokoyama, S
AF Ito, Takuhiro
   Yokoyama, Shigeyuki
TI Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions
SO NATURE
LA English
DT Article
ID structural basis; synthetase; amidotransferase; crystallography; recruitment; glutamine
AB In most bacteria and all archaea, glutamyl-tRNA synthetase (GluRS) glutamylates both tRNA(Glu) and tRNA(Gln), and then Glu-tRNA(Gln) is selectively converted to Gln-tRNA(Gln) by a tRNAdependent amidotransferase(1,2). The mechanisms by which the two enzymes recognize their substrate tRNA(s), and how they cooperate with each other in Gln-tRNA(Gln) synthesis, remain to be determined. Here we report the formation of the 'glutamine transamidosome' from the bacterium Thermotoga maritima, consisting of tRNA(Gln), GluRS and the heterotrimeric amidotransferase GatCAB, and its crystal structure at 3.35 angstrom resolution. The anticodon-binding body of GluRS recognizes the common features of tRNA(Gln) and tRNA(Glu), whereas the tail body of GatCAB recognizes the outer corner of the L-shaped tRNA(Gln) in a tRNA(Gln)-specific manner. GluRS is in the productive form, as its catalytic body binds to the amino-acid-acceptor arm of tRNA(Gln). In contrast, GatCAB is in the non-productive form: the catalytic body of GatCAB contacts that of GluRS and is located near the acceptor stem of tRNA(Gln), in an appropriate site to wait for the completion of Glu-tRNA(Gln) formation by GluRS. We identified the hinges between the catalytic and anticodon-binding bodies of GluRS and between the catalytic and tail bodies of GatCAB, which allow both GluRS and GatCAB to adopt the productive and non-productive forms. The catalytic bodies of the two enzymes compete for the acceptor arm of tRNA(Gln) and therefore cannot assume their productive forms simultaneously. The transition from the present glutamylation state, with the productive GluRS and the non-productive GatCAB, to the putative amidation state, with the nonproductive GluRS and the productive GatCAB, requires an intermediate state with the two enzymes in their non-productive forms, for steric reasons. The proposed mechanism explains how the transamidosome efficiently performs the two consecutive steps of Gln-tRNA(Gln) formation, with a low risk of releasing the unstable intermediate Glu-tRNA(Gln).
C1 [Ito, Takuhiro; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Bunkyo Ku, Tokyo 1130033, Japan.
   [Ito, Takuhiro; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Struct Biol Lab, Bunkyo Ku, Tokyo 1130033, Japan.
   [Ito, Takuhiro; Yokoyama, Shigeyuki] RIKEN Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
C3 University of Tokyo; University of Tokyo; RIKEN
RP Yokoyama, S (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM yokoyama@biochem.s.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT); Japan Society for the Promotion of Science
NR 24
TC 46
Z9 60
U1 0
U2 17
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 2010
VL 467
IS 7315
BP 612
EP U143
DI 10.1038/nature09411
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100044
PM 20882017
DA 2026-03-09
ER

PT J
AU Bajpai, R
   Chen, DA
   Rada-Iglesias, A
   Zhang, JM
   Xiong, YQ
   Helms, J
   Chang, CP
   Zhao, YM
   Swigut, T
   Wysocka, J
AF Bajpai, Ruchi
   Chen, Denise A.
   Rada-Iglesias, Alvaro
   Zhang, Junmei
   Xiong, Yiqin
   Helms, Jill
   Chang, Ching-Pin
   Zhao, Yingming
   Swigut, Tomek
   Wysocka, Joanna
TI CHD7 cooperates with PBAF to control multipotent neural crest formation
SO NATURE
LA English
DT Article
ID embryonic stem-cells; charge-syndrome; polymerase-ii; chromatin; expression; mutations; transcription; network; complex; protein
AB Heterozygous mutations in the gene encoding the CHD (chromo-domain helicase DNA-binding domain) member CHD7, an ATP-dependent chromatin remodeller homologous to the Drosophila trithorax-group protein Kismet(1,2), result in a complex constellation of congenital anomalies called CHARGE syndrome, which is a sporadic, autosomal dominant disorder characterized by malformations of the craniofacial structures, peripheral nervous system, ears, eyes and heart(3,4). Although it was postulated 25 years ago that CHARGE syndrome results from the abnormal development of the neural crest, this hypothesis remained untested(5). Here we show that, in both humans and Xenopus, CHD7 is essential for the formation of multipotent migratory neural crest (NC), a transient cell population that is ectodermal in origin but undergoes a major transcriptional reprogramming event to acquire a remarkably broad differentiation potential and ability to migrate throughout the body, giving rise to craniofacial bones and cartilages, the peripheral nervous system, pigmentation and cardiac structures(6,7). We demonstrate that CHD7 is essential for activation of the NC transcriptional circuitry, including Sox9, Twist and Slug. In Xenopus embryos, knockdown of Chd7 or overexpression of its catalytically inactive form recapitulates all major features of CHARGE syndrome. In human NC cells CHD7 associates with PBAF (polybromo-and BRG1-associated factor-containing complex) 8 and both remodellers occupy a NC-specific distal SOX9 enhancer(9) and a conserved genomic element located upstream of the TWIST1 gene. Consistently, during embryogenesis CHD7 and PBAF cooperate to promote NC gene expression and cell migration. Our work identifies an evolutionarily conserved role for CHD7 in orchestrating NC gene expression programs, provides insights into the synergistic control of distal elements by chromatin remodellers, illuminates the pathoembryology of CHARGE syndrome, and suggests a broader function for CHD7 in the regulation of cell motility.
C1 [Bajpai, Ruchi; Chen, Denise A.; Rada-Iglesias, Alvaro; Swigut, Tomek; Wysocka, Joanna] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Xiong, Yiqin] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
   [Helms, Jill; Chang, Ching-Pin] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA.
   [Wysocka, Joanna] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Zhang, Junmei] Univ Texas SW Med Ctr Dallas, Prot Chem Technol Ctr, Dallas, TX 75390 USA.
   [Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; University of Texas System; University of Texas Southwestern Medical Center; University of Chicago
RP Wysocka, J (corresponding author), Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
EM wysocka@stanford.edu
FU CIRM SEED [RS1-00323]; Keck Foundation; Searle Scholar Award; EMBO; National Institutes of Health (NIH) [R01DK082664, R01HL085345]; March of Dimes [6-FY06-335]; Oak Foundation
NR 35
TC 483
Z9 611
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 FEB 18
PY 2010
VL 463
IS 7283
BP 958
EP U135
DI 10.1038/nature08733
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700048
PM 20130577
DA 2026-03-09
ER

PT J
AU Feingold, G
   Koren, I
   Wang, HL
   Xue, HW
   Brewer, WA
AF Feingold, Graham
   Koren, Ilan
   Wang, Hailong
   Xue, Huiwen
   Brewer, Wm. Alan
TI Precipitation-generated oscillations in open cellular cloud fields
SO NATURE
LA English
DT Article
ID convection; organization; drizzle; microphysics; patterns; aerosol; cells; model
AB Cloud fields adopt many different patterns that can have a profound effect on the amount of sunlight reflected back to space, with important implications for the Earth's climate. These cloud patterns can be observed in satellite images of the Earth and often exhibit distinct cell-like structures associated with organized convection at scales of tens of kilometres(1-3). Recent evidence has shown that atmospheric aerosol particles-through their influence on precipitation formation-help to determine whether cloud fields take on closed (more reflective) or open (less reflective) cellular patterns(4,5). The physical mechanisms controlling the formation and evolution of these cells, however, are still poorly understood(6), limiting our ability to simulate realistically the effects of clouds on global reflectance. Here we use satellite imagery and numerical models to show how precipitating clouds produce an open cellular cloud pattern that oscillates between different, weakly stable states. The oscillations are a result of precipitation causing downward motion and outflow from clouds that were previously positively buoyant. The evaporating precipitation drives air down to the Earth's surface, where it diverges and collides with the outflows of neighbouring precipitating cells. These colliding outflows form surface convergence zones and new cloud formation. In turn, the newly formed clouds produce precipitation and new colliding outflow patterns that are displaced from the previous ones. As successive cycles of this kind unfold, convergence zones alternate with divergence zones and new cloud patterns emerge to replace old ones. The result is an oscillating, self-organized system with a characteristic cell size and precipitation frequency.
C1 [Feingold, Graham; Brewer, Wm. Alan] NOAA Earth Syst Res Lab, Div Chem Sci, Boulder, CO 80305 USA.
   [Koren, Ilan] Weizmann Inst Sci, Dept Environm Sci, IL-76100 Rehovot, Israel.
   [Wang, Hailong] Pacific NW Natl Lab, Richland, WA 99352 USA.
   [Xue, Huiwen] Peking Univ, Sch Phys, Dept Atmospher Sci, Beijing 100871, Peoples R China.
C3 National Oceanic Atmospheric Admin (NOAA) - USA; Weizmann Institute of Science; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Peking University
RP Feingold, G (corresponding author), NOAA Earth Syst Res Lab, Div Chem Sci, Boulder, CO 80305 USA.
EM graham.feingold@noaa.gov
FU NOAA; CIRES; Pacific Northwest National Laboratory
NR 30
TC 154
Z9 174
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 849
EP 852
DI 10.1038/nature09314
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100032
PM 20703303
DA 2026-03-09
ER

PT J
AU Smith, ZR
   Long, JA
AF Smith, Zachery R.
   Long, Jeff A.
TI Control of Arabidopsis apical-basal embryo polarity by antagonistic transcription factors
SO NATURE
LA English
DT Article
ID transgenic plants; auxin gradients; gene; meristem; shoots; transformation; phabulosa; proteins; growth; mutant
AB Plants, similarly to animals, form polarized axes during embryogenesis on which cell differentiation and organ patterning programs are orchestrated. During Arabidopsis embryogenesis, establishment of the shoot and root stem cell populations occurs at opposite ends of an apical-basal axis. Recent work has identified the PLETHORA (PLT) genes as master regulators of basal/root fate(1-3), whereas the master regulators of apical/shoot fate have remained elusive. Here we show that the PLT1 and PLT2 genes are direct targets of the transcriptional co-repressor TOPLESS (TPL) and that PLT1/2 are necessary for the homeotic conversion of shoots to roots in tpl-1 mutants. Using tpl-1 as a genetic tool, we identify the CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) transcription factors as master regulators of embryonic apical fate, and show they are sufficient to drive the conversion of the embryonic root pole into a second shoot pole. Furthermore, genetic and misexpression studies show an antagonistic relationship between the PLT and HD-ZIP III genes in specifying the root and shoot poles.
C1 [Smith, Zachery R.; Long, Jeff A.] Univ Calif San Diego, Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Smith, Zachery R.] Univ Calif San Diego, Dept Biol, La Jolla, CA 92037 USA.
C3 University of California System; University of California San Diego; Salk Institute; University of California System; University of California San Diego
RP Long, JA (corresponding author), Univ Calif San Diego, Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
EM long@salk.edu
FU Ray Thomas Edwards Foundation Career Development Award; National Institute of Health, NIGMS
NR 24
TC 153
Z9 193
U1 1
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 MAR 18
PY 2010
VL 464
IS 7287
BP 423
EP U121
DI 10.1038/nature08843
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100049
PM 20190735
DA 2026-03-09
ER

PT J
AU Jones, KL
   Adekola, AS
   Bardayan, DW
   Blackmon, JC
   Chae, KY
   Chipps, KA
   Cizewski, JA
   Erikson, L
   Harlin, C
   Hatarik, R
   Kapler, R
   Kozub, RL
   Liang, JF
   Livesay, R
   Ma, Z
   Moazen, BH
   Nesaraja, CD
   Nunes, FM
   Pain, SD
   Patterson, NP
   Shapira, D
   Shriner, JF
   Smith, MS
   Swan, TP
   Thomas, JS
AF Jones, K. L.
   Adekola, A. S.
   Bardayan, D. W.
   Blackmon, J. C.
   Chae, K. Y.
   Chipps, K. A.
   Cizewski, J. A.
   Erikson, L.
   Harlin, C.
   Hatarik, R.
   Kapler, R.
   Kozub, R. L.
   Liang, J. F.
   Livesay, R.
   Ma, Z.
   Moazen, B. H.
   Nesaraja, C. D.
   Nunes, F. M.
   Pain, S. D.
   Patterson, N. P.
   Shapira, D.
   Shriner, J. F., Jr.
   Smith, M. S.
   Swan, T. P.
   Thomas, J. S.
TI The magic nature of 132Sn explored through the single-particle states of 133Sn
SO NATURE
LA English
DT Article
ID d,p reactions; pb-208
AB Atomic nuclei have a shell structure(1) in which nuclei with 'magic numbers' of neutrons and protons are analogous to the noble gases in atomic physics. Only ten nuclei with the standard magic numbers of both neutrons and protons have so far been observed. The nuclear shell model is founded on the precept that neutrons and protons can move as independent particles in orbitals with discrete quantum numbers, subject to a mean field generated by all the other nucleons. Knowledge of the properties of single-particle states outside nuclear shell closures in exotic nuclei is important(2-5) for a fundamental understanding of nuclear structure and nucleo-synthesis (for example the r-process, which is responsible for the production of about half of the heavy elements). However, as a result of their short lifetimes, there is a paucity of knowledge about the nature of single-particle states outside exotic doubly magic nuclei. Here we measure the single-particle character of the levels in Sn-133 that lie outside the double shell closure present at the short-lived nucleus Sn-132. We use an inverse kinematics technique that involves the transfer of a single nucleon to the nucleus. The purity of the measured single-particle states clearly illustrates the magic nature of Sn-132.
C1 [Jones, K. L.; Chae, K. Y.; Kapler, R.; Ma, Z.; Moazen, B. H.] Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
   [Jones, K. L.; Cizewski, J. A.; Hatarik, R.; Pain, S. D.; Swan, T. P.] Rutgers State Univ, Dept Phys & Astron, New Brunswick, NJ 08903 USA.
   [Adekola, A. S.] Ohio Univ, Dept Phys & Astron, Athens, OH 45701 USA.
   [Bardayan, D. W.; Blackmon, J. C.; Liang, J. F.; Nesaraja, C. D.; Shapira, D.; Smith, M. S.] Oak Ridge Natl Lab, Div Phys, Oak Ridge, TN 37831 USA.
   [Chipps, K. A.; Erikson, L.; Livesay, R.] Colorado Sch Mines, Dept Phys, Golden, CO 80401 USA.
   [Harlin, C.; Patterson, N. P.; Swan, T. P.; Thomas, J. S.] Univ Surrey, Dept Phys, Guildford GU2 7XH, Surrey, England.
   [Kozub, R. L.; Shriner, J. F., Jr.] Tennessee Technol Univ, Dept Phys, Cookeville, TN 38505 USA.
   [Nunes, F. M.] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Nunes, F. M.] Michigan State Univ, Natl Superconducting Cyclotron Lab, E Lansing, MI 48824 USA.
C3 University of Tennessee System; University of Tennessee Knoxville; Rutgers University System; Rutgers University New Brunswick; University System of Ohio; Ohio University; United States Department of Energy (DOE); Oak Ridge National Laboratory; Colorado School of Mines; University of Surrey; Tennessee Technological University; Michigan State University; Michigan State University
RP Jones, KL (corresponding author), Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
EM kgrzywac@utk.edu
FU US Department of Energy [DEFG02-96ER40995, DE-FG52-03NA00143, DE-AC05-00OR22725, DE-FG02-96ER40990, DE-FG03-93ER40789, DE-FG02-96ER40983, DE-FG52-08NA28552, DE-AC02-06CH11357]; National Science Foundation [NSF-PHY0354870, NSF-PHY0757678, NSF-PHY-0555893]; UK Science and Technology Funding Council [PP/F000715/1]; Science and Technology Facilities Council [PP/F000715/1] Funding Source: researchfish
NR 23
TC 209
Z9 226
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 454
EP 457
DI 10.1038/nature09048
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700029
PM 20505723
DA 2026-03-09
ER

PT J
AU Gu, HZ
   Chao, J
   Xiao, SJ
   Seeman, NC
AF Gu, Hongzhou
   Chao, Jie
   Xiao, Shou-Jun
   Seeman, Nadrian C.
TI A proximity-based programmable DNA nanoscale assembly line
SO NATURE
LA English
DT Article
ID nanotechnology; chemistry; substrate; cohesion; machine; device; motor; tiles; will
AB Our ability to synthesize nanometre-scale chemical species, such as nanoparticles with desired shapes and compositions, offers the exciting prospect of generating new functional materials and devices by combining them in a controlled fashion into larger structures. Self-assembly can achieve this task efficiently, but may be subject to thermodynamic and kinetic limitations: reactants, intermediates and products may collide with each other throughout the assembly time course to produce non-target species instead of target species. An alternative approach to nanoscale assembly uses information-containing molecules such as DNA(1) to control interactions and thereby minimize unwanted cross-talk between different components. In principle, this method should allow the stepwise and programmed construction of target products by linking individually selected nanoscale components-much as an automobile is built on an assembly line. Here we demonstrate that a nanoscale assembly line can be realized by the judicious combination of three known DNA-based modules: a DNA origami(2) tile that provides a framework and track for the assembly process, cassettes containing three independently controlled two-state DNA machines that serve as programmable cargo-donating devices(3,4) and are attached(4,5) in series to the tile, and a DNA walker that can move on the track from device to device and collect cargo. As the walker traverses the pathway prescribed by the origami tile track, it sequentially encounters the three DNA devices, each of which can be independently switched between an 'ON' state, allowing its cargo to be transferred to the walker, and an 'OFF' state, in which no transfer occurs. We use three different types of gold nanoparticle species as cargo and show that the experimental system does indeed allow the controlled fabrication of the eight different products that can be obtained with three two-state devices.
C1 [Gu, Hongzhou; Seeman, Nadrian C.] NYU, Dept Chem, New York, NY 10003 USA.
   [Chao, Jie; Xiao, Shou-Jun] Nanjing Univ, State Key Lab Coordinat Chem, Sch Chem & Chem Engn, Nanjing Natl Lab Microstruct, Nanjing 210093, Peoples R China.
C3 New York University; Nanjing University
RP Seeman, NC (corresponding author), NYU, Dept Chem, New York, NY 10003 USA.
EM ned.seeman@nyu.edu
FU US National Institute of General Medical Sciences [GM-29544]; US National Science Foundation [CTS-0608889, CCF-0726378]; US Army Research Office [48681-EL, W911NF-07-1-0439]; US Office of Naval Research [N000140910181, N000140911118]; W. M. Keck Foundation; National Basic Research Program of China [2007CB925101]; National Natural Science Foundation of China [20721002]; New York University; Chinese Scholarship Council
NR 21
TC 666
Z9 802
U1 5
U2 607
PU 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 13
PY 2010
VL 465
IS 7295
BP 202
EP U86
DI 10.1038/nature09026
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500031
PM 20463734
DA 2026-03-09
ER

PT J
AU Ma, LJ
   van der Does, HC
   Borkovich, KA
   Coleman, JJ
   Daboussi, MJ
   Di Pietro, A
   Dufresne, M
   Freitag, M
   Grabherr, M
   Henrissat, B
   Houterman, PM
   Kang, S
   Shim, WB
   Woloshuk, C
   Xie, XH
   Xu, JR
   Antoniw, J
   Baker, SE
   Bluhm, BH
   Breakspear, A
   Brown, DW
   Butchko, RAE
   Chapman, S
   Coulson, R
   Coutinho, PM
   Danchin, EGJ
   Diener, A
   Gale, LR
   Gardiner, DM
   Goff, S
   Hammond-Kosack, KE
   Hilburn, K
   Hua-Van, A
   Jonkers, W
   Kazan, K
   Kodira, CD
   Koehrsen, M
   Kumar, L
   Lee, YH
   Li, LD
   Manners, JM
   Miranda-Saavedra, D
   Mukherjee, M
   Park, G
   Park, J
   Park, SY
   Proctor, RH
   Regev, A
   Ruiz-Roldan, MC
   Sain, D
   Sakthikumar, S
   Sykes, S
   Schwartz, DC
   Turgeon, BG
   Wapinski, I
   Yoder, O
   Young, S
   Zeng, QD
   Zhou, SG
   Galagan, J
   Cuomo, CA
   Kistler, HC
   Rep, M
AF Ma, Li-Jun
   van der Does, H. Charlotte
   Borkovich, Katherine A.
   Coleman, Jeffrey J.
   Daboussi, Marie-Josee
   Di Pietro, Antonio
   Dufresne, Marie
   Freitag, Michael
   Grabherr, Manfred
   Henrissat, Bernard
   Houterman, Petra M.
   Kang, Seogchan
   Shim, Won-Bo
   Woloshuk, Charles
   Xie, Xiaohui
   Xu, Jin-Rong
   Antoniw, John
   Baker, Scott E.
   Bluhm, Burton H.
   Breakspear, Andrew
   Brown, Daren W.
   Butchko, Robert A. E.
   Chapman, Sinead
   Coulson, Richard
   Coutinho, Pedro M.
   Danchin, Etienne G. J.
   Diener, Andrew
   Gale, Liane R.
   Gardiner, Donald M.
   Goff, Stephen
   Hammond-Kosack, Kim E.
   Hilburn, Karen
   Hua-Van, Aurelie
   Jonkers, Wilfried
   Kazan, Kemal
   Kodira, Chinnappa D.
   Koehrsen, Michael
   Kumar, Lokesh
   Lee, Yong-Hwan
   Li, Liande
   Manners, John M.
   Miranda-Saavedra, Diego
   Mukherjee, Mala
   Park, Gyungsoon
   Park, Jongsun
   Park, Sook-Young
   Proctor, Robert H.
   Regev, Aviv
   Carmen Ruiz-Roldan, M.
   Sain, Divya
   Sakthikumar, Sharadha
   Sykes, Sean
   Schwartz, David C.
   Turgeon, B. Gillian
   Wapinski, Ilan
   Yoder, Olen
   Young, Sarah
   Zeng, Qiandong
   Zhou, Shiguo
   Galagan, James
   Cuomo, Christina A.
   Kistler, H. Corby
   Rep, Martijn
TI Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium
SO NATURE
LA English
DT Article
ID maximum-likelihood; oxysporum; gene; sequence; tomato; expression; resistance; polymorphism; annotation; infection
AB Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
C1 [Breakspear, Andrew; Gale, Liane R.; Hilburn, Karen; Kistler, H. Corby] Univ Minnesota, USDA ARS, St Paul, MN 55108 USA.
   [Ma, Li-Jun; Grabherr, Manfred; Chapman, Sinead; Kodira, Chinnappa D.; Koehrsen, Michael; Kumar, Lokesh; Regev, Aviv; Sakthikumar, Sharadha; Sykes, Sean; Wapinski, Ilan; Young, Sarah; Zeng, Qiandong; Galagan, James; Cuomo, Christina A.] Broad Inst, Cambridge, MA 02141 USA.
   [van der Does, H. Charlotte; Houterman, Petra M.; Jonkers, Wilfried; Rep, Martijn] Univ Amsterdam, NL-1098 XH Amsterdam, Netherlands.
   [Borkovich, Katherine A.; Li, Liande; Park, Gyungsoon; Sain, Divya] Univ Calif Riverside, Riverside, CA 92521 USA.
   [Coleman, Jeffrey J.] Univ Arizona, Tucson, AZ 85721 USA.
   [Daboussi, Marie-Josee; Hua-Van, Aurelie] Univ Paris 11, F-91405 Paris, France.
   [Di Pietro, Antonio; Carmen Ruiz-Roldan, M.] Univ Cordoba, E-14071 Cordoba, Spain.
   [Freitag, Michael] Oregon State Univ, Corvallis, OR 97331 USA.
   [Henrissat, Bernard; Coutinho, Pedro M.; Danchin, Etienne G. J.] Univ Aix Marseille, CNRS, F-13628 Aix En Provence, France.
   [Kang, Seogchan; Park, Sook-Young] Penn State Univ, University Pk, PA 16802 USA.
   [Shim, Won-Bo; Mukherjee, Mala] Texas A&M Univ, College Stn, TX 77843 USA.
   [Woloshuk, Charles; Xu, Jin-Rong; Bluhm, Burton H.] Purdue Univ, W Lafayette, IN 47907 USA.
   [Xie, Xiaohui] Univ Calif Irvine, Irvine, CA 92697 USA.
   [Antoniw, John; Hammond-Kosack, Kim E.] Ctr Sustainable Pest & Dis Management, Harpenden AL5 2JQ, Herts, England.
   [Baker, Scott E.] Pacific NW Natl Lab, Richland, WA 99352 USA.
   [Brown, Daren W.; Butchko, Robert A. E.; Proctor, Robert H.] USDA ARS NCAUR, Peoria, IL 61604 USA.
   [Coulson, Richard] European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Diener, Andrew] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Gardiner, Donald M.; Kazan, Kemal; Manners, John M.] CSIRO Plant Ind, Brisbane, Qld 4067, Australia.
   [Goff, Stephen] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA.
   [Lee, Yong-Hwan; Park, Jongsun] Seoul Natl Univ, Seoul 151742, South Korea.
   [Miranda-Saavedra, Diego] Cambridge Inst Med Res, Cambridge CB2 0XY, England.
   [Schwartz, David C.; Zhou, Shiguo] Univ Wisconsin, Madison, WI 53706 USA.
   [Turgeon, B. Gillian] Cornell Univ, Ithaca, NY 14853 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; United States Department of Agriculture (USDA); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Amsterdam; University of California System; University of California Riverside; University of Arizona; Universite Paris Saclay; Universidad de Cordoba; Oregon State University; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Texas A&M University System; Texas A&M University College Station; Purdue University System; Purdue University; University of California System; University of California Irvine; United States Department of Energy (DOE); Pacific Northwest National Laboratory; United States Department of Agriculture (USDA); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of California System; University of California Los Angeles; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Arizona; Seoul National University (SNU); University of Cambridge; University of Wisconsin System; University of Wisconsin Madison; Cornell University
RP Kistler, HC (corresponding author), Univ Minnesota, USDA ARS, St Paul, MN 55108 USA.
EM hckist@umn.edu; m.rep@uva.nl
FU USDA's National Institute of Food and Agriculture [2005-35600-16405]; Direct For Biological Sciences; Div Of Biological Infrastructure [0846218] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Materials Research [0832760] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BBS/E/C/00004973] Funding Source: researchfish; BBSRC [BBS/E/C/00004973] Funding Source: UKRI
NR 37
TC 1281
Z9 2027
U1 16
U2 417
PU 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 18
PY 2010
VL 464
IS 7287
BP 367
EP 373
DI 10.1038/nature08850
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100037
PM 20237561
DA 2026-03-09
ER

PT J
AU Haigh, JD
   Winning, AR
   Toumi, R
   Harder, JW
AF Haigh, Joanna D.
   Winning, Ann R.
   Toumi, Ralf
   Harder, Jerald W.
TI An influence of solar spectral variations on radiative forcing of climate
SO NATURE
LA English
DT Article
ID irradiance variations; uv irradiance; reconstruction; model
AB The thermal structure and composition of the atmosphere is determined fundamentally by the incoming solar irradiance. Radiation at ultraviolet wavelengths dissociates atmospheric molecules, initiating chains of chemical reactions-specifically those producing stratospheric ozone-and providing the major source of heating for the middle atmosphere, while radiation at visible and near-infrared wavelengths mainly reaches and warms the lower atmosphere and the Earth's surface(1). Thus the spectral composition of solar radiation is crucial in determining atmospheric structure, as well as surface temperature, and it follows that the response of the atmosphere to variations in solar irradiance depends on the spectrum(2). Daily measurements of the solar spectrum between 0.2 mu m and 2.4 mu m, made by the Spectral Irradiance Monitor (SIM) instrument on the Solar Radiation and Climate Experiment (SORCE) satellite(3) since April 2004, have revealed(4) that over this declining phase of the solar cycle there was a four to six times larger decline in ultraviolet than would have been predicted on the basis of our previous understanding. This reduction was partially compensated in the total solar output by an increase in radiation at visible wavelengths. Here we show that these spectral changes appear to have led to a significant decline from 2004 to 2007 in stratospheric ozone below an altitude of 45 km, with an increase above this altitude. Our results, simulated with a radiative-photochemical model, are consistent with contemporaneous measurements of ozone from the Aura-MLS satellite, although the short time period makes precise attribution to solar effects difficult. We also show, using the SIM data, that solar radiative forcing of surface climate is out of phase with solar activity. Currently there is insufficient observational evidence to validate the spectral variations observed by SIM, or to fully characterize other solar cycles, but our findings raise the possibility that the effects of solar variability on temperature throughout the atmosphere may be contrary to current expectations.
C1 [Haigh, Joanna D.; Winning, Ann R.; Toumi, Ralf] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, London SW7 2AZ, England.
   [Harder, Jerald W.] Univ Colorado, Atmospher & Space Phys Lab, Boulder, CO 80303 USA.
C3 Imperial College London; University of Colorado System; University of Colorado Boulder
RP Haigh, JD (corresponding author), Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Prince Consort Rd, London SW7 2AZ, England.
EM j.haigh@imperial.ac.uk
FU UK Natural Environment Research Council SOLCLI consortium; Natural Environment Research Council [NE/D002753/1] Funding Source: researchfish; NERC [NE/D002753/1] Funding Source: UKRI
NR 19
TC 198
Z9 220
U1 1
U2 84
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 7
PY 2010
VL 467
IS 7316
BP 696
EP 699
DI 10.1038/nature09426
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500035
PM 20930841
DA 2026-03-09
ER

PT J
AU Xiao, SM
   Drachev, VP
   Kildishev, AV
   Ni, XJ
   Chettiar, UK
   Yuan, HK
   Shalaev, VM
AF Xiao, Shumin
   Drachev, Vladimir P.
   Kildishev, Alexander V.
   Ni, Xingjie
   Chettiar, Uday K.
   Yuan, Hsiao-Kuan
   Shalaev, Vladimir M.
TI Loss-free and active optical negative-index metamaterials
SO NATURE
LA English
DT Article
ID refractive-index; light; gain
AB The recently emerged fields of metamaterials and transformation optics promise a family of exciting applications such as invisibility, optical imaging with deeply subwavelength resolution and nanophotonics with the potential for much faster information processing. The possibility of creating optical negative-index metamaterials (NIMs) using nanostructured metal-dielectric composites has triggered intense basic and applied research over the past several years(1-10). However, the performance of all NIM applications is significantly limited by the inherent and strong energy dissipation in metals, especially in the near-infrared and visible wavelength ranges(11,12). Generally the losses are orders of magnitude too large for the proposed applications, and the reduction of losses with optimized designs seems to be out of reach. One way of addressing this issue is to incorporate gain media into NIM designs(13-16). However, whether NIMs with low loss can be achieved has been the subject of theoretical debate(17,18). Here we experimentally demonstrate that the incorporation of gain material in the high-local-field areas of a metamaterial makes it possible to fabricate an extremely low-loss and active optical NIM. The original loss-limited negative refractive index and the figure of merit (FOM) of the device have been drastically improved with loss compensation in the visible wavelength range between 722 and 738 nm. In this range, the NIM becomes active such that the sum of the light intensities in transmission and reflection exceeds the intensity of the incident beam. At a wavelength of 737 nm, the negative refractive index improves from -0.66 to -1.017 and the FOM increases from 1 to 26. At 738 nm, the FOM is expected to become macroscopically large, of the order of 10(6). This study demonstrates the possibility of fabricating an optical negative-index metamaterial that is not limited by the inherent loss in its metal constituent.
C1 [Xiao, Shumin; Drachev, Vladimir P.; Kildishev, Alexander V.; Ni, Xingjie; Chettiar, Uday K.; Yuan, Hsiao-Kuan; Shalaev, Vladimir M.] Purdue Univ, Birck Nanotechnol Ctr, W Lafayette, IN 47907 USA.
   [Xiao, Shumin; Drachev, Vladimir P.; Kildishev, Alexander V.; Ni, Xingjie; Chettiar, Uday K.; Yuan, Hsiao-Kuan; Shalaev, Vladimir M.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Purdue University System; Purdue University
RP Shalaev, VM (corresponding author), Purdue Univ, Birck Nanotechnol Ctr, W Lafayette, IN 47907 USA.
EM shalaev@purdue.edu
FU ARO-MURI [50342-PH-MUR, W911NF-09-1-0539]; NSF [DMR 0611430]
NR 35
TC 703
Z9 781
U1 7
U2 465
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 735
EP U6
DI 10.1038/nature09278
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500034
PM 20686570
DA 2026-03-09
ER

PT J
AU Chow, BY
   Han, X
   Dobry, AS
   Qian, XF
   Chuong, AS
   Li, MJ
   Henninger, MA
   Belfort, GM
   Lin, YX
   Monahan, PE
   Boyden, ES
AF Chow, Brian Y.
   Han, Xue
   Dobry, Allison S.
   Qian, Xiaofeng
   Chuong, Amy S.
   Li, Mingjie
   Henninger, Michael A.
   Belfort, Gabriel M.
   Lin, Yingxi
   Monahan, Patrick E.
   Boyden, Edward S.
TI High-performance genetically targetable optical neural silencing by light-driven proton pumps
SO NATURE
LA English
DT Article
ID in-vivo; millisecond-timescale; clamp analysis; ph-dependence; bacteriorhodopsin; neurons; halorhodopsin; rhodopsins; brain; archaerhodopsin
AB The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch)(1) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins(2,3) or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans(4) (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuro-scientific, biological, neurological and psychiatric investigations.
C1 [Chow, Brian Y.; Han, Xue; Dobry, Allison S.; Qian, Xiaofeng; Chuong, Amy S.; Li, Mingjie; Henninger, Michael A.; Monahan, Patrick E.; Boyden, Edward S.] MIT, Media Lab, Synthet Neurobiol Grp, Cambridge, MA 02139 USA.
   [Chow, Brian Y.; Han, Xue; Dobry, Allison S.; Qian, Xiaofeng; Chuong, Amy S.; Li, Mingjie; Henninger, Michael A.; Monahan, Patrick E.; Boyden, Edward S.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Chow, Brian Y.; Han, Xue; Dobry, Allison S.; Qian, Xiaofeng; Chuong, Amy S.; Li, Mingjie; Henninger, Michael A.; Belfort, Gabriel M.; Lin, Yingxi; Monahan, Patrick E.; Boyden, Edward S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Chow, Brian Y.; Han, Xue; Dobry, Allison S.; Qian, Xiaofeng; Chuong, Amy S.; Li, Mingjie; Henninger, Michael A.; Belfort, Gabriel M.; Lin, Yingxi; Monahan, Patrick E.; Boyden, Edward S.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Boyden, ES (corresponding author), MIT, Media Lab, Synthet Neurobiol Grp, Cambridge, MA 02139 USA.
EM esb@media.mit.edu
FU NIH [DP2 OD002002-01, 1K99MH085944]; NSF [0835878, 0848804]; McGovern Institute Neurotechnology; Department of Defense, NARSAD; Alfred P. Sloan Foundation, Jerry and Marge Burnett; SFN Research Award for Innovation in Neuroscience; MIT Media Lab; Benesse Foundation; Wallace H. Coulter Foundation; Division Of Mathematical Sciences; Direct For Mathematical & Physical Scien [0848469] Funding Source: National Science Foundation; Division Of Mathematical Sciences; Direct For Mathematical & Physical Scien [0848804] Funding Source: National Science Foundation
NR 30
TC 920
Z9 1230
U1 0
U2 245
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 98
EP 102
DI 10.1038/nature08652
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900038
PM 20054397
DA 2026-03-09
ER

PT J
AU Kanchanawong, P
   Shtengel, G
   Pasapera, AM
   Ramko, EB
   Davidson, MW
   Hess, HF
   Waterman, CM
AF Kanchanawong, Pakorn
   Shtengel, Gleb
   Pasapera, Ana M.
   Ramko, Ericka B.
   Davidson, Michael W.
   Hess, Harald F.
   Waterman, Clare M.
TI Nanoscale architecture of integrin-based cell adhesions
SO NATURE
LA English
DT Article
ID focal adhesions; actin-filaments; protein; force; talin; microscopy; probes
AB Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing(1,2). Focal adhesions are multifunctional organelles that mediate cell-ECM adhesion, force transmission, cytoskeletal regulation and signalling(1-3). Focal adhesions consist of a complex network(4) of trans-plasma-membrane integrins and cytoplasmic proteins that form a <200-nm plaque(5,6) linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine(7,8). However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photo-activated localization microscopy)(9) to map nanoscale protein organization in focal adhesions. Our results reveal that integrins and actin are vertically separated by a similar to 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signalling layer containing integrin cytoplasmic tails, focal adhesion kinase and paxillin; an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein and alpha-actinin. By localizing amino- and carboxyterminally tagged talins, we reveal talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. The composite multilaminar protein architecture provides a molecular blueprint for understanding focal adhesion functions.
C1 [Kanchanawong, Pakorn; Pasapera, Ana M.; Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Shtengel, Gleb; Hess, Harald F.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Ramko, Ericka B.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Howard Hughes Medical Institute; State University System of Florida; Florida State University; State University System of Florida; Florida State University
RP Waterman, CM (corresponding author), NHLBI, NIH, Bethesda, MD 20892 USA.
EM davidson@magnet.fsu.edu; hessh@janelia.hhmi.org; watermancm@nhlbi.nih.gov
FU Division of Intramural Research, NHLBI; Howard Hughes Medical Institute; National Heart Lung and Blood Institute [ZIAHL005105] Funding Source: NIH RePORTER
NR 35
TC 1213
Z9 1522
U1 7
U2 485
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 580
EP U262
DI 10.1038/nature09621
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200046
PM 21107430
DA 2026-03-09
ER

PT J
AU O'Connor, PM
   Sertich, JJW
   Stevens, NJ
   Roberts, EM
   Gottfried, MD
   Hieronymus, TL
   Jinnah, ZA
   Ridgely, R
   Ngasala, SE
   Temba, J
AF O'Connor, Patrick M.
   Sertich, Joseph J. W.
   Stevens, Nancy J.
   Roberts, Eric M.
   Gottfried, Michael D.
   Hieronymus, Tobin L.
   Jinnah, Zubair A.
   Ridgely, Ryan
   Ngasala, Sifa E.
   Temba, Jesuit
TI The evolution of mammal-like crocodyliforms in the Cretaceous Period of Gondwana
SO NATURE
LA English
DT Article
ID red sandstone group; rukwa rift basin; mesoeucrocodylia; crocodylomorpha; remains
AB Fossil crocodyliforms discovered in recent years(1-5) have revealed a level of morphological and ecological diversity not exhibited by extant members of the group. This diversity is particularly notable among taxa of the Cretaceous Period (144-65 million years ago) recovered from former Gondwanan landmasses. Here we report the discovery of a new species of Cretaceous notosuchian crocodyliform from the Rukwa Rift Basin(6) of southwestern Tanzania. This small-bodied form deviates significantly from more typical crocodyliform craniodental morphologies, having a short, broad skull, robust lower jaw, and a dentition with relatively few teeth that nonetheless show marked heterodonty. The presence of morphologically complex, complementary upper and lower molariform teeth suggests a degree of crown-crown contact during jaw adduction that is unmatched among known crocodyliforms, paralleling the level of occlusal complexity seen in mammals and their extinct relatives(7-12). The presence of another small-bodied mammal-like crocodyliform in the Cretaceous of Gondwana indicates that notosuchians probably filled niches and inhabited ecomorphospace that were otherwise occupied by mammals on northern continents.
C1 [O'Connor, Patrick M.; Stevens, Nancy J.; Ridgely, Ryan] Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA.
   [O'Connor, Patrick M.; Stevens, Nancy J.] Ohio Univ, Ohio Ctr Ecol & Evolutionary Studies, Athens, OH 45701 USA.
   [Sertich, Joseph J. W.] SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Roberts, Eric M.] So Utah Univ, Dept Phys Sci, Cedar City, UT 84720 USA.
   [Roberts, Eric M.] James Cook Univ, Sch Earth & Environm Sci, Townsville, Qld 4811, Australia.
   [Gottfried, Michael D.; Ngasala, Sifa E.] Michigan State Univ, Dept Geol Sci, E Lansing, MI 48824 USA.
   [Hieronymus, Tobin L.] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Dept Anat & Neurobiol, Rootstown, OH 44272 USA.
   [Hieronymus, Tobin L.] Northeastern Ohio Univ Coll Med & Pharm, Coll Pharm, Rootstown, OH 44272 USA.
   [Jinnah, Zubair A.] Univ Witwatersrand, Sch Geosci, Johannesburg, South Africa.
   [Ngasala, Sifa E.] Univ Dar Es Salaam, Dept Geol, Dar Es Salaam, Tanzania.
   [Temba, Jesuit] Tanzania Antiqu Unit, Dar Es Salaam, Tanzania.
C3 University System of Ohio; Ohio University; University System of Ohio; Ohio University; State University of New York (SUNY) System; Stony Brook University; Utah System of Higher Education; Southern Utah University; James Cook University; Michigan State University; University System of Ohio; Northeast Ohio Medical University (NEOMED); University System of Ohio; Northeast Ohio Medical University (NEOMED); University of Witwatersrand; University of Dar es Salaam
RP O'Connor, PM (corresponding author), Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, 228 Irvine Hall, Athens, OH 45701 USA.
EM oconnorp@ohio.edu
FU Tanzania Antiquities Unit; Tanzania Museum of House of Culture; University of Dar es Salaam; Tanzania Commission for Science and Technology; US National Science Foundation (NSF) [EAR-0617561, EAR-0854218]; National Geographic Society (CRE); University of the Witwatersrand; Michigan State University Office of Research and Graduate Studies; Ohio University College of Osteopathic Medicine; Ohio University Office of Research and Sponsored Programs; Directorate For Geosciences; Division Of Earth Sciences [0933619] Funding Source: National Science Foundation
NR 30
TC 122
Z9 137
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 748
EP 751
DI 10.1038/nature09061
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500037
PM 20686573
DA 2026-03-09
ER

PT J
AU Nadj-Perge, S
   Frolov, SM
   Bakkers, EPAM
   Kouwenhoven, LP
AF Nadj-Perge, S.
   Frolov, S. M.
   Bakkers, E. P. A. M.
   Kouwenhoven, L. P.
TI Spin-orbit qubit in a semiconductor nanowire
SO NATURE
LA English
DT Article
ID single-electron spin; quantum-dot; manipulation; field
AB Motion of electrons can influence their spins through a fundamental effect called spin-orbit interaction. This interaction provides a way to control spins electrically and thus lies at the foundation of spintronics(1). Even at the level of single electrons, the spin-orbit interaction has proven promising for coherent spin rotations(2). Here we implement a spin-orbit quantum bit (qubit) in an indium arsenide nanowire, where the spin-orbit interaction is so strong that spin and motion can no longer be separated(3,4). In this regime, we realize fast qubit rotations and universal single-qubit control using only electric fields; the qubits are hosted in single-electron quantum dots that are individually addressable. We enhance coherence by dynamically decoupling the qubits from the environment. Nanowires offer various advantages for quantum computing: they can serve as one-dimensional templates for scalable qubit registers, and it is possible to vary the material even during wire growth(5). Such flexibility can be used to design wires with suppressed decoherence and to push semiconductor qubit fidelities towards error correction levels. Furthermore, electrical dots can be integrated with optical dots in p-n junction nanowires(6). The coherence times achieved here are sufficient for the conversion of an electronic qubit into a photon, which can serve as a flying qubit for long-distance quantum communication.
C1 [Nadj-Perge, S.; Frolov, S. M.; Bakkers, E. P. A. M.; Kouwenhoven, L. P.] Delft Univ Technol, Kavli Inst Nanosci, NL-2600 GA Delft, Netherlands.
   [Bakkers, E. P. A. M.] Eindhoven Univ Technol, Dept Appl Phys, NL-5600 MB Eindhoven, Netherlands.
C3 Delft University of Technology; Eindhoven University of Technology
RP Kouwenhoven, LP (corresponding author), Delft Univ Technol, Kavli Inst Nanosci, NL-2600 GA Delft, Netherlands.
EM l.p.kouwenhoven@tudelft.nl
FU NWO/FOM (the Netherlands Organization for Scientific Research); ERC; DARPA
NR 30
TC 619
Z9 689
U1 2
U2 273
PU 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 23
PY 2010
VL 468
IS 7327
BP 1084
EP 1087
DI 10.1038/nature09682
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800054
PM 21179164
DA 2026-03-09
ER

PT J
AU Tagami, S
   Sekine, S
   Kumarevel, T
   Hino, N
   Murayama, Y
   Kamegamori, S
   Yamamoto, M
   Sakamoto, K
   Yokoyama, S
AF Tagami, Shunsuke
   Sekine, Shun-ichi
   Kumarevel, Thirumananseri
   Hino, Nobumasa
   Murayama, Yuko
   Kamegamori, Syunsuke
   Yamamoto, Masaki
   Sakamoto, Kensaku
   Yokoyama, Shigeyuki
TI Crystal structure of bacterial RNA polymerase bound with a transcription inhibitor protein
SO NATURE
LA English
DT Article
ID 3.3 angstrom resolution; ii elongation complex; thermus-thermophilus; escherichia-coli; crystallographic analysis; active-center; coiled-coil; gre factors; amino-acid; nmr system
AB The multi-subunit DNA-dependent RNA polymerase (RNAP) is the principal enzyme of transcription for gene expression. Transcription is regulated by various transcription factors. Gre factor homologue 1 (Gfh1), found in the Thermus genus, is a close homologue of the well-conserved bacterial transcription factor GreA, and inhibits transcription initiation and elongation by binding directly to RNAP(1-8). The structural basis of transcription inhibition by Gfh1 has remained elusive, although the crystal structures of RNAP and Gfh1 have been determined separately(6-9). Here we report the crystal structure of Thermus thermophilus RNAP complexed with Gfh1. The amino-terminal coiled-coil domain of Gfh1 fully occludes the channel formed between the two central modules of RNAP; this channel would normally be used for nucleotide triphosphate (NTP) entry into the catalytic site. Furthermore, the tip of the coiled-coil domain occupies the NTP beta-gamma phosphate-binding site. The NTP-entry channel is expanded, because the central modules are 'ratcheted' relative to each other by similar to 7 degrees, as compared with the previously reported elongation complexes. This 'ratcheted state' is an alternative structural state, defined by a newly acquired contact between the central modules. Therefore, the shape of Gfh1 is appropriate to maintain RNAP in the ratcheted state. Simultaneously, the ratcheting expands the nucleic-acid-binding channel, and kinks the bridge helix, which connects the central modules. Taken together, the present results reveal that Gfh1 inhibits transcription by preventing NTP binding and freezing RNAP in the alternative structural state. The ratcheted state might also be associated with other aspects of transcription, such as RNAP translocation and transcription termination.
C1 [Tagami, Shunsuke; Sekine, Shun-ichi; Murayama, Yuko; Kamegamori, Syunsuke; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan.
   [Tagami, Shunsuke; Sekine, Shun-ichi; Hino, Nobumasa; Murayama, Yuko; Kamegamori, Syunsuke; Sakamoto, Kensaku; Yokoyama, Shigeyuki] RIKEN Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Sekine, Shun-ichi; Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Struct Biol Lab, Bunkyo Ku, Tokyo 1130033, Japan.
   [Kumarevel, Thirumananseri] RIKEN SPring 8 Ctr, Harima Inst, Struct & Mol Biol Lab, Sayo, Hyogo 6795148, Japan.
   [Yamamoto, Masaki] RIKEN SPring 8 Ctr, Harima Inst, SR Life Sci Instrumentat Unit, Sayo, Hyogo 6795148, Japan.
C3 University of Tokyo; RIKEN; University of Tokyo; RIKEN; RIKEN
RP Sekine, S (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM sekine@biochem.s.u-tokyo.ac.jp; yokoyama@biochem.s.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; JSPS Global Centers of Excellence; Grants-in-Aid for Scientific Research [22570175] Funding Source: KAKEN
NR 41
TC 127
Z9 145
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 DEC 16
PY 2010
VL 468
IS 7326
BP 978
EP U282
DI 10.1038/nature09573
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600050
PM 21124318
DA 2026-03-09
ER

PT J
AU Ito, T
   Kwon, HY
   Zimdahl, B
   Congdon, KL
   Blum, J
   Lento, WE
   Zhao, C
   Lagoo, A
   Gerrard, G
   Foroni, L
   Goldman, J
   Goh, H
   Kim, SH
   Kim, DW
   Chuah, C
   Oehler, VG
   Radich, JP
   Jordan, CT
   Reya, T
AF Ito, Takahiro
   Kwon, Hyog Young
   Zimdahl, Bryan
   Congdon, Kendra L.
   Blum, Jordan
   Lento, William E.
   Zhao, Chen
   Lagoo, Anand
   Gerrard, Gareth
   Foroni, Letizia
   Goldman, John
   Goh, Harriet
   Kim, Soo-Hyun
   Kim, Dong-Wook
   Chuah, Charles
   Oehler, Vivian G.
   Radich, Jerald P.
   Jordan, Craig T.
   Reya, Tannishtha
TI Regulation of myeloid leukaemia by the cell-fate determinant Musashi
SO NATURE
LA English
DT Article
ID chronic myelogenous leukemia; binding protein musashi-1; cml blast crisis; stem-cells; bcr-abl; gene-expression; translational repression; murine model; numb; rna
AB Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase(1), but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML(2,3) to show that disease progression is regulated by the Musashi-Numb signalling axis(4,5). Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML(6,7), can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.
C1 [Ito, Takahiro; Kwon, Hyog Young; Zimdahl, Bryan; Congdon, Kendra L.; Blum, Jordan; Lento, William E.; Zhao, Chen; Reya, Tannishtha] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
   [Lagoo, Anand] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [Gerrard, Gareth; Foroni, Letizia; Goldman, John] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Haematol, London W12 0NN, England.
   [Goh, Harriet; Kim, Soo-Hyun; Kim, Dong-Wook] Catholic Univ Korea, Seoul St Marys Hosp, Div Hematol, Seoul, South Korea.
   [Chuah, Charles] Duke NUS Grad Med Sch, Canc & Stem Cell Biol Program, Singapore Gen Hosp, Dept Haematol, Singapore, Singapore.
   [Oehler, Vivian G.; Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Jordan, Craig T.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
C3 Duke University; Duke University; Imperial College London; Seoul St. Mary's Hospital; Catholic University of Korea; Singapore General Hospital; National University of Singapore; Fred Hutchinson Cancer Center; University of Rochester
RP Reya, T (corresponding author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
EM t.reya@duke.edu
FU Astellas Foundation for Research on Metabolic Disorders; American Heart Association; Leukemia and Lymphoma Society; ASH; NIH [CA18029, CA140371, CA122206, DK63031, DK072234, AI067798, HL097767, DP1OD006430]; Alexander and Margaret Stewart Fund; Lisa Stafford Research Prize;  [T32 GM007184-33]; National Cancer Institute [P01CA018029] Funding Source: NIH RePORTER; NIH Office of the Director [U19AI067798] Funding Source: NIH RePORTER
NR 35
TC 301
Z9 353
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 AUG 5
PY 2010
VL 466
IS 7307
BP 765
EP U13
DI 10.1038/nature09171
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500041
PM 20639863
DA 2026-03-09
ER

PT J
AU Ko, M
   Huang, Y
   Jankowska, AM
   Pape, UJ
   Tahiliani, M
   Bandukwala, HS
   An, J
   Lamperti, ED
   Koh, KP
   Ganetzky, R
   Liu, XS
   Aravind, L
   Agarwal, S
   Maciejewski, JP
   Rao, A
AF Ko, Myunggon
   Huang, Yun
   Jankowska, Anna M.
   Pape, Utz J.
   Tahiliani, Mamta
   Bandukwala, Hozefa S.
   An, Jungeun
   Lamperti, Edward D.
   Koh, Kian Peng
   Ganetzky, Rebecca
   Liu, X. Shirley
   Aravind, L.
   Agarwal, Suneet
   Maciejewski, Jaroslaw P.
   Rao, Anjana
TI Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2
SO NATURE
LA English
DT Article
ID dna methylation; mutations; malignancy; therapy; common; hypomethylation; myelofibrosis; epigenetics; conversion; neoplasms
AB TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA(1,2). The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies(3). Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML)(4-12). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.
C1 [Ko, Myunggon; Huang, Yun; Pape, Utz J.; Tahiliani, Mamta; Bandukwala, Hozefa S.; An, Jungeun; Lamperti, Edward D.; Koh, Kian Peng; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA.
   [Ko, Myunggon; Huang, Yun; Pape, Utz J.; Tahiliani, Mamta; Bandukwala, Hozefa S.; An, Jungeun; Lamperti, Edward D.; Koh, Kian Peng; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Jankowska, Anna M.; Ganetzky, Rebecca; Maciejewski, Jaroslaw P.] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA.
   [Jankowska, Anna M.; Ganetzky, Rebecca; Maciejewski, Jaroslaw P.] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA.
   [Pape, Utz J.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Pape, Utz J.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Agarwal, Suneet] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Agarwal, Suneet] Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 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); Cleveland Clinic Foundation; Cleveland Clinic Foundation; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Rao, A (corresponding author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM maciejj@ccf.org; arao@idi.harvard.edu
FU NIH [R01 AI44432, RC1 DA028422, K24 HL077522, R01 HL098522, R01 HG4069]; Aplastic Anemia MDS Foundation; Bob Duggan Memorial Research Fund; Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH) [1 UL1 RR 025758-02]; GlaxoSmithKline-Immune Disease Institute (GSK-IDI) Alliance; Leukemia and Lymphoma Society of America
NR 26
TC 1109
Z9 1290
U1 4
U2 191
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 9
PY 2010
VL 468
IS 7325
BP 839
EP 843
DI 10.1038/nature09586
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700049
PM 21057493
DA 2026-03-09
ER

PT J
AU Oler, JA
   Fox, AS
   Shelton, SE
   Rogers, J
   Dyer, TD
   Davidson, RJ
   Shelledy, W
   Oakes, TR
   Blangero, J
   Kalin, NH
AF Oler, Jonathan A.
   Fox, Andrew S.
   Shelton, Steven E.
   Rogers, Jeffrey
   Dyer, Thomas D.
   Davidson, Richard J.
   Shelledy, Wendy
   Oakes, Terrence R.
   Blangero, John
   Kalin, Ned H.
TI Amygdalar and hippocampal substrates of anxious temperament differ in their heritability
SO NATURE
LA English
DT Article
ID behavioral-inhibition; genetic-variation; anxiety; emotion; disorders; brain; fear; mechanisms; expression; childhood
AB Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli(1-4). Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse(5). Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
C1 [Oler, Jonathan A.; Shelton, Steven E.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA.
   [Fox, Andrew S.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
   [Oler, Jonathan A.; Shelton, Steven E.; Davidson, Richard J.; Kalin, Ned H.] Univ Wisconsin, HealthEmot Res Inst, Madison, WI 53719 USA.
   [Fox, Andrew S.; Davidson, Richard J.; Oakes, Terrence R.; Kalin, Ned H.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53705 USA.
   [Rogers, Jeffrey] Baylor Coll Med, Houston, TX 77030 USA.
   [Rogers, Jeffrey; Dyer, Thomas D.; Shelledy, Wendy; Blangero, John] SW Fdn Biomed Res, San Antonio, TX 78227 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; University of Wisconsin System; University of Wisconsin Madison; Baylor College of Medicine; Texas Biomedical Research Institute
RP Kalin, NH (corresponding author), Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA.
EM nkalin@wisc.edu
FU National Institutes of Health [MH046729, MH081884, MH084051, MH018931, MH059490]; HealthEmotions Research Institute; National Institute of Mental Health [R01MH046729, T32MH018931, R01MH081884] Funding Source: NIH RePORTER
NR 31
TC 170
Z9 212
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 864
EP 868
DI 10.1038/nature09282
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100036
PM 20703306
DA 2026-03-09
ER

PT J
AU Saenz, SA
   Siracusa, MC
   Perrigoue, JG
   Spencer, SP
   Urban, JF
   Tocker, JE
   Budelsky, AL
   Kleinschek, MA
   Kastelein, RA
   Kambayashi, T
   Bhandoola, A
   Artis, D
AF Saenz, Steven A.
   Siracusa, Mark C.
   Perrigoue, Jacqueline G.
   Spencer, Sean P.
   Urban, Joseph F., Jr.
   Tocker, Joel E.
   Budelsky, Alison L.
   Kleinschek, Melanie A.
   Kastelein, Robert A.
   Kambayashi, Taku
   Bhandoola, Avinash
   Artis, David
TI IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; type-2 immunity; in-vivo; il-4; innate; inflammation; expression; basophils
AB CD4(+) T helper 2 (T(H)2) cells secrete interleukin (IL)4, IL5 and IL13, and are required for immunity to gastrointestinal helminth infections(1). However, T(H)2 cells also promote chronic inflammation associated with asthma and allergic disorders(2). The nonhaematopoietic-cell-derived cytokines thymic stromal lymphopoietin, IL33 and IL25 (also known as IL17E) have been implicated in inducing T(H)2 cell-dependent inflammation at mucosal sites(3-6), but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL25, a member of the IL17 cytokine family, promotes the accumulation of a lineage-negative (Lin(-)) multipotent progenitor (MPP) cell population in the gut-associated lymphoid tissue that promotes T(H)2 cytokine responses. The IL25-elicited cell population, termed MPPtype2 cells, was defined by the expression of Sca-1 (also known as Ly6a) and intermediate expression of c-Kit (c-Kit(int)), and exhibited multipotent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both in vitro and in vivo. Progeny of MPPtype2 cells were competent antigen presenting cells, and adoptive transfer of MPPtype2 cells could promote T(H)2 cytokine responses and confer protective immunity to helminth infection in normally susceptible Il25(-/-) mice. The ability of IL25 to induce the emergence of an MPPtype2 cell population identifies a link between the IL17 cytokine family and extramedullary haematopoiesis, and suggests a previously unrecognized innate immune pathway that promotes T(H)2 cytokine responses at mucosal sites.
C1 [Saenz, Steven A.; Siracusa, Mark C.; Perrigoue, Jacqueline G.; Spencer, Sean P.; Artis, David] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA.
   [Kambayashi, Taku; Bhandoola, Avinash] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Urban, Joseph F., Jr.] USDA, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
   [Tocker, Joel E.; Budelsky, Alison L.] Amgen Inc, Dept Inflammat Res, Seattle, WA 98119 USA.
   [Kleinschek, Melanie A.; Kastelein, Robert A.] Schering Plough Biopharma, Discovery Res, Palo Alto, CA 94304 USA.
C3 University of Pennsylvania; University of Pennsylvania; United States Department of Agriculture (USDA); Amgen; Merck & Company
RP Artis, D (corresponding author), Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA.
EM dartis@vet.upenn.edu
FU National Institutes of Health [AI61570, AI074878, AI083480, GM082187, AI007532-08]; Burroughs Wellcome Fund; National Institute of Diabetes and Digestive Kidney Disease Center [P30 DK50306]; University of Pennsylvania (URF, VCID and PGI); National Heart Lung and Blood Institute [T32HL007775] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI095466, T32AI007532] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK050306] Funding Source: NIH RePORTER
NR 30
TC 462
Z9 550
U1 0
U2 70
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1362
EP U8
DI 10.1038/nature08901
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000049
PM 20200520
DA 2026-03-09
ER

PT J
AU Swain, MR
   Deroo, P
   Griffith, CA
   Tinetti, G
   Thatte, A
   Vasisht, G
   Chen, P
   Bouwman, J
   Crossfield, IJ
   Angerhausen, D
   Afonso, C
   Henning, T
AF Swain, Mark R.
   Deroo, Pieter
   Griffith, Caitlin A.
   Tinetti, Giovanna
   Thatte, Azam
   Vasisht, Gautam
   Chen, Pin
   Bouwman, Jeroen
   Crossfield, Ian J.
   Angerhausen, Daniel
   Afonso, Cristina
   Henning, Thomas
TI A ground-based near-infrared emission spectrum of the exoplanet HD 189733b
SO NATURE
LA English
DT Article
ID atmospheric circulation; transmission spectrum; extrasolar planet; dayside spectrum; hot jupiters; water; methane; absorption; 209458b; sodium
AB Detection of molecules using infrared spectroscopy probes the conditions and compositions of exoplanet atmospheres. Water (H(2)O), methane (CH(4)), carbon dioxide (CO(2)), and carbon monoxide (CO) have been detected(1-5) in two hot Jupiters. These previous results relied on space-based telescopes that do not provide spectroscopic capability in the 2.4-5.2 mu m spectral region. Here we report ground-based observations of the dayside emission spectrum for HD189733b between 2.0-2.4 mu m and 3.1-4.1 mu m, where we find a bright emission feature. Where overlap with space-based instruments exists, our results are in excellent agreement with previous measurements(2,6). A feature at similar to 3.25 mu m is unexpected and difficult to explain with models that assume local thermodynamic equilibrium (LTE) conditions at the 1 bar to 1 x 10(-6) bar pressures typically sampled by infrared measurements. The most likely explanation for this feature is that it arises fromnon-LTE emission from CH(4), similar to what is seen in the atmospheres of planets in our own Solar System(7-9). These results suggest that non-LTE effects may need to be considered when interpreting measurements of strongly irradiated exoplanets.
C1 [Swain, Mark R.; Deroo, Pieter; Vasisht, Gautam; Chen, Pin] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Griffith, Caitlin A.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Tinetti, Giovanna] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Crossfield, Ian J.] Univ Calif Los Angeles, Dept Astron, Los Angeles, CA 90034 USA.
   [Thatte, Azam] Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
   [Bouwman, Jeroen; Afonso, Cristina; Henning, Thomas] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Angerhausen, Daniel] German SOFIA Inst, Inst Space Syst, Stuttgart, Germany.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Arizona; University of London; University College London; University of California System; University of California Los Angeles; University System of Georgia; Georgia Institute of Technology; Max Planck Society
RP Swain, MR (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM mark.r.swain@jpl.nasa.gov
FU UK Sciences and Technology Facilities Council; European Space Agency; National Aeronautics and Space Administration
NR 16
TC 158
Z9 174
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 FEB 4
PY 2010
VL 463
IS 7281
BP 637
EP 639
DI 10.1038/nature08775
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900030
PM 20130645
DA 2026-03-09
ER

PT J
AU Bellott, DW
   Skaletsky, H
   Pyntikova, T
   Mardis, ER
   Graves, T
   Kremitzki, C
   Brown, LG
   Rozen, S
   Warren, WC
   Wilson, RK
   Page, DC
AF Bellott, Daniel W.
   Skaletsky, Helen
   Pyntikova, Tatyana
   Mardis, Elaine R.
   Graves, Tina
   Kremitzki, Colin
   Brown, Laura G.
   Rozen, Steve
   Warren, Wesley C.
   Wilson, Richard K.
   Page, David C.
TI Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition
SO NATURE
LA English
DT Article
ID sex-chromosm; rapid evolution; genome; region; sequence; platypus; synteny; strata; bird; map
AB In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex-the W and Y chromosomes(1-5). By contrast, the sex chromosomes found in both sexes-the Z and X chromosomes-are assumed to have diverged little from their autosomal progenitors(2). Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.
C1 [Bellott, Daniel W.; Skaletsky, Helen; Pyntikova, Tatyana; Brown, Laura G.; Rozen, Steve; Page, David C.] MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA.
   [Bellott, Daniel W.; Skaletsky, Helen; Pyntikova, Tatyana; Brown, Laura G.; Rozen, Steve; Page, David C.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Mardis, Elaine R.; Graves, Tina; Kremitzki, Colin; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
C3 Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Washington University (WUSTL)
RP Page, DC (corresponding author), MIT, Howard Hughes Med Inst, Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dcpage@wi.mit.edu
FU National Institutes of Health; Howard Hughes Medical Institute
NR 39
TC 176
Z9 207
U1 2
U2 59
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 612
EP U3
DI 10.1038/nature09172
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100051
PM 20622855
DA 2026-03-09
ER

PT J
AU Aguirre, A
   Rubio, ME
   Gallo, V
AF Aguirre, Adan
   Rubio, Maria E.
   Gallo, Vittorio
TI Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal
SO NATURE
LA English
DT Article
ID adult hippocampal neurogenesis; growth-factor receptor; subventricular zone; progenitor cells; in-vivo; intracellular domain; mammalian brain; proliferation; niche; visualization
AB Specialized cellular microenvironments, or 'niches', modulate stem cell properties, including cell number, self-renewal and fate decisions(1,2). In the adult brain, niches that maintain a source of neural stem cells (NSCs) and neural progenitor cells (NPCs) are the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus(3-5). The size of the NSC population of the SVZ at any time is the result of several ongoing processes, including self-renewal, cell differentiation, and cell death. Maintaining the balance between NSCs and NPCs in the SVZ niche is critical to supply the brain with specific neural populations, both under normal conditions or after injury. A fundamental question relevant to both normal development and to cell-based repair strategies in the central nervous system is how the balance of different NSC and NPC populations is maintained in the niche. EGFR (epidermal growth factor receptor) and Notch signalling pathways have fundamental roles during development of multicellular organisms(6). In Drosophila and in Caenorhabditis elegans these pathways may have either cooperative or antagonistic functions(7-9). In the SVZ, Notch regulates NSC identity and self-renewal, whereas EGFR specifically affects NPC proliferation and migration(10-13). This suggests that interplay of these two pathways may maintain the balance between NSC and NPC numbers. Here we show that functional cell-cell interaction between NPCs and NSCs through EGFR and Notch signalling has a crucial role in maintaining the balance between these cell populations in the SVZ. Enhanced EGFR signalling in vivo results in the expansion of the NPC pool, and reduces NSC number and self-renewal. This occurs through a non-cell-autonomous mechanism involving EGFR-mediated regulation of Notch signalling. Our findings define a novel interaction between EGFR and Notch pathways in the adult SVZ, and thus provide a mechanism for NSC and NPC pool maintenance.
C1 [Aguirre, Adan; Gallo, Vittorio] Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA.
   [Rubio, Maria E.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15261 USA.
C3 Children's National Health System; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Gallo, V (corresponding author), Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA.
EM vgallo@cnmcresearch.org
FU NIH [R01NS045702, R01NS056427, K99NS057944, ROO NS057944-03, R01DC006881]; NIH IDDRC [P30HD40677]; NSF [DBI-0420580]
NR 38
TC 377
Z9 465
U1 3
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 SEP 16
PY 2010
VL 467
IS 7313
BP 323
EP U101
DI 10.1038/nature09347
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900038
PM 20844536
DA 2026-03-09
ER

PT J
AU Maruyama, H
   Morino, H
   Ito, H
   Izumi, Y
   Kato, H
   Watanabe, Y
   Kinoshita, Y
   Kamada, M
   Nodera, H
   Suzuki, H
   Komure, O
   Matsuura, S
   Kobatake, K
   Morimoto, N
   Abe, K
   Suzuki, N
   Aoki, M
   Kawata, A
   Hirai, T
   Kato, T
   Ogasawara, K
   Hirano, A
   Takumi, T
   Kusaka, H
   Hagiwara, K
   Kaji, R
   Kawakami, H
AF Maruyama, Hirofumi
   Morino, Hiroyuki
   Ito, Hidefumi
   Izumi, Yuishin
   Kato, Hidemasa
   Watanabe, Yasuhito
   Kinoshita, Yoshimi
   Kamada, Masaki
   Nodera, Hiroyuki
   Suzuki, Hidenori
   Komure, Osamu
   Matsuura, Shinya
   Kobatake, Keitaro
   Morimoto, Nobutoshi
   Abe, Koji
   Suzuki, Naoki
   Aoki, Masashi
   Kawata, Akihiro
   Hirai, Takeshi
   Kato, Takeo
   Ogasawara, Kazumasa
   Hirano, Asao
   Takumi, Toru
   Kusaka, Hirofumi
   Hagiwara, Koichi
   Kaji, Ryuji
   Kawakami, Hideshi
TI Mutations of optineurin in amyotrophic lateral sclerosis
SO NATURE
LA English
DT Article
ID open-angle glaucoma; myosin-vi; protein; gene; expression; complex; nemo
AB Amyotrophic lateral sclerosis (ALS) has its onset in middle age and is a progressive disorder characterized by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord(1). Most cases of ALS are sporadic, but about 10% are familial. Genes known to cause classic familial ALS (FALS) are superoxide dismutase 1 (SOD1)(2), ANG encoding angiogenin(3), TARDP encoding transactive response (TAR) DNA-binding protein TDP-43 (ref. 4) and fused in sarcoma/translated in liposarcoma (FUS, also known as TLS)(5,6). However, these genetic defects occur in only about 20-30% of cases of FALS, and most genes causing FALS are unknown. Here we show that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma (POAG)(7), in patients with ALS. We found three types of mutation of OPTN: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Analysis of cell transfection showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B (NF-kappa B), and the E478G mutation revealed a cytoplasmic distribution different from that of the wild type or a POAG mutation. A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic inclusions. Furthermore, TDP-43- or SOD1-positive inclusions of sporadic and SOD1 cases of ALS were also noticeably immunolabelled by anti-OPTN antibodies. Our findings strongly suggest that OPTN is involved in the pathogenesis of ALS. They also indicate that NF-kB inhibitors could be used to treat ALS and that transgenic mice bearing various mutations of OPTN will be relevant in developing new drugs for this disorder.
C1 [Maruyama, Hirofumi; Morino, Hiroyuki; Kamada, Masaki; Kawakami, Hideshi] Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
   [Ito, Hidefumi; Kinoshita, Yoshimi; Kusaka, Hirofumi] Kansai Med Univ, Dept Neurol, Moriguchi, Osaka 5708506, Japan.
   [Izumi, Yuishin; Kamada, Masaki; Nodera, Hiroyuki; Kaji, Ryuji] Univ Tokushima, Grad Sch, Dept Clin Neurosci, Tokushima 7708503, Japan.
   [Kato, Hidemasa] Saitama Med Univ, Res Ctr Genom Med, Div Dev Biol, Saitama 3501241, Japan.
   [Watanabe, Yasuhito] Hiroshima Univ, Grad Sch Biomed Sci, Lab Integrat Biosci, Hiroshima 7348553, Japan.
   [Suzuki, Hidenori] Hiroshima Bunkyo Womens Univ, Fac Human Sci, Hiroshima 7310295, Japan.
   [Komure, Osamu] S Osaka Neurosurg Hosp, Osakasayama 5890011, Japan.
   [Matsuura, Shinya] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Genet & Cell Biol, Hiroshima 7348553, Japan.
   [Kobatake, Keitaro] Kobatake Hosp, Dept Neurol, Fukuyama, Hiroshima 7201142, Japan.
   [Morimoto, Nobutoshi; Abe, Koji] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol, Okayama 7008558, Japan.
   [Suzuki, Naoki; Aoki, Masashi] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 9808574, Japan.
   [Kawata, Akihiro; Hirai, Takeshi] Tokyo Metropolitan Neurol Hosp, Dept Neurol, Tokyo 1830042, Japan.
   [Kato, Takeo] Yamagata Univ, Fac Med, Dept Neurol Haematol Metab Endocrinol & Diabetol, Yamagata 9909585, Japan.
   [Ogasawara, Kazumasa] Shiga Univ Med Sci, Sch Med, Dept Pathol, Otsu, Shiga 5202192, Japan.
   [Hirano, Asao] Montefiore Med Ctr, Dept Pathol, Div Neuropathol, New York, NY 10467 USA.
   [Hagiwara, Koichi] Saitama Med Univ, Dept Resp Med, Saitama 3500495, Japan.
C3 Hiroshima University; Kansai Medical University; Tokushima University; Saitama Medical University; Hiroshima University; Hiroshima University; Okayama University; Tohoku University; Tokyo Metropolitan Institute for Neuroscience; Yamagata University; Shiga University of Medical Science; Montefiore Medical Center; Saitama Medical University
RP Kawakami, H (corresponding author), Hiroshima Univ, Dept Epidemiol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
EM hkawakam@hiroshima-u.ac.jp
FU Ministry of Education, Science, and Culture of Japan; Smoking Research Foundation; Japan Science and Technology Agency, Core Research for Evolutional Science Technology; Grants-in-Aid for Scientific Research [21500336] Funding Source: KAKEN
NR 23
TC 1037
Z9 1234
U1 1
U2 131
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 223
EP U109
DI 10.1038/nature08971
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500036
PM 20428114
DA 2026-03-09
ER

PT J
AU Marois, C
   Zuckerman, B
   Konopacky, QM
   Macintosh, B
   Barman, T
AF Marois, Christian
   Zuckerman, B.
   Konopacky, Quinn M.
   Macintosh, Bruce
   Barman, Travis
TI Images of a fourth planet orbiting HR 8799
SO NATURE
LA English
DT Article
ID extrasolar giant planets; debris disk; brown dwarfs; system; spectroscopy; stars; luminosity
AB High-contrast near-infrared imaging of the nearby star HR 8799 has shown three giant planets(1). Such images were possible because of the wide orbits (>25 astronomical units, where 1 AU is the Earth-Sun distance) and youth (<100 Myr) of the imaged planets, which are still hot and bright as they radiate away gravitational energy acquired during their formation. An important area of contention in the exoplanet community is whether outer planets (>10 AU) more massive than Jupiter form by way of one-step gravitational instabilities(2) or, rather, through a two-step process involving accretion of a core followed by accumulation of a massive outer envelope composed primarily of hydrogen and helium(3). Here we report the presence of a fourth planet, interior to and of about the same mass as the other three. The system, with this additional planet, represents a challenge for current planet formation models as none of them can explain the in situ formation of all four planets. With its four young giant planets and known cold/warm debris belts(4), the HR 8799 planetary system is a unique laboratory in which to study the formation and evolution of giant planets at wide (>10 AU) separations.
C1 [Marois, Christian] Natl Res Council Canada, Herzberg Inst Astrophys, Victoria, BC V9E 2E7, Canada.
   [Zuckerman, B.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Konopacky, Quinn M.; Macintosh, Bruce] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Barman, Travis] Lowell Observ, Flagstaff, AZ 86001 USA.
C3 National Research Council Canada; University of California System; University of California Los Angeles; United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Marois, C (corresponding author), Natl Res Council Canada, Herzberg Inst Astrophys, 5071 W Saanich Rd, Victoria, BC V9E 2E7, Canada.
EM christian.marois@nrc-cnrc.gc.ca
FU US Department of Energy by LLNL; NSF Center for Adaptive Optics; NASA
NR 30
TC 739
Z9 840
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1080
EP 1083
DI 10.1038/nature09684
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800053
PM 21150902
DA 2026-03-09
ER

PT J
AU Bokoch, MP
   Zou, YZ
   Rasmussen, SGF
   Liu, CW
   Nygaard, R
   Rosenbaum, DM
   Fung, JJ
   Choi, HJ
   Thian, FS
   Kobilka, TS
   Puglisi, JD
   Weis, WI
   Pardo, L
   Prosser, RS
   Mueller, L
   Kobilka, BK
AF Bokoch, Michael P.
   Zou, Yaozhong
   Rasmussen, Soren G. F.
   Liu, Corey W.
   Nygaard, Rie
   Rosenbaum, Daniel M.
   Fung, Juan Jose
   Choi, Hee-Jung
   Thian, Foon Sun
   Kobilka, Tong Sun
   Puglisi, Joseph D.
   Weis, William I.
   Pardo, Leonardo
   Prosser, R. Scott
   Mueller, Luciano
   Kobilka, Brian K.
TI Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor
SO NATURE
LA English
DT Article
ID toggle switch model; crystal-structure; binding-site; beta(2)-adrenergic receptor; adrenergic-receptor; lysine residues; helix movement; activation; rhodopsin; recognition
AB G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs(1-5) have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.
C1 [Bokoch, Michael P.; Zou, Yaozhong; Rasmussen, Soren G. F.; Nygaard, Rie; Rosenbaum, Daniel M.; Fung, Juan Jose; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
   [Liu, Corey W.; Puglisi, Joseph D.] Stanford Univ, Stanford Magnet Resonance Lab, Sch Med, Stanford, CA 94305 USA.
   [Choi, Hee-Jung; Puglisi, Joseph D.; Weis, William I.] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
   [Pardo, Leonardo] Univ Autonoma Barcelona, Lab Med Computac, Unitat Bioestadist, E-08193 Barcelona, Spain.
   [Prosser, R. Scott] Univ Toronto, UTM, Dept Chem, Mississauga, ON L5L 1C6, Canada.
   [Mueller, Luciano] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA.
C3 Stanford University; Stanford University; Stanford University; Autonomous University of Barcelona; University of Toronto; University Toronto Mississauga; Bristol-Myers Squibb
RP Kobilka, BK (corresponding author), Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
EM kobilka@stanford.edu
FU National Institutes of Health [NS028471, GM56169]; Stanford Medical Scientist Training Program; Lundbeck Foundation; University of Copenhagen and 7TM Pharma; Instituto de Salud Carlos III; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER; Lundbeck Foundation [R37-2009-3457, R19-2008-2113] Funding Source: researchfish
NR 37
TC 417
Z9 485
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 JAN 7
PY 2010
VL 463
IS 7277
BP 108
EP U121
DI 10.1038/nature08650
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900040
PM 20054398
DA 2026-03-09
ER

PT J
AU Schlereth, A
   Möller, B
   Liu, WL
   Kientz, M
   Flipse, J
   Rademacher, EH
   Schmid, M
   Jürgens, G
   Weijers, D
AF Schlereth, Alexandra
   Moller, Barbara
   Liu, Weilin
   Kientz, Marika
   Flipse, Jacky
   Rademacher, Eike H.
   Schmid, Markus
   Juergens, Gerd
   Weijers, Dolf
TI MONOPTEROS controls embryonic root initiation by regulating a mobile transcription factor
SO NATURE
LA English
DT Article
ID auxin-response factors; loop-helix proteins; arabidopsis-thaliana; gene-expression; family; embryogenesis; activation; mutation; receptor; encodes
AB Acquisition of cell identity in plants relies strongly on positional information(1), hence cell-cell communication and inductive signalling are instrumental for developmental patterning. During Arabidopsis embryogenesis, an extra-embryonic cell is specified to become the founder cell of the primary root meristem, hypophysis, in response to signals from adjacent embryonic cells(2). The auxin-dependent transcription factor MONOPTEROS (MP) drives hypophysis specification by promoting transport of the hormone auxin from the embryo to the hypophysis precursor. However, auxin accumulation is not sufficient for hypophysis specification, indicating that additional MP-dependent signals are required(3). Here we describe the microarray-based isolation of MP target genes that mediate signalling from embryo to hypophysis. Of three direct transcriptional target genes, TARGET OF MP5 (TMO5) and TMO7 encode basic helix-loop-helix (bHLH) transcription factors that are expressed in the hypophysis-adjacent embryo cells, and are required and partially sufficient for MP-dependent root initiation. Importantly, the small TMO7 transcription factor moves from its site of synthesis in the embryo to the hypophysis precursor, thus representing a novel MP-dependent intercellular signal in embryonic root specification.
C1 [Schlereth, Alexandra; Kientz, Marika; Juergens, Gerd; Weijers, Dolf] Univ Tubingen, ZMBP, D-72076 Tubingen, Germany.
   [Moller, Barbara; Liu, Weilin; Flipse, Jacky; Rademacher, Eike H.; Weijers, Dolf] Wageningen Univ, Biochem Lab, NL-6703 HA Wageningen, Netherlands.
   [Schmid, Markus] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Wageningen University & Research; Max Planck Society
RP Jürgens, G (corresponding author), Univ Tubingen, ZMBP, Morgenstelle 3, D-72076 Tubingen, Germany.
EM gerd.juergens@zmbp.uni-tuebingen.de; dolf.weijers@wur.nl
FU Netherlands Organization for Scientific Research (NWO) [VIDI 864.06.012]; Deutsche Forschungsgemeinschaft (DFG) [SFB446]; Netherlands Proteomics Centre (NPC)
NR 36
TC 472
Z9 550
U1 1
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 913
EP U128
DI 10.1038/nature08836
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300042
PM 20220754
DA 2026-03-09
ER

PT J
AU Nakagawa, K
   Hirota, Y
   Sawada, N
   Yuge, N
   Watanabe, M
   Uchino, Y
   Okuda, N
   Shimomura, Y
   Suhara, Y
   Okano, T
AF Nakagawa, Kimie
   Hirota, Yoshihisa
   Sawada, Natsumi
   Yuge, Naohito
   Watanabe, Masato
   Uchino, Yuri
   Okuda, Naoko
   Shimomura, Yuka
   Suhara, Yoshitomo
   Okano, Toshio
TI Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme
SO NATURE
LA English
DT Article
ID dietary phylloquinone; gene; vitamin-k-2; conversion; accumulation; metabolism; mutations; tissue; rats
AB Vitamin K occurs in the natural world in several forms, including a plant form, phylloquinone (PK), and a bacterial form, menaquinones (MKs). In many species, including humans, PK is a minor constituent of hepatic vitamin K content, with most hepatic vitamin K content comprising long-chain MKs. Menaquinone-4 (MK-4) is ubiquitously present in extrahepatic tissues, with particularly high concentrations in the brain, kidney and pancreas of humans and rats(1-3). It has consistently been shown that PK is endogenously converted to MK-4 (refs 4-8). This occurs either directly within certain tissues or by interconversion to menadione (K-3), followed by prenylation to MK-4 (refs 9-12). No previous study has sought to identify the human enzyme responsible for MK-4 biosynthesis. Previously we provided evidence for the conversion of PK and K3 into MK-4 in mouse cerebra(13). However, the molecular mechanisms for these conversion reactions are unclear. Here we identify a human MK-4 biosynthetic enzyme. We screened the human genome database for prenylation enzymes and found UbiA prenyltransferase containing 1 (UBIAD1), a human homologue of Escherichia coli prenyltransferase menA. We found that short interfering RNA against the UBIAD1 gene inhibited the conversion of deuterium-labelled vitamin K derivatives into deuterium-labelled-MK-4 (MK-4-d(7)) in human cells. We confirmed that the UBIAD1 gene encodes an MK-4 biosynthetic enzyme through its expression and conversion of deuterium-labelled vitamin K derivatives into MK-4-d(7) in insect cells infected with UBIAD1 baculovirus. Converted MK-4-d(7) was chemically identified by H-2-NMR analysis. MK-4 biosynthesis by UBIAD1 was not affected by the vitamin K antagonist warfarin. UBIAD1 was localized in endoplasmic reticulum and ubiquitously expressed in several tissues of mice. Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin K intake and bone health.
C1 [Nakagawa, Kimie; Hirota, Yoshihisa; Sawada, Natsumi; Yuge, Naohito; Watanabe, Masato; Uchino, Yuri; Okuda, Naoko; Shimomura, Yuka; Suhara, Yoshitomo; Okano, Toshio] Kobe Pharmaceut Univ, Dept Hyg Sci, Higashinada Ku, Kobe, Hyogo 6588558, Japan.
C3 Kobe Pharmaceutical University
RP Okano, T (corresponding author), Kobe Pharmaceut Univ, Dept Hyg Sci, Higashinada Ku, 4-19-1 Motoyamakita Machi, Kobe, Hyogo 6588558, Japan.
EM t-okano@kobepharma-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology
NR 30
TC 268
Z9 329
U1 1
U2 69
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 117
EP +
DI 10.1038/nature09464
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900047
PM 20953171
DA 2026-03-09
ER

PT J
AU Shen, B
   Makley, DM
   Johnston, JN
AF Shen, Bo
   Makley, Dawn M.
   Johnston, Jeffrey N.
TI Umpolung reactivity in amide and peptide synthesis
SO NATURE
LA English
DT Article
ID nitroaldol henry reaction; chiral proton catalysis; staudinger ligation; enantioselective synthesis; oxidative amidation; acid-derivatives; bond formation; bronsted acid; cathepsin-k; aldehydes
AB The amide bond is one of nature's most common functional and structural elements, as the backbones of all natural peptides and proteins are composed of amide bonds. Amides are also present in many therapeutic small molecules. The construction of amide bonds using available methods relies principally on dehydrative approaches, although oxidative and radical-based methods are representative alternatives. In nearly every example, carbon and nitrogen bear electrophilic and nucleophilic character, respectively, during the carbon-nitrogen bond-forming step. Here we show that activation of amines and nitroalkanes with an electrophilic iodine source can lead directly to amide products. Preliminary observations support a mechanism in which the polarities of the two reactants are reversed (German, umpolung) during carbon-nitrogen bond formation relative to traditional approaches. The use of nitroalkanes as acyl anion equivalents provides a conceptually innovative approach to amide and peptide synthesis, and one that might ultimately provide for efficient peptide synthesis that is fully reliant on enantioselective methods.
C1 [Shen, Bo; Makley, Dawn M.; Johnston, Jeffrey N.] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Dept Chem, Nashville, TN 37235 USA.
C3 Vanderbilt University
RP Johnston, JN (corresponding author), Vanderbilt Univ, Vanderbilt Inst Chem Biol, Dept Chem, Nashville, TN 37235 USA.
EM jeffrey.n.johnston@vanderbilt.edu
FU Vanderbilt Institute of Chemical Biology; NIH [GM084333, T32 GM065086]; National Institute of General Medical Sciences [T32GM065086, R01GM063557] Funding Source: NIH RePORTER
NR 45
TC 278
Z9 297
U1 1
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1027
EP U82
DI 10.1038/nature09125
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900042
PM 20577205
DA 2026-03-09
ER

PT J
AU Richards-Dinger, K
   Stein, RS
   Toda, S
AF Richards-Dinger, Keith
   Stein, Ross S.
   Toda, Shinji
TI Decay of aftershock density with distance does not indicate triggering by dynamic stress
SO NATURE
LA English
DT Article
ID long-valley caldera; earthquake catalogs; seismicity; magnitude; california; completeness; constraints; landers
AB Resolving whether static(1-3) or dynamic(4-8) stress triggers most aftershocks and subsequent mainshocks is essential to understand earthquake interaction and to forecast seismic hazard(9). Felzer and Brodsky(10) examined the distance distribution of earthquakes occurring in the first five minutes after 2 <= M < 3 and 3 <= M < 4 mainshocks and found that their magnitude M >= 2 aftershocks showed a uniform power-law decay with slope -1.35 out to 50 km from the mainshocks. From this they argued that the distance decay could be explained only by dynamic triggering. Here we propose an alternative explanation for the decay, and subject their hypothesis to a series of tests, none of which it passes. At distances more than 300 m from the 2 <= M < 3 mainshocks, the seismicity decay 5 min before the mainshocks is indistinguishable from the decay five minutes afterwards, indicating that the mainshocks have no effect at distances outside their static triggering range. Omori temporal decay, the fundamental signature of aftershocks, is absent at distances exceeding 10 km from the mainshocks. Finally, the distance decay is found among aftershocks that occur before the arrival of the seismic wave front from the mainshock, which violates causality. We argue that Felzer and Brodsky(10) implicitly assume that the first of two independent aftershocks along a fault rupture triggers the second, and that the first of two shocks in a creep-or intrusion-driven swarm triggers the second, when this need not be the case.
C1 [Richards-Dinger, Keith] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Stein, Ross S.] US Geol Survey, Menlo Pk, CA 94025 USA.
   [Toda, Shinji] Kyoto Univ, Disaster Prevent Res Inst, Kyoto 6110011, Japan.
C3 University of California System; University of California Riverside; United States Department of the Interior; United States Geological Survey; Kyoto University
RP Richards-Dinger, K (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM keithrd@ucr.edu
NR 31
TC 92
Z9 101
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 583
EP U105
DI 10.1038/nature09402
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100037
PM 20882015
DA 2026-03-09
ER

PT J
AU Akiyoshi, B
   Sarangapani, KK
   Powers, AF
   Nelson, CR
   Reichow, SL
   Arellano-Santoyo, H
   Gonen, T
   Ranish, JA
   Asbury, CL
   Biggins, S
AF Akiyoshi, Bungo
   Sarangapani, Krishna K.
   Powers, Andrew F.
   Nelson, Christian R.
   Reichow, Steve L.
   Arellano-Santoyo, Hugo
   Gonen, Tamir
   Ranish, Jeffrey A.
   Asbury, Charles L.
   Biggins, Sue
TI Tension directly stabilizes reconstituted kinetochore-microtubule attachments
SO NATURE
LA English
DT Article
ID single kinesin molecules; saccharomyces-cerevisiae; budding yeast; mitotic spindle; protein-kinase; catch bonds; aurora b; complex; mitosis; force
AB Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes(1,2). Accurate segregation depends on selective stabilization of correct 'bi-oriented' kinetochore-microtubule attachments, which come under tension as the result of opposing forces exerted by microtubules(3). Tension is thought to stabilize these bi-oriented attachments indirectly, by suppressing the destabilizing activity of a kinase, Aurora B-4,B-5. However, a complete mechanistic understanding of the role of tension requires reconstitution of kinetochore-microtubule attachments for biochemical and biophysical analyses in vitro. Here we show that native kinetochore particles retaining the majority of kinetochore proteins can be purified from budding yeast and used to reconstitute dynamic microtubule attachments. Individual kinetochore particles maintain load-bearing associations with assembling and disassembling ends of single microtubules for >30 min, providing a close match to the persistent coupling seen in vivo between budding yeast kinetochores and single microtubules(6). Moreover, tension increases the lifetimes of the reconstituted attachments directly, through a catch bond-like mechanism that does not require Aurora B7-10. On the basis of these findings, we propose that tension selectively stabilizes proper kinetochore-microtubule attachments in vivo through a combination of direct mechanical stabilization and tension-dependent phosphoregulation.
C1 [Akiyoshi, Bungo; Nelson, Christian R.; Arellano-Santoyo, Hugo; Biggins, Sue] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Akiyoshi, Bungo; Arellano-Santoyo, Hugo] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA.
   [Sarangapani, Krishna K.; Powers, Andrew F.; Arellano-Santoyo, Hugo; Asbury, Charles L.] Univ Washington, Dept Physiol Biophys, Seattle, WA 98195 USA.
   [Reichow, Steve L.; Gonen, Tamir] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Gonen, Tamir] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Ranish, Jeffrey A.] Inst Syst Biol, Seattle, WA 98103 USA.
C3 Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Institute for Systems Biology (ISB)
RP Biggins, S (corresponding author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
EM casbury@u.washington.edu; sbiggins@fhcrc.org
FU NSF IGERT [DGE-0504573]; NIH [T32GM07270, T32HL007312, GM078069, GM064386]; NCI Cancer Center [CA015704]; NIGMS [PM50 GM076547, R01GM79373]; Searle Scholar Award [06-L-111]; Packard Fellowship for Science and Engineering [2006-30521]; National Cancer Institute [P30CA015704] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM064386] Funding Source: NIH RePORTER
NR 39
TC 367
Z9 462
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 576
EP U255
DI 10.1038/nature09594
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200045
PM 21107429
DA 2026-03-09
ER

PT J
AU Reynolds, LE
   Watson, AR
   Baker, M
   Jones, TA
   D'Amico, G
   Robinson, SD
   Joffre, C
   Garrido-Urbani, S
   Rodriguez-Manzaneque, JC
   Martino-Echarri, E
   Aurrand-Lions, M
   Sheer, D
   Dagna-Bricarelli, F
   Nizetic, D
   McCabe, CJ
   Turnell, AS
   Kermorgant, S
   Imhof, BA
   Adams, R
   Fisher, EMC
   Tybulewicz, VLJ
   Hart, IR
   Hodivala-Dilke, KM
AF Reynolds, Louise E.
   Watson, Alan R.
   Baker, Marianne
   Jones, Tania A.
   D'Amico, Gabriela
   Robinson, Stephen D.
   Joffre, Carine
   Garrido-Urbani, Sarah
   Carlos Rodriguez-Manzaneque, Juan
   Martino-Echarri, Estefania
   Aurrand-Lions, Michel
   Sheer, Denise
   Dagna-Bricarelli, Franca
   Nizetic, Dean
   McCabe, Christopher J.
   Turnell, Andrew S.
   Kermorgant, Stephanie
   Imhof, Beat A.
   Adams, Ralf
   Fisher, Elizabeth M. C.
   Tybulewicz, Victor L. J.
   Hart, Ian R.
   Hodivala-Dilke, Kairbaan M.
TI Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome
SO NATURE
LA English
DT Article
ID endothelial-cell proliferation; growth; mice; apoptosis; vegf; ets2; adamts-1; cadherin; dscr1; gene
AB Down's syndrome (DS) is a genetic disorder caused by full or partial trisomy of human chromosome 21 and presents with many clinical phenotypes including a reduced incidence of solid tumours(1,2). Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref. 3) or DS candidate region 1 (DSCR1) genes(4) (a previously known suppressor of angiogenesis(5,6)) is sufficient to inhibit tumour growth. Here we use the Tc1 transchromosomic mouse model of DS(7) to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses roughly 81% of Hsa21 genes but not the human DSCR1 region. We transplanted B16F0 and Lewis lung carcinoma tumour cells into Tc1 mice and showed that growth of these tumours was substantially reduced compared with wild-type littermate controls. Furthermore, tumour angiogenesis was significantly repressed in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS1(8,9) and ERG(10)) and novel endothelial cell-specific genes(11), never previously shown to be involved in angiogenesis (JAM-B(12) and PTTG1IP), that, when overexpressed, are responsible for inhibiting angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis, explaining the reduced tumour growth in DS. Furthermore, we expect that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will permit the identification of other endothelium-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients.
C1 [Reynolds, Louise E.; Watson, Alan R.; Baker, Marianne; D'Amico, Gabriela; Robinson, Stephen D.; Hodivala-Dilke, Kairbaan M.] Queen Mary Univ London, John Vane Sci Ctr, Adhes & Angiogenesis Lab, Barts Inst Canc,Barts & London Sch Med & Dent, London EC1M 6BQ, England.
   [Joffre, Carine; Kermorgant, Stephanie; Hart, Ian R.] Queen Mary Univ London, John Vane Sci Ctr, Tumor Biol Ctr, Inst Canc,Barts & London Sch Med & Dent, London EC1M 6BQ, England.
   [Jones, Tania A.; Sheer, Denise] Queen Mary Univ London, Ctr Neurosci, Barts & London Sch Med & Dent, Inst Cell & Mol Sci, London E1 2AD, England.
   [Nizetic, Dean] Queen Mary Univ London, Paediat Ctr, Barts & London Sch Med & Dent, Inst Cell & Mol Sci, London E1 2AD, England.
   [Garrido-Urbani, Sarah; Imhof, Beat A.] Univ Geneva, Sch Med CMU, Dept Pathol & Immunol, Ctr Med Univ, CH-1211 Geneva, Switzerland.
   [Carlos Rodriguez-Manzaneque, Juan; Martino-Echarri, Estefania] GENYO, Granada, Spain.
   [Aurrand-Lions, Michel] INSERM, F-13009 Marseille, France.
   [Dagna-Bricarelli, Franca] Galliera Hosp, Inst Human Genet, I-16128 Genoa, Italy.
   [McCabe, Christopher J.] Univ Birmingham, Sch Clin & Expt Med, Birmingham B15 2TT, W Midlands, England.
   [Turnell, Andrew S.] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England.
   [Adams, Ralf] Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
   [Fisher, Elizabeth M. C.] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.
   [Tybulewicz, Victor L. J.] Natl Inst Med Res, MRC, Div Immune Cell Biol, London NW7 1AA, England.
C3 University of London; Queen Mary University London; University of London; Queen Mary University London; University of London; Queen Mary University London; University of London; Queen Mary University London; University of Geneva; Institut National de la Sante et de la Recherche Medicale (Inserm); Ente Ospedaliero Ospedali Galliera; University of Birmingham; University of Birmingham; Max Planck Society; University of London; University College London; MRC National Institute for Medical Research
RP Reynolds, LE (corresponding author), Queen Mary Univ London, John Vane Sci Ctr, Adhes & Angiogenesis Lab, Barts Inst Canc,Barts & London Sch Med & Dent, Charterhouse Sq, London EC1M 6BQ, England.
EM l.reynolds@qmul.ac.uk
FU Cancer Research UK [12007, A3585, A12007] Funding Source: Medline; Medical Research Council [G0501003, G0501003(75694), G0901609, MC_U117527252, U.1175.02.001.00001(60485), G0601056] Funding Source: Medline; Wellcome Trust [080174] Funding Source: Medline; Cancer Research UK [12007] Funding Source: researchfish; Medical Research Council [MC_U117527252, G0501003, G0601056] Funding Source: researchfish; MRC [G0501003, G0601056, MC_U117527252] Funding Source: UKRI
NR 29
TC 101
Z9 113
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 10
PY 2010
VL 465
IS 7299
BP 813
EP U13
DI 10.1038/nature09106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800052
PM 20535211
DA 2026-03-09
ER

PT J
AU Surolia, I
   Pirnie, SP
   Chellappa, V
   Taylor, KN
   Cariappa, A
   Moya, J
   Liu, H
   Bell, DW
   Driscoll, DR
   Diederichs, S
   Haider, K
   Netravali, I
   Le, S
   Elia, R
   Dow, E
   Lee, A
   Freudenberg, J
   De Jager, PL
   Chretien, Y
   Varki, A
   MacDonald, ME
   Gillis, T
   Behrens, TW
   Bloch, D
   Collier, D
   Korzenik, J
   Podolsky, DK
   Hafler, D
   Murali, M
   Sands, B
   Stone, JH
   Gregersen, PK
   Pillai, S
AF Surolia, Ira
   Pirnie, Stephan P.
   Chellappa, Vasant
   Taylor, Kendra N.
   Cariappa, Annaiah
   Moya, Jesse
   Liu, Haoyuan
   Bell, Daphne W.
   Driscoll, David R.
   Diederichs, Sven
   Haider, Khaleda
   Netravali, Ilka
   Le, Sheila
   Elia, Roberto
   Dow, Ethan
   Lee, Annette
   Freudenberg, Jan
   De Jager, Philip L.
   Chretien, Yves
   Varki, Ajit
   MacDonald, Marcy E.
   Gillis, Tammy
   Behrens, Timothy W.
   Bloch, Donald
   Collier, Deborah
   Korzenik, Joshua
   Podolsky, Daniel K.
   Hafler, David
   Murali, Mandakolathur
   Sands, Bruce
   Stone, John H.
   Gregersen, Peter K.
   Pillai, Shiv
TI Functionally defective germline variants of sialic acid acetylesterase in autoimmunity
SO NATURE
LA English
DT Article
ID mutations; disease; marker
AB Sialic acid acetylesterase (SIAE) is an enzyme that negatively regulates B lymphocyte antigen receptor signalling and is required for the maintenance of immunological tolerance in mice(1,2). Heterozygous loss-of-function germline rare variants and a homozygous defective polymorphic variant of SIAE were identified in 24/923 subjects of European origin with relatively common autoimmune disorders and in 2/648 controls of European origin. All heterozygous loss-of-function SIAE mutations tested were capable of functioning in a dominant negative manner. Ahomozygous secretion-defective polymorphic variant of SIAE was catalytically active, lacked the ability to function in a dominant negative manner, and was seen in eight autoimmune subjects but in no control subjects. The odds ratio for inheriting defective SIAE alleles was 8.6 in all autoimmune subjects, 8.3 in subjects with rheumatoid arthritis, and 7.9 in subjects with type I diabetes. Functionally defective SIAE rare and polymorphic variants represent a strong genetic link to susceptibility in relatively common human autoimmune disorders.
C1 [Surolia, Ira; Pirnie, Stephan P.; Chellappa, Vasant; Taylor, Kendra N.; Cariappa, Annaiah; Moya, Jesse; Liu, Haoyuan; Bell, Daphne W.; Driscoll, David R.; Diederichs, Sven; Haider, Khaleda; Netravali, Ilka; Le, Sheila; Elia, Roberto; Dow, Ethan; Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
   [Lee, Annette; Freudenberg, Jan; Gregersen, Peter K.] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA.
   [De Jager, Philip L.; Hafler, David] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA.
   [De Jager, Philip L.; Hafler, David] Partners Ctr Personalized Genet Med, Boston, MA 02115 USA.
   [De Jager, Philip L.; Hafler, David] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [De Jager, Philip L.; Hafler, David] MIT, Cambridge, MA 02142 USA.
   [Chretien, Yves] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
   [Varki, Ajit] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Varki, Ajit] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [MacDonald, Marcy E.; Gillis, Tammy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Behrens, Timothy W.] Genentech Inc, San Francisco, CA 94080 USA.
   [Bloch, Donald; Collier, Deborah; Stone, John H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol, Boston, MA 02114 USA.
   [Korzenik, Joshua; Podolsky, Daniel K.; Sands, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
   [Murali, Mandakolathur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Immunol Lab, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Northwell Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; University of California System; University of California San Diego; University of California System; University of California San Diego; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Roche Holding; Genentech; Roche Holding USA; 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 Medical Affiliates; Massachusetts General Hospital; Harvard Medical School
RP Pillai, S (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
EM pillai@helix.mgh.harvard.edu
FU Alliance for Lupus Research; Center for the Study of Inflammatory Bowel Disease at MGH; NIH [AI 064930, AI 076505, AR 058481, NS 32765]; NIH for NARAC [AR 044422, AR 022263]; MADGC [AI 068759]; National Human Genome Research Institute [ZIAHG200338] Funding Source: NIH RePORTER
NR 16
TC 140
Z9 162
U1 1
U2 25
PU 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 8
PY 2010
VL 466
IS 7303
BP 243
EP U118
DI 10.1038/nature09115
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800038
PM 20555325
DA 2026-03-09
ER

PT J
AU Kawabata, KS
   Maeda, K
   Nomoto, K
   Taubenberger, S
   Tanaka, M
   Deng, J
   Pian, E
   Hattori, T
   Itagaki, K
AF Kawabata, K. S.
   Maeda, K.
   Nomoto, K.
   Taubenberger, S.
   Tanaka, M.
   Deng, J.
   Pian, E.
   Hattori, T.
   Itagaki, K.
TI A massive star origin for an unusual helium-rich supernova in an elliptical galaxy
SO NATURE
LA English
DT Article
ID core-collapse supernovae; nebular spectra; light curves; sn 2002ap; evolution; nucleosynthesis; 1994i; explosion; stellar; 1998bw
AB The unusual helium-rich (type Ib) supernova SN 2005E is distinguished from all supernovae hitherto observed by its faint and rapidly fading light curve, prominent calcium lines in late-phase spectra and lack of any mark of recent star formation near the supernova location. These properties are claimed(1) to be explained by a helium detonation in a thin surface layer of an accreting white dwarf. Here we report that the observed properties of SN 2005cz, which appeared in an elliptical galaxy, resemble those of SN 2005E. We argue that these properties are best explained by a core-collapse supernova at the low-mass end (8-12 solar masses) of the range of massive stars that explode(2). Such a low-mass progenitor lost its hydrogen-rich envelope through binary interaction, had very thin oxygen-rich and silicon-rich layers above the collapsing core, and accordingly ejected a very small amount of radioactive (56)Ni and oxygen. Although the host galaxy NGC 4589 is an elliptical, some studies have revealed evidence of recent star-formation activity(3), consistent with the core-collapse model.
C1 [Kawabata, K. S.] Hiroshima Univ, Hiroshima Astrophys Sci Ctr, Hiroshima 7398526, Japan.
   [Maeda, K.; Nomoto, K.; Tanaka, M.] Univ Tokyo, IPMU, Chiba 2778583, Japan.
   [Taubenberger, S.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Tanaka, M.] Univ Tokyo, Sch Sci, Dept Astron, Bunkyo Ku, Tokyo 1130033, Japan.
   [Deng, J.] CAS, Natl Astron Observ, Beijing 100012, Peoples R China.
   [Pian, E.] INAF Osservatorio Astron Trieste, I-3413 Trieste, Italy.
   [Hattori, T.] Natl Inst Nat Sci, Natl Astron Observ Japan, Subaru Telescope, Hilo, HI 96720 USA.
   [Itagaki, K.] Itagaki Astron Observ, Teppo, Yamagata 9902492, Japan.
C3 Hiroshima University; University of Tokyo; Max Planck Society; University of Tokyo; Chinese Academy of Sciences; National Astronomical Observatory, CAS; National Institutes of Natural Sciences (NINS) - Japan; National Astronomical Observatory of Japan (NAOJ)
RP Kawabata, KS (corresponding author), Hiroshima Univ, Hiroshima Astrophys Sci Ctr, 1-3-1 Kagamiyama, Hiroshima 7398526, Japan.
EM kawabtkj@hiroshima-u.ac.jp
FU World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan; Japan Society for the Promotion of Science (JSPS); MEXT; NSFC; 973 Program of China; Grants-in-Aid for Scientific Research [19047003] Funding Source: KAKEN
NR 29
TC 73
Z9 81
U1 0
U2 14
PU 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 20
PY 2010
VL 465
IS 7296
BP 326
EP 328
DI 10.1038/nature09055
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200035
PM 20485430
DA 2026-03-09
ER

PT J
AU Aoki, SK
   Diner, EJ
   de Roodenbeke, CT
   Burgess, BR
   Poole, SJ
   Braaten, BA
   Jones, AM
   Webb, JS
   Hayes, CS
   Cotter, PA
   Low, DA
AF Aoki, Stephanie K.
   Diner, Elie J.
   de Roodenbeke, Claire t'Kint
   Burgess, Brandt R.
   Poole, Stephen J.
   Braaten, Bruce A.
   Jones, Allison M.
   Webb, Julia S.
   Hayes, Christopher S.
   Cotter, Peggy A.
   Low, David A.
TI A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria
SO NATURE
LA English
DT Article
ID iii secretion system; escherichia-coli; inhibition; growth
AB Bacteria have developed mechanisms to communicate and compete with one another in diverse environments(1). A new form of intercellular communication, contact-dependent growth inhibition (CDI), was discovered recently in Escherichia coli(2). CDI is mediated by the CdiB/CdiA two-partner secretion (TPS) system. CdiB facilitates secretion of the CdiA 'exoprotein' onto the cell surface. An additional small immunity protein (CdiI) protects CDI+ cells from autoinhibition(2,3). The mechanisms by which CDI blocks cell growth and by which CdiI counteracts this growth arrest are unknown. Moreover, the existence of CDI activity in other bacteria has not been explored. Here we show that the CDI growth inhibitory activity resides within the carboxy-terminal region of CdiA (CdiA-CT), and that CdiI binds and inactivates cognate CdiA-CT, but not heterologous CdiA-CT. Bioinformatic and experimental analyses show that multiple bacterial species encode functional CDI systems with high sequence variability in the CdiA-CT and CdiI coding regions. CdiA-CT heterogeneity implies that a range of toxic activities are used during CDI. Indeed, CdiA-CTs from uropathogenic E. coli and the plant pathogen Dickeya dadantii have different nuclease activities, each providing a distinct mechanism of growth inhibition. Finally, we show that bacteria lacking the CdiA-CT and CdiI coding regions are unable to compete with isogenic wild-type CDI+ cells both in laboratory media and on a eukaryotic host. Taken together, these results suggest that CDI systems constitute an intricate immunity network with an important function in bacterial competition.
C1 [Aoki, Stephanie K.; de Roodenbeke, Claire t'Kint; Burgess, Brandt R.; Poole, Stephen J.; Braaten, Bruce A.; Jones, Allison M.; Webb, Julia S.; Hayes, Christopher S.; Cotter, Peggy A.; Low, David A.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   [Diner, Elie J.; Hayes, Christopher S.; Cotter, Peggy A.; Low, David A.] Univ Calif Santa Barbara, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara
RP Low, DA (corresponding author), Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
EM low@lifesci.ucsb.edu
FU National Science Foundation [0642052]; Tri-Counties Blood Bank; National Institutes of Health [GM078634, AI043986, U54AI065359]; United States Department of Agriculture Cooperative State Research, Education, and Extension Service [2001-52100-11316]; Direct For Biological Sciences [0642052] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience [0642052] Funding Source: National Science Foundation
NR 14
TC 258
Z9 338
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 439
EP 442
DI 10.1038/nature09490
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100043
PM 21085179
DA 2026-03-09
ER

PT J
AU Paragi, Z
   Taylor, GB
   Kouveliotou, C
   Granot, J
   Ramirez-Ruiz, E
   Bietenholz, M
   van der Horst, AJ
   Pidopryhora, Y
   van Langevelde, HJ
   Garrett, MA
   Szomoru, A
   Argo, MK
   Bourke, S
   Paczynski, B
AF Paragi, Z.
   Taylor, G. B.
   Kouveliotou, C.
   Granot, J.
   Ramirez-Ruiz, E.
   Bietenholz, M.
   van der Horst, A. J.
   Pidopryhora, Y.
   van Langevelde, H. J.
   Garrett, M. A.
   Szomoru, A.
   Argo, M. K.
   Bourke, S.
   Paczynski, B.
TI A mildly relativistic radio jet from the otherwise normal type Ic supernova 2007gr
SO NATURE
LA English
DT Article
ID gamma-ray bursts; sn 2007gr; emission
AB The class of type Ic supernovae have drawn increasing attention since 1998 owing to their sparse association (only four so far) with long duration gamma-ray bursts (GRBs)(1-4). Although both phenomena originate from the core collapse of a massive star, supernovae emit mostly at optical wavelengths, whereas GRBs emit mostly in soft gamma-rays or hard X-rays. Though the GRB central engine generates ultra-relativistic jets, which beam the early emission into a narrow cone, no relativistic outflows have hitherto been found in type Ib/c supernovae explosions, despite theoretical expectations(5-7) and searches(8). Here we report radio (interferometric) observations that reveal a mildly relativistic expansion in a nearby type Ic supernova, SN 2007gr. Using two observational epochs 60 days apart, we detect expansion of the source and establish a conservative lower limit for the average apparent expansion velocity of 0.6c. Independently, a second mildly relativistic supernova has been reported(9). Contrary to the radio data, optical observations(10-13) of SN 2007gr indicate a typical type Ic supernova with ejecta velocities similar to 6,000 km s(-1), much lower than in GRB-associated supernovae. We conclude that in SN 2007gr a small fraction of the ejecta produced a low-energy mildly relativistic bipolar radio jet, while the bulk of the ejecta were slower and, as shown by optical spectropolarimetry(14), mildly aspherical.
C1 [Paragi, Z.; Pidopryhora, Y.; van Langevelde, H. J.; Szomoru, A.; Bourke, S.] JIVE, NL-7990 AA Dwingeloo, Netherlands.
   [Paragi, Z.] MTA Res Grp Phys Geodesy & Geodynam, H-1521 Budapest, Hungary.
   [Taylor, G. B.] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA.
   [Kouveliotou, C.; van der Horst, A. J.] NASA, George C Marshall Space Flight Ctr, Space Sci Off, Huntsville, AL 35812 USA.
   [Granot, J.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Ramirez-Ruiz, E.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Bietenholz, M.] Hartebeesthoek Radio Observ, ZA-1740 Krugersdorp, South Africa.
   [Bietenholz, M.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Garrett, M. A.] Netherlands Inst Radio Astron ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [van Langevelde, H. J.; Garrett, M. A.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Garrett, M. A.] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [Argo, M. K.] Curtin Univ Technol, Curtin Inst Radio Astron, Perth, WA 6845, Australia.
C3 University of New Mexico; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; University of Hertfordshire; University of California System; University of California Santa Cruz; National Research Foundation - South Africa; Hartebeesthoek Radio Astronomy Observatory; York University - Canada; Leiden University; Leiden University - Excl LUMC; Swinburne University of Technology; Curtin University
RP Paragi, Z (corresponding author), JIVE, Postbus 2, NL-7990 AA Dwingeloo, Netherlands.
EM zparagi@jive.nl
FU Hungarian Scientific Research Fund (OTKA) [K72515]; EC [02662]; national research councils; Netherlands Foundation for Scientific Research (NWO); European Community [R113CT 2003 5058187]; Royal Society; NASA; Science and Technology Facilities Council [ST/G002630/1] Funding Source: researchfish; STFC [ST/G002630/1] Funding Source: UKRI
NR 17
TC 46
Z9 50
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 516
EP 518
DI 10.1038/nature08713
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100045
PM 20110996
DA 2026-03-09
ER

PT J
AU Demorest, PB
   Pennucci, T
   Ransom, SM
   Roberts, MSE
   Hessels, JWT
AF Demorest, P. B.
   Pennucci, T.
   Ransom, S. M.
   Roberts, M. S. E.
   Hessels, J. W. T.
TI A two-solar-mass neutron star measured using Shapiro delay
SO NATURE
LA English
DT Article
ID millisecond pulsar; mass; binary; equation; matter
AB Neutron stars are composed of the densest form of matter known to exist in our Universe, the composition and properties of which are still theoretically uncertain. Measurements of the masses or radii of these objects can strongly constrain the neutron star matter equation of state and rule out theoretical models of their composition(1,2). The observed range of neutron star masses, however, has hitherto been too narrow to rule out many predictions of 'exotic' non-nucleonic components(3-6). The Shapiro delay is a general-relativistic increase in light travel time through the curved space-time near a massive body(7). For highly inclined (nearly edge-on) binary millisecond radio pulsar systems, this effect allows us to infer the masses of both the neutron star and its binary companion to high precision(8,9). Here we present radio timing observations of the binary millisecond pulsar J1614-2230(10,11) that show a strong Shapiro delay signature. We calculate the pulsar mass to be (1.97 +/- 0.04) M(circle dot), which rules out almost all currently proposed(2-5) hyperon or boson condensate equations of state (M(circle dot), solar mass). Quark matter can support a star this massive only if the quarks are strongly interacting and are therefore not 'free' quarks(12).
C1 [Demorest, P. B.; Ransom, S. M.] Natl Radio Astron Observ, Charlottesville, VA 22093 USA.
   [Pennucci, T.] Univ Virginia, Dept Astron, Charlottesville, VA 22094 USA.
   [Roberts, M. S. E.] Eureka Sci Inc, Oakland, CA 94602 USA.
   [Hessels, J. W. T.] Netherlands Inst Radio Astron ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Hessels, J. W. T.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 SJ Amsterdam, Netherlands.
C3 National Radio Astronomy Observatory (NRAO); University of Virginia; Eureka Scientific; University of Amsterdam
RP Demorest, PB (corresponding author), Natl Radio Astron Observ, 520 Edgemont Rd, Charlottesville, VA 22093 USA.
EM pdemores@nrao.edu
FU Office Of Internatl Science &Engineering; Office Of The Director [0968296] Funding Source: National Science Foundation
NR 29
TC 3234
Z9 3534
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 28
PY 2010
VL 467
IS 7319
BP 1081
EP 1083
DI 10.1038/nature09466
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600041
PM 20981094
DA 2026-03-09
ER

PT J
AU Atwell, S
   Huang, YS
   Vilhjálmsson, BJ
   Willems, G
   Horton, M
   Li, Y
   Meng, DZ
   Platt, A
   Tarone, AM
   Hu, TT
   Jiang, R
   Muliyati, NW
   Zhang, X
   Amer, MA
   Baxter, I
   Brachi, B
   Chory, J
   Dean, C
   Debieu, M
   de Meaux, J
   Ecker, JR
   Faure, N
   Kniskern, JM
   Jones, JDG
   Michael, T
   Nemri, A
   Roux, F
   Salt, DE
   Tang, CL
   Todesco, M
   Traw, MB
   Weigel, D
   Marjoram, P
   Borevitz, JO
   Bergelson, J
   Nordborg, M
AF Atwell, Susanna
   Huang, Yu S.
   Vilhjalmsson, Bjarni J.
   Willems, Glenda
   Horton, Matthew
   Li, Yan
   Meng, Dazhe
   Platt, Alexander
   Tarone, Aaron M.
   Hu, Tina T.
   Jiang, Rong
   Muliyati, N. Wayan
   Zhang, Xu
   Amer, Muhammad Ali
   Baxter, Ivan
   Brachi, Benjamin
   Chory, Joanne
   Dean, Caroline
   Debieu, Marilyne
   de Meaux, Juliette
   Ecker, Joseph R.
   Faure, Nathalie
   Kniskern, Joel M.
   Jones, Jonathan D. G.
   Michael, Todd
   Nemri, Adnane
   Roux, Fabrice
   Salt, David E.
   Tang, Chunlao
   Todesco, Marco
   Traw, M. Brian
   Weigel, Detlef
   Marjoram, Paul
   Borevitz, Justin O.
   Bergelson, Joy
   Nordborg, Magnus
TI Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines
SO NATURE
LA English
DT Article
ID flowering-locus-c; linkage disequilibrium; population-structure; model; diseases; protein; frigida; time
AB Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases(1,2), genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits(3). Our results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms.
C1 [Marjoram, Paul; Nordborg, Magnus] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
   [Horton, Matthew; Li, Yan; Muliyati, N. Wayan; Zhang, Xu; Kniskern, Joel M.; Roux, Fabrice; Traw, M. Brian; Borevitz, Justin O.; Bergelson, Joy] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Baxter, Ivan] Bindley Biosci Ctr, W Lafayette, IN 47907 USA.
   [Salt, David E.] Purdue Univ, W Lafayette, IN 47907 USA.
   [Brachi, Benjamin; Faure, Nathalie; Roux, Fabrice] Univ Sci & Technol Lille 1, CNRS, UMR 8016, Lab Genet & Evolut Populat Vegetales, F-59655 Villeneuve Dascq, France.
   [Chory, Joanne] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
   [Chory, Joanne; Ecker, Joseph R.; Michael, Todd] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Dean, Caroline] John Innes Ctr Plant Sci Res, Dept Cell & Dev Biol, Norwich NR4 7UH, Norfolk, England.
   [Debieu, Marilyne; de Meaux, Juliette] Max Planck Inst Plant Breeding Res, D-50829 Cologne, Germany.
   [Jones, Jonathan D. G.; Nemri, Adnane] Sainsbury Lab, Norwich NR4 7UH, Norfolk, England.
   [Todesco, Marco; Weigel, Detlef] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany.
   [Nordborg, Magnus] Gregor Mendel Inst, A-1030 Vienna, Austria.
C3 University of Southern California; University of Chicago; Purdue University System; Purdue University; Purdue University System; Purdue University; Centre National de la Recherche Scientifique (CNRS); Universite de Lille; Howard Hughes Medical Institute; Salk Institute; Salk Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Max Planck Society; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Max Planck Society; Austrian Academy of Sciences; Vienna Biocenter (VBC); Gregor Mendel Institute of Molecular Plant Biology (GMI)
RP Nordborg, M (corresponding author), Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
EM magnus.nordborg@gmi.oeaw.ac.at
FU US National Science Foundation (NSF) [DEB-0519961, DEB-0723935, MCB-0603515]; US National Institutes of Health (NIH) [GM073822, GM057994, GM078536, P42ES007373, GM62932]; Dropkin Foundation; Max Planck Society; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft (DFG) [SFB 680]; Marie Curie [220833]; BBSRC [BBS/E/J/000CA355] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/J/000CA355] Funding Source: researchfish
NR 28
TC 1346
Z9 1594
U1 7
U2 577
PU NATURE PUBLISHING 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 3
PY 2010
VL 465
IS 7298
BP 627
EP 631
DI 10.1038/nature08800
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000044
PM 20336072
DA 2026-03-09
ER

PT J
AU Kaida, D
   Berg, MG
   Younis, I
   Kasim, M
   Singh, LN
   Wan, L
   Dreyfuss, G
AF Kaida, Daisuke
   Berg, Michael G.
   Younis, Ihab
   Kasim, Mumtaz
   Singh, Larry N.
   Wan, Lili
   Dreyfuss, Gideon
TI U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
SO NATURE
LA English
DT Article
ID disease gene-product; mammalian-cells; minor class; spliceosome; complex; smn; transcription; deficiency; insights
AB In eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockdown in HeLa cells, and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. In addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation in numerous pre-mRNAs at cryptic polyadenylation signals, frequently in introns near (<5 kilobases) the start of the transcript. This did not occur when splicing was inhibited with U2 snRNA antisense morpholino oligonucleotide or the U2-snRNP-inactivating drug spliceostatin A unless U1 antisense morpholino oligonucleotide was also included. We further show that U1 snRNA-pre-mRNA base pairing was required to suppress premature cleavage and polyadenylation from nearby cryptic polyadenylation signals located in introns. These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance.
C1 [Kaida, Daisuke; Berg, Michael G.; Younis, Ihab; Kasim, Mumtaz; Singh, Larry N.; Wan, Lili; Dreyfuss, Gideon] Univ Penn, Sch Med, Howard Hughes Med Inst, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Howard Hughes Medical Institute
RP Dreyfuss, G (corresponding author), Univ Penn, Sch Med, Howard Hughes Med Inst, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
EM gdreyfuss@hhmi.upenn.edu
FU Association Francaise Contre les Myopathies (AFM)
NR 42
TC 517
Z9 634
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 664
EP U81
DI 10.1038/nature09479
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700034
PM 20881964
DA 2026-03-09
ER

PT J
AU Filippakopoulos, P
   Qi, J
   Picaud, S
   Shen, Y
   Smith, WB
   Fedorov, O
   Morse, EM
   Keates, T
   Hickman, TT
   Felletar, I
   Philpott, M
   Munro, S
   McKeown, MR
   Wang, YC
   Christie, AL
   West, N
   Cameron, MJ
   Schwartz, B
   Heightman, TD
   La Thangue, N
   French, CA
   Wiest, O
   Kung, AL
   Knapp, S
   Bradner, JE
AF Filippakopoulos, Panagis
   Qi, Jun
   Picaud, Sarah
   Shen, Yao
   Smith, William B.
   Fedorov, Oleg
   Morse, Elizabeth M.
   Keates, Tracey
   Hickman, Tyler T.
   Felletar, Ildiko
   Philpott, Martin
   Munro, Shonagh
   McKeown, Michael R.
   Wang, Yuchuan
   Christie, Amanda L.
   West, Nathan
   Cameron, Michael J.
   Schwartz, Brian
   Heightman, Tom D.
   La Thangue, Nicholas
   French, Christopher A.
   Wiest, Olaf
   Kung, Andrew L.
   Knapp, Stefan
   Bradner, James E.
TI Selective inhibition of BET bromodomains
SO NATURE
LA English
DT Article
ID abl tyrosine kinase; protein brd4; p-tefb; aggressive carcinoma; mitotic chromosm; signal-transduction; structural basis; chemical probes; in-vivo; leukemia
AB Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.
C1 [Filippakopoulos, Panagis; Picaud, Sarah; Fedorov, Oleg; Keates, Tracey; Felletar, Ildiko; Philpott, Martin; Heightman, Tom D.; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Dept Clin Med, Oxford OX3 7DQ, England.
   [Qi, Jun; Smith, William B.; Morse, Elizabeth M.; McKeown, Michael R.; West, Nathan; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Shen, Yao; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
   [Shen, Yao; Wiest, Olaf] Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA.
   [Hickman, Tyler T.; Cameron, Michael J.; Schwartz, Brian; French, Christopher A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Munro, Shonagh; La Thangue, Nicholas; Knapp, Stefan] Univ Oxford, Dept Clin Pharmacol, Oxford OX3 7DQ, England.
   [McKeown, Michael R.; Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Wang, Yuchuan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
   [Christie, Amanda L.; Kung, Andrew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
   [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Kung, Andrew L.] Childrens Hosp, Boston, MA 02115 USA.
C3 University of Oxford; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Notre Dame; Walther Cancer Foundation; University of Notre Dame; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Oxford; Harvard University; 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; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Knapp, S (corresponding author), Univ Oxford, Struct Genom Consortium, Dept Clin Med, Old Rd Campus,Roosevelt Dr, Oxford OX3 7DQ, England.
EM stefan.knapp@sgc.ox.ac.uk; james_bradner@dfci.harvard.edu
FU Canadian Institutes for Health Research [1097737]; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust; University of Notre Dame; NIGMS [T32-075762]; DF/HCC; National Institutes of Health; Burroughs Wellcome Fund; Leukemia & Lymphoma Society; MRC [G0500905, G9400953] Funding Source: UKRI; Medical Research Council [G0500905, G9400953] Funding Source: researchfish
NR 43
TC 3459
Z9 4226
U1 8
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 DEC 23
PY 2010
VL 468
IS 7327
BP 1067
EP 1073
DI 10.1038/nature09504
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800051
PM 20871596
DA 2026-03-09
ER

PT J
AU Sun, ZZ
   Yan, Z
   Yao, J
   Beitler, E
   Zhu, Y
   Tour, JM
AF Sun, Zhengzong
   Yan, Zheng
   Yao, Jun
   Beitler, Elvira
   Zhu, Yu
   Tour, James M.
TI Growth of graphene from solid carbon sources
SO NATURE
LA English
DT Article
ID large-area; transistors; scattering; bandgap; films; gas
AB Monolayer graphene was first obtained(1) as a transferable material in 2004 and has stimulated intense activity among physicists, chemists and material scientists(1-4). Much research has been focused on developing routes for obtaining large sheets of monolayer or bilayer graphene. This has been recently achieved by chemical vapour deposition (CVD) of CH4 or C2H2 gases on copper or nickel substrates(5-7). But CVD is limited to the use of gaseous raw materials, making it difficult to apply the technology to a wider variety of potential feedstocks. Here we demonstrate that large area, high-quality graphene with controllable thickness can be grown from different solid carbon sources-such as polymer films or small molecules-deposited on a metal catalyst substrate at temperatures as low as 800 degrees C. Both pristine graphene and doped graphene were grown with this one-step process using the same experimental set-up.
C1 [Sun, Zhengzong; Yan, Zheng; Beitler, Elvira; Zhu, Yu; Tour, James M.] Rice Univ, Dept Chem, Houston, TX 77005 USA.
   [Yao, Jun] Rice Univ, Dept Bioengn, Appl Phys Program, Houston, TX 77005 USA.
   [Tour, James M.] Rice Univ, Dept Mech Engn & Mat Sci, Richard E Smalley Inst Nanoscale Sci & Technol, Houston, TX 77005 USA.
C3 Rice University; Rice University; Rice University
RP Tour, JM (corresponding author), Rice Univ, Dept Chem, 6100 Main St, Houston, TX 77005 USA.
EM tour@rice.edu
FU AFOSR [FA9550-09-1-0581]; ONR MURI [00006766]
NR 31
TC 1243
Z9 1440
U1 9
U2 1529
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 549
EP 552
DI 10.1038/nature09579
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200039
PM 21068724
DA 2026-03-09
ER

PT J
AU Hagn, F
   Eisoldt, L
   Hardy, JG
   Vendrely, C
   Coles, M
   Scheibel, T
   Kessler, H
AF Hagn, Franz
   Eisoldt, Lukas
   Hardy, John G.
   Vendrely, Charlotte
   Coles, Murray
   Scheibel, Thomas
   Kessler, Horst
TI A conserved spider silk domain acts as a molecular switch that controls fibre assembly
SO NATURE
LA English
DT Article
ID terminal domain; exchange-rates; protein; dragline; assignment; stability; mechanism; sequence; shift
AB A huge variety of proteins are able to form fibrillar structures(1), especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand(2,3). Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal(4,5) and carboxy-terminal(6) domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation(7) initiated by changes in ionic composition(8,9) and mechanical stimuli known to align the repetitive sequence elements and promote beta-sheet formation(10-14). However, despite recent structural data(15), little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.
C1 [Hagn, Franz; Kessler, Horst] Tech Univ Munich, Ctr Integrated Prot Sci CIPSM, D-85747 Garching, Germany.
   [Hagn, Franz; Kessler, Horst] Tech Univ Munich, Inst Adv Study, D-85747 Garching, Germany.
   [Eisoldt, Lukas; Hardy, John G.; Vendrely, Charlotte; Scheibel, Thomas] Univ Bayreuth, Fak Angew Nat Wissensch, Lehrstuhl Biomat, D-95440 Bayreuth, Germany.
   [Coles, Murray] Max Planck Inst Dev Biol, Dept Prot Evolut, D-72076 Tubingen, Germany.
C3 Technical University of Munich; Technical University of Munich; University of Bayreuth; Max Planck Society
RP Kessler, H (corresponding author), Tech Univ Munich, Ctr Integrated Prot Sci CIPSM, D-85747 Garching, Germany.
EM thomas.scheibel@uni-bayreuth.de; horst.kessler@ch.tum.de
FU Center for Integrated Protein Science Munich (CIPSM); Deutsche Forschungsgemeinschaft [SCHE 603/4-3]; Elitenetzwerk Bayern, CompInt; Alexander von Humboldt Foundation
NR 36
TC 384
Z9 444
U1 5
U2 207
PU NATURE PUBLISHING 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 13
PY 2010
VL 465
IS 7295
BP 239
EP U131
DI 10.1038/nature08936
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500040
PM 20463741
DA 2026-03-09
ER

PT J
AU Chen, DL
   Shan, J
   Zhu, WG
   Qin, J
   Gu, W
AF Chen, Delin
   Shan, Jing
   Zhu, Wei-Guo
   Qin, Jun
   Gu, Wei
TI Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses (Publication with Expression of Concern. See FEB, 2026)
SO NATURE
LA English
DT Article; Publication with Expression of Concern
ID tumor-suppressor; nucleophosmin; protein; expression; polyubiquitination; induction; targets; b23
AB The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress(1-6). Recent studies showed that p53 activation mediated by ARF, but not that induced by DNA damage, acts as a major protection against tumorigenesis in vivo under certain biological settings(7,8), suggesting that the ARF-p53 axis has more fundamental functions in tumour suppression than originally thought. Because ARF is a very stable protein in most human cell lines, it has been widely assumed that ARF induction is mediated mainly at the transcriptional level and that activation of the ARF-p53 pathway by oncogenes is a much slower and largely irreversible process by comparison with p53 activation after DNA damage. Here we report that ARF is very unstable in normal human cells but that its degradation is inhibited in cancerous cells. Through biochemical purification, we identified a specific ubiquitin ligase for ARF and named it ULF. ULF interacts with ARF both in vitro and in vivo and promotes the lysine-independent ubiquitylation and degradation of ARF. ULF knockdown stabilizes ARF in normal human cells, triggering ARF-dependent, p53-mediated growth arrest. Moreover, nucleophosmin (NPM) and c-Myc, both of which are commonly overexpressed in cancer cells, are capable of abrogating ULF-mediated ARF ubiquitylation through distinct mechanisms, and thereby promote ARF stabilization in cancer cells. These findings reveal the dynamic feature of the ARF-p53 pathway and suggest that transcription-independent mechanisms are critically involved in ARF regulation during responses to oncogenic stress.
C1 [Chen, Delin; Shan, Jing; Gu, Wei] Columbia Univ, Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA.
   [Chen, Delin; Shan, Jing; Gu, Wei] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA.
   [Zhu, Wei-Guo] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China.
   [Qin, Jun] Baylor Coll Med, Dept Biochem & Cell Biol, Houston, TX 77030 USA.
C3 Columbia University; Columbia University; Peking University; Baylor College of Medicine
RP Gu, W (corresponding author), Columbia Univ, Coll Phys & Surg, Inst Canc Genet, 1130 St Nicholas Ave, New York, NY 10032 USA.
EM wg8@columbia.edu
FU National Institutes of Health/National Cancer Institute; Leukemia and Lymphoma Society; NSFC [30628028]; National Cancer Institute [R01CA085533] Funding Source: NIH RePORTER
NR 32
TC 136
Z9 166
U1 1
U2 33
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 624
EP U193
DI 10.1038/nature08820
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200055
PM 20208519
DA 2026-03-09
ER

PT J
AU Reich, D
   Green, RE
   Kircher, M
   Krause, J
   Patterson, N
   Durand, EY
   Viola, B
   Briggs, AW
   Stenzel, U
   Johnson, PLF
   Maricic, T
   Good, JM
   Marques-Bonet, T
   Alkan, C
   Fu, QM
   Mallick, S
   Li, H
   Meyer, M
   Eichler, EE
   Stoneking, M
   Richards, M
   Talamo, S
   Shunkov, MV
   Derevianko, AP
   Hublin, JJ
   Kelso, J
   Slatkin, M
   Pääbo, S
AF Reich, David
   Green, Richard E.
   Kircher, Martin
   Krause, Johannes
   Patterson, Nick
   Durand, Eric Y.
   Viola, Bence
   Briggs, Adrian W.
   Stenzel, Udo
   Johnson, Philip L. F.
   Maricic, Tomislav
   Good, Jeffrey M.
   Marques-Bonet, Tomas
   Alkan, Can
   Fu, Qiaomei
   Mallick, Swapan
   Li, Heng
   Meyer, Matthias
   Eichler, Evan E.
   Stoneking, Mark
   Richards, Michael
   Talamo, Sahra
   Shunkov, Michael V.
   Derevianko, Anatoli P.
   Hublin, Jean-Jacques
   Kelso, Janet
   Slatkin, Montgomery
   Paeaebo, Svante
TI Genetic history of an archaic hominin group from Denisova Cave in Siberia
SO NATURE
LA English
DT Article
ID mitochondrial-dna; genome sequence; neanderthal; patterns; flores; sima
AB Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.
C1 [Reich, David; Briggs, Adrian W.; Mallick, Swapan] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Reich, David; Patterson, Nick; Mallick, Swapan; Li, Heng] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Reich, David; Patterson, Nick; Mallick, Swapan; Li, Heng] Harvard Univ, Cambridge, MA 02142 USA.
   [Green, Richard E.; Kircher, Martin; Krause, Johannes; Viola, Bence; Briggs, Adrian W.; Stenzel, Udo; Maricic, Tomislav; Fu, Qiaomei; Meyer, Matthias; Stoneking, Mark; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
   [Green, Richard E.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Krause, Johannes] Univ Tubingen, Inst Nat Wissensch Archaol, D-72070 Tubingen, Germany.
   [Durand, Eric Y.; Slatkin, Montgomery] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Viola, Bence; Richards, Michael; Talamo, Sahra; Hublin, Jean-Jacques] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
   [Good, Jeffrey M.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Marques-Bonet, Tomas; Alkan, Can; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Dept Genome Sci, Seattle, WA 98195 USA.
   [Marques-Bonet, Tomas] Inst Evolutionary Biol UPF CSIC, Barcelona 08003, Spain.
   [Fu, Qiaomei] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, CAS MPS Joint Lab Human Evolut & Archeometry, Beijing 100044, Peoples R China.
   [Richards, Michael] Univ British Columbia, Dept Anthropol, Vancouver, BC V6T 1Z1, Canada.
   [Shunkov, Michael V.; Derevianko, Anatoli P.] Russian Acad Sci, Inst Archaeol Ethnog, Siberian Branch, Palaeolith Dept, Novosibirsk 630090, Russia.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Max Planck Society; University of California System; University of California Santa Cruz; Eberhard Karls University of Tubingen; University of California System; University of California Berkeley; Max Planck Society; Emory University; University of Montana System; University of Montana; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University of British Columbia; Russian Academy of Sciences; Institute of Archaeology & Ethnography, Siberian Branch of Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences
RP Reich, D (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM reich@genetics.med.harvard.edu; bence.viola@eva.mpg.de; paabo@eva.mpg.de
FU Max Planck Society; Krekeler Foundation; US National Institutes of Health [R01-GM40282]; National Science Foundation [OISE-0754461, 1032255]; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1032255] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0906041] Funding Source: National Science Foundation
NR 40
TC 1241
Z9 1507
U1 8
U2 561
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 23
PY 2010
VL 468
IS 7327
BP 1053
EP 1060
DI 10.1038/nature09710
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 697XT
UT WOS:000285553800049
PM 21179161
DA 2026-03-09
ER

PT J
AU Su, XH
   Chakravarti, D
   Cho, MS
   Liu, LZ
   Gi, YJ
   Lin, YL
   Leung, ML
   El-Naggar, A
   Creighton, CJ
   Suraokar, MB
   Wistuba, I
   Flores, ER
AF Su, Xiaohua
   Chakravarti, Deepavali
   Cho, Min Soon
   Liu, Lingzhi
   Gi, Young Jin
   Lin, Yu-Li
   Leung, Marco L.
   El-Naggar, Adel
   Creighton, Chad J.
   Suraokar, Milind B.
   Wistuba, Ignacio
   Flores, Elsa R.
TI TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs
SO NATURE
LA English
DT Article
ID li-fraumeni-syndrome; p63 expression; p53; cancer; p73; mutant; mice; progression; carcinoma; family
AB Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours(1-6), but the mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
C1 [Su, Xiaohua; Chakravarti, Deepavali; Cho, Min Soon; Liu, Lingzhi; Gi, Young Jin; Lin, Yu-Li; Leung, Marco L.; Flores, Elsa R.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Chakravarti, Deepavali; Cho, Min Soon; Flores, Elsa R.] Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA.
   [El-Naggar, Adel; Suraokar, Milind B.; Wistuba, Ignacio] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Creighton, Chad J.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Baylor College of Medicine
RP Flores, ER (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM elsaflores@mdanderson.org
FU NCI [CA16672]; American Cancer Society [RSG-07-082-01-MGO]; Susan G. Komen Foundation [BCTR600208]; Hildegardo E. and Olga M. Flores Foundation; NCI-Cancer Center [CA-16672]; Genitourinary Cancer SPORE [P50CA091846]; Lung Cancer SPORE [P50CA070907, U01DE019765]; Rita Allen Foundation; V Foundation for Cancer Research; National Cancer Institute [P30CA016672, P50CA070907] Funding Source: NIH RePORTER
NR 29
TC 362
Z9 406
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 21
PY 2010
VL 467
IS 7318
BP 986
EP U168
DI 10.1038/nature09459
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700043
PM 20962848
DA 2026-03-09
ER

PT J
AU Salter, CL
   Stevenson, RM
   Farrer, I
   Nicoll, CA
   Ritchie, DA
   Shields, AJ
AF Salter, C. L.
   Stevenson, R. M.
   Farrer, I.
   Nicoll, C. A.
   Ritchie, D. A.
   Shields, A. J.
TI An entangled-light-emitting diode
SO NATURE
LA English
DT Article
ID photon pairs; quantum
AB An optical quantum computer, powerful enough to solve problems so far intractable using conventional digital logic, requires a large number of entangled photons(1,2). At present, entangled-light sources are optically driven with lasers(3-7), which are impractical for quantum computing owing to the bulk and complexity of the optics required for large-scale applications. Parametric down-conversion is the most widely used source of entangled light, and has been used to implement non-destructive quantum logic gates(8,9). However, these sources are Poissonian(4,5) and probabilistically emit zero or multiple entangled photon pairs in most cycles, fundamentally limiting the success probability of quantum computational operations. These complications can be overcome by using an electrically driven on-demand source of entangled photon pairs(10), but so far such a source has not been produced. Here we report the realization of an electrically driven source of entangled photon pairs, consisting of a quantum dot embedded in a semiconductor light-emitting diode (LED) structure. We show that the device emits entangled photon pairs under d.c. and a.c. injection, the latter achieving an entanglement fidelity of up to 0.82. Entangled light with such high fidelity is sufficient for application in quantum relays(11), in core components of quantum computing such as teleportation(12-14), and in entanglement swapping(15,16). The a.c. operation of the entangled-lightemitting diode (ELED) indicates its potential function as an ondemand source without the need for a complicated laser driving system; consequently, the ELED is at present the best source on which to base future scalable quantum information applications(17).
C1 [Salter, C. L.; Stevenson, R. M.; Shields, A. J.] Toshiba Res Europe Ltd, Cambridge CB4 0GZ, England.
   [Salter, C. L.; Farrer, I.; Nicoll, C. A.; Ritchie, D. A.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
C3 Toshiba Corporation; University of Cambridge
RP Shields, AJ (corresponding author), Toshiba Res Europe Ltd, 208 Cambridge Sci Pk, Cambridge CB4 0GZ, England.
EM andrew.shields@crl.toshiba.co.uk
FU Engineering and Physical Sciences Research Council; Quantum Information Processing Interdisciplinary Research Collaboration; EU; EPSRC [EP/E058019/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/E058019/1] Funding Source: researchfish
NR 30
TC 303
Z9 330
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 JUN 3
PY 2010
VL 465
IS 7298
BP 594
EP 597
DI 10.1038/nature09078
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000036
PM 20520709
DA 2026-03-09
ER

PT J
AU Hughes, JF
   Skaletsky, H
   Pyntikova, T
   Graves, TA
   van Daalen, SKM
   Minx, PJ
   Fulton, RS
   McGrath, SD
   Locke, DP
   Friedman, C
   Trask, BJ
   Mardis, ER
   Warren, WC
   Repping, S
   Rozen, S
   Wilson, RK
   Page, DC
AF Hughes, Jennifer F.
   Skaletsky, Helen
   Pyntikova, Tatyana
   Graves, Tina A.
   van Daalen, Saskia K. M.
   Minx, Patrick J.
   Fulton, Robert S.
   McGrath, Sean D.
   Locke, Devin P.
   Friedman, Cynthia
   Trask, Barbara J.
   Mardis, Elaine R.
   Warren, Wesley C.
   Repping, Sjoerd
   Rozen, Steve
   Wilson, Richard K.
   Page, David C.
TI Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content
SO NATURE
LA English
DT Article
ID sex-chromosome; x-chromosome; human genome; evolution; sequence; palindrm; region; recombination; degeneration; polymorphism
AB The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome(1,2). Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis(3,4). These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes(5-8), but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, 'genetic hitchhiking' effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.
C1 [Hughes, Jennifer F.; Skaletsky, Helen; Pyntikova, Tatyana; Rozen, Steve; Page, David C.] Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
   [Hughes, Jennifer F.; Skaletsky, Helen; Pyntikova, Tatyana; Rozen, Steve; Page, David C.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Graves, Tina A.; Minx, Patrick J.; Fulton, Robert S.; McGrath, Sean D.; Locke, Devin P.; Mardis, Elaine R.; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [van Daalen, Saskia K. M.; Repping, Sjoerd] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynecol, Ctr Reprod Med, NL-1105 AZ Amsterdam, Netherlands.
   [Friedman, Cynthia; Trask, Barbara J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
C3 Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Washington University (WUSTL); University of Amsterdam; Academic Medical Center Amsterdam; Fred Hutchinson Cancer Center
RP Page, DC (corresponding author), Whitehead Inst, Howard Hughes Med Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dcpage@wi.mit.edu
FU National Institutes of Health; Howard Hughes Medical Institute
NR 30
TC 292
Z9 338
U1 1
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 536
EP 539
DI 10.1038/nature08700
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100050
PM 20072128
DA 2026-03-09
ER

PT J
AU Hagberg, CE
   Falkevall, A
   Wang, X
   Larsson, E
   Huusko, J
   Nilsson, I
   van Meeteren, LA
   Samen, E
   Lu, L
   Vanwildemeersch, M
   Klar, J
   Genove, G
   Pietras, K
   Stone-Elander, S
   Claesson-Welsh, L
   Ylä-Herttuala, S
   Lindahl, P
   Eriksson, U
AF Hagberg, Carolina E.
   Falkevall, Annelie
   Wang, Xun
   Larsson, Erik
   Huusko, Jenni
   Nilsson, Ingrid
   van Meeteren, Laurens A.
   Samen, Erik
   Lu, Li
   Vanwildemeersch, Maarten
   Klar, Joakim
   Genove, Guillem
   Pietras, Kristian
   Stone-Elander, Sharon
   Claesson-Welsh, Lena
   Yla-Herttuala, Seppo
   Lindahl, Per
   Eriksson, Ulf
TI Vascular endothelial growth factor B controls endothelial fatty acid uptake
SO NATURE
LA English
DT Article
ID vegf-b; lipid-metabolism; transport; angiogenesis; mouse; lacking; flt-1; permeability; receptor-1; lethality
AB The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology(1). However, the detailed role of VEGF-B in blood vessel function has remained unclear(2,3). Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood(4). Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
C1 [Hagberg, Carolina E.; Falkevall, Annelie; Wang, Xun; Nilsson, Ingrid; Vanwildemeersch, Maarten; Pietras, Kristian; Eriksson, Ulf] Karolinska Inst, Tissue Biol Grp, Div Matrix Biol, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
   [Hagberg, Carolina E.; Falkevall, Annelie; Wang, Xun; Vanwildemeersch, Maarten; Klar, Joakim; Pietras, Kristian; Eriksson, Ulf] Ludwig Inst Canc Res Ltd, Stockholm Branch, Karolinska Inst, SE-17177 Stockholm, Sweden.
   [Larsson, Erik; Lindahl, Per] Univ Gothenburg, Inst Biomed, SE-40530 Gothenburg, Sweden.
   [Huusko, Jenni; Yla-Herttuala, Seppo] Univ Kuopio, AI Virtanen Inst, Dept Biotechnol & Mol Med, FIN-70211 Kuopio, Finland.
   [van Meeteren, Laurens A.; Klar, Joakim; Claesson-Welsh, Lena] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden.
   [Samen, Erik; Stone-Elander, Sharon] Karolinska Pharm, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
   [Samen, Erik; Lu, Li; Stone-Elander, Sharon] Karolinska Inst, SE-17176 Stockholm, Sweden.
   [Genove, Guillem] Karolinska Inst, Lab Vasc Biol, Div Matrix Biol, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
   [Lindahl, Per] Sahlgrens Univ Hosp, Wallenberg Lab Cardiovasc Res, SE-41345 Gothenburg, Sweden.
C3 Karolinska Institutet; Ludwig Institute for Cancer Research; Karolinska Institutet; University of Gothenburg; University of Eastern Finland; Uppsala University; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Karolinska Institutet; Sahlgrenska University Hospital
RP Eriksson, U (corresponding author), Karolinska Inst, Tissue Biol Grp, Div Matrix Biol, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
EM ulf.pe.eriksson@ki.se
FU Wilhelm och Else Stockmanns Stiftelse; Frans Wilhelm och Waldemar von Frenckells fond; European Commission [LSHG-CT-2004-503573]; Dutch Cancer Society; Novo Nordisk Foundation; Swedish Cancer Foundation; Swedish Research Council; Dr. Peter Wallenbergs Foundation for Economics and Technology; LeDucq Foundation; Swedish Brain Foundation and Hallstens Forskningsstiftelse; Karolinska Institutet
NR 38
TC 413
Z9 484
U1 2
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 APR 8
PY 2010
VL 464
IS 7290
BP 917
EP U136
DI 10.1038/nature08945
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300043
PM 20228789
DA 2026-03-09
ER

PT J
AU Shopsowitz, KE
   Qi, H
   Hamad, WY
   MacLachlan, MJ
AF Shopsowitz, Kevin E.
   Qi, Hao
   Hamad, Wadood Y.
   MacLachlan, Mark J.
TI Free-standing mesoporous silica films with tunable chiral nematic structures
SO NATURE
LA English
DT Article
ID cholesteric liquid-crystals; cellulose; order; suspensions; germanium; band
AB Chirality at the molecular level is found in diverse biological structures, such as polysaccharides, proteins and DNA, and is responsible for many of their unique properties(1). Introducing chirality into porous inorganic solids may produce new types of materials that could be useful for chiral separation, stereospecific catalysis, chiral recognition (sensing) and photonic materials(2-5). Template synthesis of inorganic solids using the self-assembly of lyotropic liquid crystals offers access to materials with well-defined porous structures(6-12), but only recently has chirality been introduced into hexagonal mesostructures through the use of a chiral surfactant(13,14). Efforts to impart chirality at a larger length scale using self-assembly are almost unknown. Here we describe the development of a photonic mesoporous inorganic solid that is a cast of a chiral nematic liquid crystal formed from nanocrystalline cellulose. These materials may be obtained as free-standing films with high surface area. The peak reflected wavelength of the films can be varied across the entire visible spectrum and into the near-infrared through simple changes in the synthetic conditions. To the best of our knowledge these are the first materials to combine mesoporosity with long-range chiral ordering that produces photonic properties. Our findings could lead to the development of new materials for applications in, for example, tuneable reflective filters and sensors. In addition, this type of material could be used as a hard template to generate other new materials with chiral nematic structures.
C1 [Shopsowitz, Kevin E.; Qi, Hao; MacLachlan, Mark J.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
   [Hamad, Wadood Y.] FPInnovations, Vancouver, BC V6S 2L9, Canada.
C3 University of British Columbia
RP MacLachlan, MJ (corresponding author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
EM mmaclach@chem.ubc.ca
FU Natural Sciences and Engineering Research Council (NSERC) of Canada; FPInnovations; UBC
NR 28
TC 849
Z9 941
U1 11
U2 1245
PU 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 18
PY 2010
VL 468
IS 7322
BP 422
EP U246
DI 10.1038/nature09540
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100039
PM 21085176
DA 2026-03-09
ER

PT J
AU Green, HW
   Chen, WP
   Brudzinski, MR
AF Green, Harry W., II
   Chen, Wang-Ping
   Brudzinski, Michael R.
TI Seismic evidence of negligible water carried below 400-km depth in subducting lithosphere
SO NATURE
LA English
DT Article
ID metastable olivine wedge; mantle; zone; serpentinization; dehydration; remnant; phase; japan; slab; h2o
AB Strong evidence exists that water is carried from the surface into the upper mantle by hydrous minerals in the uppermost 10-12 km of subducting lithosphere, and more water may be added as the lithosphere bends and goes downwards. Significant amounts of that water are released as the lithosphere heats up, triggering earthquakes and fluxing arc volcanism(1). In addition, there is experimental evidence for high solubility of water in olivine, the most abundant mineral in the upper mantle, for even higher solubility in olivine's high-pressure polymorphs, wadsleyite and ringwoodite(2), and for the existence of dense hydrous magnesium silicates that potentially could carry water well into the lower mantle(3) (deeper than 1,000 km). Here we compare experimental and seismic evidence to test whether patterns of seismicity and the stabilities of these potentially relevant hydrous phases are consistent with a wet lithosphere. We show that there is nearly a one-to-one correlation between dehydration of minerals and seismicity at depths less than about 250 km, and conclude that the dehydration of minerals is the trigger of instability that leads to seismicity. At greater depths, however, we find no correlation between occurrences of earthquakes and depths where breakdown of hydrous phases is expected. Lastly, we note that there is compelling evidence for the existence of metastable olivine (which, if present, can explain the distribution of deep-focus earthquakes(4-7)) west of and within the subducting Tonga slab(8) and also in three other subduction zones, despite metastable olivine being incompatible with even extremely small amounts of water (of the order of 100 p.p.m. by weight(7)). We conclude that subducting slabs are essentially dry at depths below 400 km and thus do not provide a pathway for significant amounts of water to enter the mantle transition zone or the lower mantle.
C1 [Green, Harry W., II] Univ Calif Riverside, Inst Geophys & Planetary Phys, Riverside, CA 92521 USA.
   [Green, Harry W., II] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Chen, Wang-Ping] Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
   [Brudzinski, Michael R.] Miami Univ, Dept Geol, Oxford, OH 45056 USA.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside; University of Illinois System; University of Illinois Urbana-Champaign; University System of Ohio; Miami University
RP Green, HW (corresponding author), Univ Calif Riverside, Inst Geophys & Planetary Phys, Riverside, CA 92521 USA.
EM harry.green@ucr.edu
FU NSF [EAR0552011, EAR-0652626, EAR-0125938, EAR9909362, EAR0551995, EAR552002]; National Science Council of Taiwan at the Academia Sinica; Division Of Earth Sciences; Directorate For Geosciences [0847688] Funding Source: National Science Foundation
NR 33
TC 90
Z9 107
U1 0
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 828
EP 831
DI 10.1038/nature09401
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700064
PM 20927105
DA 2026-03-09
ER

PT J
AU Lin, HK
   Chen, ZB
   Wang, GC
   Nardella, C
   Lee, SW
   Chan, CH
   Yang, WL
   Wang, J
   Egia, A
   Nakayama, KI
   Cordon-Cardo, C
   Teruya-Feldstein, J
   Pandolfi, PP
AF Lin, Hui-Kuan
   Chen, Zhenbang
   Wang, Guocan
   Nardella, Caterina
   Lee, Szu-Wei
   Chan, Chan-Hsin
   Yang, Wei-Lei
   Wang, Jing
   Egia, Ainara
   Nakayama, Keiichi I.
   Cordon-Cardo, Carlos
   Teruya-Feldstein, Julie
   Pandolfi, Pier Paolo
TI Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
SO NATURE
LA English
DT Article
ID oncogene-induced senescence; box protein skp2; tumor suppression; p53; pten; expression; accumulation; restoration; inhibitor; complex
AB Cellular senescence has been recently shown to have an important role in opposing tumour initiation and promotion. Senescence induced by oncogenes or by loss of tumour suppressor genes is thought to critically depend on induction of the p19(Arf)-p53 pathway. The Skp2 E3-ubiquitin ligase can act as a proto-oncogene and its aberrant overexpression is frequently observed in human cancers. Here we show that although Skp2 inactivation on its own does not induce cellular senescence, aberrant proto-oncogenic signals as well as inactivation of tumour suppressor genes do trigger a potent, tumour-suppressive senescence response in mice and cells devoid of Skp2. Notably, Skp2 inactivation and oncogenic-stress-driven senescence neither elicit activation of the p19(Arf)-p53 pathway nor DNA damage, but instead depend on Atf4, p27 and p21. We further demonstrate that genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies. Our findings therefore provide proof-of-principle evidence that pharmacological inhibition of Skp2 may represent a general approach for cancer prevention and therapy.
C1 [Lin, Hui-Kuan; Chen, Zhenbang; Wang, Guocan; Nardella, Caterina; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA.
   [Lin, Hui-Kuan; Chen, Zhenbang; Wang, Guocan; Nardella, Caterina; Cordon-Cardo, Carlos; Teruya-Feldstein, Julie; Pandolfi, Pier Paolo] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Pathol, New York, NY 10021 USA.
   [Lin, Hui-Kuan; Lee, Szu-Wei; Chan, Chan-Hsin; Yang, Wei-Lei; Wang, Jing] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Chen, Zhenbang; Wang, Guocan; Nardella, Caterina; Egia, Ainara] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Chen, Zhenbang; Wang, Guocan; Nardella, Caterina; Egia, Ainara] Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA 02215 USA.
   [Nakayama, Keiichi I.] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Kyushu University
RP Pandolfi, PP (corresponding author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA.
EM ppandolf@bidmc.harvard.edu
FU NIH; Anderson Trust Scholar Award; DOD Prostate Cancer New Investigator Award
NR 41
TC 340
Z9 406
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 MAR 18
PY 2010
VL 464
IS 7287
BP 374
EP U66
DI 10.1038/nature08815
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100038
PM 20237562
DA 2026-03-09
ER

PT J
AU Huang, F
   Chakraborty, P
   Lundstrom, CC
   Holmden, C
   Glessner, JJG
   Kieffer, SW
   Lesher, CE
AF Huang, F.
   Chakraborty, P.
   Lundstrom, C. C.
   Holmden, C.
   Glessner, J. J. G.
   Kieffer, S. W.
   Lesher, C. E.
TI Isotope fractionation in silicate melts by thermal diffusion
SO NATURE
LA English
DT Article
ID temperature-dependence; separation; exchange; liquids; ca; nd
AB The phenomenon of thermal diffusion (mass diffusion driven by a temperature gradient, known as the Ludwig-Soret effect(1,2)) has been investigated for over 150 years, but an understanding of its underlying physical basis remains elusive. A significant hurdle in studying thermal diffusion has been the difficulty of characterizing it. Extensive experiments over the past century have established that the Soret coefficient, S-T (a single parameter that describes the steady-state result of thermal diffusion), is highly sensitive to many factors(3-9). This sensitivity makes it very difficult to obtain a robust characterization of thermal diffusion, even for a single material. Here we show that for thermal diffusion experiments that span a wide range in composition and temperature, the difference in ST between isotopes of diffusing elements that are network modifiers ( iron, calcium and magnesium) is independent of the composition and temperature. On the basis of this finding, we propose an additive decomposition for the functional form of ST and argue that a theoretical approach based on local thermodynamic equilibrium(3,5,10) holds promise for describing thermal diffusion in silicate melts and other complex solutions. Our results lead to a simple and robust framework for characterizing isotope fractionation by thermal diffusion in natural and synthetic systems.
C1 [Huang, F.; Chakraborty, P.; Lundstrom, C. C.; Glessner, J. J. G.; Kieffer, S. W.] Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
   [Holmden, C.] Univ Saskatchewan, Dept Geol Sci, Saskatoon, SK S7N 5E2, Canada.
   [Lesher, C. E.] Univ Calif Davis, Dept Geol, Davis, CA 95616 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Saskatchewan; University of California System; University of California Davis
RP Lundstrom, CC (corresponding author), Univ Illinois, Dept Geol, Urbana, IL 61801 USA.
EM lundstro@illinois.edu
FU US National Science Foundation [NSF EAR 0609726, NSF EAR 0944169, NSF EAR 0943991, NSF EAR 0732481]; Roscoe G. Jackson II Research; S.W.K.'s Walgreen Chair funds; Directorate For Geosciences [1019887] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [0944169] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [0943992] Funding Source: National Science Foundation; Division Of Earth Sciences [1019887] Funding Source: National Science Foundation
NR 32
TC 201
Z9 237
U1 3
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 MAR 18
PY 2010
VL 464
IS 7287
BP 396
EP U89
DI 10.1038/nature08840
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100043
PM 20237567
DA 2026-03-09
ER

PT J
AU Gao, J
   Wang, WY
   Mao, YW
   Gräff, J
   Guan, JS
   Pan, L
   Mak, G
   Kim, D
   Su, SC
   Tsai, LH
AF Gao, Jun
   Wang, Wen-Yuan
   Mao, Ying-Wei
   Graeff, Johannes
   Guan, Ji-Song
   Pan, Ling
   Mak, Gloria
   Kim, Dohoon
   Su, Susan C.
   Tsai, Li-Huei
TI A novel pathway regulates memory and plasticity via SIRT1 and miR-134
SO NATURE
LA English
DT Article
ID long-term-memory; synaptic plasticity; bdnf transcription; neuronal-activity; circadian control; recognition; hippocampus; expression; neurodegeneration; inhibition
AB The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies(1,2). Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders.
C1 [Gao, Jun; Wang, Wen-Yuan; Mao, Ying-Wei; Graeff, Johannes; Guan, Ji-Song; Pan, Ling; Mak, Gloria; Kim, Dohoon; Su, Susan C.; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Gao, Jun; Wang, Wen-Yuan; Mao, Ying-Wei; Guan, Ji-Song; Pan, Ling; Mak, Gloria; Kim, Dohoon; Su, Susan C.; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Gao, Jun] Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Peoples R China.
   [Graeff, Johannes; Tsai, Li-Huei] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Nanjing University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Tsai, LH (corresponding author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA.
EM lhtsai@mit.edu
FU NIH [PO1 AG027916]; Simons Foundation; Swiss National Science Foundation; Howard Hughes Medical Institute
NR 30
TC 831
Z9 958
U1 3
U2 169
PU 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 26
PY 2010
VL 466
IS 7310
BP 1105
EP U120
DI 10.1038/nature09271
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600040
PM 20622856
DA 2026-03-09
ER

PT J
AU Cai, JM
   Ruffieux, P
   Jaafar, R
   Bieri, M
   Braun, T
   Blankenburg, S
   Muoth, M
   Seitsonen, AP
   Saleh, M
   Feng, XL
   Müllen, K
   Fasel, R
AF Cai, Jinming
   Ruffieux, Pascal
   Jaafar, Rached
   Bieri, Marco
   Braun, Thomas
   Blankenburg, Stephan
   Muoth, Matthias
   Seitsonen, Ari P.
   Saleh, Moussa
   Feng, Xinliang
   Muellen, Klaus
   Fasel, Roman
TI Atomically precise bottom-up fabrication of graphene nanoribbons
SO NATURE
LA English
DT Article
ID carbon; form
AB Graphene nanoribbons-narrow and straight-edged stripes of graphene, or single-layer graphite-are predicted to exhibit electronic properties that make them attractive for the fabrication of nanoscale electronic devices(1-3). In particular, although the twodimensional parent material graphene(4,5) exhibits semimetallic behaviour, quantum confinement and edge effects(2,6) should render all graphene nanoribbons with widths smaller than 10 nm semiconducting. But exploring the potential of graphene nanoribbons is hampered by their limited availability: although they have been made using chemical(7-9), sonochemical(10) and lithographic(11,12) methods as well as through the unzipping of carbon nanotubes(13-16), the reliable production of graphene nanoribbons smaller than 10 nm with chemical precision remains a significant challenge. Here we report a simple method for the production of atomically precise graphene nanoribbons of different topologies and widths, which uses surface-assisted coupling(17,18) of molecular precursors into linear polyphenylenes and their subsequent cyclodehydrogenation(19,20). The topology, width and edge periphery of the graphene nanoribbon products are defined by the structure of the precursor monomers, which can be designed to give access to a wide range of different graphene nanoribbons. We expect that our bottom-up approach to the atomically precise fabrication of graphene nanoribbons will finally enable detailed experimental investigations of the properties of this exciting class of materials. It should even provide a route to graphene nanoribbon structures with engineered chemical and electronic properties, including the theoretically predicted intraribbon quantum dots(21), superlattice structures(22) and magnetic devices based on specific graphene nanoribbon edge states(3).
C1 [Cai, Jinming; Ruffieux, Pascal; Jaafar, Rached; Bieri, Marco; Braun, Thomas; Blankenburg, Stephan; Fasel, Roman] Empa, Swiss Fed Labs Mat Sci & Technol, Nanotech Surfaces Lab, CH-3602 Thun, Switzerland.
   [Cai, Jinming; Ruffieux, Pascal; Jaafar, Rached; Bieri, Marco; Braun, Thomas; Blankenburg, Stephan; Fasel, Roman] Empa, Swiss Fed Labs Mat Sci & Technol, Nanotech Surfaces Lab, CH-8600 Dubendorf, Switzerland.
   [Muoth, Matthias] ETH, Dept Mech & Proc Engn Micro & Nanosyst, CH-8092 Zurich, Switzerland.
   [Seitsonen, Ari P.] Univ Zurich, Inst Phys Chem, CH-8057 Zurich, Switzerland.
   [Seitsonen, Ari P.] CNRS, IMPMC, F-75252 Paris, France.
   [Seitsonen, Ari P.] Univ Paris 06, F-75252 Paris, France.
   [Saleh, Moussa; Feng, Xinliang; Muellen, Klaus] Max Planck Inst Polymer Res, D-55124 Mainz, Germany.
   [Fasel, Roman] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; Sorbonne Universite; Max Planck Society; University of Bern
RP Fasel, R (corresponding author), Empa, Swiss Fed Labs Mat Sci & Technol, Nanotech Surfaces Lab, CH-3602 Thun, Switzerland.
EM muellen@mpip-mainz.mpg.de; roman.fasel@empa.ch
FU Swiss National Science Foundation; NCCR Nanoscale Science; Max Planck Society; German Science Foundation (Korean-German IRTG); DFG [SPP 1355, DFG MU 334/32-1]
NR 30
TC 3139
Z9 3547
U1 17
U2 2458
PU NATURE PUBLISHING 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 22
PY 2010
VL 466
IS 7305
BP 470
EP 473
DI 10.1038/nature09211
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200031
PM 20651687
DA 2026-03-09
ER

PT J
AU Kloppenborg, B
   Stencel, R
   Monnier, JD
   Schaefer, G
   Zhao, M
   Baron, F
   McAlister, H
   ten Brummelaar, T
   Che, X
   Farrington, C
   Pedretti, E
   Sallave-Goldfinger, PJ
   Sturmann, J
   Sturmann, L
   Thureau, N
   Turner, N
   Carroll, SM
AF Kloppenborg, Brian
   Stencel, Robert
   Monnier, John D.
   Schaefer, Gail
   Zhao, Ming
   Baron, Fabien
   McAlister, Hal
   ten Brummelaar, Theo
   Che, Xiao
   Farrington, Chris
   Pedretti, Ettore
   Sallave-Goldfinger, P. J.
   Sturmann, Judit
   Sturmann, Laszlo
   Thureau, Nathalie
   Turner, Nils
   Carroll, Sean M.
TI Infrared images of the transiting disk in the ε Aurigae system
SO NATURE
LA English
DT Article
ID eclipse
AB Epsilon Aurigae (epsilon Aur) is a visually bright, eclipsing binary star system with a period of 27.1 years. The cause of each 18-month-long eclipse has been a subject of controversy for nearly 190 years(1) because the companion has hitherto been undetectable. The orbital elements imply that the opaque object has roughly the same mass as the visible component, which for much of the last century was thought to be an F-type supergiant star with a mass of similar to 15M(circle dot) (M(circle dot), mass of the Sun). The high mass-to-luminosity ratio of the hidden object was originally explained by supposing it to be a hyperextended infrared star(2) or, later, a black hole(3) with an accretion disk, although the preferred interpretation was as a disk of opaque material(4,5) at a temperature of 500 K, tilted to the line of sight(6,7) and with a central opening(8). Recent work implies that the system consists of a low-mass (2.2M(circle dot)-3.3M(circle dot)) visible F-type star, with a disk at 550K that enshrouds a single B5V-type star(9). Here we report interferometric images that show the eclipsing body moving in front of the F star. The body is an opaque disk and appears tilted as predicted(7). Adopting a mass of 5.9M(circle dot) for the B star, we derive a mass of similar to(3.6 +/- 0.7)M(circle dot) for the F star. The disk mass is dynamically negligible; we estimate it to contain similar to 0.07M(circle plus) (M(circle plus), mass of the Earth) if it consists purely of dust.
C1 [Kloppenborg, Brian; Stencel, Robert] Univ Denver, Dept Phys & Astron, Denver, CO 80208 USA.
   [Monnier, John D.; Baron, Fabien; Che, Xiao] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Schaefer, Gail; McAlister, Hal; ten Brummelaar, Theo; Farrington, Chris; Sallave-Goldfinger, P. J.; Sturmann, Judit; Sturmann, Laszlo; Turner, Nils] Georgia State Univ, Ctr High Angular Resolut Astron, Atlanta, GA 30302 USA.
   [Zhao, Ming] Jet Prop Lab, Pasadena, CA 91101 USA.
   [Pedretti, Ettore; Thureau, Nathalie] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Carroll, Sean M.] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
C3 University of Denver; University of Michigan System; University of Michigan; University System of Georgia; Georgia State University; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of St Andrews; California Institute of Technology
RP Kloppenborg, B (corresponding author), Univ Denver, Dept Phys & Astron, 2112 E Wesley Ave, Denver, CO 80208 USA.
EM bkloppen@du.edu; rstencel@du.edu
FU US National Science Foundation (NSF); Georgia State University; W. M. Keck Foundation; David and Lucile Packard Foundation; office of the Dean of the College of Arts and Science at Georgia State University; University of Michigan; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908253] Funding Source: National Science Foundation
NR 21
TC 144
Z9 155
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 APR 8
PY 2010
VL 464
IS 7290
BP 870
EP 872
DI 10.1038/nature08968
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300032
PM 20376144
DA 2026-03-09
ER

PT J
AU Wilson, CA
   Tsuchida, MA
   Allen, GM
   Barnhart, EL
   Applegate, KT
   Yam, PT
   Ji, L
   Keren, K
   Danuser, G
   Theriot, JA
AF Wilson, Cyrus A.
   Tsuchida, Mark A.
   Allen, Greg M.
   Barnhart, Erin L.
   Applegate, Kathryn T.
   Yam, Patricia T.
   Ji, Lin
   Keren, Kinneret
   Danuser, Gaudenz
   Theriot, Julie A.
TI Myosin II contributes to cell-scale actin network treadmilling through network disassembly
SO NATURE
LA English
DT Article
ID f-actin; migrating cells; motility; cytokinesis; filaments; turnover; dynamics; blebbistatin; localization; protrusion
AB Crawling locomotion of eukaryotic cells is achieved by a process dependent on the actin cytoskeleton(1): protrusion of the leading edge requires assembly of a network of actin filaments(2), which must be disassembled at the cell rear for sustained motility. Although ADF/cofilin proteins have been shown to contribute to actin disassembly(3), it is not clear how activity of these locally acting proteins could be coordinated over the distance scale of the whole cell. Here we show that non-muscle myosin II has a direct role in actin network disassembly in crawling cells. In fish keratocytes undergoing motility, myosin II is concentrated in regions at the rear with high rates of network disassembly. Activation of myosin II by ATP in detergent-extracted cytoskeletons results in rear-localized disassembly of the actin network. Inhibition of myosin II activity and stabilization of actin filaments synergistically impede cell motility, suggesting the existence of two disassembly pathways, one of which requires myosin II activity. Our results establish the importance of myosin II as an enzyme for actin network disassembly; we propose that gradual formation and reorganization of an actomyosin network provides an intrinsic destruction timer, enabling long-range coordination of actin network treadmilling in motile cells.
C1 [Wilson, Cyrus A.; Tsuchida, Mark A.; Allen, Greg M.; Barnhart, Erin L.; Yam, Patricia T.; Keren, Kinneret; Theriot, Julie A.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Wilson, Cyrus A.; Tsuchida, Mark A.; Allen, Greg M.; Barnhart, Erin L.; Yam, Patricia T.; Keren, Kinneret; Theriot, Julie A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Applegate, Kathryn T.; Ji, Lin; Danuser, Gaudenz] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Theriot, Julie A.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University; Scripps Research Institute; Stanford University
RP Theriot, JA (corresponding author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
EM theriot@stanford.edu
FU National Institutes of Health [R01AI067712, T32GM007276, U54GM64346, U01GM67230]; Stanford Medical Scientist Training Program; Howard Hughes Medical Institute; Stanford Graduate Fellowship; Skye International Foundation; National Science Foundation; Damon Runyon Cancer Research Foundation (DRG) [1854-05]; National Institute of General Medical Sciences [T32GM007276] Funding Source: NIH RePORTER
NR 29
TC 322
Z9 398
U1 0
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 20
PY 2010
VL 465
IS 7296
BP 373
EP U137
DI 10.1038/nature08994
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200046
PM 20485438
DA 2026-03-09
ER

PT J
AU Hedges, MP
   Longdell, JJ
   Li, YM
   Sellars, MJ
AF Hedges, Morgan P.
   Longdell, Jevon J.
   Li, Yongmin
   Sellars, Matthew J.
TI Efficient quantum memory for light
SO NATURE
LA English
DT Article
ID fields
AB Storing and retrieving a quantum state of light on demand, without corrupting the information it carries, is an important challenge in the field of quantum information processing. Classical measurement and reconstruction strategies for storing light must necessarily destroy quantum information as a consequence of the Heisenberg uncertainty principle. There has been significant effort directed towards the development of devices so-called quantum memories-capable of avoiding this penalty. So far, successful demonstrations(1-6) of non-classical storage and on-demand recall have used atomic vapours and have been limited to low efficiencies, of less than 17 per cent, using weak quantum states with an average photon number of around one. Here we report a low-noise, highly efficient (up to 69 per cent) quantum memory for light that uses a solid-state medium. The device allows the storage and recall of light more faithfully than is possible using a classical memory, for weak coherent states at the single-photon level through to bright states of up to 500 photons. For input coherent states containing on average 30 photons or fewer, the performance exceeded the no-cloning limit. This guaranteed that more information about the inputs was retrieved from the memory than was left behind or destroyed, a feature that will provide security in communications applications.
C1 [Hedges, Morgan P.; Sellars, Matthew J.] Australian Natl Univ, Res Sch Phys & Engn, Laser Phys Ctr, Canberra, ACT 0200, Australia.
   [Longdell, Jevon J.] Univ Otago, Dept Phys, Jack Dodd Ctr, Dunedin 9016, New Zealand.
   [Li, Yongmin] Shanxi Univ, State Key Lab Quantum Opt & Quantum Opt Devices, Inst Optoelect, Taiyuan 030006, Peoples R China.
C3 Australian National University; University of Otago; Shanxi University; State Key Laboratory of Quantum Optics & Quantum Optics Devices
RP Hedges, MP (corresponding author), Australian Natl Univ, Res Sch Phys & Engn, Laser Phys Ctr, GPO Box 4, Canberra, ACT 0200, Australia.
EM mph111@physics.anu.edu.au
FU Australian Research Council; New Zealand Foundation for Research Science and Technology
NR 31
TC 521
Z9 563
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 JUN 24
PY 2010
VL 465
IS 7301
BP 1052
EP 1056
DI 10.1038/nature09081
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900047
PM 20577210
DA 2026-03-09
ER

PT J
AU Wörner, HJ
   Bertrand, JB
   Kartashov, DV
   Corkum, PB
   Villeneuve, DM
AF Woerner, H. J.
   Bertrand, J. B.
   Kartashov, D. V.
   Corkum, P. B.
   Villeneuve, D. M.
TI Following a chemical reaction using high-harmonic interferometry
SO NATURE
LA English
DT Article
ID multiphoton ionization; multielectron dynamics; cross-sections; generation; molecules; spectroscopy; diffraction; continuum
AB The study of chemical reactions on the molecular (femtosecond) timescale typically uses pump laser pulses to excite molecules and subsequent probe pulses to interrogate them. The ultrashort pump pulse can excite only a small fraction of molecules, and the probe wavelength must be carefully chosen to discriminate between excited and unexcited molecules. The past decade has seen the emergence of new methods that are also aimed at imaging chemical reactions as they occur, based on X-ray diffraction(1), electron diffraction(2) or laser-induced recollision(3,4)-with spectral selection not available for any of these new methods. Here we show that in the case of high-harmonic spectroscopy based on recollision, this apparent limitation becomes a major advantage owing to the coherent nature of the attosecond high-harmonic pulse generation. The coherence allows the unexcited molecules to act as local oscillators against which the dynamics are observed, so a transient grating technique(5,6) can be used to reconstruct the amplitude and phase of emission from the excited molecules. We then extract structural information from the amplitude, which encodes the internuclear separation, by quantum interference at short times and by scattering of the recollision electron at longer times. The phase records the attosecond dynamics of the electrons, giving access to the evolving ionization potentials and the electronic structure of the transient molecule. In our experiment, we are able to document a temporal shift of the high-harmonic field of less than an attosecond (1 as = 10(-18) s) between the stretched and compressed geometry of weakly vibrationally excited Br-2 in the electronic ground state. The ability to probe structural and electronic features, combined with high time resolution, make high-harmonic spectroscopy ideally suited to measuring coupled electronic and nuclear dynamics occurring in photochemical reactions and to characterizing the electronic structure of transition states.
C1 [Woerner, H. J.; Bertrand, J. B.; Kartashov, D. V.; Corkum, P. B.; Villeneuve, D. M.] Natl Res Council Canada, Joint Lab Attosecond Sci, Ottawa, ON K1A 0R6, Canada.
   [Woerner, H. J.; Bertrand, J. B.; Kartashov, D. V.; Corkum, P. B.; Villeneuve, D. M.] Univ Ottawa, Ottawa, ON K1A 0R6, Canada.
   [Kartashov, D. V.] Vienna Univ Technol, Inst Photon, A-1040 Vienna, Austria.
C3 National Research Council Canada; University of Ottawa; Technische Universitat Wien
RP Villeneuve, DM (corresponding author), Natl Res Council Canada, Joint Lab Attosecond Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada.
EM david.villeneuve@nrc.ca
FU Canadian Institute for Photonic Innovation; NSERC; AFOSR; Swiss National Science Foundation (SNF)
NR 30
TC 403
Z9 443
U1 1
U2 200
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 604
EP 607
DI 10.1038/nature09185
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100049
PM 20671706
DA 2026-03-09
ER

PT J
AU Kissa, K
   Herbomel, P
AF Kissa, Karima
   Herbomel, Philippe
TI Blood stem cells emerge from aortic endothelium by a novel type of cell transition
SO NATURE
LA English
DT Article
ID haemogenic endothelium; zebrafish development; transgenic zebrafish; hematopoietic-cells; embryos
AB The ontogeny of haematopoietic stem cells (HSCs) during embryonic development is still highly debated, especially their possible lineage relationship to vascular endothelial cells(1,2). The first anatomical site from which cells with long-term HSC potential have been isolated is the aorta-gonad-mesonephros (AGM), more specifically the vicinity of the dorsal aortic floor(3). But although some authors have presented evidence that HSCs may arise directly from the aortic floor into the dorsal aortic lumen(4), others support the notion that HSCs first emerge within the underlying mesenchyme(5). Here we show by non-invasive, high-resolution imaging of live zebrafish embryos, that HSCs emerge directly from the aortic floor, through a stereotyped process that does not involve cell division but a strong bending then egress of single endothelial cells from the aortic ventral wall into the sub-aortic space, and their concomitant transformation into haematopoietic cells. The process is polarized not only in the dorso-ventral but also in the rostro-caudal versus medio-lateral direction, and depends on Runx1 expression: in Runx1-deficient embryos, the exit events are initially similar, but much rarer, and abort into violent death of the exiting cell. These results demonstrate that the aortic floor is haemogenic and that HSCs emerge from it into the sub-aortic space, not by asymmetric cell division but through a new type of cell behaviour, which we call an endothelial haematopoietic transition.
C1 [Kissa, Karima; Herbomel, Philippe] Inst Pasteur, Unite Macrophages & Dev Immun, F-75724 Paris 15, France.
   [Kissa, Karima; Herbomel, Philippe] CNRS, URA2578, F-75724 Paris 15, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS)
RP Herbomel, P (corresponding author), Inst Pasteur, Unite Macrophages & Dev Immun, 25 Rue Dr Roux, F-75724 Paris 15, France.
EM philippe.herbomel@pasteur.fr
NR 21
TC 771
Z9 925
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 112
EP U125
DI 10.1038/nature08761
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500044
PM 20154732
DA 2026-03-09
ER

PT J
AU Cejka, P
   Cannavo, E
   Polaczek, P
   Masuda-Sasa, T
   Pokharel, S
   Campbell, JL
   Kowalczykowski, SC
AF Cejka, Petr
   Cannavo, Elda
   Polaczek, Piotr
   Masuda-Sasa, Taro
   Pokharel, Subhash
   Campbell, Judith L.
   Kowalczykowski, Stephen C.
TI DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2
SO NATURE
LA English
DT Article
ID replication-protein-a; double-strand breaks; recombinational repair; mre11 nuclease; recq helicase; recbcd enzyme; blm helicase; in-vivo; sgs1; yeast
AB The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3'-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases(2-4). Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5'-terminated strand of the DNA break and to inhibit 39 to 59 degradation by Dna2, actions that generate and protect the 3'-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11-Rad50-Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3-Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes.
C1 [Cejka, Petr; Cannavo, Elda; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Cejka, Petr; Cannavo, Elda; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Polaczek, Piotr; Masuda-Sasa, Taro; Pokharel, Subhash; Campbell, Judith L.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis; California Institute of Technology
RP Kowalczykowski, SC (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM sckowalczykowski@ucdavis.edu
FU Swiss National Science Foundation; National Institutes of Health [GM-78666, GM-41347, GM-62653]
NR 35
TC 373
Z9 473
U1 1
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 SEP 2
PY 2010
VL 467
IS 7311
BP 112
EP U149
DI 10.1038/nature09355
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200046
PM 20811461
DA 2026-03-09
ER

PT J
AU Schulze, S
   Köster, S
   Geldmacher, U
   van Scheltinga, ACT
   Kühlbrandt, W
AF Schulze, Sabrina
   Koester, Stefan
   Geldmacher, Ulrike
   van Scheltinga, Anke C. Terwisscha
   Kuehlbrandt, Werner
TI Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT
SO NATURE
LA English
DT Article
ID solutes glycine betaine; cation-pi interaction; crystal-structure; carnitine transporter; escherichia-coli; binding; mechanism; determinants; symporter; alignment
AB Transport of solutes across biological membranes is performed by specialized secondary transport proteins in the lipid bilayer(1), and is essential for life. Here we report the structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from Proteus mirabilis (PmCaiT) at 2.3-angstrom and from Escherichia coli (EcCaiT) at 3.5-angstrom resolution. CaiT belongs to the family of betaine/carnitine/choline transporters (BCCT), which are mostly Na+ or H+ dependent, whereas EcCaiT is Na+ and H+ independent(2). The three-dimensional architecture of CaiT resembles that of the Na+-dependent transporters LeuT(3) and BetP(4), but in CaiT a methionine sulphur takes the place of the Na+ ion to coordinate the substrate in the central transport site, accounting for Na+-independent transport. Both CaiT structures show the fully open, inward-facing conformation, and thus complete the set of functional states that describe the alternating access mechanism(5). EcCaiT contains two bound butyrobetaine substrate molecules, one in the central transport site, the other in an extracellular binding pocket. In the structure of PmCaiT, a tryptophan side chain occupies the transport site, and access to the extracellular site is blocked. Binding of both substrates to CaiT reconstituted into proteoliposomes is cooperative, with Hill coefficients up to 1.7, indicating that the extracellular site is regulatory. We propose a mechanism whereby the occupied regulatory site increases the binding affinity of the transport site and initiates substrate translocation.
C1 [Schulze, Sabrina; Koester, Stefan; Geldmacher, Ulrike; van Scheltinga, Anke C. Terwisscha; Kuehlbrandt, Werner] Max Planck Inst Biophys, Dept Biol Struct, D-60438 Frankfurt, Germany.
C3 Max Planck Society
RP Kühlbrandt, W (corresponding author), Max Planck Inst Biophys, Dept Biol Struct, Max von Laue Str 3, D-60438 Frankfurt, Germany.
EM werner.kuehlbrandt@biophys.mpg.de
NR 36
TC 103
Z9 124
U1 0
U2 20
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 233
EP U129
DI 10.1038/nature09310
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300040
PM 20829798
DA 2026-03-09
ER

PT J
AU Polli, D
   Altoè, P
   Weingart, O
   Spillane, KM
   Manzoni, C
   Brida, D
   Tomasello, G
   Orlandi, G
   Kukura, P
   Mathies, RA
   Garavelli, M
   Cerullo, G
AF Polli, Dario
   Altoe, Piero
   Weingart, Oliver
   Spillane, Katelyn M.
   Manzoni, Cristian
   Brida, Daniele
   Tomasello, Gaia
   Orlandi, Giorgio
   Kukura, Philipp
   Mathies, Richard A.
   Garavelli, Marco
   Cerullo, Giulio
TI Conical intersection dynamics of the primary photoisomerization event in vision
SO NATURE
LA English
DT Article
ID initio molecular-dynamics; excited-state dynamics; 1st step; femtosecond isomerization; perturbation-theory; chromophore models; visual pigments; energy-storage; rhodopsin; spectroscopy
AB Ever since the conversion of the 11-cis retinal chromophore to its all-trans form in rhodopsin was identified as the primary photochemical event in vision(1), experimentalists and theoreticians have tried to unravel the molecular details of this process. The high quantum yield of 0.65 (ref. 2), the production of the primary ground-state rhodopsin photoproduct within a mere 200 fs (refs 3-7), and the storage of considerable energy in the first stable bathorhodopsin intermediate(8) all suggest an unusually fast and efficient photoactivated one-way reaction(9). Rhodopsin's unique reactivity is generally attributed to a conical intersection between the potential energy surfaces of the ground and excited electronic states(10,11) enabling the efficient and ultrafast conversion of photon energy into chemical energy(12-16). But obtaining direct experimental evidence for the involvement of a conical intersection is challenging: the energy gap between the electronic states of the reacting molecule changes significantly over an ultrashort time-scale, which calls for observational methods that combine high temporal resolution with a broad spectral observation window. Here we show that ultrafast optical spectroscopy with sub-20-fs time resolution and spectral coverage from the visible to the near-infrared allows us to follow the dynamics leading to the conical intersection in rhodopsin isomerization. We track coherent wave-packet motion from the photoexcited Franck-Condon region to the photoproduct by monitoring the loss of reactant emission and the subsequent appearance of photoproduct absorption, and find excellent agreement between the experimental observations and molecular dynamics calculations that involve a true electronic state crossing. Taken together, these findings constitute the most compelling evidence to date for the existence and importance of conical intersections in visual photochemistry.
C1 [Altoe, Piero; Tomasello, Gaia; Orlandi, Giorgio; Garavelli, Marco] Univ Bologna, Dipartimento Chim G Ciamician, I-40126 Bologna, Italy.
   [Polli, Dario; Manzoni, Cristian; Brida, Daniele; Cerullo, Giulio] Politecn Milan, IFN, CNR, Dipartimento Fis, I-20133 Milan, Italy.
   [Weingart, Oliver] Univ Duisburg Essen, Lehrstuhl Theoret Chem, D-45117 Essen, Germany.
   [Weingart, Oliver] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
   [Spillane, Katelyn M.; Mathies, Richard A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Kukura, Philipp] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
C3 University of Bologna; Consiglio Nazionale delle Ricerche (CNR); Istituto di Fotonica e Nanotecnologie (IFN-CNR); Polytechnic University of Milan; University of Duisburg Essen; Max Planck Society; University of California System; University of California Berkeley; University of Oxford
RP Garavelli, M (corresponding author), Univ Bologna, Dipartimento Chim G Ciamician, Via F Selmi 2, I-40126 Bologna, Italy.
EM marco.garavelli@unibo.it; giulio.cerullo@fisi.polimi.it
FU DFG [FOR490]; PRIN programme [2008JKBBK4]; UK Engineering and Physical Sciences Research Council [EP/H003541/1]; Engineering and Physical Sciences Research Council [EP/H003541/1] Funding Source: researchfish; EPSRC [EP/H003541/1] Funding Source: UKRI
NR 45
TC 796
Z9 895
U1 3
U2 476
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 440
EP U88
DI 10.1038/nature09346
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200038
PM 20864998
DA 2026-03-09
ER

PT J
AU Voss, JE
   Vaney, MC
   Duquerroy, S
   Vonrhein, C
   Girard-Blanc, C
   Crublet, E
   Thompson, A
   Bricogne, G
   Rey, FA
AF Voss, James E.
   Vaney, Marie-Christine
   Duquerroy, Stephane
   Vonrhein, Clemens
   Girard-Blanc, Christine
   Crublet, Elodie
   Thompson, Andrew
   Bricogne, Gerard
   Rey, Felix A.
TI Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography
SO NATURE
LA English
DT Article
ID semliki-forest-virus; membrane-fusion; conformational-change; spike protein; envelope; surface; replacement; e1; ph
AB Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused widespread outbreaks of debilitating human disease in the past five years(1). CHIKV invasion of susceptible cells is mediated by two viral glycoproteins, E1 and E2, which carry the main antigenic determinants and form an icosahedral shell at the virion surface. Glycoprotein E2, derived from furin cleavage of the p62 precursor into E3 and E2, is responsible for receptor binding, and E1 for membrane fusion. In the context of a concerted multidisciplinary effort to understand the biology of CHIKV2, here we report the crystal structures of the precursor p62-E1 heterodimer and of the mature E3-E2-E1 glycoprotein complexes. The resulting atomic models allow the synthesis of a wealth of genetic, biochemical, immunological and electron microscopy data accumulated over the years on alphaviruses in general. This combination yields a detailed picture of the functional architecture of the 25 MDa alphavirus surface glycoprotein shell. Together with the accompanying report on the structure of the Sindbis virus E2-E1 heterodimer at acidic pH (ref. 3), this work also provides new insight into the acid-triggered conformational change on the virus particle and its inbuilt inhibition mechanism in the immature complex.
C1 [Voss, James E.; Vaney, Marie-Christine; Duquerroy, Stephane; Rey, Felix A.] Inst Pasteur, Dept Virol, Unite Virol Struct, F-75724 Paris 15, France.
   [Voss, James E.; Vaney, Marie-Christine; Duquerroy, Stephane; Rey, Felix A.] CNRS, URA 3015, F-75724 Paris 15, France.
   [Duquerroy, Stephane] Univ Paris Sud, Fac Orsay, F-91405 Orsay, France.
   [Vonrhein, Clemens; Bricogne, Gerard] Global Phasing Ltd, Cambridge CB3 0AX, England.
   [Girard-Blanc, Christine; Crublet, Elodie] Inst Pasteur, Dept Biol Struct & Chim, F-75724 Paris 15, France.
   [Girard-Blanc, Christine; Crublet, Elodie] CNRS, URA 2185, F-75724 Paris 15, France.
   [Thompson, Andrew] Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Global Phasing Limited; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); SOLEIL Synchrotron
RP Rey, FA (corresponding author), Inst Pasteur, Dept Virol, Unite Virol Struct, 25 Rue Dr Roux, F-75724 Paris 15, France.
EM rey@pasteur.fr
FU European Union Research Traning Network; French 'Agence Nationale de la Recherche'; Merck-Serono; Pediatric Dengue Vaccine Initiative; Institut Pasteur [PTR201 CHIKV]
NR 44
TC 539
Z9 625
U1 2
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 709
EP U137
DI 10.1038/nature09555
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700044
PM 21124458
DA 2026-03-09
ER

PT J
AU Meyer-Lindenberg, A
AF Meyer-Lindenberg, Andreas
TI From maps to mechanisms through neuroimaging of schizophrenia
SO NATURE
LA English
DT Article
ID val(108/158) met genotype; o-methyltransferase comt; genome-wide association; prefrontal cortex; functional connectivity; gene-expression; gray-matter; reward prediction; cortical function; dopamine function
AB Functional and structural brain imaging has identified neural and neurotransmitter systems involved in schizophrenia and their link to cognitive and behavioural disturbances such as psychosis. Mapping such abnormalities in patients, however, cannot fully capture the strong neurodevelopmental component of schizophrenia that pre-dates manifest illness. A recent strategy to address this issue has been to focus on mechanisms of disease risk. Imaging genetics techniques have made it possible to define neural systems that mediate heritable risk linked to candidate and genome-wide-supported common variants, and mechanisms for environmental risk and gene-environment interactions are emerging. Characterizing the neural risk architecture of schizophrenia provides a translational research strategy for future treatments.
C1 Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, D-68159 Mannheim, Germany.
C3 Ruprecht Karls University Heidelberg; Central Institute of Mental Health
RP Meyer-Lindenberg, A (corresponding author), Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, J5, D-68159 Mannheim, Germany.
EM a.meyer-lindenberg@zi-mannheim.de
FU Deutsche Forschungsgemeinschaft [SFB 636]; BMBF; EU; NARSAD
NR 112
TC 241
Z9 261
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 NOV 11
PY 2010
VL 468
IS 7321
BP 194
EP 202
DI 10.1038/nature09569
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000035
PM 21068827
DA 2026-03-09
ER

PT J
AU Zalmout, IS
   Sanders, WJ
   MacLatchy, LM
   Gunnell, GF
   Al-Mufarreh, YA
   Ali, MA
   Nasser, AAH
   Al-Masari, AM
   Al-Sobhi, SA
   Nadhra, AO
   Matari, AH
   Wilson, JA
   Gingerich, PD
AF Zalmout, Iyad S.
   Sanders, William J.
   MacLatchy, Laura M.
   Gunnell, Gregg F.
   Al-Mufarreh, Yahya A.
   Ali, Mohammad A.
   Nasser, Abdul-Azziz H.
   Al-Masari, Abdu M.
   Al-Sobhi, Salih A.
   Nadhra, Ayman O.
   Matari, Adel H.
   Wilson, Jeffrey A.
   Gingerich, Philip D.
TI New Oligocene primate from Saudi Arabia and the divergence of apes and Old World monkeys
SO NATURE
LA English
DT Article
ID catarrhine primates; early miocene; aegyptopithecus; morphology; evolution
AB It is widely understood that Hominoidea (apes and humans) and Cercopithecoidea (Old World monkeys) have a common ancestry as Catarrhini deeply rooted in Afro-Arabia(1-4). The oldest stem Catarrhini in the fossil record are Propliopithecoidea, known from the late Eocene to early Oligocene epochs (roughly 35-30 Myr ago) of Egypt, Oman and possibly Angola(5-10). Genome-based estimates for divergence of hominoids and cercopithecoids range into the early Oligocene(11); however, the mid-to-late Oligocene interval from 30 to 23 Myr ago has yielded little fossil evidence documenting the morphology of the last common ancestor of hominoids and cercopithecoids, the timing of their divergence, or the relationship of early stem and crown catarrhines. Here we describe the partial cranium of a new medium-sized (about 15-20 kg) fossil catarrhine, Saadanius hijazensis, dated to 29-28 Myr ago. Comparative anatomy and cladistic analysis shows that Saadanius is an advanced stem catarrhine close to the base of the hominoid-cercopithecoid clade. Saadanius is important for assessing competing hypotheses about the ancestral morphotype for crown catarrhines(1,12-14), early catarrhine phylogeny(12,15) and the age of hominoid-cercopithecoid divergence(11). Saadanius has a tubular ectotympanic but lacks synapomorphies of either group of crown Catarrhini, and we infer that the hominoid-cercopithecoid split happened later, between 29-28 and 24 Myr ago.
C1 [Zalmout, Iyad S.; Sanders, William J.; MacLatchy, Laura M.; Gunnell, Gregg F.; Wilson, Jeffrey A.; Gingerich, Philip D.] Univ Michigan, Museum Paleontol, Ann Arbor, MI 48109 USA.
   [Zalmout, Iyad S.; Wilson, Jeffrey A.; Gingerich, Philip D.] Univ Michigan, Dept Geol Sci, Ann Arbor, MI 48109 USA.
   [Sanders, William J.; MacLatchy, Laura M.; Gingerich, Philip D.] Univ Michigan, Dept Anthropol, Ann Arbor, MI 48109 USA.
   [Al-Mufarreh, Yahya A.; Ali, Mohammad A.; Nasser, Abdul-Azziz H.; Al-Masari, Abdu M.; Al-Sobhi, Salih A.; Nadhra, Ayman O.; Matari, Adel H.] Saudi Geol Survey, Paleontol Unit, Jeddah 21514, Saudi Arabia.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Saudi Geological Survey
RP Zalmout, IS (corresponding author), Univ Michigan, Museum Paleontol, 1109 Geddes Ave, Ann Arbor, MI 48109 USA.
EM zalmouti@umich.edu; wsanders@umich.edu; gingeric@umich.edu
FU US National Science Foundation [EAR-0517773]; Directorate For Geosciences [0920972] Funding Source: National Science Foundation; Division Of Earth Sciences [0920972] Funding Source: National Science Foundation
NR 30
TC 77
Z9 91
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 360
EP U111
DI 10.1038/nature09094
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100047
PM 20631798
DA 2026-03-09
ER

PT J
AU Joshi, PA
   Jackson, HW
   Beristain, AG
   Di Grappa, MA
   Mote, PA
   Clarke, CL
   Stingl, J
   Waterhouse, PD
   Khokha, R
AF Joshi, Purna A.
   Jackson, Hartland W.
   Beristain, Alexander G.
   Di Grappa, Marco A.
   Mote, Patricia A.
   Clarke, Christine L.
   Stingl, John
   Waterhouse, Paul D.
   Khokha, Rama
TI Progesterone induces adult mammary stem cell expansion
SO NATURE
LA English
DT Article
ID breast-cancer; gland development; epithelial-cells; estrous-cycle; receptor-b; differentiation; risk; 17-beta-estradiol; proliferation; morphogenesis
AB Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density(1,2). Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown(3-5). Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation(6). The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49f(hi) cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49f(hi) cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer.
C1 [Joshi, Purna A.; Jackson, Hartland W.; Beristain, Alexander G.; Di Grappa, Marco A.; Waterhouse, Paul D.; Khokha, Rama] Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Joshi, Purna A.; Jackson, Hartland W.; Beristain, Alexander G.; Di Grappa, Marco A.; Waterhouse, Paul D.; Khokha, Rama] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 2M9, Canada.
   [Mote, Patricia A.; Clarke, Christine L.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia.
   [Stingl, John] Li Ka Shing Ctr, Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England.
C3 University of Toronto; University Health Network Toronto; University of Toronto; University of Sydney; Westmead Institute for Medical Research; Cancer Research UK; University of Cambridge; CRUK Cambridge Institute
RP Khokha, R (corresponding author), Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
EM rkhokha@uhnres.utoronto.ca
FU Canadian Breast Cancer Research Alliance; National Cancer Institute of Canada; Canadian Breast Cancer Foundation, Ontario; MRC [G0800784] Funding Source: UKRI; Medical Research Council [G0800784, G0300723B, G0800784B] Funding Source: researchfish
NR 30
TC 552
Z9 642
U1 4
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 803
EP 807
DI 10.1038/nature09091
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800050
PM 20445538
DA 2026-03-09
ER

PT J
AU Dorrn, AL
   Yuan, K
   Barker, AJ
   Schreiner, CE
   Froemke, RC
AF Dorrn, Anja L.
   Yuan, Kexin
   Barker, Alison J.
   Schreiner, Christoph E.
   Froemke, Robert C.
TI Developmental sensory experience balances cortical excitation and inhibition
SO NATURE
LA English
DT Article
ID primary auditory-cortex; visual-cortex; synaptic depression; receptive-fields; barrel cortex; in-vivo; plasticity; rat; neurons; competition
AB Early in life, neural circuits are highly susceptible to outside influences. The organization of the primary auditory cortex (A1) in particular is governed by acoustic experience during the critical period, an epoch near the beginning of postnatal development throughout which cortical synapses and networks are especially plastic(1-8). This neonatal sensitivity to the pattern of sensory inputs is believed to be essential for constructing stable and adequately adapted representations of the auditory world and for the acquisition of language skills by children(5,9,10). One important principle of synaptic organization in mature brains is the balance between excitation and inhibition, which controls receptive field structure and spatiotemporal flow of neural activity(11-15), but it is unknown how and when this excitatory-inhibitory balance is initially established and calibrated. Here we use whole-cell recording to determine the processes underlying the development of synaptic receptive fields in rat A1. We find that, immediately after the onset of hearing, sensory-evoked excitatory and inhibitory responses are equally strong, although inhibition is less stimulus-selective and mismatched with excitation. However, during the third week of postnatal development, excitation and inhibition become highly correlated. Patterned sensory stimulation drives coordinated synaptic changes across receptive fields, rapidly improves excitatory-inhibitory coupling and prevents further exposure-induced modifications. Thus, the pace of cortical synaptic receptive field development is set by progressive, experience-dependent refinement of intracortical inhibition.
C1 [Dorrn, Anja L.; Yuan, Kexin; Barker, Alison J.; Schreiner, Christoph E.; Froemke, Robert C.] Univ Calif San Francisco, Coleman Mem Lab, San Francisco, CA 94143 USA.
   [Dorrn, Anja L.; Yuan, Kexin; Barker, Alison J.; Schreiner, Christoph E.; Froemke, Robert C.] Univ Calif San Francisco, Coleman Mem Lab, WM Keck Fdn Ctr Integrat Neurosci, Neurosci Grad Program,Dept Otolaryngol, San Francisco, CA 94143 USA.
   [Dorrn, Anja L.] Max Delbruck Ctr Mol Med, Dept Neurosci, D-13125 Berlin, Germany.
   [Dorrn, Anja L.] NeuroCure Neurosci Res Ctr NWFZ, D-13125 Berlin, Germany.
   [Froemke, Robert C.] NYU, Sch Med, Mol Neurobiol Program, Helen & Martin Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Froemke, Robert C.] NYU, Sch Med, Skirball Inst Biomol Med, Dept Otolaryngol, New York, NY 10016 USA.
   [Froemke, Robert C.] NYU, Sch Med, Dept Physiol, New York, NY 10016 USA.
   [Froemke, Robert C.] NYU, Sch Med, Dept Neurosci, New York, NY 10016 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Helmholtz Association; Max Delbruck Center for Molecular Medicine; New York University; New York University; New York University; New York University
RP Froemke, RC (corresponding author), Univ Calif San Francisco, Coleman Mem Lab, San Francisco, CA 94143 USA.
EM robert.froemke@med.nyu.edu
FU National Institute on Deafness and Other Communication Disorders [K99/R00]; Silvio O. Conte Center for Neuroscience Research at the University of California, San Francisco; Hearing Research Inc.; John C. and Edward Coleman Fund; Jane Coffin Childs Postdoctoral Research Fellowship; Sandler Translational Research Fellowship; National Science Foundation
NR 29
TC 242
Z9 295
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 17
PY 2010
VL 465
IS 7300
BP 932
EP U9
DI 10.1038/nature09119
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500039
PM 20559387
DA 2026-03-09
ER

PT J
AU Berry, MPR
   Graham, CM
   McNab, FW
   Xu, ZH
   Bloch, SAA
   Oni, T
   Wilkinson, KA
   Banchereau, R
   Skinner, J
   Wilkinson, RJ
   Quinn, C
   Blankenship, D
   Dhawan, R
   Cush, JJ
   Mejias, A
   Ramilo, O
   Kon, OM
   Pascual, V
   Banchereau, J
   Chaussabel, D
   O'Garra, A
AF Berry, Matthew P. R.
   Graham, Christine M.
   McNab, Finlay W.
   Xu, Zhaohui
   Bloch, Susannah A. A.
   Oni, Tolu
   Wilkinson, Katalin A.
   Banchereau, Romain
   Skinner, Jason
   Wilkinson, Robert J.
   Quinn, Charles
   Blankenship, Derek
   Dhawan, Ranju
   Cush, John J.
   Mejias, Asuncion
   Ramilo, Octavio
   Kon, Onn M.
   Pascual, Virginia
   Banchereau, Jacques
   Chaussabel, Damien
   O'Garra, Anne
TI An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
SO NATURE
LA English
DT Article
ID gene-expression patterns; mycobacterium-tuberculosis; infection; responses; immunity; cells
AB Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment(1,2). Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease(3). The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines(4,5). Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alpha beta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alpha beta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.
C1 [Berry, Matthew P. R.; Graham, Christine M.; McNab, Finlay W.; O'Garra, Anne] Natl Inst Med Res, MRC, Div Immunoregulat, London NW7 1AA, England.
   [Wilkinson, Katalin A.; Wilkinson, Robert J.] Natl Inst Med Res, MRC, Div Mycobacterial Res, London NW7 1AA, England.
   [Bloch, Susannah A. A.; Kon, Onn M.] Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Resp Med, London W2 1NY, England.
   [Oni, Tolu; Wilkinson, Katalin A.; Wilkinson, Robert J.] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Observatory, South Africa.
   [Oni, Tolu] Univ London Imperial Coll Sci Technol & Med, Wright Fleming Inst, Div Med, London W2 1PG, England.
   [Xu, Zhaohui; Skinner, Jason; Quinn, Charles; Cush, John J.; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien] ANRS Ctr Human Vaccines, INSERM, U899, Baylor Inst Immunol Res, Dallas, TX 75204 USA.
   [Blankenship, Derek] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA.
   [Dhawan, Ranju] Imperial Coll Healthcare NHS Trust, St Marys Hosp, Dept Radiol, London W2 1NY, England.
   [Banchereau, Romain] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Mejias, Asuncion; Ramilo, Octavio] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Res Inst, Columbus, OH 43205 USA.
C3 MRC National Institute for Medical Research; MRC National Institute for Medical Research; Imperial College London; University of Cape Town; Imperial College London; Baylor Scott & White Health; Institut National de la Sante et de la Recherche Medicale (Inserm); Baylor Scott & White Health; Imperial College London; University of Texas System; University of Texas Southwestern Medical Center; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; Center for Vaccines & Immunity
RP O'Garra, A (corresponding author), Natl Inst Med Res, MRC, Div Immunoregulat, Mill Hill, London NW7 1AA, England.
EM aogarra@nimr.mrc.ac.uk
FU MRC; Dana Foundation; Medical Research Council, UK [U117565642]; National Institutes of Health (NIH) [R01 AR050770-01, P50 ARO54083, 1 U19 AI082715-01, U19 AIO57234-02, U01 AI082110, P01 CA084512]; Baylor Health Care System Foundation; MRC [MC_U117565642, MC_U117588499] Funding Source: UKRI; Medical Research Council [MC_U117565642, MC_U117588499] Funding Source: researchfish
NR 30
TC 1521
Z9 1758
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 AUG 19
PY 2010
VL 466
IS 7309
BP 973
EP U98
DI 10.1038/nature09247
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300034
PM 20725040
DA 2026-03-09
ER

PT J
AU Chen, ZC
   Borek, D
   Padrick, SB
   Gomez, TS
   Metlagel, Z
   Ismail, AM
   Umetani, J
   Billadeau, DD
   Otwinowski, Z
   Rosen, MK
AF Chen, Zhucheng
   Borek, Dominika
   Padrick, Shae B.
   Gomez, Timothy S.
   Metlagel, Zoltan
   Ismail, Ayman M.
   Umetani, Junko
   Billadeau, Daniel D.
   Otwinowski, Zbyszek
   Rosen, Michael K.
TI Structure and control of the actin regulatory WAVE complex
SO NATURE
LA English
DT Article
ID wasp/scar proteins; tyrosine kinase; cell-migration; wasp family; phosphorylation; activation; membrane; model; rac1; integration
AB Members of the Wiskott-Aldrich syndrome protein (WASP) family control cytoskeletal dynamics by promoting actin filament nucleation with the Arp2/3 complex. The WASP relative WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric WAVE regulatory complex (WRC). The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols. Here we report the 2.3-angstrom crystal structure of the WRC and complementary mechanistic analyses. The structure shows that the activity-bearing VCA motif of WAVE is sequestered by a combination of intramolecular and intermolecular contacts within the WRC. Rac and kinases appear to destabilize a WRC element that is necessary for VCA sequestration, suggesting the way in which these signals stimulate WRC activity towards the Arp2/3 complex. The spatial proximity of the Rac binding site and the large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes.
C1 [Chen, Zhucheng; Borek, Dominika; Padrick, Shae B.; Metlagel, Zoltan; Ismail, Ayman M.; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Chen, Zhucheng; Padrick, Shae B.; Metlagel, Zoltan; Ismail, Ayman M.; Umetani, Junko; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Gomez, Timothy S.; Billadeau, Daniel D.] Mayo Clin, Coll Med, Schulze Ctr Novel Therapeut, Div Oncol Res, Rochester, MN 55905 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Mayo Clinic
RP Rosen, MK (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM michael.rosen@utsouthwestern.edu
FU Cancer Research Institute; NIH [1F32-GM06917902, R01-AI065474, R01-GM053163, R01-GM056322]; Allergic Diseases Training grant [AI07047]; Welch Foundation [I-1544]; Howard Hughes Medical Institute; US DOE [DE-AC02-06CH11357]
NR 50
TC 375
Z9 486
U1 1
U2 41
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 533
EP U207
DI 10.1038/nature09623
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200035
PM 21107423
DA 2026-03-09
ER

PT J
AU Lavrentovich, OD
   Lazo, I
   Pishnyak, OP
AF Lavrentovich, Oleg D.
   Lazo, Israel
   Pishnyak, Oleg P.
TI Nonlinear electrophoresis of dielectric and metal spheres in a nematic liquid crystal
SO NATURE
LA English
DT Article
ID electric-field
AB Electrophoresis is a motion of charged dispersed particles relative to a fluid in a uniform electric field(1). The effect is widely used to separate macromolecules, to assemble colloidal structures and to transport particles in nano- and microfluidic devices and displays(2-4). Typically, the fluid is isotropic (for example, water) and the electrophoretic velocity is linearly proportional to the electric field. In linear electrophoresis, only a direct-current (d.c.) field can drive the particles. An alternating-current (a.c.) field is more desirable because it makes it possible to overcome problems such as electrolysis and the absence of steady flows(5,6). Here we show that when the electrophoresis is performed in a liquid-crystalline nematic fluid, the effect becomes strongly nonlinear, with a velocity component that is quadratic in the applied voltage and has a direction that generally differs from the direction of linear velocity. The new phenomenon is caused by distortions of the liquid-crystal orientation around the particle that break the fore-aft (or left-right) symmetry. The effect makes it possible to transport both charged and neutral particles, even when the particles themselves are perfectly symmetric (spherical), thus allowing new approaches in display technologies, colloidal assembly and separation, microfluidic and micromotor applications.
C1 [Lavrentovich, Oleg D.; Lazo, Israel; Pishnyak, Oleg P.] Kent State Univ, Inst Liquid Crystal, Kent, OH 44242 USA.
   [Lavrentovich, Oleg D.; Lazo, Israel; Pishnyak, Oleg P.] Kent State Univ, Chem Phys Interdisciplinary Program, Kent, OH 44242 USA.
C3 University System of Ohio; Kent State University; Kent State University Salem; Kent State University Kent; University System of Ohio; Kent State University; Kent State University Salem; Kent State University Kent
RP Lavrentovich, OD (corresponding author), Kent State Univ, Inst Liquid Crystal, Kent, OH 44242 USA.
EM olavrent@kent.edu
FU NSF [DMR 0906751]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0906751] Funding Source: National Science Foundation
NR 20
TC 133
Z9 156
U1 1
U2 137
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 21
PY 2010
VL 467
IS 7318
BP 947
EP 950
DI 10.1038/nature09427
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700034
PM 20962842
DA 2026-03-09
ER

PT J
AU Runguphan, W
   Qu, XD
   O'Connor, SE
AF Runguphan, Weerawat
   Qu, Xudong
   O'Connor, Sarah E.
TI Integrating carbon-halogen bond formation into medicinal plant metabolism
SO NATURE
LA English
DT Article
ID indole alkaloid biosynthesis; flavin-dependent halogenases; catharanthus-roseus; benzylisoquinoline alkaloids; immature seeds; pisum sativum; rebh; chlorination; periwinkle; strategy
AB Halogenation, which was once considered a rare occurrence in nature, has now been observed in many natural product biosynthetic pathways(1). However, only a small fraction of halogenated compounds have been isolated from terrestrial plants(2). Given the impact that halogenation can have on the biological activity of natural products(1), we reasoned that the introduction of halides into medicinal plant metabolism would provide the opportunity to rationally bioengineer a broad variety of novel plant products with altered, and perhaps improved, pharmacological properties. Here we report that chlorination biosynthetic machinery from soil bacteria can be successfully introduced into the medicinal plant Catharanthus roseus (Madagascar periwinkle). These prokaryotic halogenases function within the context of the plant cell to generate chlorinated tryptophan, which is then shuttled into monoterpene indole alkaloid metabolism to yield chlorinated alkaloids. A new functional group-a halide-is thereby introduced into the complex metabolism of C. roseus, and is incorporated in a predictable and regioselective manner onto the plant alkaloid products. Medicinal plants, despite their genetic and developmental complexity, therefore seem to be a viable platform for synthetic biology efforts.
C1 [Runguphan, Weerawat; Qu, Xudong; O'Connor, Sarah E.] MIT, Dept Chem, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP O'Connor, SE (corresponding author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM soc@mit.edu
FU NIH [GM074820]; American Cancer Society [RSG-07-025-01-CDD]
NR 32
TC 181
Z9 211
U1 3
U2 132
PU 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 18
PY 2010
VL 468
IS 7322
BP 461
EP U294
DI 10.1038/nature09524
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100048
PM 21048708
DA 2026-03-09
ER

PT J
AU Liu, XD
   Yang, PS
   Yang, WJ
   Yue, DT
AF Liu, Xiaodong
   Yang, Philemon S.
   Yang, Wanjun
   Yue, David T.
TI Enzyme-inhibitor-like tuning of Ca2+ channel connectivity with calmodulin
SO NATURE
LA English
DT Article
ID ca2+-dependent inactivation; calcium-channels; mechanisms; proteins; mice
AB Ca2+ channels and calmodulin (CaM) are two prominent signalling hubs(1) that synergistically affect functions as diverse as cardiac excitability(2), synaptic plasticity(3) and gene transcription(4). It is therefore fitting that these hubs are in some sense coordinated, as the opening of Ca(V)1-2 Ca2+ channels are regulated by a single CaM constitutively complexed with channels(5). The Ca2+-free form of CaM (apoCaM) is already pre-associated with the isoleucine-glutamine (IQ) domain on the channel carboxy terminus, and subsequent Ca2+ binding to this 'resident' CaM drives conformational changes that then trigger regulation of channel opening(6). Another potential avenue for channel-CaM coordination could arise from the absence of Ca2+ regulation in channels lacking a pre-associated CaM6,7. Natural fluctuations in CaM concentrations might then influence the fraction of regulable channels and, thereby, the overall strength of Ca2+ feedback. However, the prevailing view has been that the ultrastrong affinity of channels for apoCaM ensures their saturation with CaM8, yielding a significant form of concentration independence between Ca2+ channels and CaM. Here we show that significant exceptions to this autonomy exist, by combining electrophysiology (to characterize channel regulation) with optical fluorescence resonance energy transfer (FRET) sensor determination of free-apoCaM concentration in live cells(9). This approach translates quantitative CaM biochemistry from the traditional test-tube context into the realm of functioning holochannels within intact cells. From this perspective, we find that long splice forms of Ca(V)1.3 and Ca(V)1.4 channels include a distal carboxy tail(10-12) that resembles an enzyme competitive inhibitor that retunes channel affinity for apoCaM such that natural CaM variations affect the strength of Ca2+ feedback modulation. Given the ubiquity of these channels(13,14), the connection between ambient CaM levels and Ca2+ entry through channels is broadly significant for Ca2+ homeostasis. Strategies such as ours promise key advances for the in situ analysis of signalling molecules resistant to in vitro reconstitution, such as Ca2+ channels.
C1 [Liu, Xiaodong; Yang, Philemon S.; Yang, Wanjun; Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Calcium Signals Lab, Baltimore, MD 21205 USA.
   [Liu, Xiaodong; Yang, Philemon S.; Yang, Wanjun; Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University
RP Yue, DT (corresponding author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Calcium Signals Lab, Ross Bldg,Room 713,720 Rutland Ave, Baltimore, MD 21205 USA.
EM dyue@jhmi.edu
FU US National Institute of Mental Health; US National Heart, Lung, and Blood Institute; US National Institute of Neurological Disorders and Stroke
NR 30
TC 83
Z9 93
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 968
EP U149
DI 10.1038/nature08766
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700050
PM 20139964
DA 2026-03-09
ER

PT J
AU Law, RHP
   Lukoyanova, N
   Voskoboinik, I
   Caradoc-Davies, TT
   Baran, K
   Dunstone, MA
   D'Angelo, ME
   Orlova, EV
   Coulibaly, F
   Verschoor, S
   Browne, KA
   Ciccone, A
   Kuiper, MJ
   Bird, PI
   Trapani, JA
   Saibil, HR
   Whisstock, JC
AF Law, Ruby H. P.
   Lukoyanova, Natalya
   Voskoboinik, Ilia
   Caradoc-Davies, Tom T.
   Baran, Katherine
   Dunstone, Michelle A.
   D'Angelo, Michael E.
   Orlova, Elena V.
   Coulibaly, Fasseli
   Verschoor, Sandra
   Browne, Kylie A.
   Ciccone, Annette
   Kuiper, Michael J.
   Bird, Phillip I.
   Trapani, Joseph A.
   Saibil, Helen R.
   Whisstock, James C.
TI The structural basis for membrane binding and pore formation by lymphocyte perforin
SO NATURE
LA English
DT Article
ID cholesterol-dependent cytolysin; granzyme-b; crystal-structure; human-complement; 9th component; cell-death; t-cells; domain; cytotoxicity; identification
AB Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell(1-6). The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL)(7). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain(8,9) followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca2+-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs10,11. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.
C1 [Voskoboinik, Ilia; Baran, Katherine; Verschoor, Sandra; Browne, Kylie A.; Ciccone, Annette; Trapani, Joseph A.] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic 3002, Australia.
   [Law, Ruby H. P.; Dunstone, Michelle A.; D'Angelo, Michael E.; Coulibaly, Fasseli; Bird, Phillip I.; Whisstock, James C.] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3800, Australia.
   [Law, Ruby H. P.; Whisstock, James C.] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Melbourne, Vic 3800, Australia.
   [Lukoyanova, Natalya; Orlova, Elena V.; Saibil, Helen R.] Univ London Birkbeck Coll, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Voskoboinik, Ilia] Univ Melbourne, Dept Genet, Parkville, Vic 3010, Australia.
   [Caradoc-Davies, Tom T.] Australian Synchrotron, Melbourne, Vic 3168, Australia.
   [Dunstone, Michelle A.] Monash Univ, Dept Microbiol, Melbourne, Vic 3800, Australia.
   [Kuiper, Michael J.] Victorian Partnership Adv Comp, Dept Life Sci, Carlton, Vic 3053, Australia.
   [Trapani, Joseph A.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
C3 Peter Maccallum Cancer Center; Monash University; Monash University; University of London; Birkbeck University London; University of Melbourne; Australian Synchrotron; Monash University; University of Melbourne
RP Trapani, JA (corresponding author), Peter MacCallum Canc Ctr, Canc Immunol Program, St Andrews Pl, Melbourne, Vic 3002, Australia.
EM joe.trapani@petermac.org; h.saibil@mail.cryst.bbk.ac.uk; james.whisstock@monash.edu
FU NHMRC; ARC; UK BBSRC; Wellcome Trust; Biotechnology and Biological Sciences Research Council [BB/D008573/1] Funding Source: researchfish; BBSRC [BB/D008573/1] Funding Source: UKRI
NR 57
TC 329
Z9 375
U1 4
U2 81
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 447
EP U277
DI 10.1038/nature09518
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100045
PM 21037563
DA 2026-03-09
ER

PT J
AU Navarro, P
   Oldfield, A
   Legoupi, J
   Festuccia, N
   Dubois, A
   Attia, M
   Schoorlemmer, J
   Rougeulle, C
   Chambers, I
   Avner, P
AF Navarro, Pablo
   Oldfield, Andrew
   Legoupi, Julie
   Festuccia, Nicola
   Dubois, Agnes
   Attia, Mikael
   Schoorlemmer, Jon
   Rougeulle, Claire
   Chambers, Ian
   Avner, Philip
TI Molecular coupling of Tsix regulation and pluripotency
SO NATURE
LA English
DT Article
ID x-chromosome; transcriptional network; xist transcription; inactivation; expression; ctcf
AB The reprogramming of X-chromosome inactivation during the acquisition of pluripotency in vivo and in vitro(1) is accompanied by the repression of Xist(2), the trigger of X-inactivation(3), and the upregulation of its antisense counterpart Tsix(4). We have shown that key factors supporting pluripotency-Nanog, Oct4 and Sox2-bind within Xist intron 1 in undifferentiated embryonic stem cells (ESC) to repress Xist transcription(5). However, the relationship between transcription factors of the pluripotency network and Tsix regulation has remained unclear(5,6). Here we show that Tsix upregulation in embryonic stem cells depends on the recruitment of the pluripotent marker Rex1, and of the reprogramming-associated factors Klf4 and c-Myc, by the DXPas34 minisatellite associated with the Tsix promoter. Upon deletion of DXPas34, binding of the three factors is abrogated and the transcriptional machinery is no longer efficiently recruited to the Tsix promoter. Additional analyses including knockdown experiments further demonstrate that Rex1 is critically important for efficient transcription elongation of Tsix. Hence, distinct embryonic-stem-cell-specific complexes couple X-inactivation reprogramming and pluripotency, with Nanog, Oct4 and Sox2 repressing Xist to facilitate the reactivation of the inactive X, and Klf4, c-Myc and Rex1 activating Tsix to remodel Xist chromatin(7-10) and ensure random X-inactivation upon differentiation(1). The holistic pattern of Xist/Tsix regulation by pluripotent factors that we have identified suggests a general direct governance of complex epigenetic processes by the machinery dedicated to pluripotency.
C1 [Navarro, Pablo; Oldfield, Andrew; Legoupi, Julie; Dubois, Agnes; Attia, Mikael; Rougeulle, Claire; Avner, Philip] Inst Pasteur, URA 2578, Unite Genet Mol Murine, F-75724 Paris 15, France.
   [Navarro, Pablo; Festuccia, Nicola; Chambers, Ian] Univ Edinburgh, Sch Biol Sci, Inst Stem Cell Res, Ctr Dev Stem Cell Biol,MRC, Edinburgh EH9 3JQ, Midlothian, Scotland.
   [Oldfield, Andrew; Rougeulle, Claire] Univ Paris Diderot, CNRS, UMR Epigenet & Destin Cellulaire 7216, F-75205 Paris 13, France.
   [Schoorlemmer, Jon] ARAID Fdn, Zaragoza 50013, Spain.
   [Schoorlemmer, Jon] Fac Vet, Inst Aragones Ciencias Salud, Dept Anat & Embriol, Zaragoza 50013, Spain.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; University of Edinburgh; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite
RP Avner, P (corresponding author), Inst Pasteur, URA 2578, Unite Genet Mol Murine, F-75724 Paris 15, France.
EM pablo.navarro@ed.ac.uk; pavner@pasteur.fr
FU Institut Pasteur; Royal Society; Centre National de la Recherche Scientifique; Agence Nationale de la Recherche [05-JCJC-0166-01, 07-BLAN-0047-01]; EU Epigenome Network of Excellence; INSERM; European Research Council; Wellcome Trust; EU; Medical Research Council; Medical Research Council [G0700711B] Funding Source: researchfish
NR 30
TC 160
Z9 179
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 457
EP U287
DI 10.1038/nature09496
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100047
PM 21085182
DA 2026-03-09
ER

PT J
AU Xiang, Y
   Yuan, QA
   Vogt, N
   Looger, LL
   Jan, LY
   Jan, YN
AF Xiang, Yang
   Yuan, Quan
   Vogt, Nina
   Looger, Loren L.
   Jan, Lily Yeh
   Jan, Yuh Nung
TI Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall
SO NATURE
LA English
DT Article
ID deg/enac protein pickpocket1; programmed cell-death; sensory neurons; c-elegans; gene; expression; channels; transduction; nociception; vertebrates
AB Photoreceptors for visual perception, phototaxis or light avoidance are typically clustered in eyes or related structures such as the Bolwig organ of Drosophila larvae. Unexpectedly, we found that the class IV dendritic arborization neurons of Drosophila melanogaster larvae respond to ultraviolet, violet and blue light, and are major mediators of light avoidance, particularly at high intensities. These class IV dendritic arborization neurons, which are present in every body segment, have dendrites tiling the larval body wall nearly completely without redundancy. Dendritic illumination activates class IV dendritic arborization neurons. These novel photoreceptors use phototransduction machinery distinct from other photoreceptors in Drosophila and enable larvae to sense light exposure over their entire bodies and move out of danger.
C1 [Xiang, Yang; Yuan, Quan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA.
   [Xiang, Yang; Yuan, Quan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem, San Francisco, CA 94158 USA.
   [Xiang, Yang; Yuan, Quan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biophys, San Francisco, CA 94158 USA.
   [Vogt, Nina] NYU, Ctr Dev Genet, New York, NY 10003 USA.
   [Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; New York University; Howard Hughes Medical Institute
RP Jan, YN (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA.
EM yuhnung.jan@ucsf.edu
FU Human Frontier Science Program; Deutsche Forschungsgemeinschaft; NIH [2R37NS040929]; Howard Hughes Medical Institute, Janelia Farm Campus
NR 49
TC 356
Z9 446
U1 4
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 DEC 16
PY 2010
VL 468
IS 7326
BP 921
EP U312
DI 10.1038/nature09576
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600038
PM 21068723
DA 2026-03-09
ER

PT J
AU Hart, M
   Milton, NM
   Baranec, C
   Powell, K
   Stalcup, T
   McCarthy, D
   Kulesa, C
   Bendek, E
AF Hart, M.
   Milton, N. M.
   Baranec, C.
   Powell, K.
   Stalcup, T.
   McCarthy, D.
   Kulesa, C.
   Bendek, E.
TI A ground-layer adaptive optics system with multiple laser guide stars
SO NATURE
LA English
DT Article
ID wide-field; arches cluster; mass function; motions; tests; mmt
AB To determine the influence of the environment on star formation, we need to study the process in the extreme conditions of massive young star clusters (similar to 10(4) solar masses) near the centre of our own Galaxy(1,2). Observations must be carried out in the near infrared because of very high extinction in visible light within the Galactic plane. We need high resolution to identify cluster members from their peculiar motions 3, and because most such clusters span more than 1', efficient observation demands a wide field of view. There is at present no space-based facility that meets all these criteria. Ground-based telescopes can in principle make such observations when fitted with ground-layer adaptive optics (GLAO)(4-6), which removes the optical aberration caused by atmospheric turbulence up to an altitude of similar to 500 m (refs 7-10). A GLAO system that uses multiple laser guide stars(11-13) has been developed at the 6.5-m MMT telescope, in Arizona. In previous tests(13), the system improved the resolution of the telescope by 30-50%, limited by wavefront error in the optics, but that was insufficient to allow rapid determination of cluster membership. Here we report observations of the core of the globular cluster M3 made after commissioning a sensor to monitor and remove slowly varying aberration in the optics. In natural seeing of 0.7 '', the point spread function at 2.2-mu m wavelength was sharpened uniformly to 0.3 '' over a field of at least 2'. The wide-field resolution was enhanced by a factor of two to three over previous work(13), with better uniformity, and extends to a wavelength of 1.2 mu m. Entire stellar clusters may be examined in a single pointing, and cluster membership can be determined from two such observations separated by just one year(14-17).
C1 [Hart, M.; Milton, N. M.; Powell, K.; McCarthy, D.; Kulesa, C.; Bendek, E.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Baranec, C.] CALTECH, Caltech Opt Observ, Pasadena, CA 91125 USA.
   [Stalcup, T.] WM Keck Observ, Kamuela, HI 96743 USA.
C3 University of Arizona; California Institute of Technology
RP Hart, M (corresponding author), Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
EM mhart@as.arizona.edu
FU National Science Foundation
NR 25
TC 39
Z9 48
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 AUG 5
PY 2010
VL 466
IS 7307
BP 727
EP 729
DI 10.1038/nature09311
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500032
PM 20686568
DA 2026-03-09
ER

PT J
AU Bienvenu, F
   Jirawatnotai, S
   Elias, JE
   Meyer, CA
   Mizeracka, K
   Marson, A
   Frampton, GM
   Cole, MF
   Odom, DT
   Odajima, J
   Geng, Y
   Zagozdzon, A
   Jecrois, M
   Young, RA
   Liu, XS
   Cepko, CL
   Gygi, SP
   Sicinski, P
AF Bienvenu, Frederic
   Jirawatnotai, Siwanon
   Elias, Joshua E.
   Meyer, Clifford A.
   Mizeracka, Karolina
   Marson, Alexander
   Frampton, Garrett M.
   Cole, Megan F.
   Odom, Duncan T.
   Odajima, Junko
   Geng, Yan
   Zagozdzon, Agnieszka
   Jecrois, Marie
   Young, Richard A.
   Liu, X. Shirley
   Cepko, Constance L.
   Gygi, Steven P.
   Sicinski, Piotr
TI Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
SO NATURE
LA English
DT Article
ID kinase-independent mechanism; cell-cycle; estrogen-receptor; mouse retina; breast; transformation; recruitment; expression; represses; cancer
AB Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers(1,2). The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag-and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas-an organ that critically requires cyclin D1 function(3,4)-cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1(-/-)) retinas. Transduction of an activated allele of Notch1 into Ccnd1(-/-) retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein.
C1 [Bienvenu, Frederic; Jirawatnotai, Siwanon; Odajima, Junko; Geng, Yan; Zagozdzon, Agnieszka; Jecrois, Marie; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Bienvenu, Frederic; Jirawatnotai, Siwanon; Odajima, Junko; Geng, Yan; Zagozdzon, Agnieszka; Jecrois, Marie; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Elias, Joshua E.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Mizeracka, Karolina; Cepko, Constance L.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya 73170, Nakhon Prathom, Thailand.
   [Marson, Alexander; Frampton, Garrett M.; Cole, Megan F.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Marson, Alexander; Frampton, Garrett M.; Cole, Megan F.; Young, Richard A.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Odom, Duncan T.] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard Medical School; Mahidol University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; CRUK Cambridge Institute; University of Cambridge; Cancer Research UK
RP Sicinski, P (corresponding author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM Peter_Sicinski@dfci.harvard.edu
FU Cancer Research UK; European Research Council; EMBO Young Investigator Award;  [R01 CA108420];  [P01 CA080111];  [P01 CA109901];  [HG3456];  [R01 EYO9676];  [HG004069]; Cancer Research UK [15603] Funding Source: researchfish
NR 30
TC 228
Z9 271
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 374
EP 378
DI 10.1038/nature08684
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100048
PM 20090754
DA 2026-03-09
ER

PT J
AU Fazzari, P
   Paternain, AV
   Valiente, M
   Pla, R
   Luján, R
   Lloyd, K
   Lerma, J
   Marín, O
   Rico, B
AF Fazzari, Pietro
   Paternain, Ana V.
   Valiente, Manuel
   Pla, Ramon
   Lujan, Rafael
   Lloyd, Kent
   Lerma, Juan
   Marin, Oscar
   Rico, Beatriz
TI Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling
SO NATURE
LA English
DT Article
ID gabaergic interneurons; neuregulin-1; neurons; rat; schizophrenia; receptors; susceptibility; origin; cells; cat
AB Schizophrenia is a complex disorder that interferes with the function of several brain systems required for cognition and normal social behaviour. Although the most notable clinical aspects of the disease only become apparent during late adolescence or early adulthood, many lines of evidence suggest that schizophrenia is a neurodevelopmental disorder with a strong genetic component(1,2). Several independent studies have identified neuregulin 1 (NRG1) and its receptor ERBB4 as important risk genes for schizophrenia(3,4), although their precise role in the disease process remains unknown. Here we show that Nrg1 and ErbB4 signalling controls the development of inhibitory circuitries in the mammalian cerebral cortex by cell-autonomously regulating the connectivity of specific GABA (gamma-aminobutyric acid)-containing interneurons. In contrast to the prevalent view, which supports a role for these genes in the formation and function of excitatory synapses between pyramidal cells, we found that ErbB4 expression in the mouse neocortex and hippocampus is largely confined to certain classes of interneurons. In particular, ErbB4 is expressed by many parvalbumin-expressing chandelier and basket cells, where it localizes to axon terminals and postsynaptic densities receiving glutamatergic input. Gain- and loss-of-function experiments, both in vitro and in vivo, demonstrate that ErbB4 cell-autonomously promotes the formation of axo-axonic inhibitory synapses over pyramidal cells, and that this function is probably mediated by Nrg1. In addition, ErbB4 expression in GABA-containing interneurons regulates the formation of excitatory synapses onto the dendrites of these cells. By contrast, ErbB4 is dispensable for excitatory transmission between pyramidal neurons. Altogether, our results indicate that Nrg1 and ErbB4 signalling is required for the wiring of GABA-mediated circuits in the postnatal cortex, providing a new perspective to the involvement of these genes in the aetiology of schizophrenia.
C1 [Fazzari, Pietro; Paternain, Ana V.; Valiente, Manuel; Pla, Ramon; Lerma, Juan; Marin, Oscar; Rico, Beatriz] CSIC, Inst Neurociencias, Sant Joan dAlacant 03550, Spain.
   [Fazzari, Pietro; Paternain, Ana V.; Valiente, Manuel; Pla, Ramon; Lerma, Juan; Marin, Oscar; Rico, Beatriz] Univ Miguel Hernandez, Sant Joan dAlacant 03550, Spain.
   [Lujan, Rafael] Univ Castilla La Mancha, Fac Med, Dept Ciencias Med, Albacete 02006, Spain.
   [Lloyd, Kent] Univ Calif Davis, Dept Internal Med, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Miguel Hernandez de Elche; CSIC-UMH - Instituto de Neurociencias de Alicante (IN); Universidad Miguel Hernandez de Elche; Universidad de Castilla-La Mancha; University of California System; University of California Davis
RP Marín, O (corresponding author), CSIC, Inst Neurociencias, Sant Joan dAlacant 03550, Spain.
EM o.marin@umh.es; brico@umh.es
FU Spanish Ministry of Science and Innovation [SAF2008-00770, SAF2007-61904, BFU2006-07138, CSD2007-00023]; Consejeria de Educacion y Ciencia de la Junta de Comunidades de Castilla-La Mancha [PAI08-0174-6967]; fundacio la Caixa; EURYI; Marie Curie Intra-European Fellowship
NR 42
TC 399
Z9 466
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 APR 29
PY 2010
VL 464
IS 7293
BP 1376
EP U11
DI 10.1038/nature08928
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000052
PM 20393464
DA 2026-03-09
ER

PT J
AU Hittinger, CT
   Gonçalves, P
   Sampaio, JP
   Dover, J
   Johnston, M
   Rokas, A
AF Hittinger, Chris Todd
   Goncalves, Paula
   Sampaio, Jose Paulo
   Dover, Jim
   Johnston, Mark
   Rokas, Antonis
TI Remarkably ancient balanced polymorphisms in a multi-locus gene network
SO NATURE
LA English
DT Article
ID bayesian phylogenetic inference; saccharomyces-cerevisiae; arabidopsis-thaliana; population genomics; yeast; selection; substitution; evolution; dna; kudriavzevii
AB Local adaptations within species are often governed by several interacting genes scattered throughout the genome. Single-locus models of selection cannot explain the maintenance of such complex variation because recombination separates co-adapted alleles. Here we report a previously unrecognized type of intraspecific multi-locus genetic variation that has been maintained over a vast period. The galactose (GAL) utilization gene network of Saccharomyces kudriavzevii, a relative of brewer's yeast, exists in two distinct states: a functional gene network in Portuguese strains and, in Japanese strains, a non-functional gene network of allelic pseudogenes. Genome sequencing of all available S. kudriavzevii strains revealed that none of the functional GAL genes were acquired from other species. Rather, these polymorphisms have been maintained for nearly the entire history of the species, despite more recent gene flow genome-wide. Experimental evidence suggests that inactivation of the GAL3 and GAL80 regulatory genes facilitated the origin and long-term maintenance of the two gene network states. This striking example of a balanced unlinked gene network polymorphism introduces a remarkable type of intraspecific variation that may be widespread.
C1 [Hittinger, Chris Todd; Dover, Jim; Johnston, Mark] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
   [Hittinger, Chris Todd; Dover, Jim; Johnston, Mark] Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci, St Louis, MO 63108 USA.
   [Goncalves, Paula; Sampaio, Jose Paulo] Univ Nova Lisboa, Ctr Recursos Microbiol, Dept Ciencias Vida, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal.
   [Rokas, Antonis] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
C3 University of Colorado System; University of Colorado Anschutz Medical Campus; Washington University (WUSTL); Universidade Nova de Lisboa; Vanderbilt University
RP Johnston, M (corresponding author), Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
EM mark.johnston@ucdenver.edu
FU James S. McDonnell Foundation; National Institutes of Health [2T32HG00045, 5R01GM032540]; Fundacao para a Ciencia e a Tecnologia, Portugal [PTDC/BIA-BDE/71734/2006]; Searle Scholars Program; National Science Foundation [DEB-0844968]; Vanderbilt University; Fundação para a Ciência e a Tecnologia [PTDC/BIA-BDE/71734/2006] Funding Source: FCT; National Human Genome Research Institute [T32HG000045] Funding Source: NIH RePORTER; Division Of Environmental Biology; Direct For Biological Sciences [0844968] Funding Source: National Science Foundation
NR 61
TC 119
Z9 143
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 4
PY 2010
VL 464
IS 7285
BP 54
EP U61
DI 10.1038/nature08791
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500032
PM 20164837
DA 2026-03-09
ER

PT J
AU Grubb, MS
   Burrone, J
AF Grubb, Matthew S.
   Burrone, Juan
TI Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability
SO NATURE
LA English
DT Article
ID action-potential initiation; ca1 pyramidal neurons; ca2+ channels; homeostasis; generation; hippocampal; propagation; na(v)1.6; site
AB In neurons, the axon initial segment (AIS) is a specialized region near the start of the axon that is the site of action potential initiation(1-6). The precise location of the AIS varies across and within different neuronal types(7,8), and has been linked to cells' information-processing capabilities(8); however, the factors determining AIS position in individual neurons remain unknown. Here we show that changes in electrical activity can alter the location of the AIS. In dissociated hippocampal cultures, chronic depolarization with high extracellular potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 mu m away from the soma of excitatory neurons. This movement reverses when neurons are returned to non-depolarized conditions, and depends on the activation of T- and/or L-type voltage-gated calcium channels. The AIS also moved distally when we combined long-term LED (light-emitting diode) photostimulation with sparse neuronal expression of the light-activated cation channel channelrhodopsin-2; here, burst patterning of activity was successful where regular stimulation at the same frequency failed. Furthermore, changes in AIS position correlate with alterations in current thresholds for action potential spiking. Our results show that neurons can regulate the position of an entire subcellular structure according to their ongoing levels and patterns of electrical activity. This novel form of activity-dependent plasticity may fine-tune neuronal excitability during development.
C1 [Grubb, Matthew S.; Burrone, Juan] Kings Coll London, MRC Ctr Dev Neurobiol, London SE1 1UL, England.
C3 University of London; King's College London
RP Grubb, MS (corresponding author), Kings Coll London, MRC Ctr Dev Neurobiol, 4th Floor,New Hunts House,Guys Campus, London SE1 1UL, England.
EM matthew.grubb@kcl.ac.uk; juan.burrone@kcl.ac.uk
FU Wellcome Trust; Lister Institute; Medical Research Council [G0901899, G0901899B] Funding Source: researchfish; MRC [G0901899] Funding Source: UKRI
NR 32
TC 507
Z9 591
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1070
EP U131
DI 10.1038/nature09160
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900051
PM 20543823
DA 2026-03-09
ER

PT J
AU Jin, X
   Costa, RM
AF Jin, Xin
   Costa, Rui M.
TI Start/stop signals emerge in nigrostriatal circuits during sequence learning
SO NATURE
LA English
DT Article
ID dopamine neurons encode; huntingtons-disease; basal ganglia; striatum; representation; pattern; time; populations; initiation; movements
AB Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson's and Huntington's diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.
C1 [Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
   [Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-2780156 Oeiras, Portugal.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Instituto Gulbenkian de Ciencia; Fundacao Champalimaud
RP Costa, RM (corresponding author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM ruicosta@fchampalimaud.org
FU NIAAA Division of Intramural Clinical and Biological Research; Institute Gulbenkian de Ciencia; European Research Council [243393]; European Research Council (ERC) [243393] Funding Source: European Research Council (ERC); National Institute on Alcohol Abuse and Alcoholism [ZIAAA000416] Funding Source: NIH RePORTER
NR 40
TC 447
Z9 549
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 JUL 22
PY 2010
VL 466
IS 7305
BP 457
EP 462
DI 10.1038/nature09263
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200028
PM 20651684
DA 2026-03-09
ER

PT J
AU Mouquet, H
   Scheid, JF
   Zoller, MJ
   Krogsgaard, M
   Ott, RG
   Shukair, S
   Artyomov, MN
   Pietzsch, J
   Connors, M
   Pereyra, F
   Walker, BD
   Ho, DD
   Wilson, PC
   Seaman, MS
   Eisen, HN
   Chakraborty, AK
   Hope, TJ
   Ravetch, JV
   Wardemann, H
   Nussenzweig, MC
AF Mouquet, Hugo
   Scheid, Johannes F.
   Zoller, Markus J.
   Krogsgaard, Michelle
   Ott, Rene G.
   Shukair, Shetha
   Artyomov, Maxim N.
   Pietzsch, John
   Connors, Mark
   Pereyra, Florencia
   Walker, Bruce D.
   Ho, David D.
   Wilson, Patrick C.
   Seaman, Michael S.
   Eisen, Herman N.
   Chakraborty, Arup K.
   Hope, Thomas J.
   Ravetch, Jeffrey V.
   Wardemann, Hedda
   Nussenzweig, Michel C.
TI Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; human monoclonal-antibody; memory b-cells; neutralizing antibody; envelope glycoprotein; type-1; autoreactivity; individuals; modulation; generation
AB During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding(1-3). Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development(4), it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients(5) with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.
C1 [Mouquet, Hugo; Scheid, Johannes F.; Pietzsch, John; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Scheid, Johannes F.] Charite, D-10117 Berlin, Germany.
   [Zoller, Markus J.; Wardemann, Hedda] Max Planck Inst Infect Biol, D-10117 Berlin, Germany.
   [Krogsgaard, Michelle] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Krogsgaard, Michelle] NYU, Sch Med, Inst Canc, New York, NY 10016 USA.
   [Ott, Rene G.; Ravetch, Jeffrey V.] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10065 USA.
   [Shukair, Shetha; Hope, Thomas J.] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
   [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
   [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Pietzsch, John] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany.
   [Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Connors, Mark] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Pereyra, Florencia; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
   [Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Ho, David D.] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
   [Wilson, Patrick C.] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA.
   [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Rockefeller University; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Max Planck Society; New York University; New York University; Rockefeller University; Northwestern University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Free University of Berlin; 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); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Chicago; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Howard Hughes Medical Institute; Rockefeller University
RP Nussenzweig, MC (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussenzweig@rockefeller.edu
FU Rockefeller University; National Institutes of Health [NIH 1 PO1 AI081677, R01 AI047770]; International AIDS Vaccine Initiative; Bill and Melinda Gates Foundation; German Research Foundation [GRK1121]; National Institute of Allergy and Infectious Diseases [ZIAAI000855, ZIAAI001090] Funding Source: NIH RePORTER
NR 31
TC 358
Z9 421
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 591
EP U117
DI 10.1038/nature09385
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100039
PM 20882016
DA 2026-03-09
ER

PT J
AU Jain, D
   Hebden, AK
   Nakamura, TM
   Miller, KM
   Cooper, JP
AF Jain, Devanshi
   Hebden, Anna K.
   Nakamura, Toru M.
   Miller, Kyle M.
   Cooper, Julia Promisel
TI HAATI survivors replace canonical telomeres with blocks of generic heterochromatin
SO NATURE
LA English
DT Article
ID fission yeast; schizosaccharomyces-pombe; drosophila telomeres; epigenetic control; binding-protein; domain protein; 2 modes; recombination; maintenance; centromere
AB The notion that telomeres are essential for chromosome linearity stems from the existence of two chief dangers: inappropriate DNA damage response (DDR) reactions that mistake natural chromosome ends for double-strand DNA breaks (DSBs), and the progressive loss of DNA from chromosomal termini due to the end replication problem. Telomeres avert the former peril by binding sequence-specific end-protection factors that control the access of DDR activities(1,2). The latter threat is tackled by recruiting telomerase, a reverse transcriptase that uses an integral RNA subunit to template the addition of telomere repeats to chromosome ends(3). Here we describe an alternative mode of linear chromosome maintenance in which canonical telomeres are superseded by blocks of heterochromatin. We show that in the absence of telomerase, Schizosaccharomyces pombe cells can survive telomere sequence loss by continually amplifying and rearranging heterochromatic sequences. Because the heterochromatin assembly machinery is required for this survival mode, we have termed it 'HAATI' (heterochromatin amplification-mediated and telomerase-independent). HAATI uses the canonical end-protection protein Pot1 (ref. 4) and its interacting partner Ccq1 (ref. 5) to preserve chromosome linearity. The data suggest a model in which Ccq1 is recruited by the amplified heterochromatin and provides an anchor for Pot1, which accomplishes its end-protection function in the absence of its cognate DNA-binding sequence. HAATI resembles the chromosome end-maintenance strategy found in Drosophila melanogaster, which lacks specific telomere sequences but nonetheless assembles terminal heterochromatin structures that recruit end-protection factors. These findings reveal a previously unrecognized mode by which cancer cells might escape the requirement for telomerase activation, and offer a tool for studying genomes that sustain unusually high levels of heterochromatinization.
C1 [Jain, Devanshi; Cooper, Julia Promisel] Canc Res UK, London Res Inst, London WC2A 3PX, England.
   [Hebden, Anna K.] Univ London Imperial Coll Sci Technol & Med, Ovarian Canc Act Grp, London W12 0NN, England.
   [Nakamura, Toru M.] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
   [Miller, Kyle M.] Gurdon Inst, Cambridge CB2 1QN, England.
C3 Cancer Research UK; Imperial College London; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Cooper, JP (corresponding author), Canc Res UK, London Res Inst, 44 Lincolns Inn Fields, London WC2A 3PX, England.
EM julie.cooper@cancer.org.uk
FU Cancer Research UK
NR 37
TC 76
Z9 87
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 SEP 9
PY 2010
VL 467
IS 7312
BP 223
EP U118
DI 10.1038/nature09374
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300038
PM 20829796
DA 2026-03-09
ER

PT J
AU Zalzman, M
   Falco, G
   Sharova, LV
   Nishiyama, A
   Thomas, M
   Lee, SL
   Stagg, CA
   Hoang, HG
   Yang, HT
   Indig, FE
   Wersto, RP
   Ko, MSH
AF Zalzman, Michal
   Falco, Geppino
   Sharova, Lioudmila V.
   Nishiyama, Akira
   Thomas, Marshall
   Lee, Sung-Lim
   Stagg, Carole A.
   Hoang, Hien G.
   Yang, Hsih-Te
   Indig, Fred E.
   Wersto, Robert P.
   Ko, Minoru S. H.
TI Zscan4 regulates telomere elongation and genomic stability in ES cells
SO NATURE
LA English
DT Article
ID embryonic stem-cells; double-strand breaks; dna; expression; length; lines; recombination; maintenance; mice; identification
AB Exceptional genomic stability is one of the hallmarks of mouse embryonic stem (ES) cells. However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells. Here we show that Zscan4 is involved in telomere maintenance and long-term genomic stability in ES cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once during nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis-specific homologous recombination genes, which encode proteins that are colocalized with ZSCAN4 on telomeres. Furthermore, Zscan4 knockdown shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by passage eight. Together, our data show a unique mode of genome maintenance in ES cells.
C1 [Zalzman, Michal; Falco, Geppino; Sharova, Lioudmila V.; Nishiyama, Akira; Thomas, Marshall; Lee, Sung-Lim; Stagg, Carole A.; Hoang, Hien G.; Yang, Hsih-Te; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA.
   [Indig, Fred E.; Wersto, Robert P.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
RP Ko, MSH (corresponding author), NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA.
EM kom@mail.nih.gov
FU National Institute on Aging, National Institutes of Health; National Institute on Aging [ZICAG000618, ZICAG000615] Funding Source: NIH RePORTER
NR 52
TC 354
Z9 408
U1 2
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 8
PY 2010
VL 464
IS 7290
BP 858
EP U66
DI 10.1038/nature08882
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300030
PM 20336070
DA 2026-03-09
ER

PT J
AU Buonocore, S
   Ahern, PP
   Uhlig, HH
   Ivanov, II
   Littman, DR
   Maloy, KJ
   Powrie, F
AF Buonocore, Sofia
   Ahern, Philip P.
   Uhlig, Holm H.
   Ivanov, Ivaylo I.
   Littman, Dan R.
   Maloy, Kevin J.
   Powrie, Fiona
TI Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology
SO NATURE
LA English
DT Article
ID ror-gamma-t; differentiation; mucosal; il-23; mice; populations
AB The key role of interleukin (IL)-23 in the pathogenesis of autoimmune and chronic inflammatory disorders is supported by the identification of IL-23 receptor (IL-23R) susceptibility alleles associated with inflammatory bowel disease, psoriasis and ankylosing spondylitis. IL-23-driven inflammation has primarily been linked to the actions of T-helper type 17 (T(H)17) cells(1). Somewhat overlooked, IL-23 also has inflammatory effects on innate immune cells(2) and can drive T-cell-independent colitis. However, the downstream cellular and molecular pathways involved in this innate intestinal inflammatory response are poorly characterized. Here we show that bacteria-driven innate colitis is associated with an increased production of IL-17 and interferon-gamma in the colon. Stimulation of colonic leukocytes with IL-23 induced the production of IL-17 and interferon-gamma exclusively by innate lymphoid cells expressing Thy1, stem cell antigen 1 (SCA-1), retinoic-acid-related orphan receptor (ROR)-gamma t and IL-23R, and these cells markedly accumulated in the inflamed colon. IL-23-responsive innate intestinal cells are also a feature of T-cell-dependent models of colitis. The transcription factor ROR-gamma t, which controls IL-23R expression, has a functional role, because Rag(-/-) Rorc(-/-) mice failed to develop innate colitis. Last, depletion of Thy1(+) innate lymphoid cells completely abrogated acute and chronic innate colitis. These results identify a previously unrecognized IL-23-responsive innate lymphoid population that mediates intestinal immune pathology and may therefore represent a target in inflammatory bowel disease.
C1 [Buonocore, Sofia; Ahern, Philip P.; Maloy, Kevin J.; Powrie, Fiona] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Powrie, Fiona] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Translat Gastroenterol Unit, Oxford OX3 9DU, England.
   [Uhlig, Holm H.] Univ Childrens Hosp, D-04317 Leipzig, Germany.
   [Ivanov, Ivaylo I.; Littman, Dan R.] NYU, Sch Med, Kimmel Ctr Biol & Med,Skirball Inst, Mol Pathogenesis Program,Howard Hughes Med Inst, New York, NY 10016 USA.
C3 University of Oxford; University of Oxford; Leipzig University; New York University; Howard Hughes Medical Institute
RP Powrie, F (corresponding author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England.
EM kevin.maloy@path.ox.ac.uk; fiona.powrie@path.ox.ac.uk
FU Wellcome Trust; Marie-Curie Network [MRTN-CT2004-006532]; Philippe Wiener-Maurice Anspach; European Crohn's & Colitis Organisation (ECCO); European Commission [223151]; Howard Hughes Medical Institute Exchange Programme
NR 27
TC 925
Z9 1090
U1 0
U2 118
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1371
EP 1375
DI 10.1038/nature08949
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000051
PM 20393462
DA 2026-03-09
ER

PT J
AU Wood, SN
AF Wood, Simon N.
TI Statistical inference for noisy nonlinear ecological dynamic systems
SO NATURE
LA English
DT Article
ID populations; models
AB Chaotic ecological dynamic systems defy conventional statistical analysis. Systems with near-chaotic dynamics are little better. Such systems are almost invariably driven by endogenous dynamic processes plus demographic and environmental process noise, and are only observable with error. Their sensitivity to history means that minute changes in the driving noise realization, or the system parameters, will cause drastic changes in the system trajectory(1). This sensitivity is inherited and amplified by the joint probability density of the observable data and the process noise, rendering it useless as the basis for obtaining measures of statistical fit. Because the joint density is the basis for the fit measures used by all conventional statistical methods(2), this is a major theoretical shortcoming. The inability to make well-founded statistical inferences about biological dynamic models in the chaotic and near-chaotic regimes, other than on an ad hoc basis, leaves dynamic theory without the methods of quantitative validation that are essential tools in the rest of biological science. Here I show that this impasse can be resolved in a simple and general manner, using a method that requires only the ability to simulate the observed data on a system from the dynamic model about which inferences are required. The raw data series are reduced to phase-insensitive summary statistics, quantifying local dynamic structure and the distribution of observations. Simulation is used to obtain the mean and the covariance matrix of the statistics, given model parameters, allowing the construction of a 'synthetic likelihood' that assesses model fit. This likelihood can be explored using a straightforward Markov chain Monte Carlo sampler, but one further post-processing step returns pure likelihood-based inference. I apply the method to establish the dynamic nature of the fluctuations in Nicholson's classic blowfly experiments(3-5).
C1 Univ Bath, Bath BA2 7AY, Avon, England.
C3 University of Bath
RP Wood, SN (corresponding author), Univ Bath, Bath BA2 7AY, Avon, England.
EM s.wood@bath.ac.uk
FU EPSRC/NERC
NR 18
TC 403
Z9 460
U1 1
U2 96
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 26
PY 2010
VL 466
IS 7310
BP 1102
EP +
DI 10.1038/nature09319
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600039
PM 20703226
DA 2026-03-09
ER

PT J
AU Dillon, ME
   Wang, G
   Huey, RB
AF Dillon, Michael E.
   Wang, George
   Huey, Raymond B.
TI Global metabolic impacts of recent climate warming
SO NATURE
LA English
DT Article
ID temperature; ectotherms; animals; ecology; plants; shift; size; mass
AB Documented shifts in geographical ranges(1,2), seasonal phenology(3,4), community interactions(5), genetics(3,6) and extinctions(7) have been attributed to recent global warming(8-10). Many such biotic shifts have been detected at mid-to high latitudes in the Northern Hemisphere(4,9,10)-a latitudinal pattern that is expected(4,8,10,11) because warming is fastest in these regions(8). In contrast, shifts in tropical regions are expected to be less marked(4,8,10,11) because warming is less pronounced there(8). However, biotic impacts of warming are mediated through physiology, and metabolic rate, which is a fundamental measure of physiological activity and ecological impact, increases exponentially rather than linearly with temperature in ectotherms(12). Therefore, tropical ectotherms (with warm baseline temperatures) should experience larger absolute shifts in metabolic rate than the magnitude of tropical temperature change itself would suggest, but the impact of climate warming on metabolic rate has never been quantified on a global scale. Here we show that estimated changes in terrestrial metabolic rates in the tropics are large, are equivalent in magnitude to those in the north temperate-zone regions, and are in fact far greater than those in the Arctic, even though tropical temperature change has been relatively small. Because of temperature's nonlinear effects on metabolism, tropical organisms, which constitute much of Earth's biodiversity, should be profoundly affected by recent and projected climate warming(2,13,14).
C1 [Dillon, Michael E.] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
   [Wang, George; Huey, Raymond B.] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
C3 University of Wyoming; University of Washington; University of Washington Seattle
RP Dillon, ME (corresponding author), Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
EM Michael.Dillon@uwyo.edu
FU NSF [IOB-041684]
NR 32
TC 780
Z9 899
U1 11
U2 650
PU 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 7
PY 2010
VL 467
IS 7316
BP 704
EP U88
DI 10.1038/nature09407
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500037
PM 20930843
DA 2026-03-09
ER

PT J
AU Paczolt, KA
   Jones, AG
AF Paczolt, Kimberly A.
   Jones, Adam G.
TI Post-copulatory sexual selection and sexual conflict in the evolution of male pregnancy
SO NATURE
LA English
DT Article
ID pipefish species syngnathidae; role-reversed pipefish; mate choice; differential-allocation; gulf pipefish; brood pouch; seahorses; competition; investment; hypothesis
AB Male pregnancy in seahorses, pipefishes and sea dragons ( family Syngnathidae) represents a striking reproductive adaptation that has shaped the evolution of behaviour and morphology in this group of fishes(1-4). In many syngnathid species, males brood their offspring in a specialized pouch, which presumably evolved to facilitate male parental care(5,6). However, an unexplored possibility is that brood pouch evolution was partly shaped by parent-offspring or sexual conflict, processes that would result in trade-offs between current and future pregnancies. Here we report a controlled breeding experiment using the sexually dimorphic Gulf pipefish, Syngnathus scovelli, to test for post-copulatory sexual selection within broods and for trade-offs between successive male pregnancies as functions of female attractiveness. Offspring survivorship within a pregnancy was affected by the size of a male's mate, the number of eggs transferred and the male's sexual responsiveness. Significantly, we also found that embryo survivorship in a current pregnancy was negatively related to survivorship in the prior pregnancy, clearly demonstrating fitness trade-offs between broods. Overall, our data indicate that post-copulatory sexual selection and sexual conflict occur in Gulf pipefishes. The conflict seems to be mediated by a strategy of cryptic choice in which males increase rates of offspring abortion in pregnancies from unattractive mothers to retain resources for future reproductive opportunities. Hence, the male brood pouch of syngnathid fishes, which nurtures offspring(7-9), also seems to have an important role as an arbiter of conflict between the sexes.
C1 [Paczolt, Kimberly A.; Jones, Adam G.] Texas A&M Univ, Dept Biol, College Stn, TX 77845 USA.
C3 Texas A&M University System; Texas A&M University College Station
RP Paczolt, KA (corresponding author), Texas A&M Univ, Dept Biol, 3258 TAMU, College Stn, TX 77845 USA.
EM kpaczolt@mail.bio.tamu.edu
FU US National Science Foundation [IOS-0455927]
NR 31
TC 72
Z9 87
U1 0
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 401
EP U94
DI 10.1038/nature08861
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100044
PM 20237568
DA 2026-03-09
ER

PT J
AU Smith, IB
   Holt, JW
AF Smith, Isaac B.
   Holt, John W.
TI Onset and migration of spiral troughs on Mars revealed by orbital radar
SO NATURE
LA English
DT Article
ID polar layered deposits; geologic history; region; flow; stratigraphy; evolution; surface; origin; cap
AB The landscape of the north polar layered deposits of Mars (NPLD) is dominated by a pinwheel array of enigmatic spiral troughs(1). The troughs have intrigued planetary scientists since the Mariner 9 spacecraft returned the first close-up image in 1972, but conclusive evidence of their origin has remained elusive. Debate continues regarding all aspects of the troughs, including the possibility that they have migrated(2-5), their age in relation to the current NPLD surface(6), and whether they are fundamentally erosional(6,7) or constructional(2,4) features. The troughs are probably related to climatic processes(2,8), yet the nature of this relationship has remained a mystery. Previous data characterizing only the exposed NLPD surface were insufficient to test these hypotheses. Here we show that the central spiral troughs initiated after deposition of three-quarters of the NPLD, quickly reached a stable morphology and migrated approximately 65 kilometres poleward and 600 metres in altitude over the past two million years or so. Our radar stratigraphy rules out hypotheses of erosional incision post-dating deposition(6,7,9,10), and instead largely validates an early hypothesis for constructional trough migration(2-5) with wind transport and atmospheric deposition as dominant processes. These results provide hard constraints for palaeo-climate models and a new context for evaluating imagery, spectral data, and now radar sounding data, the better to understand the link between orbital parameters and climate, the role of climate in shaping the polar ice of Mars, and eventually, the age of the polar deposits themselves(8,11-13).
C1 [Smith, Isaac B.; Holt, John W.] Univ Texas Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
RP Smith, IB (corresponding author), Univ Texas Inst Geophys, Jackson Sch Geosci, Austin, TX 78758 USA.
EM isaac@ig.utexas.edu
FU NASA [NAG5-12693]; Gayle White Fellowship at the University of Texas Institute for Geophysics
NR 29
TC 65
Z9 79
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 450
EP 453
DI 10.1038/nature09049
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700028
PM 20505722
DA 2026-03-09
ER

PT J
AU Cuello, LG
   Jogini, V
   Cortes, DM
   Pan, AC
   Gagnon, DG
   Dalmas, O
   Cordero-Morales, JF
   Chakrapani, S
   Roux, B
   Perozo, E
AF Cuello, Luis G.
   Jogini, Vishwanath
   Cortes, D. Marien
   Pan, Albert C.
   Gagnon, Dominique G.
   Dalmas, Olivier
   Cordero-Morales, Julio F.
   Chakrapani, Sudha
   Roux, Benoit
   Perozo, Eduardo
TI Structural basis for the coupling between activation and inactivation gates in K+ channels
SO NATURE
LA English
DT Article
ID molecular architecture; external k+; potassium; ion; dynamics; kcsa; pore; mechanisms; mutations; state
AB The coupled interplay between activation and inactivation gating is a functional hallmark of K+ channels(1,2). This coupling has been experimentally demonstrated through ion interaction effects(3,4) and cysteine accessibility(1), and is associated with a well defined boundary of energetically coupled residues(2). The structure of the K+ channel KcsA in its fully open conformation, in addition to four other partial channel openings, richly illustrates the structural basis of activation-inactivation gating(5). Here, we identify the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the non-conductive C-type inactivated state. Analysis of a series of KcsA open structures suggests that, as a consequence of the hinge-bending and rotation of the TM2 helix, the aromatic ring of Phe 103 tilts towards residues Thr 74 and Thr 75 in the pore-helix and towards Ile 100 in the neighbouring subunit. This allows the network of hydrogen bonds among residues Trp 67, Glu 71 and Asp 80 to destabilize the selectivity filter(6,7), allowing entry to its non-conductive conformation. Mutations at position 103 have a size-dependent effect on gating kinetics: small side-chain substitutions F103A and F103C severely impair inactivation kinetics, whereas larger side chains such as F103W have more subtle effects. This suggests that the allosteric coupling between the inner helical bundle and the selectivity filter might rely on straightforward mechanical deformation propagated through a network of steric contacts. Average interactions calculated from molecular dynamics simulations show favourable open-state interaction-energies between Phe 103 and the surrounding residues. We probed similar interactions in the Shaker K+ channel where inactivation was impaired in the mutant I470A. We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K+ channels.
C1 [Cuello, Luis G.; Jogini, Vishwanath; Cortes, D. Marien; Pan, Albert C.; Gagnon, Dominique G.; Dalmas, Olivier; Cordero-Morales, Julio F.; Chakrapani, Sudha; Roux, Benoit; Perozo, Eduardo] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Roux, Benoit; Perozo, Eduardo] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Perozo, E (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 929 E 57th St, Chicago, IL 60637 USA.
EM eperozo@uchcicago.edu
FU NIH [R01-GM57846]; Palmer family [R01-GM62342]; NRSA; National Institute of General Medical Sciences [R01GM062342] Funding Source: NIH RePORTER
NR 44
TC 252
Z9 290
U1 2
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 272
EP U154
DI 10.1038/nature09136
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800044
PM 20613845
DA 2026-03-09
ER

PT J
AU Cady, SD
   Schmidt-Rohr, K
   Wang, J
   Soto, CS
   DeGrado, WF
   Hong, M
AF Cady, Sarah D.
   Schmidt-Rohr, Klaus
   Wang, Jun
   Soto, Cinque S.
   DeGrado, William F.
   Hong, Mei
TI Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers
SO NATURE
LA English
DT Article
ID solid-state nmr; antiviral drug amantadine; side-chain conformation; selective ion-channel; a virus; transmembrane peptide; distance measurements; protein; inhibition; domain
AB The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine(1). Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore(2), indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices(3), suggesting an allosteric mechanism. Here we show by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen, surrounded by residues mutated in amantadine-resistant viruses. Quantification of the protein-amantadine distances resulted in a 0.3 angstrom-resolution structure of the high-affinity binding site. The second, low-affinity, site was observed on the C-terminal protein surface, but only when the drug reaches high concentrations in the bilayer. The orientation and dynamics of the drug are distinct in the two sites, as shown by H-2 NMR. These results indicate that amantadine physically occludes the M2 channel, thus paving the way for developing new antiviral drugs against influenza viruses. The study demonstrates the ability of solid-state NMR to elucidate small-molecule interactions with membrane proteins and determine high-resolution structures of their complexes.
C1 [Cady, Sarah D.; Schmidt-Rohr, Klaus; Hong, Mei] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
   [Wang, Jun; Soto, Cinque S.; DeGrado, William F.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
   [Wang, Jun; Soto, Cinque S.; DeGrado, William F.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
C3 Iowa State University; University of Pennsylvania; University of Pennsylvania
RP Hong, M (corresponding author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
EM mhong@iastate.edu
FU NSF [MCB-0543473]; NIH [GM088204, GM56423, AI74571]; Iowa State University Foundation; National Institute of General Medical Sciences [R01GM088204] Funding Source: NIH RePORTER
NR 30
TC 556
Z9 637
U1 1
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 FEB 4
PY 2010
VL 463
IS 7281
BP 689
EP U127
DI 10.1038/nature08722
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900042
PM 20130653
DA 2026-03-09
ER

PT J
AU Zhang, L
   Ren, XY
   Alt, E
   Bai, XW
   Huang, SY
   Xu, ZM
   Lynch, PM
   Moyer, MP
   Wen, XF
   Wu, XW
AF Zhang, Ling
   Ren, Xiaoyang
   Alt, Eckhard
   Bai, Xiaowen
   Huang, Shaoyi
   Xu, Zhengming
   Lynch, Patrick M.
   Moyer, Mary P.
   Wen, Xian-Feng
   Wu, Xiangwei
TI Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis
SO NATURE
LA English
DT Article
ID multiple intestinal neoplasia; stem-cells; c-myc; trail; gene; mutation; ligand; mouse; identification; sensitivity
AB Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer(1). It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.
C1 [Zhang, Ling; Ren, Xiaoyang; Huang, Shaoyi; Xu, Zhengming; Wen, Xian-Feng; Wu, Xiangwei] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
   [Alt, Eckhard; Bai, Xiaowen] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA.
   [Lynch, Patrick M.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
   [Wu, Xiangwei] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Moyer, Mary P.] INCELL Corp, San Antonio, TX 78249 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Incell Corporation LLC
RP Wu, XW (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM xwwu@mdanderson.org
FU NIH [AI063063]; M. D. Anderson Cancer Center; Alliance of Cardiovascular Researchers [543102]
NR 27
TC 114
Z9 122
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 APR 15
PY 2010
VL 464
IS 7291
BP 1058
EP U128
DI 10.1038/nature08871
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000042
PM 20348907
DA 2026-03-09
ER

PT J
AU Boisset, JC
   van Cappellen, W
   Andrieu-Soler, C
   Galjart, N
   Dzierzak, E
   Robin, C
AF Boisset, Jean-Charles
   van Cappellen, Wiggert
   Andrieu-Soler, Charlotte
   Galjart, Niels
   Dzierzak, Elaine
   Robin, Catherine
TI In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium
SO NATURE
LA English
DT Article
ID stem-cells; agm region; definitive hematopoiesis; haemogenic endothelium; embryo; expression; generation; marks; colonization; migration
AB Haematopoietic stem cells (HSCs), responsible for blood production in the adult mouse, are first detected in the dorsal aorta starting at embryonic day 10.5 (E10.5)(1-3). Immunohistological analysis of fixed embryo sections has revealed the presence of haematopoietic cell clusters attached to the aortic endothelium where HSCs might localize(4-6). The origin of HSCs has long been controversial and several candidates of the direct HSC precursors have been proposed (for review see ref. 7), including a specialized endothelial cell population with a haemogenic potential. Such cells have been described both in vitro in the embryonic stem cell (ESC) culture system(8,9) and retrospectively in vivo by endothelial lineage tracing(5,10) and conditional deletion experiments(11). Whether the transition from haemogenic endothelium to HSC actually occurs in the mouse embryonic aorta is still unclear and requires direct and real-time in vivo observation. To address this issue we used time-lapse confocal imaging and a new dissection procedure to visualize the deeply located aorta. Here we show the dynamic de novo emergence of phenotypically defined HSCs (Sca1(+), c-kit(+), CD41(+)) directly from ventral aortic haemogenic endothelial cells.
C1 [Boisset, Jean-Charles; Andrieu-Soler, Charlotte; Galjart, Niels; Dzierzak, Elaine; Robin, Catherine] Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands.
   [Boisset, Jean-Charles; Dzierzak, Elaine; Robin, Catherine] Erasmus MC, Erasmus Stem Cell Inst, NL-3000 CA Rotterdam, Netherlands.
   [van Cappellen, Wiggert] Erasmus MC, Dept Reprod & Dev, NL-3000 CA Rotterdam, Netherlands.
C3 Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC
RP Robin, C (corresponding author), Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands.
EM c.robin@erasmusmc.nl
FU NWO [917-76-345]; NIH [R37 DKO54077]; BSIK [SCDD 03038]
NR 30
TC 744
Z9 887
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 116
EP U131
DI 10.1038/nature08764
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500045
PM 20154729
DA 2026-03-09
ER

PT J
AU Pauwels, L
   Barbero, GF
   Geerinck, J
   Tilleman, S
   Grunewald, W
   Perez, AC
   Chico, JM
   Vanden Bossche, R
   Sewell, J
   Gil, E
   García-Casado, G
   Witters, E
   Inzé, D
   Long, JA
   De Jaeger, G
   Solano, R
   Goossens, A
AF Pauwels, Laurens
   Barbero, Gemma Fernandez
   Geerinck, Jan
   Tilleman, Sofie
   Grunewald, Wim
   Perez, Amparo Cuellar
   Chico, Jose Manuel
   Vanden Bossche, Robin
   Sewell, Jared
   Gil, Eduardo
   Garcia-Casado, Gloria
   Witters, Erwin
   Inze, Dirk
   Long, Jeff A.
   De Jaeger, Geert
   Solano, Roberto
   Goossens, Alain
TI NINJA connects the co-repressor TOPLESS to jasmonate signalling
SO NATURE
LA English
DT Article
ID tandem affinity purification; functional genomics; stress-response; protein family; arabidopsis; degradation; defense; genes; biosynthesis; metabolism
AB Jasmonoyl-isoleucine (JA-Ile) is a plant hormone that regulates a broad array of plant defence and developmental processes(1-5). JA-Ile-responsive gene expression is regulated by the transcriptional activator MYC2 that interacts physically with the jasmonate ZIM-domain (JAZ) repressor proteins. On perception of JA-Ile, JAZ proteins are degraded and JA-Ile-dependent gene expression is activated(6,7). The molecular mechanisms by which JAZ proteins repress gene expression remain unknown. Here we show that the Arabidopsis JAZ proteins recruit the Groucho/Tup1-type corepressor TOPLESS (TPL)(8) and TPL-related proteins (TPRs) through a previously uncharacterized adaptor protein, designated Novel Interactor of JAZ (NINJA). NINJA acts as a transcriptional repressor whose activity is mediated by a functional TPL-binding EAR repression motif. Accordingly, both NINJA and TPL proteins function as negative regulators of jasmonate responses. Our results point to TPL proteins as general co-repressors that affect multiple signalling pathways through the interaction with specific adaptor proteins. This new insight reveals how stress-related and growth-related signalling cascades use common molecular mechanisms to regulate gene expression in plants.
C1 [Pauwels, Laurens; Geerinck, Jan; Tilleman, Sofie; Grunewald, Wim; Perez, Amparo Cuellar; Vanden Bossche, Robin; Inze, Dirk; De Jaeger, Geert; Goossens, Alain] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Pauwels, Laurens; Geerinck, Jan; Tilleman, Sofie; Grunewald, Wim; Perez, Amparo Cuellar; Vanden Bossche, Robin; Inze, Dirk; De Jaeger, Geert; Goossens, Alain] Univ Ghent, Dept Plant Biotechnol & Genet, B-9052 Ghent, Belgium.
   [Barbero, Gemma Fernandez; Chico, Jose Manuel; Solano, Roberto] Ctr Nacl Biotecnol CSIC, Dept Genet Mol Plantas, Madrid 28049, Spain.
   [Gil, Eduardo; Garcia-Casado, Gloria; Solano, Roberto] Ctr Nacl Biotecnol CSIC, Genom Unit, Madrid 28049, Spain.
   [Grunewald, Wim] Univ Ghent, Dept Mol Biotechnol, Fac Biosci Engn, B-9000 Ghent, Belgium.
   [Sewell, Jared; Long, Jeff A.] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Witters, Erwin] Univ Antwerp, EBT CEPROMA, Dept Biol, B-2020 Antwerp, Belgium.
   [Witters, Erwin] VITO MANT, Flemish Inst Technol Res, B-2400 Mol, Belgium.
C3 Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); Ghent University; Salk Institute; University of Antwerp; VITO
RP Goossens, A (corresponding author), Univ Ghent VIB, Dept Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.
EM alain.goossens@psb.vib-ugent.be
FU Research Foundation-Flanders; Agency for Innovation by Science and Technology in Flanders ('Generisch Basisonderzoek aan de Universiteiten'); Ghent University; National Institutes of Health; Spanish Ministerio de Ciencia y Tecnologia; Comunidad de Madrid
NR 41
TC 820
Z9 983
U1 5
U2 370
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 788
EP U169
DI 10.1038/nature08854
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000051
PM 20360743
DA 2026-03-09
ER

PT J
AU Duan, Z
   Andronescu, M
   Schutz, K
   McIlwain, S
   Kim, YJ
   Lee, C
   Shendure, J
   Fields, S
   Blau, CA
   Noble, WS
AF Duan, Zhijun
   Andronescu, Mirela
   Schutz, Kevin
   McIlwain, Sean
   Kim, Yoo Jung
   Lee, Choli
   Shendure, Jay
   Fields, Stanley
   Blau, C. Anthony
   Noble, William S.
TI A three-dimensional model of the yeast genome
SO NATURE
LA English
DT Article
ID spatial-organization; chromatin; genes; architecture; principles; dynamics; nuclei
AB Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes(1-3). Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations(4-7). Disparate DNA elements co-localize into functionally defined aggregates or 'factories' for transcription(8) and DNA replication(9). In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope(10-12). Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra-and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.
C1 [Duan, Zhijun; Kim, Yoo Jung; Blau, C. Anthony] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA.
   [Duan, Zhijun; Kim, Yoo Jung; Fields, Stanley; Blau, C. Anthony] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Andronescu, Mirela; McIlwain, Sean; Lee, Choli; Shendure, Jay; Fields, Stanley; Blau, C. Anthony; Noble, William S.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Schutz, Kevin] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA.
   [Fields, Stanley] Howard Hughes Med Inst, Chevy Chase, MD USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Blau, CA (corresponding author), Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA.
EM tblau@u.washington.edu; william-noble@u.washington.edu
FU NIH [P01GM081619, P41RR0011823]; Natural Sciences and Engineering Research Council of Canada; Howard Hughes Medical Institute
NR 30
TC 753
Z9 924
U1 1
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 363
EP 367
DI 10.1038/nature08973
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200044
PM 20436457
DA 2026-03-09
ER

PT J
AU Frank, F
   Sonenberg, N
   Nagar, B
AF Frank, Filipp
   Sonenberg, Nahum
   Nagar, Bhushan
TI Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2
SO NATURE
LA English
DT Article
ID messenger-rna; crystal-structure; argonaute; micrornas; complexes; strand
AB MicroRNAs (miRNAs) mediate post-transcriptional gene regulation through association with Argonaute proteins (AGOs)(1). Crystal structures of archaeal and bacterial homologues of AGOs have shown that the MID(middle) domain mediates the interaction with the phosphorylated 5' end of the miRNA guide strand and this interaction is thought to be independent of the identity of the 5' nucleotide in these systems(2,3). However, analysis of the known sequences of eukaryotic miRNAs and co-immunoprecipitation experiments indicate that there is a clear bias for U or A at the 5' position(4-7). Here we report the crystal structure of a MID domain from a eukaryotic AGO protein, human AGO2. The structure, in complex with nucleoside monophosphates (AMP, CMP, GMP, and UMP) mimicking the 5' end of miRNAs, shows that there are specific contacts made between the base of UMP or AMP and a rigid loop in the MID domain. Notably, the structure of the loop discriminates against CMP and GMP and dissociation constants calculated from NMR titration experiments confirm these results, showing that AMP (0.26 mM) and UMP (0.12 mM) bind with up to 30-fold higher affinity than either CMP (3.6 mM) or GMP (3.3 mM). This study provides structural evidence for nucleotide-specific interactions in the MID domain of eukaryotic AGO proteins and explains the observed preference for U or A at the 5' end of miRNAs.
C1 [Frank, Filipp; Sonenberg, Nahum; Nagar, Bhushan] McGill Univ, Dept Biochem, Montreal, PQ H3G 0B1, Canada.
   [Frank, Filipp; Sonenberg, Nahum] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3G 0B1, Canada.
   [Frank, Filipp; Nagar, Bhushan] Grp Rech Axe Struct Prot, Montreal, PQ H3G 0B1, Canada.
C3 McGill University; McGill University
RP Nagar, B (corresponding author), McGill Univ, Dept Biochem, Montreal, PQ H3G 0B1, Canada.
EM bhushan.nagar@mcgill.ca
FU Canada Research Chair; Human Frontiers Science Program [CDA 0018/2006-C/1]; Canadian Institutes of Health Research (CIHR) [MOP-82929]; Boehringer Ingelheim Fonds
NR 30
TC 499
Z9 640
U1 1
U2 68
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 818
EP 822
DI 10.1038/nature09039
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800053
PM 20505670
DA 2026-03-09
ER

PT J
AU Wagner, CR
   Kuervers, L
   Baillie, DL
   Yanowitz, JL
AF Wagner, Cynthia R.
   Kuervers, Lynnette
   Baillie, David L.
   Yanowitz, Judith L.
TI xnd-1 regulates the global recombination landscape in Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID double-strand breaks; meiotic recombination; c-elegans; dna; complex; prdm9; crossovers; germline; hotspots; reveals
AB Meiotic crossover (CO) recombination establishes physical linkages between homologous chromosomes that are required for their proper segregation into developing gametes, and promotes genetic diversity by shuffling genetic material between parental chromosomes. COs require the formation of double strand breaks (DSBs) to create the substrate for strand exchange. DSBs occur in small intervals called hotspots(1-3) and significant variation in hotspot usage exists between and among individuals(4). This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology and/or chromosome domain organization(1,5-9). Chromosomes show different frequencies of nondisjunction (NDJ)(10), reflecting inherent differences in meiotic crossover control, yet the underlying basis of these differences remains elusive. Here we show that a novel chromatin factor, X non-disjunction factor 1 (xnd-1), is responsible for the global distribution of COs in C. elegans. xnd-1 is also required for formation of double-strand breaks (DSBs) on the X, but surprisingly XND-1 protein is autosomally enriched. We show that xnd-1 functions independently of genes required for X chromosome-specific gene silencing, revealing a novel pathway that distinguishes the X from autosomes in the germ line, and further show that xnd-1 exerts its effects on COs, at least in part, by modulating levels of H2A lysine 5 acetylation.
C1 [Wagner, Cynthia R.; Yanowitz, Judith L.] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
   [Kuervers, Lynnette; Baillie, David L.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
   [Yanowitz, Judith L.] Magee Womens Res Inst, Pittsburgh, PA 15213 USA.
   [Yanowitz, Judith L.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
C3 Carnegie Institution for Science; Simon Fraser University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Magee-Womens Research Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Yanowitz, JL (corresponding author), Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
EM yanowitzjl@mwri.magee.edu
FU Carnegie Institution of Washington, NIH [K01AG031296]; MWRI; NSERC
NR 36
TC 68
Z9 93
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 839
EP U103
DI 10.1038/nature09429
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700066
PM 20944745
DA 2026-03-09
ER

PT J
AU Johnson, KS
   Riser, SC
   Karl, DM
AF Johnson, Kenneth S.
   Riser, Stephen C.
   Karl, David M.
TI Nitrate supply from deep to near-surface waters of the North Pacific subtropical gyre
SO NATURE
LA English
DT Article
ID nitrogen-fixation; oxygen; flux; stoichiometry; chlorophyll; phosphorus; cycle; zone
AB Concentrations of dissolved inorganic carbon (DIC) decrease in the surface mixed layers during spring and summer in most of the oligotrophic ocean. Mass balance calculations require that the missing DIC is converted into particulate carbon by photosynthesis(1-3). This DIC uptake represents one of the largest components of net community production in the world ocean(2,4). However, mixed-layer waters in these regions of the ocean typically contain negligible concentrations of plant nutrients such as nitrate and phosphate(3,5). Combined nutrient supply mechanisms including nitrogen fixation, diffusive transport and vertical entrainment are believed to be insufficient to supply the required nutrients for photosynthesis(6,7). The basin-scale potential for episodic nutrient transport by eddy events is unresolved(8,9). As a result, it is not understood how biologically mediated DIC uptake can be supported in the absence of nutrients. Here we report on high-resolution measurements of nitrate (NO3-) and oxygen (O-2) concentration made over 21 months using a profiling float deployed near the Hawaii Ocean Time-series station in the North Pacific subtropical gyre. Our measurements demonstrate that as O-2 was produced and DIC was consumed over two annual cycles, a corresponding seasonal deficit in dissolved NO3- appeared in water at depths from 100 to 250 m. The deep-water deficit in NO3- was in near-stoichiometric balance with the fixed nitrogen exported to depth. Thus, when the water column from the surface to 250 m is considered as a whole, there is near equivalence between nutrient supply and demand. Short-lived transport events (<10 days) that connect deep stocks of nitrate to nutrient-poor surface waters were clearly present in 12 of the 127 vertical profiles.
C1 [Johnson, Kenneth S.] Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA.
   [Riser, Stephen C.] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
   [Karl, David M.] Univ Hawaii, Ctr Microbial Oceanog Res & Educ, Sch Ocean & Earth Sci & Technol, Honolulu, HI 96822 USA.
C3 Monterey Bay Aquarium Research Institute; University of Washington; University of Washington Seattle; University of Hawaii System
RP Johnson, KS (corresponding author), Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA.
EM johnson@mbari.org
FU David and Lucile Packard Foundation; National Science Foundation; National Oceanic and Atmospheric Administration; US Office of Naval Research; Gordon and Betty Moore Foundation; Center for Microbial Oceanography: Research and Education; Division Of Ocean Sciences; Directorate For Geosciences [0824990] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [0825348] Funding Source: National Science Foundation
NR 30
TC 222
Z9 253
U1 4
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1062
EP 1065
DI 10.1038/nature09170
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900049
PM 20577212
DA 2026-03-09
ER

PT J
AU Andresen, GB
   Ashkezari, MD
   Baquero-Ruiz, M
   Bertsche, W
   Bowe, PD
   Butler, E
   Cesar, CL
   Chapman, S
   Charlton, M
   Deller, A
   Eriksson, S
   Fajans, J
   Friesen, T
   Fujiwara, MC
   Gill, DR
   Gutierrez, A
   Hangst, JS
   Hardy, WN
   Hayden, ME
   Humphries, AJ
   Hydomako, R
   Jenkins, MJ
   Jonsell, S
   Jorgensen, LV
   Kurchaninov, L
   Madsen, N
   Menary, S
   Nolan, P
   Olchanski, K
   Olin, A
   Povilus, A
   Pusa, P
   Robicheaux, F
   Sarid, E
   el Nasr, SS
   Silveira, DM
   So, C
   Storey, JW
   Thompson, RI
   van der Werf, DP
   Wurtele, JS
   Yamazaki, Y
AF Andresen, G. B.
   Ashkezari, M. D.
   Baquero-Ruiz, M.
   Bertsche, W.
   Bowe, P. D.
   Butler, E.
   Cesar, C. L.
   Chapman, S.
   Charlton, M.
   Deller, A.
   Eriksson, S.
   Fajans, J.
   Friesen, T.
   Fujiwara, M. C.
   Gill, D. R.
   Gutierrez, A.
   Hangst, J. S.
   Hardy, W. N.
   Hayden, M. E.
   Humphries, A. J.
   Hydomako, R.
   Jenkins, M. J.
   Jonsell, S.
   Jorgensen, L. V.
   Kurchaninov, L.
   Madsen, N.
   Menary, S.
   Nolan, P.
   Olchanski, K.
   Olin, A.
   Povilus, A.
   Pusa, P.
   Robicheaux, F.
   Sarid, E.
   el Nasr, S. Seif
   Silveira, D. M.
   So, C.
   Storey, J. W.
   Thompson, R. I.
   van der Werf, D. P.
   Wurtele, J. S.
   Yamazaki, Y.
TI Trapped antihydrogen
SO NATURE
LA English
DT Article
ID magnetic trap; plasmas; antiprotons
AB Antimatter was first predicted(1) in 1931, by Dirac. Work with high-energy antiparticles is now commonplace, and anti-electrons are used regularly in the medical technique of positron emission tomography scanning. Antihydrogen, the bound state of an antiproton and a positron, has been produced(2,3) at low energies at CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is of interest for use in a precision test of nature's fundamental symmetries. The charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the foundation of the standard model of elementary particles and interactions, demands that hydrogen and antihydrogen have the same spectrum. Given the current experimental precision of measurements on the hydrogen atom (about two parts in 10(14) for the frequency of the 1s-to-2s transition(4)), subjecting antihydrogen to rigorous spectroscopic examination would constitute a compelling, model-independent test of CPT. Antihydrogen could also be used to study the gravitational behaviour of antimatter(5). However, so far experiments have produced antihydrogen that is not confined, precluding detailed study of its structure. Here we demonstrate trapping of antihydrogen atoms. From the interaction of about 10(7) antiprotons and 7 x 10(8) positrons, we observed 38 annihilation events consistent with the controlled release of trapped antihydrogen from our magnetic trap; the measured background is 1.4 +/- 1.4 events. This result opens the door to precision measurements on anti-atoms, which can soon be subjected to the same techniques as developed for hydrogen.
C1 [Andresen, G. B.; Bowe, P. D.; Hangst, J. S.] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Ashkezari, M. D.; Hayden, M. E.] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada.
   [Baquero-Ruiz, M.; Chapman, S.; Fajans, J.; Povilus, A.; So, C.; Wurtele, J. S.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Bertsche, W.; Butler, E.; Charlton, M.; Deller, A.; Eriksson, S.; Humphries, A. J.; Jenkins, M. J.; Jorgensen, L. V.; Madsen, N.; van der Werf, D. P.] Swansea Univ, Dept Phys, Swansea SA2 8PP, W Glam, Wales.
   [Cesar, C. L.] Univ Fed Rio de Janeiro, Inst Fis, BR-21941972 Rio De Janeiro, Brazil.
   [Fajans, J.; Wurtele, J. S.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Friesen, T.; Fujiwara, M. C.; Hydomako, R.; Thompson, R. I.] Univ Calgary, Dept Phys & Astron, Calgary, AB T2N 1N4, Canada.
   [Fujiwara, M. C.; Gill, D. R.; Kurchaninov, L.; Olchanski, K.; Olin, A.; Storey, J. W.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Gutierrez, A.; Hangst, J. S.; el Nasr, S. Seif] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Jonsell, S.] Stockholm Univ, SE-10691 Stockholm, Sweden.
   [Menary, S.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Nolan, P.; Pusa, P.] Univ Liverpool, Dept Phys, Liverpool L69 7ZE, Merseyside, England.
   [Robicheaux, F.] Auburn Univ, Dept Phys, Auburn, AL 36849 USA.
   [Sarid, E.] Nucl Res Ctr Negev, Dept Phys, IL-84190 Beer Sheva, Israel.
   [Silveira, D. M.; Yamazaki, Y.] RIKEN, Atom Phys Lab, Wako, Saitama 3510198, Japan.
   [Yamazaki, Y.] Univ Tokyo, Grad Sch Arts & Sci, Tokyo 1538902, Japan.
C3 Aarhus University; Simon Fraser University; University of California System; University of California Berkeley; Swansea University; Universidade Federal do Rio de Janeiro; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Calgary; University of British Columbia; University of British Columbia; Stockholm University; York University - Canada; University of Liverpool; Auburn University System; Auburn University; RIKEN; University of Tokyo
RP Hangst, JS (corresponding author), Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
EM hangst@phys.au.dk
FU CNPq (Brazil); FINEP/RENAFAE (Brazil); ISF (Israel); MEXT (Japan); FNU (Denmark); VR (Sweden); NSERC (Canada); NRC/TRIUMF (Canada); AIF (Canada); FQRNT (Canada); DOE (USA); NSF (USA); EPSRC (UK); Royal Society (UK); Leverhulme Trust (UK); Engineering and Physical Sciences Research Council [EP/D040108/1, EP/F019785/1, EP/D038707/1, EP/E048951/1] Funding Source: researchfish; EPSRC [EP/D038707/1, EP/F019785/1, EP/E048951/1, EP/D040108/1] Funding Source: UKRI
NR 28
TC 279
Z9 320
U1 1
U2 87
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 673
EP U1
DI 10.1038/nature09610
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700036
PM 21085118
DA 2026-03-09
ER

PT J
AU Nazarian, R
   Shi, HB
   Wang, Q
   Kong, XJ
   Koya, RC
   Lee, H
   Chen, ZG
   Lee, MK
   Attar, N
   Sazegar, H
   Chodon, T
   Nelson, SF
   McArthur, G
   Sosman, JA
   Ribas, A
   Lo, RS
AF Nazarian, Ramin
   Shi, Hubing
   Wang, Qi
   Kong, Xiangju
   Koya, Richard C.
   Lee, Hane
   Chen, Zugen
   Lee, Mi-Kyung
   Attar, Narsis
   Sazegar, Hooman
   Chodon, Thinle
   Nelson, Stanley F.
   McArthur, Grant
   Sosman, Jeffrey A.
   Ribas, Antoni
   Lo, Roger S.
TI Melanomas acquire resistance toB-RAF(V600E) inhibition by RTK or N-RAS upregulation
SO NATURE
LA English
DT Article
ID braf; mutations; kinase; sensitivity; pathway; craf; mek
AB Activating B-RAF(V600E) (also known as BRAF) kinase mutations occur in similar to 7% of human malignancies and similar to 60% of melanomas(1). Early clinical experience with a novel class I RAF-selective inhibitor, PLX4032, demonstrated an unprecedented 80% anti-tumour response rate among patients with B-RAF(V600E)-positive melanomas, but acquired drug resistance frequently develops after initial responses(2). Hypotheses for mechanisms of acquired resistance to B-RAF inhibition include secondary mutations in B-RAF(V600E), MAPK reactivation, and activation of alternative survival pathways(3-5). Here we show that acquired resistance to PLX4032 develops by mutually exclusive PDGFR beta (also known as PDGFRB) upregulation or N-RAS (also known as NRAS) mutations but not through secondary mutations in B-RAF(V600E). We used PLX4032-resistant sub-lines artificially derived from B-RAF(V600E)-positive melanoma cell lines and validated key findings in PLX4032-resistant tumours and tumour-matched, short-term cultures from clinical trial patients. Induction of PDGFR beta RNA, protein and tyrosine phosphorylation emerged as a dominant feature of acquired PLX4032 resistance in a subset of melanoma sub-lines, patient-derived biopsies and short-term cultures. PDGFR beta-upregulated tumour cells have low activated RAS levels and, when treated with PLX4032, do not reactivate the MAPK pathway significantly. In another subset, high levels of activated N-RAS resulting from mutations lead to significant MAPK pathway reactivation upon PLX4032 treatment. Knockdown of PDGFR beta or N-RAS reduced growth of the respective PLX4032-resistant subsets. Overexpression of PDGFR beta or N-RAS(Q61K) conferred PLX4032 resistance to PLX4032-sensitive parental cell lines. Importantly, MAPK reactivation predicts MEK inhibitor sensitivity. Thus, melanomas escape B-RAF(V600E) targeting not through secondary B-RAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies.
C1 [Nazarian, Ramin; Shi, Hubing; Wang, Qi; Kong, Xiangju; Lee, Mi-Kyung; Lo, Roger S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA.
   [Nazarian, Ramin; Shi, Hubing; Wang, Qi; Kong, Xiangju; Koya, Richard C.; Lee, Hane; Chen, Zugen; Lee, Mi-Kyung; Attar, Narsis; Sazegar, Hooman; Chodon, Thinle; Nelson, Stanley F.; Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Koya, Richard C.; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Surg, Div Surg Oncol, Los Angeles, CA 90095 USA.
   [Lee, Hane; Chen, Zugen; Nelson, Stanley F.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Attar, Narsis; Sazegar, Hooman; Chodon, Thinle; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
   [Nelson, Stanley F.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Pediat, Los Angeles, CA 90095 USA.
   [McArthur, Grant] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
   [Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37232 USA.
C3 UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; 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; Peter Maccallum Cancer Center; Vanderbilt University
RP Lo, RS (corresponding author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Dermatol, 52-121 CHS, Los Angeles, CA 90095 USA.
EM rlo@mednet.ucla.edu
FU Dermatology Foundation; Burroughs Wellcome Fund; STOP CANCER Foundation; Margaret E. Early Medical Trust; Ian Copeland Memorial Melanoma Fund; V Foundation for Cancer Research; Melanoma Research Foundation; American Skin Association; Caltech-UCLA Joint Center for Translational Medicine; Wesley Coyle Memorial Fund; Melanoma Research Alliance; T32 Tumor Immunology Training Grant; California Institute for Regenerative Medicine (CIRM); Jonsson Cancer Center Foundation (JCCF)
NR 18
TC 1775
Z9 2124
U1 0
U2 236
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 973
EP U377
DI 10.1038/nature09626
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600049
PM 21107323
DA 2026-03-09
ER

PT J
AU Lee, LK
   Ginsburg, MA
   Crovace, C
   Donohoe, M
   Stock, D
AF Lee, Lawrence K.
   Ginsburg, Michael A.
   Crovace, Claudia
   Donohoe, Mhairi
   Stock, Daniela
TI Structure of the torque ring of the flagellar motor and the molecular basis for rotational switching
SO NATURE
LA English
DT Article
ID salmonella-typhimurium; protein flig; 3-dimensional structure; conformational spread; mutational analysis; charged residues; rotor; region; localization; generation
AB The flagellar motor drives the rotation of flagellar filaments at hundreds of revolutions per second(1,2), efficiently propelling bacteria through viscous media(3). The motor uses the potential energy from an electrochemical gradient of cations(4,5) across the cytoplasmic membrane to generate torque. A rapid switch from anticlockwise to clockwise rotation determines whether a bacterium runs smoothly forward or tumbles to change its trajectory(6,7). A protein called FliG forms a ring in the rotor of the flagellar motor that is involved in the generation of torque(8-13) through an interaction with the cation-channel-forming stator subunit MotA(12). FliG has been suggested to adopt distinct conformations that induce switching but these structural changes and the molecular mechanism of switching are unknown. Here we report the molecular structure of the full-length FliG protein, identify conformational changes that are involved in rotational switching and uncover the structural basis for the formation of the FliG torque ring. This allows us to propose a model of the complete ring and switching mechanism in which conformational changes in FliG reverse the electrostatic charges involved in torque generation.
C1 [Lee, Lawrence K.; Ginsburg, Michael A.; Donohoe, Mhairi; Stock, Daniela] Victor Chang Cardiac Res Inst, Struct & Computat Biol Div, Darlinghurst, NSW 2010, Australia.
   [Crovace, Claudia] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   [Stock, Daniela] Univ New S Wales, Fac Med, Sydney, NSW 2052, Australia.
C3 Victor Chang Cardiac Research Institute; MRC Laboratory Molecular Biology; University of New South Wales Sydney
RP Stock, D (corresponding author), Victor Chang Cardiac Res Inst, Struct & Computat Biol Div, Lowy Packer Bldg,405 Liverpool St, Darlinghurst, NSW 2010, Australia.
EM d.stock@victorchang.edu.au
FU US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; National Institutes of Health, National Center for Research Resources [RR007707]; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Science [Y1-GM-1104]; Australian Nuclear Science Technology Organization; MRC; Medical Research Council [MC_U105170645] Funding Source: researchfish; MRC [MC_U105170645] Funding Source: UKRI
NR 40
TC 140
Z9 160
U1 3
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 996
EP U129
DI 10.1038/nature09300
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300039
PM 20676082
DA 2026-03-09
ER

PT J
AU Shizuka, D
   Lyon, BE
AF Shizuka, Daizaburo
   Lyon, Bruce E.
TI Coots use hatch order to learn to recognize and reject conspecific brood parasitic chicks
SO NATURE
LA English
DT Article
ID avian egg-recognition; host-defense; arms-race; evolution; model; discrimination; mechanisms; nestlings; cowbirds; choice
AB Avian brood parasites and their hosts provide model systems for investigating links between recognition, learning, and their fitness consequences(1-4). One major evolutionary puzzle has continued to capture the attention of naturalists for centuries: why do hosts of brood parasites generally fail to recognize parasitic offspring after they have hatched from the egg(5-9), even when the host and parasitic chicks differ to almost comic degrees(7)? One prominent theory to explain this pattern proposes that the costs of mistakenly learning to recognize the wrong offspring make recognition maladaptive(10). Here we show that American coots, Fulica americana, can recognize and reject parasitic chicks in their brood by using learned cues, despite the fact that the hosts and the brood parasites are of the same species. A series of chick cross-fostering experiments confirm that coots use first-hatched chicks in a brood as referents to learn to recognize their own chicks and then discriminate against later-hatched parasitic chicks in the same brood. When experimentally provided with the wrong reference chicks, coots can be induced to discriminate against their own offspring, confirming that the learning errors proposed by theory can exist(10). However, learning based on hatching order is reliable in naturally parasitized coot nests because host eggs hatch predictably ahead of parasite eggs. Conversely, a lack of reliable information may help to explain why the evolution of chick recognition is not more common in hosts of most interspecific brood parasites.
C1 [Shizuka, Daizaburo; Lyon, Bruce E.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
C3 University of California System; University of California Santa Cruz
RP Shizuka, D (corresponding author), Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
EM shizuka@biology.ucsc.edu
FU National Geographic Society; National Science Foundation [DDIG IOS-0808579, IOS 0443807]; Chapman Fund; Sigma Xi Society
NR 34
TC 69
Z9 78
U1 1
U2 60
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 223
EP U108
DI 10.1038/nature08655
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700034
PM 20016486
DA 2026-03-09
ER

PT J
AU Moreno, M
   Rosenau, M
   Oncken, O
AF Moreno, Marcos
   Rosenau, Matthias
   Oncken, Onno
TI 2010 Maule earthquake slip correlates with pre-seismic locking of Andean subduction zone
SO NATURE
LA English
DT Article
ID ofqui fault zone; southern andes; strain accumulation; central chile; deformation; model; gaps; pacific; america; rupture
AB The magnitude-8.8 Maule (Chile) earthquake of 27 February 2010 ruptured a segment of the Andean subduction zone megathrust that has been suspected to be of high seismic potential(1-6). It is the largest earthquake to rupture a mature seismic gap in a subduction zone that has been monitored with a dense space-geodetic network before the event. This provides an image of the pre-seismically locked state of the plate interface of unprecedentedly high resolution, allowing for an assessment of the spatial correlation of interseismic locking with coseismic slip. Pre-seismic locking might be used to anticipate future ruptures in many seismic gaps(6-12), given the fundamental assumption that locking and slip are similar. This hypothesis, however, could not be tested without the occurrence of the first gap-filling earthquake. Here we show evidence that the 2010 Maule earthquake slip distribution correlates closely with the patchwork of interseismic locking distribution as derived by inversion of global positioning system (GPS) observations during the previous decade. The earthquake nucleated in a region of high locking gradient and released most of the stresses accumulated in the area since the last major event in 1835. Two regions of high seismic slip (asperities) appeared to be nearly fully locked before the earthquake. Between these asperities, the rupture bridged a zone that was creeping interseismically with consistently low coseismic slip. The rupture stopped in areas that were highly locked before the earthquake but where pre-stress had been significantly reduced by overlapping twentieth-century earthquakes. Our work suggests that coseismic slip heterogeneity at the scale of single asperities should indicate the seismic potential of future great earthquakes, which thus might be anticipated by geodetic observations.
C1 [Moreno, Marcos; Rosenau, Matthias; Oncken, Onno] GFZ German Res Ctr Geosci, Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
C3 Helmholtz Association; GFZ Helmholtz Centre for Geosciences
RP Oncken, O (corresponding author), GFZ German Res Ctr Geosci, Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
EM oncken@gfz-potsdam.de
NR 55
TC 395
Z9 441
U1 1
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 198
EP U84
DI 10.1038/nature09349
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300032
PM 20829792
DA 2026-03-09
ER

PT J
AU Ehrenreich, IM
   Torabi, N
   Jia, Y
   Kent, J
   Martis, S
   Shapiro, JA
   Gresham, D
   Caudy, AA
   Kruglyak, L
AF Ehrenreich, Ian M.
   Torabi, Noorossadat
   Jia, Yue
   Kent, Jonathan
   Martis, Stephen
   Shapiro, Joshua A.
   Gresham, David
   Caudy, Amy A.
   Kruglyak, Leonid
TI Dissection of genetically complex traits with extremely large pools of yeast segregants
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; loci; identification; architecture; microarrays; mutation; diseases
AB Most heritable traits, including many human diseases(1), are caused by multiple loci. Studies in both humans and model organisms, such as yeast, have failed to detect a large fraction of the loci that underlie such complex traits(2,3). A lack of statistical power to identify multiple loci with small effects is undoubtedly one of the primary reasons for this problem. We have developed a method in yeast that allows the use of much larger sample sizes than previously possible and hence permits the detection of multiple loci with small effects. The method involves generating very large numbers of progeny from a cross between two Saccharomyces cerevisiae strains and then phenotyping and genotyping pools of these offspring. We applied the method to 17 chemical resistance traits and mitochondrial function, and identified loci for each of these phenotypes. We show that the level of genetic complexity underlying these quantitative traits is highly variable, with some traits influenced by one major locus and others by at least 20 loci. Our results provide an empirical demonstration of the genetic complexity of a number of traits and show that it is possible to identify many of the underlying factors using straightforward techniques. Our method should have broad applications in yeast and can be extended to other organisms.
C1 [Ehrenreich, Ian M.; Torabi, Noorossadat; Jia, Yue; Kent, Jonathan; Martis, Stephen; Shapiro, Joshua A.; Gresham, David; Caudy, Amy A.; Kruglyak, Leonid] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
   [Ehrenreich, Ian M.; Shapiro, Joshua A.; Kruglyak, Leonid] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA.
   [Ehrenreich, Ian M.; Jia, Yue; Shapiro, Joshua A.; Kruglyak, Leonid] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08540 USA.
   [Torabi, Noorossadat] Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA.
C3 Princeton University; Princeton University; Princeton University; Howard Hughes Medical Institute; Princeton University
RP Kruglyak, L (corresponding author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
EM leonid@genomics.princeton.edu
FU NIH [R37 MH59520, F32 HG51762, P50 GM071508]; James S. McDonnell Centennial Fellowship; Howard Hughes Medical Institute
NR 29
TC 332
Z9 414
U1 0
U2 87
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1039
EP U101
DI 10.1038/nature08923
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000038
PM 20393561
DA 2026-03-09
ER

PT J
AU Baumann, K
   Guerlin, C
   Brennecke, F
   Esslinger, T
AF Baumann, Kristian
   Guerlin, Christine
   Brennecke, Ferdinand
   Esslinger, Tilman
TI Dicke quantum phase transition with a superfluid gas in an optical cavity
SO NATURE
LA English
DT Article
ID bose-einstein condensate; self-organization; ultracold atoms; entanglement; model; superradiance; lattices; systems; light
AB A phase transition describes the sudden change of state of a physical system, such as melting or freezing. Quantum gases provide the opportunity to establish a direct link between experiments and generic models that capture the underlying physics. The Dicke model describes a collective matter-light interaction and has been predicted to show an intriguing quantum phase transition. Here we realize the Dicke quantum phase transition in an open system formed by a Bose-Einstein condensate coupled to an optical cavity, and observe the emergence of a self-organized supersolid phase. The phase transition is driven by infinitely long-range interactions between the condensed atoms, induced by two-photon processes involving the cavity mode and a pump field. We show that the phase transition is described by the Dicke Hamiltonian, including counter-rotating coupling terms, and that the supersolid phase is associated with a spontaneously broken spatial symmetry. The boundary of the phase transition is mapped out in quantitative agreement with the Dicke model. Our results should facilitate studies of quantum gases with long-range interactions and provide access to novel quantum phases.
C1 [Baumann, Kristian; Guerlin, Christine; Brennecke, Ferdinand; Esslinger, Tilman] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Esslinger, T (corresponding author), ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM esslinger@phys.ethz.ch
FU NAME-QUAM (European Commission) [225187]; QSIT (ETH Zurich); ETH
NR 48
TC 1314
Z9 1438
U1 1
U2 190
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1301
EP U1
DI 10.1038/nature09009
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000036
PM 20428162
DA 2026-03-09
ER

PT J
AU Gupta, RK
   Arany, Z
   Seale, P
   Mepani, RJ
   Ye, L
   Conroe, HM
   Roby, YA
   Kulaga, H
   Reed, RR
   Spiegelman, BM
AF Gupta, Rana K.
   Arany, Zoltan
   Seale, Patrick
   Mepani, Rina J.
   Ye, Li
   Conroe, Heather M.
   Roby, Yang A.
   Kulaga, Heather
   Reed, Randall R.
   Spiegelman, Bruce M.
TI Transcriptional control of preadipocyte determination by Zfp423
SO NATURE
LA English
DT Article
ID ppar-gamma; oligonucleotide arrays; cerebellar development; adipose conversion; adipocyte lineage; gene-expression; in-vivo; cells; differentiation; adipogenesis
AB The worldwide epidemic of obesity has increased the urgency to develop a deeper understanding of physiological systems related to energy balance and energy storage, including the mechanisms controlling the development of fat cells (adipocytes). The differentiation of committed preadipocytes to adipocytes is controlled by PPAR gamma and several other transcription factors(1), but the molecular basis for preadipocyte determination is not understood. Using a new method for the quantitative analysis of transcriptional components, we identified the zinc-finger protein Zfp423 as a factor enriched in preadipose versus non-preadipose fibroblasts. Ectopic expression of Zfp423 in non-adipogenic NIH 3T3 fibroblasts robustly activates expression of Pparg in undifferentiated cells and permits cells to undergo adipocyte differentiation under permissive conditions. Short hairpin RNA (shRNA)-mediated reduction of Zfp423 expression in 3T3-L1 cells blunts preadipocyte Pparg expression and diminishes the ability of these cells to differentiate. Furthermore, both brown and white adipocyte differentiation is markedly impaired in Zfp423-deficient mouse embryos. Zfp423 regulates Pparg expression, in part, through amplification of the BMP signalling pathway, an effect dependent on the SMAD-binding capacity of Zfp423. This study identifies Zfp423 as a transcriptional regulator of preadipocyte determination.
C1 [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA.
   [Gupta, Rana K.; Arany, Zoltan; Seale, Patrick; Mepani, Rina J.; Ye, Li; Conroe, Heather M.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Roby, Yang A.; Kulaga, Heather; Reed, Randall R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Ctr Sensory Biol,Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
C3 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; Johns Hopkins University
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
FU Ruth Kirstein NRSA [F32 DK079507-01]; NHLBI [K08 HL79172-01]; Smith Family Foundation; NIH [DK081605, DK31405]; NIDCD [R01DC008295]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK040561] Funding Source: NIH RePORTER
NR 27
TC 438
Z9 520
U1 2
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 25
PY 2010
VL 464
IS 7288
BP 619
EP U187
DI 10.1038/nature08816
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200054
PM 20200519
DA 2026-03-09
ER

PT J
AU Neill, DR
   Wong, SH
   Bellosi, A
   Flynn, RJ
   Daly, M
   Langford, TKA
   Bucks, C
   Kane, CM
   Fallon, PG
   Pannell, R
   Jolin, HE
   McKenzie, ANJ
AF Neill, Daniel R.
   Wong, See Heng
   Bellosi, Agustin
   Flynn, Robin J.
   Daly, Maria
   Langford, Theresa K. A.
   Bucks, Christine
   Kane, Colleen M.
   Fallon, Padraic G.
   Pannell, Richard
   Jolin, Helen E.
   McKenzie, Andrew N. J.
TI Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity
SO NATURE
LA English
DT Article
ID il-13; cells; requirement; lymphocytes; expression; mice
AB Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity-responsible for protective immune responses to helminth parasites(1,2) and the underlying cause of the pathogenesis of allergic asthma(3,4)-consists of responses dominated by the cardinal type-2 cytokines interleukin (IL) 4, IL5 and IL13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively determined. Here, through the use of novel Il13-eGFP reporter mice, we present the identification and functional characterization of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type-2-inducing cytokines IL25 and IL33, and represent the predominant early source of IL13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL25 and IL33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wild-type, but not IL13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.
C1 [Neill, Daniel R.; Wong, See Heng; Bellosi, Agustin; Flynn, Robin J.; Daly, Maria; Langford, Theresa K. A.; Pannell, Richard; Jolin, Helen E.; McKenzie, Andrew N. J.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Bucks, Christine; Kane, Colleen M.] Centocor R&D Inc, Immunol Discovery Res, Radnor, PA 19087 USA.
   [Fallon, Padraic G.] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 8, Ireland.
C3 MRC Laboratory Molecular Biology; Johnson & Johnson; Johnson & Johnson USA; Trinity College Dublin
RP McKenzie, ANJ (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM anm@mrc-lmb.cam.ac.uk
FU Asthma UK; Science Foundation Ireland; MRC [MC_U105178805] Funding Source: UKRI; Medical Research Council [MC_U105178805] Funding Source: researchfish
NR 24
TC 1738
Z9 2015
U1 2
U2 168
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1367
EP U9
DI 10.1038/nature08900
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000050
PM 20200518
DA 2026-03-09
ER

PT J
AU Chen, LQ
   Hou, BH
   Lalonde, S
   Takanaga, H
   Hartung, ML
   Qu, XQ
   Guo, WJ
   Kim, JG
   Underwood, W
   Chaudhuri, B
   Chermak, D
   Antony, G
   White, FF
   Somerville, SC
   Mudgett, MB
   Frommer, WB
AF Chen, Li-Qing
   Hou, Bi-Huei
   Lalonde, Sylvie
   Takanaga, Hitomi
   Hartung, Mara L.
   Qu, Xiao-Qing
   Guo, Woei-Jiun
   Kim, Jung-Gun
   Underwood, William
   Chaudhuri, Bhavna
   Chermak, Diane
   Antony, Ginny
   White, Frank F.
   Somerville, Shauna C.
   Mudgett, Mary Beth
   Frommer, Wolf B.
TI Sugar transporters for intercellular exchange and nutrition of pathogens
SO NATURE
LA English
DT Article
ID fanconi-bickel-syndrome; powdery mildew; endoplasmic-reticulum; glucose-transporter; bacterial-blight; petunia-hybrida; gene; arabidopsis; sucrose; resistance
AB Sugar efflux transporters are essential for the maintenance of animal blood glucose levels, plant nectar production, and plant seed and pollen development. Despite broad biological importance, the identity of sugar efflux transporters has remained elusive. Using optical glucose sensors, we identified a new class of sugar transporters, named SWEETs, and show that at least six out of seventeen Arabidopsis, two out of over twenty rice and two out of seven homologues in Caenorhabditis elegans, and the single copy human protein, mediate glucose transport. Arabidopsis SWEET8 is essential for pollen viability, and the rice homologues SWEET11 and SWEET14 are specifically exploited by bacterial pathogens for virulence by means of direct binding of a bacterial effector to the SWEET promoter. Bacterial symbionts and fungal and bacterial pathogens induce the expression of different SWEET genes, indicating that the sugar efflux function of SWEET transporters is probably targeted by pathogens and symbionts for nutritional gain. The metazoan homologues may be involved in sugar efflux from intestinal, liver, epididymis and mammary cells.
C1 [Chen, Li-Qing; Hou, Bi-Huei; Lalonde, Sylvie; Takanaga, Hitomi; Hartung, Mara L.; Qu, Xiao-Qing; Guo, Woei-Jiun; Chaudhuri, Bhavna; Chermak, Diane; Frommer, Wolf B.] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA.
   [Kim, Jung-Gun; Mudgett, Mary Beth] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Antony, Ginny; White, Frank F.] Kansas State Univ, Dept Plant Pathol, Manhattan, KS 66506 USA.
   [Underwood, William; Somerville, Shauna C.] Energy Biosci Inst, Berkeley, CA 94720 USA.
C3 Carnegie Institution for Science; Stanford University; Kansas State University
RP Frommer, WB (corresponding author), Carnegie Inst Sci, Dept Plant Biol, 290 Panama St, Stanford, CA 94305 USA.
EM wfrommer@carnegiescience.edu
FU Department of Energy [DE-FG02-04ER15542]; NIH (NIDDK) [1RO1DK079109]; Carnegie Institution; National Natural Science Foundation of China (NSFC) [30771288]; NSF [IOS-0821801]; NIH [ZRO1GM06886-06A1, F32GM083439-02]; NSF; USDA NIFA [2007-35319-18103]; NSF Plant Genome [DBI-0820831]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0821801] Funding Source: National Science Foundation
NR 61
TC 1274
Z9 1570
U1 13
U2 707
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 527
EP U199
DI 10.1038/nature09606
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200034
PM 21107422
DA 2026-03-09
ER

PT J
AU Kim, J
   Zhang, CZ
   Zhang, XH
   Springer, TA
AF Kim, Jongseong
   Zhang, Cheng-Zhong
   Zhang, Xiaohui
   Springer, Timothy A.
TI A mechanically stabilized receptor-ligand flex-bond important in the vasculature
SO NATURE
LA English
DT Article
ID von-willebrand-factor; ib-ix-v; leucine-rich repeats; factor a1 domain; platelet-adhesion; single-molecule; catch bonds; shear; complex; force
AB Haemostasis in the arteriolar circulation mediated by von Willebrand factor (VWF) binding to platelets is an example of an adhesive interaction that must withstand strong hydrodynamic forces acting on cells. VWF is a concatenated, multifunctional protein that has binding sites for platelets as well as subendothelial collagen(1,2). Binding of the A1 domain in VWF to the glycoprotein Ib alpha subunit (GPIb alpha) on the surface of platelets mediates crosslinking of platelets to one another and the formation of a platelet plug for arterioles(3,4). The importance of VWF is illustrated by its mutation in von Willebrand disease, a bleeding diathesis(1). Here, we describe a novel mechanochemical specialization of the A1-GPIb alpha bond for force-resistance. We have developed a method that enables, for the first time, repeated measurements of the binding and unbinding of a receptor and ligand in a single molecule (ReaLiSM). We demonstrate two states of the receptor-ligand bond, that is, a flex-bond. One state is seen at low force; a second state begins to engage at 10 pN with a similar to 20-fold longer lifetime and greater force resistance. The lifetimes of the two states, how force exponentiates lifetime, and the kinetics of switching between the two states are all measured. For the first time, single-molecule measurements on this system are in agreement with bulk phase measurements. The results have important implications not only for how platelets bound to VWF are able to resist force to plug arterioles, but also how increased flow activates platelet plug formation.
C1 [Kim, Jongseong; Zhang, Cheng-Zhong; Zhang, Xiaohui; Springer, Timothy A.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
   [Kim, Jongseong; Zhang, Cheng-Zhong; Zhang, Xiaohui; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, 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
RP Springer, TA (corresponding author), Childrens Hosp, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
FU NIH [HL-48675]
NR 31
TC 233
Z9 289
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 19
PY 2010
VL 466
IS 7309
BP 992
EP U123
DI 10.1038/nature09295
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300038
PM 20725043
DA 2026-03-09
ER

PT J
AU Gething, PW
   Smith, DL
   Patil, AP
   Tatem, AJ
   Snow, RW
   Hay, SI
AF Gething, Peter W.
   Smith, David L.
   Patil, Anand P.
   Tatem, Andrew J.
   Snow, Robert W.
   Hay, Simon I.
TI Climate change and the global malaria recession
SO NATURE
LA English
DT Article
ID insecticide-treated nets; combination therapy; inoculation rate; transmission; impact; populations; elimination; infection; africa; burden
AB The current and potential future impact of climate change on malaria is of major public health interest(1,2). The proposed effects of rising global temperatures on the future spread and intensification of the disease(3-5), and on existing malaria morbidity and mortality rates(3), substantively influence global health policy(6,7). The contemporary spatial limits of Plasmodium falciparum malaria and its endemicity within this range(8), when compared with comparable historical maps, offer unique insights into the changing global epidemiology of malaria over the last century. It has long been known that the range of malaria has contracted through a century of economic development and disease control(9). Here, for the first time, we quantify this contraction and the global decreases in malaria endemicity since approximately 1900. We compare the magnitude of these changes to the size of effects on malaria endemicity proposed under future climate scenarios and associated with widely used public health interventions. Our findings have two key and often ignored implications with respect to climate change and malaria. First, widespread claims that rising mean temperatures have already led to increases in worldwide malaria morbidity and mortality are largely at odds with observed decreasing global trends in both its endemicity and geographic extent. Second, the proposed future effects of rising temperatures on endemicity are at least one order of magnitude smaller than changes observed since about 1900 and up to two orders of magnitude smaller than those that can be achieved by the effective scale-up of key control measures. Predictions of an intensification of malaria in a warmer world, based on extrapolated empirical relationships or biological mechanisms, must be set against a context of a century of warming that has seen marked global declines in the disease and a substantial weakening of the global correlation between malaria endemicity and climate.
C1 [Gething, Peter W.; Patil, Anand P.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
   [Smith, David L.; Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
   [Smith, David L.] Univ Florida, Dept Biol, Gainesville, FL 32610 USA.
   [Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
   [Snow, Robert W.] KEMRI Univ Oxford Wellcome Trust Collaborat Progr, Malaria Publ Hlth & Epidemiol Grp, Ctr Geog Med, Nairobi, Kenya.
   [Snow, Robert W.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, CCVTM, Oxford OX3 7LJ, England.
C3 University of Oxford; 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 Oxford
RP Hay, SI (corresponding author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England.
EM peter.gething@zoo.ox.ac.uk; simon.hay@zoo.ox.ac.uk
FU Wellcome Trust [079091, 079080]; Bill and Melinda Gates Foundation [49446]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Wellcome Trust, UK
NR 38
TC 272
Z9 321
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 MAY 20
PY 2010
VL 465
IS 7296
BP 342
EP U94
DI 10.1038/nature09098
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200039
PM 20485434
DA 2026-03-09
ER

PT J
AU Kuehne, SA
   Cartman, ST
   Heap, JT
   Kelly, ML
   Cockayne, A
   Minton, NP
AF Kuehne, Sarah A.
   Cartman, Stephen T.
   Heap, John T.
   Kelly, Michelle L.
   Cockayne, Alan
   Minton, Nigel P.
TI The role of toxin A and toxin B in Clostridium difficile infection
SO NATURE
LA English
DT Article
ID diarrhea; strain; resistant; genome
AB Clostridium difficile infection is the leading cause of healthcare-associated diarrhoea in Europe and North America(1,2). During infection, C. difficile produces two key virulence determinants, toxin A and toxin B. Experiments with purified toxins have indicated that toxin A alone is able to evoke the symptoms of C. difficile infection, but toxin B is unable to do so unless it is mixed with toxin A or there is prior damage to the gut mucosa(3). However, a recent study indicated that toxin B is essential for C. difficile virulence and that a strain producing toxin A alone was avirulent(4). This creates a paradox over the individual importance of toxin A and toxin B. Here we show that isogenic mutants of C. difficile producing either toxin A or toxin B alone can cause fulminant disease in the hamster model of infection. By using a gene knockout system(5,6) to inactivate the toxin genes permanently, we found that C. difficile producing either one or both toxins showed cytotoxic activity in vitro that translated directly into virulence in vivo. Furthermore, by constructing the first ever double-mutant strain of C. difficile, in which both toxin genes were inactivated, we were able to completely attenuate virulence. Our findings re-establish the importance of both toxin A and toxin B and highlight the need to continue to consider both toxins in the development of diagnostic tests and effective countermeasures against C. difficile.
C1 [Kuehne, Sarah A.; Cartman, Stephen T.; Heap, John T.; Kelly, Michelle L.; Cockayne, Alan; Minton, Nigel P.] Univ Nottingham, NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Sch Mol Med Sci,Ctr Biomol Sci,Clostridia Res Grp, Nottingham NG7 2RD, England.
C3 University of Nottingham
RP Minton, NP (corresponding author), Univ Nottingham, NIHR Biomed Res Unit, Nottingham Digest Dis Ctr, Sch Mol Med Sci,Ctr Biomol Sci,Clostridia Res Grp, Nottingham NG7 2RD, England.
EM nigel.minton@nottingham.ac.uk
FU UK Medical Research Council [G0601176]; European Union [HEALTH-F3-2008-223585]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F003390/1]; Biotechnology and Biological Sciences Research Council [BB/F003390/1] Funding Source: researchfish; Medical Research Council [G0601176] Funding Source: researchfish; BBSRC [BB/F003390/1] Funding Source: UKRI; MRC [G0601176] Funding Source: UKRI
NR 26
TC 687
Z9 807
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 OCT 7
PY 2010
VL 467
IS 7316
BP 711
EP U97
DI 10.1038/nature09397
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500039
PM 20844489
DA 2026-03-09
ER

PT J
AU Chekeni, FB
   Elliott, MR
   Sandilos, JK
   Walk, SF
   Kinchen, JM
   Lazarowski, ER
   Armstrong, AJ
   Penuela, S
   Laird, DW
   Salvesen, GS
   Isakson, BE
   Bayliss, DA
   Ravichandran, KS
AF Chekeni, Faraaz B.
   Elliott, Michael R.
   Sandilos, Joanna K.
   Walk, Scott F.
   Kinchen, Jason M.
   Lazarowski, Eduardo R.
   Armstrong, Allison J.
   Penuela, Silvia
   Laird, Dale W.
   Salvesen, Guy S.
   Isakson, Brant E.
   Bayliss, Douglas A.
   Ravichandran, Kodi S.
TI Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis
SO NATURE
LA English
DT Article
ID activation; cleavage; accumulation; family; cells
AB Apoptotic cells release 'find-me' signals at the earliest stages of death to recruit phagocytes(1). The nucleotides ATP and UTP represent one class of find-me signals(2), but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells. Pharmacological inhibition and siRNA-mediated knockdown of PANX1 led to decreased nucleotide release and monocyte recruitment by apoptotic cells. Conversely, PANX1 overexpression enhanced nucleotide release from apoptotic cells and phagocyte recruitment. Patch-clamp recordings showed that PANX1 was basally inactive, and that induction of PANX1 currents occurred only during apoptosis. Mechanistically, PANX1 itself was a target of effector caspases (caspases 3 and 7), and a specific caspase-cleavage site within PANX1 was essential for PANX1 function during apoptosis. Expression of truncated PANX1 (at the putative caspase cleavage site) resulted in a constitutively open channel. PANX1 was also important for the 'selective' plasma membrane permeability of early apoptotic cells to specific dyes(3). Collectively, these data identify PANX1 as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases.
C1 [Chekeni, Faraaz B.; Elliott, Michael R.; Walk, Scott F.; Kinchen, Jason M.; Armstrong, Allison J.; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Chekeni, Faraaz B.; Sandilos, Joanna K.; Bayliss, Douglas A.] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA.
   [Elliott, Michael R.; Walk, Scott F.; Kinchen, Jason M.; Armstrong, Allison J.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Kinchen, Jason M.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Isakson, Brant E.] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Isakson, Brant E.] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
   [Lazarowski, Eduardo R.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Penuela, Silvia; Laird, Dale W.] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada.
   [Salvesen, Guy S.] Burnham Inst Med Res, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of North Carolina; University of North Carolina Chapel Hill; Western University (University of Western Ontario); Sanford Burnham Prebys Medical Discovery Institute
RP Ravichandran, KS (corresponding author), Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
EM Ravi@virgina.edu
FU NIGMS; NHLBI; AHA; National Institutes of Health; American Heart Association; American Cancer Society; American Asthma Foundation; National Institute of Allergy and Infectious Diseases [T32AI055432, T32AI007496] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007267] Funding Source: NIH RePORTER
NR 33
TC 942
Z9 1067
U1 1
U2 116
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 863
EP U136
DI 10.1038/nature09413
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700071
PM 20944749
DA 2026-03-09
ER

PT J
AU Gilfanov, M
   Bogdán, A
AF Gilfanov, Marat
   Bogdan, Akos
TI An upper limit on the contribution of accreting white dwarfs to the type Ia supernova rate
SO NATURE
LA English
DT Article
ID x-ray sources; progenitor systems; mass; binary; models; evolution; stars; m31
AB There is wide agreement that type Ia supernovae (used as standard candles for cosmology) are associated with the thermonuclear explosions of white dwarf stars(1,2). The nuclear runaway that leads to the explosion could start in a white dwarf gradually accumulating matter from a companion star until it reaches the Chandrasekhar limit(3), or could be triggered by the merger of two white dwarfs in a compact binary system(4,5). The X-ray signatures of these two possible paths are very different. Whereas no strong electromagnetic emission is expected in the merger scenario until shortly before the supernova, the white dwarf accreting material from the normal star becomes a source of copious X-rays for about 10(7) years before the explosion. This offers a means of determining which path dominates. Here we report that the observed X-ray flux from six nearby elliptical galaxies and galaxy bulges is a factor of similar to 30-50 less than predicted in the accretion scenario, based upon an estimate of the supernova rate from their K-band luminosities. We conclude that no more than about five per cent of type Ia supernovae in early-type galaxies can be produced by white dwarfs in accreting binary systems, unless their progenitors are much younger than the bulk of the stellar population in these galaxies, or explosions of sub-Chandrasekhar white dwarfs make a significant contribution to the supernova rate.
C1 [Gilfanov, Marat; Bogdan, Akos] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Gilfanov, Marat] Space Res Inst, Moscow 117997, Russia.
C3 Max Planck Society; Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences
RP Gilfanov, M (corresponding author), Max Planck Inst Astrophys, Karl Schwarzschild Str 1, D-85741 Garching, Germany.
EM gilfanov@mpa-garching.mpg.de
FU NASA; NSF
NR 23
TC 162
Z9 188
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 18
PY 2010
VL 463
IS 7283
BP 924
EP 925
DI 10.1038/nature08685
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700040
PM 20164924
DA 2026-03-09
ER

PT J
AU Wu, XW
   Nguyen, BC
   Dziunycz, P
   Chang, S
   Brooks, Y
   Lefort, K
   Hofbauer, GFL
   Dotto, GP
AF Wu, Xunwei
   Nguyen, Bach-Cuc
   Dziunycz, Piotr
   Chang, Sungeun
   Brooks, Yang
   Lefort, Karine
   Hofbauer, Guenther F. L.
   Dotto, G. Paolo
TI Opposing roles for calcineurin and ATF3 in squamous skin cancer (Publication with Expression of Concern. See FEB, 2026)
SO NATURE
LA English
DT Article; Publication with Expression of Concern
ID transformed phenotype; cellular senescence; tumor suppression; c-myc; cells; growth; p63; transcription; inhibitor; nfat
AB Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients. Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65 to 100-fold higher risk than in the normal population(1). By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent(1). Here we report that genetic and pharmacological suppression of calcineurin/nuclear factor of activated T cells (NFAT) function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-ras(V12) (also known as Hras1)-expressing primary human keratinocytes or keratinocyte-derived SCC cells. Calcineurin/NFAT inhibition counteracts p53 (also known as TRP53)-dependent cancer cell senescence, thereby increasing tumorigenic potential. ATF3, a member of the 'enlarged' AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumorigenic potential. Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.
C1 [Wu, Xunwei; Nguyen, Bach-Cuc; Chang, Sungeun; Brooks, Yang; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
   [Dziunycz, Piotr; Hofbauer, Guenther F. L.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
   [Lefort, Karine; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Zurich; University Zurich Hospital; University of Lausanne
RP Dotto, GP (corresponding author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
EM gian-paolo.dotto@unil.ch
FU NIH [AR054856, AR39190]; Swiss National Foundation [311003A-122281/1]; Oncosuisse [OCS-02361-02-2009]; European Union [LSHB-CT-2005-019067]; Korean Government Foundation [KRF-2007-013-E00044]; Olga-Mayenfisch-Stiftung; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR039190] Funding Source: NIH RePORTER
NR 37
TC 248
Z9 272
U1 0
U2 29
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 368
EP U130
DI 10.1038/nature08996
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200045
PM 20485437
DA 2026-03-09
ER

PT J
AU Rubinson, EH
   Gowda, ASP
   Spratt, TE
   Gold, B
   Eichman, BF
AF Rubinson, Emily H.
   Gowda, A. S. Prakasha
   Spratt, Thomas E.
   Gold, Barry
   Eichman, Brandt F.
TI An unprecedented nucleic acid capture mechanism for excision of DNA damage
SO NATURE
LA English
DT Article
ID human ap endonuclease-1; crystal-structure; base excision; heat repeats; substrate-specificity; glycosylase-i; alkylated dna; repair; recognition; 3-methyladenine
AB DNA glycosylases that remove alkylated and deaminated purine nucleobases are essential DNA repair enzymes that protect the genome, and at the same time confound cancer alkylation therapy, by excising cytotoxic N3-methyladenine bases formed by DNA-targeting anticancer compounds. The basis for glycosylase specificity towards N3- and N7-alkylpurines is believed to result from intrinsic instability of the modified bases and not from direct enzyme functional group chemistry. Here we present crystal structures of the recently discovered Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched and abasic nucleotides. Unlike other glycosylases, AlkD captures the extrahelical lesion in a solvent-exposed orientation, providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix. The structures and supporting biochemical analysis of base flipping and catalysis reveal how the HEAT repeats of AlkD distort the DNA backbone to detect non-Watson-Crick base pairs without duplex intercalation.
C1 [Rubinson, Emily H.; Eichman, Brandt F.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA.
   [Rubinson, Emily H.; Eichman, Brandt F.] Vanderbilt Univ, Struct Biol Ctr, Nashville, TN 37232 USA.
   [Gowda, A. S. Prakasha; Spratt, Thomas E.] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
   [Gold, Barry] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
C3 Vanderbilt University; Vanderbilt University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Penn State Health; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Eichman, BF (corresponding author), Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37232 USA.
EM brandt.eichman@vanderbilt.edu
FU US Department of Energy Office of Basic Energy Sciences; Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; American Cancer Society; NIH [RO1 CA29088]; Vanderbilt Training Program in Molecular Toxicology; National Cancer Institute [P30CA068485] Funding Source: NIH RePORTER; National Institute of Environmental Health Sciences [T32ES007028] Funding Source: NIH RePORTER
NR 65
TC 65
Z9 79
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 406
EP U309
DI 10.1038/nature09428
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100036
PM 20927102
DA 2026-03-09
ER

PT J
AU Metzger, E
   Imhof, A
   Patel, D
   Kahl, P
   Hoffmeyer, K
   Friedrichs, N
   Müller, JM
   Greschik, H
   Kirfel, J
   Ji, S
   Kunowska, N
   Beisenherz-Huss, C
   Günther, T
   Buettner, R
   Schüle, R
AF Metzger, Eric
   Imhof, Axel
   Patel, Dharmeshkumar
   Kahl, Philip
   Hoffmeyer, Katrin
   Friedrichs, Nicolaus
   Mueller, Judith M.
   Greschik, Holger
   Kirfel, Jutta
   Ji, Sujuan
   Kunowska, Natalia
   Beisenherz-Huss, Christian
   Guenther, Thomas
   Buettner, Reinhard
   Schuele, Roland
TI Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4
SO NATURE
LA English
DT Article
ID domain-containing proteins; androgen-receptor; prostate-cancer; transcriptional regulation; structural basis; lsd1; complex; gene
AB Demethylation at distinct lysine residues in histone H3 by lysine-specific demethylase 1 (LSD1) causes either gene repression or activation(1,2). As a component of co-repressor complexes, LSD1 contributes to target gene repression by removing mono-and dimethyl marks from lysine 4 of histone H3 (H3K4)(1,3). In contrast, during androgen receptor (AR)-activated gene expression, LSD1 removes mono-and dimethyl marks from lysine 9 of histone H3 (H3K9)(2). Yet, the mechanisms that control this dual specificity of demethylation are unknown. Here we show that phosphorylation of histone H3 at threonine 6 (H3T6) by protein kinase C beta I (PKC beta(I), also known as PRKCb beta) is the key event that prevents LSD1 from demethylating H3K4 during AR-dependent gene activation. In vitro, histone H3 peptides methylated at lysine 4 and phosphorylated at threonine 6 are no longer LSD1 substrates. In vivo, PKC beta(I) co-localizes with AR and LSD1 on target gene promoters and phosphorylates H3T6 after androgen-induced gene expression. RNA interference (RNAi)-mediated knockdown of PKC beta(I) abrogates H3T6 phosphorylation, enhances demethylation at H3K4, and inhibits AR-dependent transcription. Activation of PKC beta(I) requires androgen-dependent recruitment of the gatekeeper kinase protein kinase C (PKC)-related kinase 1 (PRK1)(4). Notably, increased levels of PKC beta(I) and phosphorylated H3T6 (H3T6ph) positively correlate with high Gleason scores of prostate carcinomas, and inhibition of PKC beta(I) blocks AR-induced tumour cell proliferation in vitro and cancer progression of tumour xeno-grafts in vivo. Together, our data establish that androgen-dependent kinase signalling leads to the writing of the new chromatin mark H3T6ph, which in consequence prevents removal of active methyl marks from H3K4 during AR-stimulated gene expression.
C1 [Metzger, Eric; Patel, Dharmeshkumar; Hoffmeyer, Katrin; Friedrichs, Nicolaus; Mueller, Judith M.; Greschik, Holger; Ji, Sujuan; Kunowska, Natalia; Guenther, Thomas; Schuele, Roland] Univ Freiburg Klinikum, Urol Klin, Frauenklin, D-79106 Freiburg, Germany.
   [Metzger, Eric; Patel, Dharmeshkumar; Hoffmeyer, Katrin; Friedrichs, Nicolaus; Mueller, Judith M.; Greschik, Holger; Ji, Sujuan; Kunowska, Natalia; Guenther, Thomas; Schuele, Roland] Univ Freiburg Klinikum, Zent Klin Forsch, D-79106 Freiburg, Germany.
   [Beisenherz-Huss, Christian] ProQinase, D-79106 Freiburg, Germany.
   [Imhof, Axel] Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany.
   [Imhof, Axel] Univ Munich, Munich CIPS, D-80336 Munich, Germany.
   [Kahl, Philip; Kirfel, Jutta; Buettner, Reinhard] Univ Klinikum Bonn, Inst Pathol, D-53127 Bonn, Germany.
C3 University of Freiburg; University of Freiburg; University of Munich; University of Munich; University of Bonn
RP Schüle, R (corresponding author), Univ Freiburg Klinikum, Urol Klin, Frauenklin, Breisacherstr 66, D-79106 Freiburg, Germany.
EM roland.schuele@uniklinik-freiburg.de
FU Deutsche Krebshilfe; Deutsche Forschungsgemeinschaft [SFB 746/P2, Schu 688/9-1, SFB 832/Z1]
NR 23
TC 236
Z9 291
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 APR 1
PY 2010
VL 464
IS 7289
BP 792
EP U175
DI 10.1038/nature08839
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000052
PM 20228790
DA 2026-03-09
ER

PT J
AU Wang, YD
   Nakayama, M
   Pitulescu, ME
   Schmidt, TS
   Bochenek, ML
   Sakakibara, A
   Adams, S
   Davy, A
   Deutsch, U
   Lüthi, U
   Barberis, A
   Benjamin, LE
   Mäkinen, T
   Nobes, CD
   Adams, RH
AF Wang, Yingdi
   Nakayama, Masanori
   Pitulescu, Mara E.
   Schmidt, Tim S.
   Bochenek, Magdalena L.
   Sakakibara, Akira
   Adams, Susanne
   Davy, Alice
   Deutsch, Urban
   Luethi, Urs
   Barberis, Alcide
   Benjamin, Laura E.
   Maekinen, Taija
   Nobes, Catherine D.
   Adams, Ralf H.
TI Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
SO NATURE
LA English
DT Article
ID cardiovascular development; molecular regulation; endothelial-cells; transgenic mouse; smooth-muscle; axon guidance; expression; adult; receptors; arterial
AB In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions(1-3). Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.
C1 [Wang, Yingdi; Schmidt, Tim S.; Sakakibara, Akira; Adams, Susanne; Adams, Ralf H.] Canc Res UK London Res Inst, Vasc Dev Lab, London WC2A 3PX, England.
   [Nakayama, Masanori; Pitulescu, Mara E.; Bochenek, Magdalena L.; Adams, Susanne; Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
   [Nakayama, Masanori; Pitulescu, Mara E.; Bochenek, Magdalena L.; Adams, Susanne; Adams, Ralf H.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
   [Bochenek, Magdalena L.; Nobes, Catherine D.] Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol BS6 6BS, Avon, England.
   [Bochenek, Magdalena L.; Nobes, Catherine D.] Univ Bristol, Sch Med Sci, Dept Biochem, Bristol BS6 6BS, Avon, England.
   [Davy, Alice] Univ Toulouse, CNRS, CBD UMR 5547, Ctr Dev Biol, F-31062 Toulouse 9, France.
   [Deutsch, Urban] Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland.
   [Luethi, Urs; Barberis, Alcide] Oncalis AG, Schlieren, Switzerland.
   [Benjamin, Laura E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Maekinen, Taija] Canc Res UK London Res Inst, Lymphat Dev Lab, London WC2A 3PX, England.
C3 Cancer Research UK; University of Munster; Max Planck Society; University of Bristol; University of Bristol; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; University of Bern; Theodor Kocher Institute; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Cancer Research UK
RP Adams, RH (corresponding author), Canc Res UK London Res Inst, Vasc Dev Lab, London WC2A 3PX, England.
EM ralf.adams@mpi-muenster.mpg.de
FU Cancer Research UK; Max-Planck-Society; German Research Foundation [SFB 629, SPP 1190]; EMBO LTF
NR 37
TC 1050
Z9 1193
U1 3
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 MAY 27
PY 2010
VL 465
IS 7297
BP 483
EP U108
DI 10.1038/nature09002
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700036
PM 20445537
DA 2026-03-09
ER

PT J
AU Qi, HH
   Sarkissian, M
   Hu, GQ
   Wang, ZB
   Bhattacharjee, A
   Gordon, DB
   Gonzales, M
   Lan, F
   Ongusaha, PP
   Huarte, M
   Yaghi, NK
   Lim, H
   Garcia, BA
   Brizuela, L
   Zhao, KJ
   Roberts, TM
   Shi, Y
AF Qi, Hank H.
   Sarkissian, Madathia
   Hu, Gang-Qing
   Wang, Zhibin
   Bhattacharjee, Arindam
   Gordon, D. Benjamin
   Gonzales, Michelle
   Lan, Fei
   Ongusaha, Pat P.
   Huarte, Maite
   Yaghi, Nasser K.
   Lim, Huijun
   Garcia, Benjamin A.
   Brizuela, Leonardo
   Zhao, Keji
   Roberts, Thomas M.
   Shi, Yang
TI Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development
SO NATURE
LA English
DT Article
ID structural insights; mental-retardation; genes; transcription; methylation; family; identification; lysine-20; genome; mutations
AB X-linked mental retardation (XLMR) is a complex human disease that causes intellectual disability(1). Causal mutations have been found in approximately 90 X-linked genes(2); however, molecular and biological functions of many of these genetically defined XLMR genes remain unknown. PHF8 (PHD (plant homeo domain) finger protein 8) is a JmjC domain-containing protein and its mutations have been found in patients with XLMR and craniofacial deformities. Here we provide multiple lines of evidence establishing PHF8 as the first mono-methyl histone H4 lysine 20 (H4K20me1) demethylase, with additional activities towards histone H3K9me1 and me2. PHF8 is located around the transcription start sites (TSS) of similar to 7,000 RefSeq genes and in gene bodies and intergenic regions (non-TSS). PHF8 depletion resulted in upregulation of H4K20me1 and H3K9me1 at the TSS and H3K9me2 in the non-TSS sites, respectively, demonstrating differential substrate specificities at different target locations. PHF8 positively regulates gene expression, which is dependent on its H3K4me3-binding PHD and catalytic domains. Importantly, patient mutations significantly compromised PHF8 catalytic function. PHF8 regulates cell survival in the zebrafish brain and jaw development, thus providing a potentially relevant biological context for understanding the clinical symptoms associated with PHF8 patients. Lastly, genetic and molecular evidence supports a model whereby PHF8 regulates zebrafish neuronal cell survival and jaw development in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB, which functions downstream of multiple signalling and developmental pathways(3). Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR.
C1 [Qi, Hank H.; Lan, Fei; Huarte, Maite; Yaghi, Nasser K.; Lim, Huijun; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Qi, Hank H.; Lim, Huijun; Shi, Yang] Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA.
   [Sarkissian, Madathia; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Hu, Gang-Qing; Wang, Zhibin; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Bhattacharjee, Arindam; Gordon, D. Benjamin; Brizuela, Leonardo] Agilent Technol, Santa Clara, CA 95051 USA.
   [Gonzales, Michelle; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Ongusaha, Pat P.] Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA.
   [Ongusaha, Pat P.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Agilent Technologies; Princeton University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University
RP Shi, Y (corresponding author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM Thomas_Roberts@dfci.harvard.edu; yshi@hms.harvard.edu
FU Ruth L. Kirschstein-National Service [T32 NS007473, T32 CA09031-32]; Harvard SHURP; Agency for Science, Technology and Research (A*STAR); National Science Foundation [CBET-0941143]; NIH [GM 071004, NCI118487, CA50661]; Ellison Foundation; National Heart Lung and Blood Institute [ZIAHL005801, ZIAHL006030, ZIAHL006031] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32NS007473] Funding Source: NIH RePORTER; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [0941143] Funding Source: National Science Foundation
NR 39
TC 249
Z9 295
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 22
PY 2010
VL 466
IS 7305
BP 503
EP U11
DI 10.1038/nature09261
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 628SJ
UT WOS:000280141200039
PM 20622853
DA 2026-03-09
ER

PT J
AU Thorel, F
   Népote, V
   Avril, I
   Kohno, K
   Desgraz, R
   Chera, S
   Herrera, PL
AF Thorel, Fabrizio
   Nepote, Virginie
   Avril, Isabelle
   Kohno, Kenji
   Desgraz, Renaud
   Chera, Simona
   Herrera, Pedro L.
TI Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
SO NATURE
LA English
DT Article
ID diphtheria-toxin receptor; transcription factor; mouse pancreas; in-vitro; ectopic expression; glucagon-secretion; endocrine pancreas; diabetes-mellitus; progenitor cells; regeneration
AB Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new-beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenicmodel of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
C1 [Thorel, Fabrizio; Nepote, Virginie; Avril, Isabelle; Desgraz, Renaud; Chera, Simona; Herrera, Pedro L.] Univ Geneva, Fac Med, Dept Cell Physiol & Metab, CH-1211 Geneva 4, Switzerland.
   [Kohno, Kenji] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300192, Japan.
C3 University of Geneva; Nara Institute of Science & Technology
RP Herrera, PL (corresponding author), Univ Geneva, Fac Med, Dept Cell Physiol & Metab, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland.
EM pedro.herrera@unige.ch
FU NIH/NIDDK; JDRF; Swiss National Science Foundation; EU
NR 50
TC 923
Z9 1109
U1 2
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1149
EP 1154
DI 10.1038/nature08894
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100028
PM 20364121
DA 2026-03-09
ER

PT J
AU Campbell, PJ
   Yachida, S
   Mudie, LJ
   Stephens, PJ
   Pleasance, ED
   Stebbings, LA
   Morsberger, LA
   Latimer, C
   McLaren, S
   Lin, ML
   McBride, DJ
   Varela, I
   Nik-Zainal, SA
   Leroy, C
   Jia, MM
   Menzies, A
   Butler, AP
   Teague, JW
   Griffin, CA
   Burton, J
   Swerdlow, H
   Quail, MA
   Stratton, MR
   Iacobuzio-Donahue, C
   Futreal, PA
AF Campbell, Peter J.
   Yachida, Shinichi
   Mudie, Laura J.
   Stephens, Philip J.
   Pleasance, Erin D.
   Stebbings, Lucy A.
   Morsberger, Laura A.
   Latimer, Calli
   McLaren, Stuart
   Lin, Meng-Lay
   McBride, David J.
   Varela, Ignacio
   Nik-Zainal, Serena A.
   Leroy, Catherine
   Jia, Mingming
   Menzies, Andrew
   Butler, Adam P.
   Teague, Jon W.
   Griffin, Constance A.
   Burton, John
   Swerdlow, Harold
   Quail, Michael A.
   Stratton, Michael R.
   Iacobuzio-Donahue, Christine
   Futreal, P. Andrew
TI The patterns and dynamics of genomic instability in metastatic pancreatic cancer
SO NATURE
LA English
DT Article
ID copy number analysis; human breast-cancer; genetic-heterogeneity; evolution; tumors; rearrangements; resolution; mutations; leukemia; cells
AB Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations(1-5), but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours(6,7), including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites(7), and how the tumour disseminates. Here we harness advances in DNA sequencing(8-12) to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.
C1 [Campbell, Peter J.; Mudie, Laura J.; Stephens, Philip J.; Pleasance, Erin D.; Stebbings, Lucy A.; Latimer, Calli; McLaren, Stuart; Lin, Meng-Lay; McBride, David J.; Varela, Ignacio; Nik-Zainal, Serena A.; Leroy, Catherine; Jia, Mingming; Menzies, Andrew; Butler, Adam P.; Teague, Jon W.; Burton, John; Swerdlow, Harold; Quail, Michael A.; Stratton, Michael R.; Futreal, P. Andrew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
   [Yachida, Shinichi; Morsberger, Laura A.; Griffin, Constance A.; Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA.
   [Yachida, Shinichi; Morsberger, Laura A.; Griffin, Constance A.; Iacobuzio-Donahue, Christine] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21287 USA.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
C3 Wellcome Trust Sanger Institute; University of Cambridge; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; University of London; Institute of Cancer Research - UK
RP Futreal, PA (corresponding author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
EM ciacobu@jhmi.edu; paf@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z, WT088340MA]; Uehara memorial foundation; Skip Viragh Foundation; Michael Rolphe Foundation; National Institutes of Health [CA106610, CA140599]; The International Human Frontier Science Program Organization
NR 30
TC 1067
Z9 1248
U1 1
U2 152
PU 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 28
PY 2010
VL 467
IS 7319
BP 1109
EP 1113
DI 10.1038/nature09460
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600048
PM 20981101
DA 2026-03-09
ER

PT J
AU Schmidt, BH
   Burgin, AB
   Deweese, JE
   Osheroff, N
   Berger, JM
AF Schmidt, Bryan H.
   Burgin, Alex B.
   Deweese, Joseph E.
   Osheroff, Neil
   Berger, James M.
TI A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases
SO NATURE
LA English
DT Article
ID single-stranded-dna; crystal-structure; active-site; religation reaction; purification; substrate; domain; complexes; catalysis; transport
AB Type II topoisomerases are required for the management of DNA tangles and supercoils(1), and are targets of clinical antibiotics and anticancer agents(2). These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'(3,4). For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage(5-7). Recent efforts have proposed that strand scission relies on a 'two-metal mechanism'(8-10), a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing(11,12). Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5 angstrom resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions.
C1 [Schmidt, Bryan H.; Berger, James M.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Burgin, Alex B.] Emerald BioStruct, Bainbridge Isl, WA 98110 USA.
   [Deweese, Joseph E.; Osheroff, Neil] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA.
   [Osheroff, Neil] Vanderbilt Univ, Dept Med Hematol Oncol, Sch Med, Nashville, TN 37232 USA.
C3 University of California System; University of California Berkeley; Vanderbilt University; Vanderbilt University
RP Berger, JM (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM jmberger@berkeley.edu
FU NIH [GM033944, GM053960, T32CA09592, GM08295, CA077373]; National Cancer Institute [T32CA009592, R01CA077373] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008295] Funding Source: NIH RePORTER
NR 41
TC 150
Z9 184
U1 1
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 641
EP U139
DI 10.1038/nature08974
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000047
PM 20485342
DA 2026-03-09
ER

PT J
AU Rivkin, AS
   Emery, JP
AF Rivkin, Andrew S.
   Emery, Joshua P.
TI Detection of ice and organics on an asteroidal surface
SO NATURE
LA English
DT Article
ID optical-constants; spectroscopy; spectrograph; telescope; model; belt; spex
AB Recent observations, including the discovery(1) in typical asteroidal orbits of objects with cometary characteristics (main-belt comets, or MBCs), have blurred the line between comets and asteroids, although so far neither ice nor organic material has been detected on the surface of an asteroid or directly proven to be an asteroidal constituent. Here we report the spectroscopic detection of water ice and organic material on the asteroid 24 Themis, a detection that has been independently confirmed(2). 24 Themis belongs to the same dynamical family as three of the five known MBCs, and the presence of ice on 24 Themis is strong evidence that it also is present in the MBCs. We conclude that water ice is more common on asteroids than was previously thought and may be widespread in asteroidal interiors at much smaller heliocentric distances than was previously expected.
C1 [Rivkin, Andrew S.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Emery, Joshua P.] Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; University of Tennessee System; University of Tennessee Knoxville
RP Rivkin, AS (corresponding author), Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20723 USA.
EM andy.rivkin@jhuapl.edu
FU NASA
NR 14
TC 279
Z9 305
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1322
EP 1323
DI 10.1038/nature09028
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000040
PM 20428165
DA 2026-03-09
ER

PT J
AU Uchida, M
   Tonomura, A
AF Uchida, Masaya
   Tonomura, Akira
TI Generation of electron beams carrying orbital angular momentum
SO NATURE
LA English
DT Article
ID phase-contrast; laser-beams; wave; dislocations; vortices; light
AB All forms of waves can contain phase singularities(1-4). In the case of optical waves, a light beam with a phase singularity carries orbital angular momentum, and such beams have found a range of applications in optical manipulation, quantum information and astronomy(3-9). Here we report the generation of an electron beam with a phase singularity propagating in free space, which we achieve by passing a plane electron wave through a spiral phase plate constructed naturally from a stack of graphite thin films. The interference pattern between the final beam and a plane electron wave in a transmission electron microscope shows the 'Y'-like defect pattern characteristic of a beam carrying a phase singularity with a topological charge equal to one. This fundamentally new electron degree of freedom could find application in a number of research areas, as is the case for polarized electron beams.
C1 [Uchida, Masaya; Tonomura, Akira] RIKEN, Inst Phys & Chem Res, Adv Sci Inst, Wako, Saitama 3510198, Japan.
C3 RIKEN
RP Uchida, M (corresponding author), RIKEN, Inst Phys & Chem Res, Adv Sci Inst, Wako, Saitama 3510198, Japan.
EM masaya1.uchida@gmail.com
NR 30
TC 660
Z9 751
U1 6
U2 259
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 737
EP 739
DI 10.1038/nature08904
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000040
PM 20360737
DA 2026-03-09
ER

PT J
AU Bertrand, JY
   Chi, NC
   Santoso, B
   Teng, ST
   Stainier, DYR
   Traver, D
AF Bertrand, Julien Y.
   Chi, Neil C.
   Santoso, Buyung
   Teng, Shutian
   Stainier, Didier Y. R.
   Traver, David
TI Haematopoietic stem cells derive directly from aortic endothelium during development
SO NATURE
LA English
DT Article
ID zebrafish; expression; adult; blood
AB A major goal of regenerative medicine is to instruct formation of multipotent, tissue-specific stem cells from induced pluripotent stem cells (iPSCs) for cell replacement therapies. Generation of haematopoietic stem cells (HSCs) from iPSCs or embryonic stem cells (ESCs) is not currently possible, however, necessitating a better understanding of how HSCs normally arise during embryonic development. We previously showed that haematopoiesis occurs through four distinct waves during zebrafish development, with HSCs arising in the final wave in close association with the dorsal aorta. Recent reports have suggested that murine HSCs derive from haemogenic endothelial cells (ECs) lining the aortic floor(1,2). Additional in vitro studies have similarly indicated that the haematopoietic progeny of ESCs arise through intermediates with endothelial potential(3,4). Here we have used the unique strengths of the zebrafish embryo to image directly the generation of HSCs from the ventral wall of the dorsal aorta. Using combinations of fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry, we have identified and isolated the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. Finally, using a permanent lineage tracing strategy, we demonstrate that the HSCs generated from haemogenic endothelium are the lineal founders of the adult haematopoietic system.
C1 [Bertrand, Julien Y.; Santoso, Buyung; Teng, Shutian; Traver, David] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92093 USA.
   [Bertrand, Julien Y.; Santoso, Buyung; Teng, Shutian; Traver, David] Univ Calif San Diego, Sect Cell & Dev Biol, San Diego, CA 92093 USA.
   [Chi, Neil C.] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA.
   [Chi, Neil C.; Stainier, Didier Y. R.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Francisco
RP Traver, D (corresponding author), Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92093 USA.
EM dtraver@ucsd.edu
FU Cancer Research Institute; California Institute for Regenerative Medicine (CIRM); National Institutes of Health (NIH) [HL074891, F32DK752433, HL54737, DK074482]; GlaxoSmithKline; American Heart Association; Packard Foundation; American Society of Hematology; CIRM; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK074482] Funding Source: NIH RePORTER
NR 27
TC 830
Z9 1004
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 MAR 4
PY 2010
VL 464
IS 7285
BP 108
EP U120
DI 10.1038/nature08738
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500043
PM 20154733
DA 2026-03-09
ER

PT J
AU Craven, L
   Tuppen, HA
   Greggains, GD
   Harbottle, SJ
   Murphy, JL
   Cree, LM
   Murdoch, AP
   Chinnery, PF
   Taylor, RW
   Lightowlers, RN
   Herbert, M
   Turnbull, DM
AF Craven, Lyndsey
   Tuppen, Helen A.
   Greggains, Gareth D.
   Harbottle, Stephen J.
   Murphy, Julie L.
   Cree, Lynsey M.
   Murdoch, Alison P.
   Chinnery, Patrick F.
   Taylor, Robert W.
   Lightowlers, Robert N.
   Herbert, Mary
   Turnbull, Douglass M.
TI Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease
SO NATURE
LA English
DT Article
ID real-time pcr; 1555a-greater-than-g mutation; prevalence; mouse; mtdna; quantification; segregation; disorders; deletions; insights
AB Mutations in mitochondrial DNA ( mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births(1-3) and at least 1 in 10,000 adults in the UK are affected by mtDNA disease(4). Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease(5,6). Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans.
C1 [Greggains, Gareth D.; Harbottle, Stephen J.; Murdoch, Alison P.; Herbert, Mary] Newcastle Univ, Int Ctr Life, Newcastle Fertil Ctr, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
   [Craven, Lyndsey; Tuppen, Helen A.; Murphy, Julie L.; Cree, Lynsey M.; Chinnery, Patrick F.; Taylor, Robert W.; Lightowlers, Robert N.; Turnbull, Douglass M.] Newcastle Univ, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Turnbull, Douglass M.] Newcastle Univ, Ctr Brain Ageing & Vital, Inst Ageing & Hlth, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Murdoch, Alison P.; Herbert, Mary; Turnbull, Douglass M.] Newcastle Univ, Int Ctr Life, Biosci Ctr, NE England Stem Cell Inst NESCI, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
   [Greggains, Gareth D.; Herbert, Mary] Newcastle Univ, Int Ctr Life, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
C3 Newcastle University - UK; Newcastle University - UK; Newcastle University - UK; Newcastle University - UK; Newcastle University - UK
RP Herbert, M (corresponding author), Newcastle Univ, Int Ctr Life, Newcastle Fertil Ctr, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England.
EM mary.herbert@ncl.ac.uk; d.m.turnbull@ncl.ac.uk
FU Muscular Dystrophy Campaign; Wellcome Trust [074454/Z/04/Z]; Medical Research Council [G0601157, G0601943, G0700718]; UK National Institute for Health Research Biomedical Research Centre for Ageing and Age-related Disease; Biotechnology and Biological Sciences Research Council; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Medical Research Council [G0601943B, G0700718, G0601157, G0601943, G0800674] Funding Source: researchfish; National Institute for Health Research [NF-SI-0509-10011] Funding Source: researchfish; MRC [G0601157, G0601943, G0800674, G0700718] Funding Source: UKRI
NR 30
TC 359
Z9 418
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 MAY 6
PY 2010
VL 465
IS 7294
BP 82
EP U89
DI 10.1038/nature08958
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900035
PM 20393463
DA 2026-03-09
ER

PT J
AU Collini, E
   Wong, CY
   Wilk, KE
   Curmi, PMG
   Brumer, P
   Scholes, GD
AF Collini, Elisabetta
   Wong, Cathy Y.
   Wilk, Krystyna E.
   Curmi, Paul M. G.
   Brumer, Paul
   Scholes, Gregory D.
TI Coherently wired light-harvesting in photosynthetic marine algae at ambient temperature
SO NATURE
LA English
DT Article
ID resonance energy-transfer; dynamics; molecules; excitons; protein
AB Photosynthesis makes use of sunlight to convert carbon dioxide into useful biomass and is vital for life on Earth. Crucial components for the photosynthetic process are antenna proteins, which absorb light and transmit the resultant excitation energy between molecules to a reaction centre. The efficiency of these electronic energy transfers has inspired much work on antenna proteins isolated from photosynthetic organisms to uncover the basic mechanisms at play(1-5). Intriguingly, recent work has documented(6-8) that light-absorbing molecules in some photosynthetic proteins capture and transfer energy according to quantum-mechanical probability laws instead of classical laws(9) at temperatures up to 180 K. This contrasts with the long-held view that long-range quantum coherence between molecules cannot be sustained in complex biological systems, even at low temperatures. Here we present two-dimensional photon echo spectroscopy(10-13) measurements on two evolutionarily related light-harvesting proteins isolated from marine cryptophyte algae, which reveal exceptionally long-lasting excitation oscillations with distinct correlations and anti-correlations even at ambient temperature. These observations provide compelling evidence for quantum-coherent sharing of electronic excitation across the 5-nm-wide proteins under biologically relevant conditions, suggesting that distant molecules within the photosynthetic proteins are 'wired' together by quantum coherence for more efficient light-harvesting in cryptophyte marine algae.
C1 [Collini, Elisabetta; Wong, Cathy Y.; Brumer, Paul; Scholes, Gregory D.] Univ Toronto, Dept Chem, Inst Opt Sci, Toronto, ON M5S 3H6, Canada.
   [Collini, Elisabetta; Wong, Cathy Y.; Brumer, Paul; Scholes, Gregory D.] Univ Toronto, Ctr Quantum Informat & Quantum Control, Toronto, ON M5S 3H6, Canada.
   [Wilk, Krystyna E.; Curmi, Paul M. G.] Univ New S Wales, Sch Phys, Sydney, NSW 2052, Australia.
   [Wilk, Krystyna E.; Curmi, Paul M. G.] Univ New S Wales, St Vincents Hosp, Ctr Appl Med Res, Sydney, NSW 2052, Australia.
C3 University of Toronto; University of Toronto; University of New South Wales Sydney; University of New South Wales Sydney; NSW Health; St Vincents Hospital Sydney
RP Scholes, GD (corresponding author), Univ Toronto, Dept Chem, Inst Opt Sci, 80 St George St, Toronto, ON M5S 3H6, Canada.
EM gscholes@chem.utoronto.ca
FU Natural Sciences and Engineering Research Council of Canada; Australian Research Council; EWR
NR 30
TC 1366
Z9 1530
U1 7
U2 565
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 644
EP U69
DI 10.1038/nature08811
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900032
PM 20130647
DA 2026-03-09
ER

PT J
AU Conrad, DF
   Pinto, D
   Redon, R
   Feuk, L
   Gokcumen, O
   Zhang, YJ
   Aerts, J
   Andrews, TD
   Barnes, C
   Campbell, P
   Fitzgerald, T
   Hu, M
   Ihm, CH
   Kristiansson, K
   MacArthur, DG
   MacDonald, JR
   Onyiah, I
   Pang, AWC
   Robson, S
   Stirrups, K
   Valsesia, A
   Walter, K
   Wei, J
   Tyler-Smith, C
   Carter, NP
   Lee, C
   Scherer, SW
   Hurles, ME
AF Conrad, Donald F.
   Pinto, Dalila
   Redon, Richard
   Feuk, Lars
   Gokcumen, Omer
   Zhang, Yujun
   Aerts, Jan
   Andrews, T. Daniel
   Barnes, Chris
   Campbell, Peter
   Fitzgerald, Tomas
   Hu, Min
   Ihm, Chun Hwa
   Kristiansson, Kati
   MacArthur, Daniel G.
   MacDonald, Jeffrey R.
   Onyiah, Ifejinelo
   Pang, Andy Wing Chun
   Robson, Sam
   Stirrups, Kathy
   Valsesia, Armand
   Walter, Klaudia
   Wei, John
   Tyler-Smith, Chris
   Carter, Nigel P.
   Lee, Charles
   Scherer, Stephen W.
   Hurles, Matthew E.
TI Origins and functional impact of copy number variation in the human genome
SO NATURE
LA English
DT Article
ID recombination hot-spots; structural variation; positive selection; deletion polymorphism; wide association; gene; rearrangements; instability; nucleotide; expression
AB Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
C1 [Conrad, Donald F.; Redon, Richard; Zhang, Yujun; Aerts, Jan; Andrews, T. Daniel; Barnes, Chris; Campbell, Peter; Fitzgerald, Tomas; Hu, Min; Kristiansson, Kati; MacArthur, Daniel G.; Onyiah, Ifejinelo; Robson, Sam; Stirrups, Kathy; Valsesia, Armand; Walter, Klaudia; Tyler-Smith, Chris; Carter, Nigel P.; Hurles, Matthew E.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Pinto, Dalila; Feuk, Lars; MacDonald, Jeffrey R.; Pang, Andy Wing Chun; Wei, John; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, MaRS Ctr, Toronto, ON M5G 1L7, Canada.
   [Pinto, Dalila; Feuk, Lars; MacDonald, Jeffrey R.; Pang, Andy Wing Chun; Wei, John; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genom, MaRS Ctr, Toronto, ON M5G 1L7, Canada.
   [Redon, Richard] INSERM, UMR915, Inst Thorax, F-44035 Nantes, France.
   [Feuk, Lars] Uppsala Univ, Rudbeck Lab, Uppsala Dept Genet & Pathol, S-75185 Uppsala, Sweden.
   [Gokcumen, Omer; Ihm, Chun Hwa; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Gokcumen, Omer; Ihm, Chun Hwa; Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
C3 Wellcome Trust Sanger Institute; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Nantes Universite; CHU de Nantes; Institut National de la Sante et de la Recherche Medicale (Inserm); Uppsala University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Toronto
RP Hurles, ME (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM steve@genet.sickkids.on.ca; meh@sanger.ac.uk
FU Wellcome Trust [077006/Z/05/Z]; Canada Foundation of Innovation and Ontario Innovation Trust; Canadian Institutes of Health Research (CIHR); Genome Canada/Ontario Genomics Institute; McLaughlin Centre for Molecular Medicine; Ontario Ministry of Research and Innovation; Hospital for Sick Children Foundation; Department of Pathology at Brigham and Women's Hospital; National Institutes of Health (NIH) [HG004221, GM081533]; Academy of Finland; Royal Netherlands Academy of Arts and Sciences [TMF/DA/5801]; Netherlands Organization for Scientific Research [825.06.031]
NR 50
TC 1429
Z9 1826
U1 1
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 704
EP 712
DI 10.1038/nature08516
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000035
PM 19812545
DA 2026-03-09
ER

PT J
AU Yu, XZ
   Onose, Y
   Kanazawa, N
   Park, JH
   Han, JH
   Matsui, Y
   Nagaosa, N
   Tokura, Y
AF Yu, X. Z.
   Onose, Y.
   Kanazawa, N.
   Park, J. H.
   Han, J. H.
   Matsui, Y.
   Nagaosa, N.
   Tokura, Y.
TI Real-space observation of a two-dimensional skyrmion crystal
SO NATURE
LA English
DT Article
ID magnetic phase-diagram; state
AB Crystal order is not restricted to the periodic atomic array, but can also be found in electronic systems such as the Wigner crystal(1) or in the form of orbital order(2), stripe order(3) and magnetic order. In the case of magnetic order, spins align parallel to each other in ferromagnets and antiparallel in antiferromagnets. In other, less conventional, cases, spins can sometimes form highly nontrivial structures called spin textures(4-23). Among them is the unusual, topologically stable skyrmion spin texture, in which the spins point in all the directions wrapping a sphere(4-7). The skyrmion configuration in a magnetic solid is anticipated to produce unconventional spin-electronic phenomena such as the topological Hall effect(24-26). The crystallization of skyrmions as driven by thermal fluctuations has recently been confirmed in a narrow region of the temperature/magnetic field (T-B) phase diagram in neutron scattering studies of the three-dimensional helical magnets MnSi (ref. 17) and Fe1-xCoxSi (ref. 22). Here we report real-space imaging of a two-dimensional skyrmion lattice in a thin film of Fe0.5Co0.5Si using Lorentz transmission electron microscopy. With a magnetic field of 50-70 mT applied normal to the film, we observe skyrmions in the form of a hexagonal arrangement of swirling spin textures, with a lattice spacing of 90 nm. The related T-B phase diagram is found to be in good agreement with Monte Carlo simulations. In this two-dimensional case, the skyrmion crystal seems very stable and appears over a wide range of the phase diagram, including near zero temperature. Such a controlled nanometre-scale spin topology in a thin film may be useful in observing unconventional magneto-transport effects.
C1 [Yu, X. Z.; Matsui, Y.] Natl Inst Mat Sci, Adv Elect Microscopy Grp, Tsukuba, Ibaraki 3050044, Japan.
   [Yu, X. Z.; Matsui, Y.] Natl Inst Mat Sci, High Voltage Elect Microscopy Stn, Tsukuba, Ibaraki 3050044, Japan.
   [Yu, X. Z.; Onose, Y.; Tokura, Y.] Japan Sci & Technol Agcy, Multiferro Project, Tokyo 1138656, Japan.
   [Onose, Y.; Kanazawa, N.; Nagaosa, N.; Tokura, Y.] Univ Tokyo, Dept Appl Phys, Tokyo 1138656, Japan.
   [Park, J. H.; Han, J. H.] Sungkyunkwan Univ, Dept Phys, Suwon 440746, South Korea.
   [Nagaosa, N.; Tokura, Y.] RIKEN ASI, Cross Correlated Mat Res Grp, Wako, Saitama 3510198, Japan.
   [Nagaosa, N.; Tokura, Y.] RIKEN ASI, Correlated Elect Res Grp, Wako, Saitama 3510198, Japan.
C3 National Institute for Materials Science; National Institute for Materials Science; Japan Science & Technology Agency (JST); University of Tokyo; Sungkyunkwan University (SKKU); RIKEN; RIKEN
RP Yu, XZ (corresponding author), Natl Inst Mat Sci, Adv Elect Microscopy Grp, Tsukuba, Ibaraki 3050044, Japan.
EM yu.xiuzhen@nims.go.jp; tokura@ap.t.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [ADE21005, 16076205, 17105002, 19019004, 19048008, 19048015, 20046004, 20340086, 21244053, 22014003]; Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program); Korea Research Foundation [KRF-2008-521-C00085, KRF-2008-314-C00101]; Grants-in-Aid for Scientific Research [21244053, 19019004] Funding Source: KAKEN
NR 29
TC 2985
Z9 3195
U1 29
U2 1381
PU NATURE PUBLISHING 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 17
PY 2010
VL 465
IS 7300
BP 901
EP 904
DI 10.1038/nature09124
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500032
PM 20559382
DA 2026-03-09
ER

PT J
AU Van Roy, P
   Orr, PJ
   Botting, JP
   Muir, LA
   Vinther, J
   Lefebvre, B
   el Hariri, K
   Briggs, DEG
AF Van Roy, Peter
   Orr, Patrick J.
   Botting, Joseph P.
   Muir, Lucy A.
   Vinther, Jakob
   Lefebvre, Bertrand
   el Hariri, Khadija
   Briggs, Derek E. G.
TI Ordovician faunas of Burgess Shale type
SO NATURE
LA English
DT Article
ID devonian hunsruck slate; preservation; lagerstatte; arthropod; morocco; biotas
AB The renowned soft-bodied faunas of the Cambrian period, which include the Burgess Shale, disappear from the fossil record in the late Middle Cambrian, after which the Palaeozoic fauna(1) dominates. The disappearance of faunas of Burgess Shale type curtails the stratigraphic record of a number of iconic Cambrian taxa. One possible explanation for this loss is a major extinction(2,3), but more probably it reflects the absence of preservation of similar soft-bodied faunas in later periods(4). Here we report the discovery of numerous diverse soft-bodied assemblages in the Lower and Upper Fezouata Formations (Lower Ordovician) of Morocco, which include a range of remarkable stem-group morphologies normally considered characteristic of the Cambrian. It is clear that biotas of Burgess Shale type persisted after the Cambrian and are preserved where suitable facies occur. The Fezouata biota provides a link between the Burgess Shale communities and the early stages of the Great Ordovician Biodiversification Event.
C1 [Van Roy, Peter; Vinther, Jakob; Briggs, Derek E. G.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Van Roy, Peter; Orr, Patrick J.] Univ Coll Dublin, Sch Geol Sci, Dublin 4, Ireland.
   [Botting, Joseph P.] Leeds Museum Discovery Ctr, Leeds LS10 1LB, W Yorkshire, England.
   [Lefebvre, Bertrand] Univ Lyon 1, CNRS, UMR PEPS 5125, F-69622 Villeurbanne, France.
   [el Hariri, Khadija] Univ Cadi Ayyad, Fac Sci & Tech Gueliz, Dept Sci Terre, Marrakech 40000, Morocco.
   [Briggs, Derek E. G.] Yale Univ, Yale Peabody Museum Nat Hist, New Haven, CT 06520 USA.
C3 Yale University; University College Dublin; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); Cadi Ayyad University of Marrakech; Yale University
RP Van Roy, P (corresponding author), Yale Univ, Dept Geol & Geophys, POB 208109, New Haven, CT 06520 USA.
EM peter.vanroy@yale.edu; derek.briggs@yale.edu
FU Agency for Innovation, Science and Technology (IWT); Irish Research Council for Science, Engineering and Technology (IRCSET); National Geographic Society
NR 30
TC 277
Z9 302
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 MAY 13
PY 2010
VL 465
IS 7295
BP 215
EP 218
DI 10.1038/nature09038
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500034
PM 20463737
DA 2026-03-09
ER

PT J
AU Müller, H
   Peters, A
   Chu, S
AF Mueller, Holger
   Peters, Achim
   Chu, Steven
TI A precision measurement of the gravitational redshift by the interference of matter waves
SO NATURE
LA English
DT Article
ID gravity; acceleration; clocks
AB One of the central predictions of metric theories of gravity, such as general relativity, is that a clock in a gravitational potential U will run more slowly by a factor of 1 + U/c(2), where c is the velocity of light, as compared to a similar clock outside the potential(1). This effect, known as gravitational redshift, is important to the operation of the global positioning system(2), timekeeping(3,4) and future experiments with ultra-precise, space-based clocks(5) (such as searches for variations in fundamental constants). The gravitational redshift has been measured using clocks on a tower(6), an aircraft(7) and a rocket(8), currently reaching an accuracy of 7 x 10(-5). Here we show that laboratory experiments based on quantum interference of atoms(9,10) enable a much more precise measurement, yielding an accuracy of 7 x 10(-9). Our result supports the view that gravity is a manifestation of space-time curvature, an underlying principle of general relativity that has come under scrutiny in connection with the search for a theory of quantum gravity(11). Improving the redshift measurement is particularly important because this test has been the least accurate among the experiments that are required to support curved space-time theories(1).
C1 [Mueller, Holger; Chu, Steven] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Mueller, Holger; Chu, Steven] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Peters, Achim] Humboldt Univ, Inst Phys, D-10117 Berlin, Germany.
   [Chu, Steven] US DOE, Washington, DC 20585 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Humboldt University of Berlin; United States Department of Energy (DOE)
RP Müller, H (corresponding author), Univ Calif Berkeley, Dept Phys, 366 Le Conte Hall,MS 7300, Berkeley, CA 94720 USA.
EM hm@berkeley.edu
FU National Science Foundation [9320142, 0400866, 0652332]; Air Force Office of Scientific Research; Department of Energy; David and Lucile Packard Foundation; National Institute of Standards and Technology [60NANB9D9169]; European Science Foundation; European Space Agency; German Space Agency DLR [DLR 50 WM 0346]
NR 30
TC 236
Z9 265
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 FEB 18
PY 2010
VL 463
IS 7283
BP 926
EP U96
DI 10.1038/nature08776
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700041
PM 20164925
DA 2026-03-09
ER

PT J
AU Petronis, A
AF Petronis, Arturas
TI Epigenetics as a unifying principle in the aetiology of complex traits and diseases
SO NATURE
LA English
DT Article
ID dna methylation; twins; environment; heritability; inheritance; genetics; cloning; anticipation; epimutation; expression
AB Epigenetic modifications of DNA and histones might be crucial for understanding the molecular basis of complex phenotypes. One reason for this is that epigenetic factors are sometimes malleable and plastic enough to react to cues from the external and internal environments. Such induced epigenetic changes can be solidified and propagated during cell division, resulting in permanent maintenance of the acquired phenotype. In addition, the finding that there is partial epigenetic stability in somatic and germline cells allows insight into the molecular mechanisms of heritability. Epigenetics can provide a new framework for the search of aetiological factors in complex traits and diseases.
C1 Ctr Addict & Mental Hlth, Krembil Family Epigenet Lab, Toronto, ON M5T 1R8, Canada.
C3 University of Toronto; Centre for Addiction & Mental Health - Canada
RP Petronis, A (corresponding author), Ctr Addict & Mental Hlth, Krembil Family Epigenet Lab, 250 Coll St, Toronto, ON M5T 1R8, Canada.
EM arturas_petronis@camh.net
FU Canadian Institutes of Health Research [199170, 186007]; US National Institutes of Health [MH074127, MH088413, DP3DK085698, HG004535]
NR 77
TC 512
Z9 603
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 JUN 10
PY 2010
VL 465
IS 7299
BP 721
EP 727
DI 10.1038/nature09230
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800034
PM 20535201
DA 2026-03-09
ER

PT J
AU Machida, Y
   Nakatsuji, S
   Onoda, S
   Tayama, T
   Sakakibara, T
AF Machida, Yo
   Nakatsuji, Satoru
   Onoda, Shigeki
   Tayama, Takashi
   Sakakibara, Toshiro
TI Time-reversal symmetry breaking and spontaneous Hall effect without magnetic dipole order
SO NATURE
LA English
DT Article
ID berry-phase; spin chirality; superconductivity; lattice
AB Spin liquids are magnetically frustrated systems, in which spins are prevented from ordering or freezing, owing to quantum or thermal fluctuations among degenerate states induced by the frustration. Chiral spin liquids are a hypothetical class of spin liquids in which the time-reversal symmetry is macroscopically broken in the absence of an applied magnetic field or any magnetic dipole long-range order. Even though such chiral spin-liquid states were proposed more than two decades ago(1-3), an experimental realization and observation of such states has remained a challenge. One of the characteristic order parameters in such systems is a macroscopic average of the scalar spin chirality, a solid angle subtended by three nearby spins. In previous experimental reports, however, the spin chirality was only parasitic to the non-coplanar spin structure associated with a magnetic dipole long-range order or induced by the applied magnetic field(4-10), and thus the chiral spin-liquid state has never been found. Here, we report empirical evidence that the time-reversal symmetry can be broken spontaneously on a macroscopic scale in the absence of magnetic dipole long-range order. In particular, we employ the anomalous Hall effect(4,11) to directly probe the broken time-reversal symmetry for the metallic frustrated magnet Pr2Ir2O7. An onset of the Hall effect is observed at zero field in the absence of uniform magnetization, within the experimental accuracy, suggesting an emergence of a chiral spin liquid. The origin of this spontaneous Hall effect is ascribed to chiral spin textures(4,5,12,13), which are inferred from the magnetic measurements indicating the spin ice-rule formation(14,15).
C1 [Machida, Yo; Nakatsuji, Satoru; Tayama, Takashi; Sakakibara, Toshiro] Univ Tokyo, Inst Solid State Phys, Kashiwa, Chiba 2778581, Japan.
   [Onoda, Shigeki] RIKEN, Condensed Matter Theory Lab, Wako, Saitama 3510198, Japan.
C3 University of Tokyo; RIKEN
RP Nakatsuji, S (corresponding author), Univ Tokyo, Inst Solid State Phys, Kashiwa, Chiba 2778581, Japan.
EM satoru@issp.u-tokyo.ac.jp
FU Japanese Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology, Japan; Kurata Grant; Grants-in-Aid for Scientific Research [21684019, 19052003, 20244053] Funding Source: KAKEN
NR 30
TC 387
Z9 419
U1 7
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 JAN 14
PY 2010
VL 463
IS 7278
BP 210
EP 213
DI 10.1038/nature08680
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700031
PM 20010605
DA 2026-03-09
ER

PT J
AU Altshuler, D
   Durbin, RM
   Abecasis, GR
   Bentley, DR
   Chakravarti, A
   Clark, AG
   Collins, FS
   De la Vega, FM
   Donnelly, P
   Egholm, M
   Flicek, P
   Gabriel, SB
   Gibbs, RA
   Knoppers, BM
   Lander, ES
   Lehrach, H
   Mardis, ER
   McVean, GA
   Nickerson, D
   Peltonen, L
   Schafer, AJ
   Sherry, ST
   Wang, J
   Wilson, RK
   Gibbs, RA
   Deiros, D
   Metzker, M
   Muzny, D
   Reid, J
   Wheeler, D
   Wang, J
   Li, JX
   Jian, M
   Li, G
   Li, RQ
   Liang, HQ
   Tian, G
   Wang, B
   Wang, J
   Wang, W
   Yang, HM
   Zhang, XQ
   Zheng, HS
   Lander, ES
   Altshuler, DL
   Ambrogio, L
   Bloom, T
   Cibulskis, K
   Fennell, TJ
   Gabriel, SB
   Jaffe, DB
   Shefler, E
   Sougnez, CL
   Bentley, DR
   Gormley, N
   Humphray, S
   Kingsbury, Z
   Koko-Gonzales, P
   Stone, J
   McKernan, KJ
   Costa, GL
   Ichikawa, JK
   Lee, CC
   Sudbrak, R
   Lehrach, H
   Borodina, TA
   Dahl, A
   Davydov, AN
   Marquardt, P
   Mertes, F
   Nietfeld, W
   Rosenstiel, P
   Schreiber, S
   Soldatov, AV
   Timmermann, B
   Tolzmann, M
   Egholm, M
   Affourtit, J
   Ashworth, D
   Attiya, S
   Bachorski, M
   Buglione, E
   Burke, A
   Caprio, A
   Celone, C
   Clark, S
   Conners, D
   Desany, B
   Gu, L
   Guccione, L
   Kao, K
   Kebbel, A
   Knowlton, J
   Labrecque, M
   McDade, L
   Mealmaker, C
   Minderman, M
   Nawrocki, A
   Niazi, F
   Pareja, K
   Ramenani, R
   Riches, D
   Song, W
   Turcotte, C
   Wang, S
   Mardis, ER
   Dooling, D
   Fulton, L
   Fulton, R
   Weinstock, G
   Durbin, RM
   Burton, J
   Carter, DM
   Churcher, C
   Coffey, A
   Cox, A
   Palotie, A
   Quail, M
   Skelly, T
   Stalker, J
   Swerdlow, HP
   Turner, D
   De Witte, A
   Giles, S
   Gibbs, RA
   Wheeler, D
   Bainbridge, M
   Challis, D
   Sabo, A
   Yu, F
   Yu, J
   Wang, J
   Fang, XD
   Guo, XS
   Li, RQ
   Li, YR
   Luo, RB
   Tai, S
   Wu, HL
   Zheng, HC
   Zheng, XL
   Zhou, Y
   Yang, HM
   Marth, GT
   Garrison, EP
   Huang, W
   Indap, A
   Kural, D
   Lee, WP
   Leong, WF
   Huang, WC
   Indap, A
   Kural, D
   Lee, WP
   Leong, WF
   Quinlan, AR
   Stewart, C
   Stromberg, MP
   Ward, AN
   Wu, JT
   Lee, C
   Mills, RE
   Shi, XH
   Daly, MJ
   DePristo, MA
   Altshuler, DL
   Ball, AD
   Banks, E
   Bloom, T
   Browning, BL
   Cibulskis, K
   Fennell, TJ
   Garimella, KV
   Grossman, SR
   Handsaker, RE
   Hanna, M
   Hartl, C
   Jaffe, DB
   Kernytsky, AM
   Korn, JM
   Li, H
   Maguire, JR
   McCarroll, SA
   McKenna, A
   Nemesh, JC
   Philippakis, AA
   Poplin, RE
   Price, A
   Rivas, MA
   Sabeti, PC
   Schaffner, SF
   Shefler, E
   Shlyakhter, IA
   Cooper, DN
   Ball, EV
   Mort, M
   Phillips, AD
   Stenson, PD
   Sebat, J
   Makarov, V
   Ye, K
   Yoon, SC
   Bustamante, CD
   Clark, AG
   Boyko, A
   Degenhardt, J
   Gravel, S
   Gutenkunst, RN
   Kaganovich, M
   Keinan, A
   Lacroute, P
   Ma, X
   Reynolds, A
   Clarke, L
   Flicek, P
   Cunningham, F
   Herrero, J
   Keenen, S
   Kulesha, E
   Leinonen, R
   McLaren, W
   Radhakrishnan, R
   Smith, RE
   Zalunin, V
   Zheng-Bradley, XQ
   Korbel, JO
   Stütz, AM
   Humphray, S
   Bauer, M
   Cheetham, RK
   Cox, T
   Eberle, M
   James, T
   Kahn, S
   Murray, L
   Ye, K
   De La Vega, FM
   Fu, YT
   Hyland, FCL
   Manning, JM
   McLaughlin, SF
   Peckham, HE
   Sakarya, O
   Sun, YA
   Tsung, EF
   Batzer, MA
   Konkel, MK
   Walker, JA
   Sudbrak, R
   Albrecht, MW
   Amstislavskiy, VS
   Herwig, R
   Parkhomchuk, DV
   Sherry, ST
   Agarwala, R
   Khouri, H
   Morgulis, AO
   Paschall, JE
   Phan, LD
   Rotmistrovsky, KE
   Sanders, RD
   Shumway, MF
   Xiao, CL
   McVean, GA
   Auton, A
   Iqbal, Z
   Lunter, G
   Marchini, JL
   Moutsianas, L
   Myers, S
   Tumian, A
   Desany, B
   Knight, J
   Winer, R
   Craig, DW
   Beckstrom-Sternberg, SM
   Christoforides, A
   Kurdoglu, AA
   Pearson, J
   Sinari, SA
   Tembe, WD
   Haussler, D
   Hinrichs, AS
   Katzman, SJ
   Kern, A
   Kuhn, RM
   Przeworski, M
   Hernandez, RD
   Howie, B
   Kelley, JL
   Melton, SC
   Abecasis, GR
   Li, Y
   Anderson, P
   Blackwell, T
   Chen, W
   Cookson, WO
   Ding, J
   Kang, HM
   Lathrop, M
   Liang, LM
   Moffatt, MF
   Scheet, P
   Sidore, C
   Snyder, M
   Zhan, XW
   Zöllner, S
   Awadalla, P
   Casals, F
   Idaghdour, Y
   Keebler, J
   Stone, EA
   Zilversmit, M
   Jorde, L
   Xing, JC
   Eichler, EE
   Aksay, G
   Alkan, C
   Hajirasouliha, I
   Hormozdiari, F
   Kidd, JM
   Sahinalp, SC
   Sudmant, PH
   Mardis, ER
   Chen, K
   Chinwalla, A
   Ding, L
   Koboldt, DC
   McLellan, MD
   Dooling, D
   Weinstock, G
   Wallis, JW
   Wendl, MC
   Zhang, QY
   Durbin, RM
   Albers, CA
   Ayub, Q
   Balasubramaniam, S
   Barrett, JC
   Carter, DM
   Chen, YA
   Conrad, DF
   Danecek, P
   Dermitzakis, ET
   Hu, M
   Huang, N
   Hurles, ME
   Jin, HJ
   Jostins, L
   Keane, TM
   Keane, TM
   Le, SQ
   Lindsay, S
   Long, QA
   MacArthur, DG
   Montgomery, SB
   Parts, L
   Stalker, J
   Tyler-Smith, C
   Walter, K
   Zhang, YJ
   Gerstein, MB
   Snyder, M
   Abyzov, A
   Abyzov, A
   Balasubramanian, S
   Bjornson, R
   Du, JA
   Grubert, F
   Habegger, L
   Haraksingh, R
   Jee, J
   Khurana, E
   Lam, HYK
   Leng, J
   Mu, XJ
   Urban, AE
   Zhang, ZD
   Li, YR
   Luo, RB
   Marth, GT
   Garrison, EP
   Kural, D
   Quinlan, AR
   Stewart, C
   Stromberg, MP
   Ward, AN
   Wu, JT
   Lee, C
   Mills, RE
   Shi, XH
   McCarroll, SA
   Banks, E
   DePristo, MA
   Handsaker, RE
   Hartl, C
   Korn, JM
   Li, H
   Nemesh, JC
   Sebat, J
   Makarov, V
   Ye, K
   Yoon, SC
   Degenhardt, J
   Kaganovich, M
   Clarke, L
   Smith, RE
   Zheng-Bradley, XQ
   Korbel, JO
   Humphray, S
   Cheetham, RK
   Eberle, M
   Kahn, S
   Murray, L
   Ye, K
   De la Vega, FM
   Fu, YT
   Peckham, HE
   Sun, YA
   Batzer, MA
   Konkel, MK
   Xiao, CL
   Iqbal, Z
   Desany, B
   Blackwell, T
   Snyder, M
   Xing, JC
   Eichler, EE
   Aksay, G
   Alkan, C
   Hajirasouliha, I
   Hormozdiari, F
   Kidd, JM
   Chen, K
   Chinwalla, A
   Ding, L
   McLellan, MD
   Wallis, JW
   Hurles, ME
   Conrad, DF
   Walter, K
   Zhang, YJ
   Gerstein, MB
   Snyder, M
   Abyzov, A
   Du, JA
   Grubert, F
   Haraksingh, R
   Jee, J
   Khurana, E
   Lam, HYK
   Leng, J
   Mu, XJ
   Urban, AE
   Zhang, ZD
   Gibbs, RA
   Bainbridge, M
   Challis, D
   Coafra, C
   Dinh, H
   Kovar, C
   Lee, S
   Muzny, D
   Nazareth, L
   Reid, J
   Sabo, A
   Yu, FL
   Yu, J
   Marth, GT
   Garrison, EP
   Indap, A
   Leong, WF
   Quinlan, AR
   Stewart, C
   Ward, AN
   Wu, JT
   Cibulskis, K
   Fennell, TJ
   Gabriel, SB
   Garimella, KV
   Hartl, C
   Shefler, E
   Sougnez, CL
   Wilkinson, J
   Clark, AG
   Gravel, S
   Grubert, F
   Clarke, L
   Flicek, P
   Smith, RE
   Zheng-Bradley, XQ
   Sherry, ST
   Khouri, HM
   Paschall, JE
   Shumway, MF
   Xiao, CL
   McVean, GA
   Katzman, SJ
   Abecasis, GR
   Blackwell, T
   Mardis, ER
   Dooling, D
   Fulton, L
   Fulton, R
   Koboldt, DC
   Durbin, RM
   Balasubramaniam, S
   Coffey, A
   Keane, TM
   MacArthur, DG
   Palotie, A
   Scott, C
   Stalker, J
   Tyler-Smith, C
   Gerstein, MB
   Balasubramanian, S
   Chakravarti, A
   Knoppers, BM
   Peltonen, L
   Abecasis, GR
   Bustamante, CD
   Gharani, N
   Gibbs, RA
   Jorde, L
   Kaye, JS
   Kent, A
   Li, T
   McGuire, AL
   McVean, GA
   Ossorio, PN
   Rotimi, CN
   Su, YY
   Toji, LH
   Tyler-Smith, C
   Brooks, LD
   Felsenfeld, AL
   McEwen, JE
   Abdallah, A
   Christopher, R
   Clemm, NC
   Collins, FS
   Duncanson, A
   Green, ED
   Guyer, MS
   Peterson, JL
   Schafer, AJ
   Abecasis, GR
   Altshuler, DL
   Auton, A
   Brooks, LD
   Durbin, RM
   Gibbs, RA
   Hurles, ME
   McVean, GA
AF Altshuler, David
   Durbin, Richard M.
   Abecasis, Goncalo R.
   Bentley, David R.
   Chakravarti, Aravinda
   Clark, Andrew G.
   Collins, Francis S.
   De la Vega, Francisco M.
   Donnelly, Peter
   Egholm, Michael
   Flicek, Paul
   Gabriel, Stacey B.
   Gibbs, Richard A.
   Knoppers, Bartha M.
   Lander, Eric S.
   Lehrach, Hans
   Mardis, Elaine R.
   McVean, Gil A.
   Nickerson, DebbieA.
   Peltonen, Leena
   Schafer, Alan J.
   Sherry, Stephen T.
   Wang, Jun
   Wilson, Richard K.
   Gibbs, Richard A.
   Deiros, David
   Metzker, Mike
   Muzny, Donna
   Reid, Jeff
   Wheeler, David
   Wang, Jun
   Li, Jingxiang
   Jian, Min
   Li, Guoqing
   Li, Ruiqiang
   Liang, Huiqing
   Tian, Geng
   Wang, Bo
   Wang, Jian
   Wang, Wei
   Yang, Huanming
   Zhang, Xiuqing
   Zheng, Huisong
   Lander, Eric S.
   Altshuler, David L.
   Ambrogio, Lauren
   Bloom, Toby
   Cibulskis, Kristian
   Fennell, Tim J.
   Gabriel, Stacey B.
   Jaffe, David B.
   Shefler, Erica
   Sougnez, Carrie L.
   Bentley, David R.
   Gormley, Niall
   Humphray, Sean
   Kingsbury, Zoya
   Koko-Gonzales, Paula
   Stone, Jennifer
   McKernan, Kevin J.
   Costa, Gina L.
   Ichikawa, Jeffry K.
   Lee, Clarence C.
   Sudbrak, Ralf
   Lehrach, Hans
   Borodina, Tatiana A.
   Dahl, Andreas
   Davydov, Alexey N.
   Marquardt, Peter
   Mertes, Florian
   Nietfeld, Wilfiried
   Rosenstiel, Philip
   Schreiber, Stefan
   Soldatov, Aleksey V.
   Timmermann, Bernd
   Tolzmann, Marius
   Egholm, Michael
   Affourtit, Jason
   Ashworth, Dana
   Attiya, Said
   Bachorski, Melissa
   Buglione, Eli
   Burke, Adam
   Caprio, Amanda
   Celone, Christopher
   Clark, Shauna
   Conners, David
   Desany, Brian
   Gu, Lisa
   Guccione, Lorri
   Kao, Kalvin
   Kebbel, Andrew
   Knowlton, Jennifer
   Labrecque, Matthew
   McDade, Louise
   Mealmaker, Craig
   Minderman, Melissa
   Nawrocki, Anne
   Niazi, Faheem
   Pareja, Kristen
   Ramenani, Ravi
   Riches, David
   Song, Wanmin
   Turcotte, Cynthia
   Wang, Shally
   Mardis, Elaine R.
   Dooling, David
   Fulton, Lucinda
   Fulton, Robert
   Weinstock, George
   Durbin, Richard M.
   Burton, John
   Carter, David M.
   Churcher, Carol
   Coffey, Alison
   Cox, Anthony
   Palotie, Aarno
   Quail, Michael
   Skelly, Tom
   Stalker, James
   Swerdlow, Harold P.
   Turner, Daniel
   De Witte, Anniek
   Giles, Shane
   Gibbs, Richard A.
   Wheeler, David
   Bainbridge, Matthew
   Challis, Danny
   Sabo, Aniko
   Yu, Fuli
   Yu, Jin
   Wang, Jun
   Fang, Xiaodong
   Guo, Xiaosen
   Li, Ruiqiang
   Li, Yingrui
   Luo, Ruibang
   Tai, Shuaishuai
   Wu, Honglong
   Zheng, Hancheng
   Zheng, Xiaole
   Zhou, Yan
   Yang, Huanming
   Marth, Gabor T.
   Garrison, Erik P.
   Huang, Weichun
   Indap, Amit
   Kural, Deniz
   Lee, Wan-Ping
   Leong, Wen Fung
   Huang, Weichun
   Indap, Amit
   Kural, Deniz
   Lee, Wan-Ping
   Leong, Wen Fung
   Quinlan, Aaron R.
   Stewart, Chip
   Stromberg, Michael P.
   Ward, Alistair N.
   Wu, Jiantao
   Lee, Charles
   Mills, Ryan E.
   Shi, Xinghua
   Daly, Mark J.
   DePristo, Mark A.
   Altshuler, David L.
   Ball, Aaron D.
   Banks, Eric
   Bloom, Toby
   Browning, Brian L.
   Cibulskis, Kristian
   Fennell, Tim J.
   Garimella, Kiran V.
   Grossman, Sharon R.
   Handsaker, Robert E.
   Hanna, Matt
   Hartl, Chris
   Jaffe, David B.
   Kernytsky, Andrew M.
   Korn, Joshua M.
   Li, Heng
   Maguire, Jared R.
   McCarroll, Steven A.
   McKenna, Aaron
   Nemesh, James C.
   Philippakis, Anthony A.
   Poplin, Ryan E.
   Price, Alkes
   Rivas, Manuel A.
   Sabeti, Pardis C.
   Schaffner, Stephen F.
   Shefler, Erica
   Shlyakhter, Ilya A.
   Cooper, David N.
   Ball, Edward V.
   Mort, Matthew
   Phillips, Andrew D.
   Stenson, Peter D.
   Sebat, Jonathan
   Makarov, Vladimir
   Ye, Kenny
   Yoon, Seungtai C.
   Bustamante, Carlos D.
   Clark, Andrew G.
   Boyko, Adam
   Degenhardt, Jeremiah
   Gravel, Simon
   Gutenkunst, Ryan N.
   Kaganovich, Mark
   Keinan, Alon
   Lacroute, Phil
   Ma, Xia
   Reynolds, Andy
   Clarke, Laura
   Flicek, Paul
   Cunningham, Fiona
   Herrero, Javier
   Keenen, Stephen
   Kulesha, Eugene
   Leinonen, Rasko
   McLaren, WilliamM.
   Radhakrishnan, Rajesh
   Smith, Richard E.
   Zalunin, Vadim
   Zheng-Bradley, Xiangqun
   Korbel, Jan O.
   Stuetz, Adrian M.
   Humphray, Sean
   Bauer, Markus
   Cheetham, R. Keira
   Cox, Tony
   Eberle, Michael
   James, Terena
   Kahn, Scott
   Murray, Lisa
   Ye, Kai
   De La Vega, Francisco M.
   Fu, Yutao
   Hyland, Fiona C. L.
   Manning, Jonathan M.
   McLaughlin, Stephen F.
   Peckham, Heather E.
   Sakarya, Onur
   Sun, Yongming A.
   Tsung, Eric F.
   Batzer, Mark A.
   Konkel, Miriam K.
   Walker, Jerilyn A.
   Sudbrak, Ralf
   Albrecht, Marcus W.
   Amstislavskiy, Vyacheslav S.
   Herwig, Ralf
   Parkhomchuk, Dimitri V.
   Sherry, Stephen T.
   Agarwala, Richa
   Khouri, Hodam.
   Morgulis, Aleksandr O.
   Paschall, Justin E.
   Phan, Lon D.
   Rotmistrovsky, Kirill E.
   Sanders, Robert D.
   Shumway, Martin F.
   Xiao, Chunlin
   McVean, Gil A.
   Auton, Adam
   Iqbal, Zamin
   Lunter, Gerton
   Marchini, Jonathan L.
   Moutsianas, Loukas
   Myers, Simon
   Tumian, Afidalina
   Desany, Brian
   Knight, James
   Winer, Roger
   Craig, David W.
   Beckstrom-Sternberg, Steve M.
   Christoforides, Alexis
   Kurdoglu, Ahmet A.
   Pearson, Johnv.
   Sinari, Shripad A.
   Tembe, Waibhav D.
   Haussler, David
   Hinrichs, Angie S.
   Katzman, Sol J.
   Kern, Andrew
   Kuhn, Robert M.
   Przeworski, Molly
   Hernandez, Ryan D.
   Howie, Bryan
   Kelley, Joanna L.
   Melton, S. Cord
   Abecasis, Goncalo R.
   Li, Yun
   Anderson, Paul
   Blackwell, Tom
   Chen, Wei
   Cookson, William O.
   Ding, Jun
   Kang, Hyun Min
   Lathrop, Mark
   Liang, Liming
   Moffatt, Miriam F.
   Scheet, Paul
   Sidore, Carlo
   Snyder, Matthew
   Zhan, Xiaowei
   Zoellner, Sebastian
   Awadalla, Philip
   Casals, Ferran
   Idaghdour, Youssef
   Keebler, John
   Stone, Eric A.
   Zilversmit, Martine
   Jorde, Lynn
   Xing, Jinchuan
   Eichler, Evan E.
   Aksay, Gozde
   Alkan, Can
   Hajirasouliha, Iman
   Hormozdiari, Fereydoun
   Kidd, Jeffrey M.
   Sahinalp, S. Cenk
   Sudmant, Peter H.
   Mardis, Elaine R.
   Chen, Ken
   Chinwalla, Asif
   Ding, Li
   Koboldt, Daniel C.
   McLellan, Mike D.
   Dooling, David
   Weinstock, George
   Wallis, John W.
   Wendl, Michael C.
   Zhang, Qunyuan
   Durbin, Richard M.
   Albers, Cornelis A.
   Ayub, Qasim
   Balasubramaniam, Senduran
   Barrett, Jeffrey C.
   Carter, David M.
   Chen, Yuan
   Conrad, Donald F.
   Danecek, Petr
   Dermitzakis, Emmanouil T.
   Hu, Min
   Huang, Ni
   Hurles, Matt E.
   Jin, Hanjun
   Jostins, Luke
   Keane, Thomas M.
   Keane, Thomas M.
   Le, Si Quang
   Lindsay, Sarah
   Long, Quan
   MacArthur, Daniel G.
   Montgomery, Stephen B.
   Parts, Leopold
   Stalker, James
   Tyler-Smith, Chris
   Walter, Klaudia
   Zhang, Yujun
   Gerstein, Mark B.
   Snyder, Michael
   Abyzov, Alexej
   Abyzov, Alexej
   Balasubramanian, Suganthi
   Bjornson, Robert
   Du, Jiang
   Grubert, Fabian
   Habegger, Lukas
   Haraksingh, Rajini
   Jee, Justin
   Khurana, Ekta
   Lam, Hugo Y. K.
   Leng, Jing
   Mu, Xinmeng Jasmine
   Urban, Alexander E.
   Zhang, Zhengdong
   Li, Yingrui
   Luo, Ruibang
   Marth, Gabor T.
   Garrison, Erik P.
   Kural, Deniz
   Quinlan, Aaron R.
   Stewart, Chip
   Stromberg, Michael P.
   Ward, Alistair N.
   Wu, Jiantao
   Lee, Charles
   Mills, Ryan E.
   Shi, Xinghua
   McCarroll, Steven A.
   Banks, Eric
   DePristo, Mark A.
   Handsaker, Robert E.
   Hartl, Chris
   Korn, Joshua M.
   Li, Heng
   Nemesh, James C.
   Sebat, Jonathan
   Makarov, Vladimir
   Ye, Kenny
   Yoon, Seungtai C.
   Degenhardt, Jeremiah
   Kaganovich, Mark
   Clarke, Laura
   Smith, Richard E.
   Zheng-Bradley, Xiangqun
   Korbel, Jan O.
   Humphray, Sean
   Cheetham, R. Keira
   Eberle, Michael
   Kahn, Scott
   Murray, Lisa
   Ye, Kai
   De la Vega, Francisco M.
   Fu, Yutao
   Peckham, Heather E.
   Sun, Yongming A.
   Batzer, Mark A.
   Konkel, Miriam K.
   Xiao, Chunlin
   Iqbal, Zamin
   Desany, Brian
   Blackwell, Tom
   Snyder, Matthew
   Xing, Jinchuan
   Eichler, Evan E.
   Aksay, Gozde
   Alkan, Can
   Hajirasouliha, Iman
   Hormozdiari, Fereydoun
   Kidd, Jeffrey M.
   Chen, Ken
   Chinwalla, Asif
   Ding, Li
   McLellan, Mike D.
   Wallis, John W.
   Hurles, Matt E.
   Conrad, Donald F.
   Walter, Klaudia
   Zhang, Yujun
   Gerstein, Mark B.
   Snyder, Michael
   Abyzov, Alexej
   Du, Jiang
   Grubert, Fabian
   Haraksingh, Rajini
   Jee, Justin
   Khurana, Ekta
   Lam, Hugo Y. K.
   Leng, Jing
   Mu, Xinmeng Jasmine
   Urban, Alexander E.
   Zhang, Zhengdong
   Gibbs, Richard A.
   Bainbridge, Matthew
   Challis, Danny
   Coafra, Cristian
   Dinh, Huyen
   Kovar, Christie
   Lee, Sandy
   Muzny, Donna
   Nazareth, Lynne
   Reid, Jeff
   Sabo, Aniko
   Yu, Fuli
   Yu, Jin
   Marth, Gabor T.
   Garrison, Erik P.
   Indap, Amit
   Leong, Wen Fung
   Quinlan, Aaron R.
   Stewart, Chip
   Ward, Alistair N.
   Wu, Jiantao
   Cibulskis, Kristian
   Fennell, Tim J.
   Gabriel, Stacey B.
   Garimella, Kiran V.
   Hartl, Chris
   Shefler, Erica
   Sougnez, Carrie L.
   Wilkinson, Jane
   Clark, Andrew G.
   Gravel, Simon
   Grubert, Fabian
   Clarke, Laura
   Flicek, Paul
   Smith, Richard E.
   Zheng-Bradley, Xiangqun
   Sherry, Stephen T.
   Khouri, Hoda M.
   Paschall, Justin E.
   Shumway, Martin F.
   Xiao, Chunlin
   McVean, Gil A.
   Katzman, Sol J.
   Abecasis, Goncalo R.
   Blackwell, Tom
   Mardis, Elaine R.
   Dooling, David
   Fulton, Lucinda
   Fulton, Robert
   Koboldt, Daniel C.
   Durbin, Richard M.
   Balasubramaniam, Senduran
   Coffey, Allison
   Keane, Thomas M.
   MacArthur, Daniel G.
   Palotie, Aarno
   Scott, Carol
   Stalker, James
   Tyler-Smith, Chris
   Gerstein, Mark B.
   Balasubramanian, Suganthi
   Chakravarti, Aravinda
   Knoppers, Bartha M.
   Peltonen, Leena
   Abecasis, Goncalo R.
   Bustamante, Carlos D.
   Gharani, Neda
   Gibbs, Richard A.
   Jorde, Lynn
   Kaye, Jane S.
   Kent, Alastair
   Li, Taosha
   McGuire, Amy L.
   McVean, Gil A.
   Ossorio, Pilar N.
   Rotimi, Charles N.
   Su, Yeyang
   Toji, Lorraine H.
   Tyler-Smith, Chris
   Brooks, Lisa D.
   Felsenfeld, Adam L.
   McEwen, Jean E.
   Abdallah, Assya
   Juenger, Christopher R.
   Clemm, Nicholas C.
   Collins, Francis S.
   Duncanson, Audrey
   Green, Eric D.
   Guyer, Mark S.
   Peterson, Jane L.
   Schafer, Alan J.
   Abecasis, Goncalo R.
   Altshuler, David L.
   Auton, Adam
   Brooks, Lisa D.
   Durbin, Richard M.
   Gibbs, Richard A.
   Hurles, Matt E.
   McVean, Gil A.
TI A map of human genome variation from population-scale sequencing
SO NATURE
LA English
DT Article
ID wide association; rare variants; gene; nucleotide; prdm9; imputation; motif
AB The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.
C1 [Gabriel, Stacey B.; Lander, Eric S.; Lander, Eric S.; Ambrogio, Lauren; Cibulskis, Kristian; Fennell, Tim J.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Daly, Mark J.; DePristo, Mark A.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Fu, Yutao; Banks, Eric; DePristo, Mark A.; Hartl, Chris; Korn, Joshua M.; Nemesh, James C.; Garimella, Kiran V.; Sougnez, Carrie L.; Wilkinson, Jane; Altshuler, David L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Tyler-Smith, Chris; Coffey, Allison; Palotie, Aarno; Scott, Carol; Tyler-Smith, Chris] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Altshuler, David L.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02115 USA.
   [Abecasis, Goncalo R.; Korbel, Jan O.; Li, Yun; Anderson, Paul; Chen, Wei; Ding, Jun; Kang, Hyun Min; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zoellner, Sebastian; Blackwell, Tom; Snyder, Matthew] Univ Michigan, Ctr Stat Genet & Biostat, Ann Arbor, MI 48109 USA.
   [Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; Timmermann, Bernd; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Kahn, Scott] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
   [Chakravarti, Aravinda; Abdallah, Assya] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Clark, Andrew G.; Degenhardt, Jeremiah; Keinan, Alon; Ma, Xia; Reynolds, Andy] Cornell Univ, Ctr Comparative & Populat Genom, Ithaca, NY 14850 USA.
   [De la Vega, Francisco M.; Hyland, Fiona C. L.; Sakarya, Onur; Sun, Yongming A.] Life Technol, Foster City, CA 94404 USA.
   [Donnelly, Peter; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Myers, Simon; McVean, Gil A.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Egholm, Michael] Pall Corp, Port Washington, NY 11050 USA.
   [Flicek, Paul; Clarke, Laura; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, WilliamM.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun] European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Nazareth, Lynne] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Knoppers, Bartha M.; Parkhomchuk, Dimitri V.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada.
   [Lehrach, Hans; Sudbrak, Ralf; Borodina, Tatiana A.; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; McLellan, Mike D.; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Koboldt, Daniel C.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
   [Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; McVean, Gil A.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
   [Nickerson, DebbieA.; Aksay, Gozde; Sudmant, Peter H.; Kidd, Jeffrey M.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Schafer, Alan J.; Duncanson, Audrey] Wellcome Trust Res Labs, London NW1 2BE, England.
   [Sherry, Stephen T.; Agarwala, Richa; Khouri, Hodam.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; Khouri, Hoda M.] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
   [Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Fang, Xiaodong; Guo, Xiaosen; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Luo, Ruibang; Li, Taosha; Su, Yeyang] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Fu, Yutao; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Tsung, Eric F.] Life Technol, Beverly, MA 01915 USA.
   [Dahl, Andreas] Biotechnol Ctr TU Dresden, Deep Sequencing Grp, D-01307 Dresden, Germany.
   [Rosenstiel, Philip; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Knight, James; Winer, Roger] Roche Appl Sci, Branford, CT 06405 USA.
   [Palotie, Aarno; Palotie, Aarno] Univ Helsinki, Dept Med Genet, Inst Mol Med FIMM, FIN-00290 Helsinki, Finland.
   [Palotie, Aarno; Palotie, Aarno] Helsinki Univ Hosp, Helsinki 00290, Finland.
   [De Witte, Anniek; Giles, Shane] Agilent Technol, Santa Clara, CA 95051 USA.
   [Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA.
   [Huang, Weichun] US Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
   [Quinlan, Aaron R.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
   [Stromberg, Michael P.] Illumina, San Diego, CA 92121 USA.
   [Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Altshuler, David L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Shi, Xinghua; Altshuler, David L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Browning, Brian L.] Univ Washington, Dept Med, Div Gen Med, Seattle, WA 98195 USA.
   [Grossman, Sharon R.; Sabeti, Pardis C.; Shlyakhter, Ilya A.] Harvard Univ, Ctr Syst Biol, Dept Organism & Evolut Biol, Cambridge, MA 02138 USA.
   [Price, Alkes] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, Wales.
   [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Makarov, Vladimir] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY 10029 USA.
   [Makarov, Vladimir] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [Yoon, Seungtai C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Bustamante, Carlos D.; Boyko, Adam; Gravel, Simon; Kaganovich, Mark; Lacroute, Phil; Du, Jiang; Lam, Hugo Y. K.; Urban, Alexander E.; Kidd, Jeffrey M.; Snyder, Michael; Grubert, Fabian; Lam, Hugo Y. K.; Urban, Alexander E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Gutenkunst, Ryan N.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA.
   [Korbel, Jan O.; Stuetz, Adrian M.] Genome Biol Res Unit, European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Ye, Kai] Leiden Univ Med Ctr, Mol Epidemiol Sect, NL-2333 ZA Leiden, Netherlands.
   [Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, Johnv.; Sinari, Shripad A.; Tembe, Waibhav D.] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
   [Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Przeworski, Molly] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Przeworski, Molly] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
   [Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
   Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Cookson, William O.; Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2, England.
   [Lathrop, Mark] Ctr Natl Genotypage, F-91000 Evry, France.
   [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Awadalla, Philip] Univ Montreal, Fac Med, Dept Pediat, Ste Justine Hosp Res Ctr, Montreal, PQ H3T IC5, Canada.
   [Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine] Univ Montreal, Dept Med, Ctr Hosp, Univ Montreal Res Ctr, Montreal, PQ H2L 2W5, Canada.
   [Jorde, Lynn; Xing, Jinchuan; Xing, Jinchuan; Jorde, Lynn] Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA.
   [Eichler, Evan E.; Alkan, Can; Alkan, Can] Univ Washington, Sch Med, Depat Genome Sci, Seattle, WA 98195 USA.
   [Eichler, Evan E.; Alkan, Can; Alkan, Can] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Hajirasouliha, Iman; Hormozdiari, Fereydoun; Sahinalp, S. Cenk; Hajirasouliha, Iman; Hormozdiari, Fereydoun] Simon Fraser Univ, Dept Comp Sci, Burnaby, BC V5A 1S6, Canada.
   [Albers, Cornelis A.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England.
   [Albers, Cornelis A.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 1TN, England.
   [Dermitzakis, Emmanouil T.; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Jin, Hanjun] Korea Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea.
   [Abyzov, Alexej; Habegger, Lukas; Haraksingh, Rajini; Gerstein, Mark B.; Abyzov, Alexej; Haraksingh, Rajini; Jee, Justin; Leng, Jing; Mu, Xinmeng Jasmine] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Balasubramanian, Suganthi; Bjornson, Robert; Gerstein, Mark B.; Du, Jiang] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Abyzov, Alexej; Khurana, Ekta; Urban, Alexander E.; Zhang, Zhengdong; Balasubramanian, Suganthi] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Urban, Alexander E.; Urban, Alexander E.] Stanford Univ, Dept Psychiat & Behav Studies, Stanford, CA 94305 USA.
   [Gharani, Neda; Toji, Lorraine H.] Corell Inst, Camden, NJ 08103 USA.
   [Kaye, Jane S.] Univ Oxford, Ctr Hlth Law & Emerging Technol, Oxford OX3 7LF, England.
   [Kent, Alastair] Genet Alliance, London N1 3QP, England.
   [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
   [Ossorio, Pilar N.] Univ Wisconsin Madison, Dept Med Hist & Bioeth, Madison, WI 53706 USA.
   [Rotimi, Charles N.] US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
   [Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Clemm, Nicholas C.; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Brooks, Lisa D.] US Natl Inst Hlth, NHGRI, Bethesda, MD 20892 USA.
   [Abdallah, Assya] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA.
   [Juenger, Christopher R.] US FDA, Rockville, MD 20857 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Wellcome Trust Sanger Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; University of Michigan System; University of Michigan; Illumina; Johns Hopkins University; Cornell University; Thermo Fisher Scientific; University of Oxford; Wellcome Centre for Human Genetics; Pall Corporation; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Baylor College of Medicine; McGill University; Max Planck Society; Washington University (WUSTL); University of Oxford; University of Washington; University of Washington Seattle; National Institutes of Health (NIH) - USA; Beijing Genomics Institute (BGI); University of Copenhagen; Thermo Fisher Scientific; Technische Universitat Dresden; University of Kiel; Roche Holding; Roche Holding USA; University of Helsinki; University of Helsinki; Helsinki University Central Hospital; Agilent Technologies; Boston College; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); University of Virginia; Illumina; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Washington; University of Washington Seattle; Harvard University; Harvard University; Harvard T.H. Chan School of Public Health; Cardiff University; University of California System; University of California San Diego; University of California System; University of California San Diego; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Icahn School of Medicine at Mount Sinai; Stanford University; University of Arizona; European Molecular Biology Laboratory (EMBL); Leiden University; Leiden University Medical Center (LUMC); Louisiana State University System; Louisiana State University; Translational Genomics Research Institute; University of California System; University of California Santa Cruz; University of Chicago; Howard Hughes Medical Institute; University of Chicago; University of California System; University of California San Francisco; University of Chicago; Imperial College London; Universite Paris Saclay; CEA; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; University of Texas System; UTMD Anderson Cancer Center; Universite de Montreal; Universite de Montreal; Utah System of Higher Education; University of Utah; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Simon Fraser University; University of Cambridge; NHS Blood & Transplant (NHSBT); University of Geneva; Korea Disease Control & Prevention Agency (KDCA); Korea National Institute of Health (KNIH); Korea CDC Center for Genome Science; Yale University; Yale University; Yale University; Stanford University; University of Oxford; Baylor College of Medicine; University of Wisconsin System; University of Wisconsin Madison; National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); George Washington University; US Food & Drug Administration (FDA)
RP Durbin, RM (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
FU Wellcome Trust [WT089088/Z/09/Z, WT085532AIA, WT086084/Z/08/Z, WT081407/Z/06/Z, WT075491/Z/04, WT077009]; Medical Research Council [G0801823]; British Heart Foundation [RG/09/012/28096]; The Leverhulme Trust; EPSRC; Louis-Jeantet Foundation; Swiss National Science Foundation; NGI/EBI [050-72-436]; 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, CXB200903110066A, ZYC200903240077A, ZYC200903240076A, ZYC200903240080A]; Danish Natural Science Research Council; German Research Foundation (Deutsche Forschungsgemeinschaft); BMBF [01GS08201, PREDICT 0315428A]; BMBF NGFN PLUS; EU [242257]; Max Planck Society; Genome Quebec; Ministry of Economic Development, Innovation and Trade [PSR-SIIRI-195]; National Library of Medicine; National Institute of Environmental Health Sciences; NIH [P41HG4221, U01HG5209, P41HG4222, R01GM59290, R01GM72861, R01HG2651, R01MH84698, U01HG5214, P01HG4120, U54HG2750, U54HG2757, U01HG5210, U01HG5208, U01HG5211, R01HG3698, R01HG4719, RC2HG5552, R01HG3229, P50HG2357, R01HG4960, P41HG2371, U41HG4568, R01HG4333]; BWF and Packard Foundation; Pew Charitable Trust; NSF;  [S10RR025056]; National Human Genome Research Institute [ZIAHG000024, U41HG002371] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER; British Heart Foundation [RG/09/012/28096] Funding Source: researchfish; Medical Research Council [G0801823] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10212] Funding Source: researchfish; MRC [G0801823] Funding Source: UKRI
NR 50
TC 6085
Z9 7097
U1 16
U2 1045
PU NATURE PUBLISHING 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 28
PY 2010
VL 467
IS 7319
BP 1061
EP 1073
DI 10.1038/nature09534
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600039
PM 20981092
DA 2026-03-09
ER

PT J
AU Vilhais-Neto, GC
   Maruhashi, M
   Smith, KT
   Vasseur-Cognet, M
   Peterson, AS
   Workman, JL
   Pourquié, O
AF Vilhais-Neto, Goncalo C.
   Maruhashi, Mitsuji
   Smith, Karen T.
   Vasseur-Cognet, Mireille
   Peterson, Andrew S.
   Workman, Jerry L.
   Pourquie, Olivier
TI Rere controls retinoic acid signalling and somite bilateral symmetry
SO NATURE
LA English
DT Article
ID left-right axis; histone deacetylase; mouse gene; expression; fgf8; somitogenesis; mesoderm; notch; chick
AB One of the most notable features of the vertebrate body plan organization is its bilateral symmetry, evident at the level of vertebrae and skeletal muscles. Here we show that a mutation in Rere (also known as atrophin2) leads to the formation of asymmetrical somites in mouse embryos, similar to embryos deprived of retinoic acid(1-4). Furthermore, we also demonstrate that Rere controls retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8 in the left-right signalling pathway. Rere forms a complex with Nr2f2, p300 (also known as Ep300) and a retinoic acid receptor, which is recruited to the retinoic acid regulatory element of retinoic acid targets, such as the Rarb promoter. Furthermore, the knockdown of Nr2f2 and/or Rere decreases retinoic acid signalling, suggesting that this complex is required to promote transcriptional activation of retinoic acid targets. The asymmetrical expression of Nr2f2 in the pre-somitic mesoderm overlaps with the asymmetry of the retinoic acid signalling response, supporting its implication in the control of somitic symmetry. Misregulation of this mechanism could be involved in symmetry defects of the human spine, such as those observed in patients with scoliosis.
C1 [Vilhais-Neto, Goncalo C.; Maruhashi, Mitsuji; Smith, Karen T.; Workman, Jerry L.; Pourquie, Olivier] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Maruhashi, Mitsuji; Pourquie, Olivier] Howard Hughes Med Inst, Kansas City, MO 64110 USA.
   [Vasseur-Cognet, Mireille] Univ Paris 05, Inst Cochin, CNRS,UMR 8104, Dept Endocrinol Metab & Canc,Inserm,U567, Paris, France.
   [Peterson, Andrew S.] Genentech Inc, San Francisco, CA 94080 USA.
   [Pourquie, Olivier] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; Howard Hughes Medical Institute; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Roche Holding; Roche Holding USA; Genentech; University of Kansas; University of Kansas Medical Center
RP Pourquié, O (corresponding author), Univ Strasbourg, INSERM, U964, Inst Genet & Biol Mol & Cellulaire,CNRS,UMR 7104, F-67400 Illkirch Graffenstaden, France.
EM pourquie@igbmc.fr
FU Portuguese Fundacao para a Ciencia e Tecnologia (FCT); American Cancer Society; ALFEDIAM-GlaxoSmithKline; Bonus Qualite Recherche, Universite Paris Descartes; Howard Hughes Medical Institute; Stowers Institute for Medical Research; Muscular Dystrophy Association
NR 30
TC 101
Z9 119
U1 2
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 953
EP 957
DI 10.1038/nature08763
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700047
PM 20164929
DA 2026-03-09
ER

PT J
AU Breslow, DK
   Collins, SR
   Bodenmiller, B
   Aebersold, R
   Simons, K
   Shevchenko, A
   Ejsing, CS
   Weissman, JS
AF Breslow, David K.
   Collins, Sean R.
   Bodenmiller, Bernd
   Aebersold, Ruedi
   Simons, Kai
   Shevchenko, Andrej
   Ejsing, Christer S.
   Weissman, Jonathan S.
TI Orm family proteins mediate sphingolipid homeostasis
SO NATURE
LA English
DT Article
ID genome-wide association; serine palmitoyltransferase; saccharomyces-cerevisiae; yeast; asthma; metabolism; ceramide; sphingosine-1-phosphate; enzyme; gene
AB Despite the essential roles of sphingolipids both as structural components of membranes and critical signalling molecules, we have a limited understanding of how cells sense and regulate their levels. Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma. Starting from an unbiased functional genomic approach in Saccharomyces cerevisiae, we identify Orm proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma.
C1 [Breslow, David K.; Collins, Sean R.; Weissman, Jonathan S.] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA.
   [Breslow, David K.; Collins, Sean R.; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Breslow, David K.] Univ Calif San Francisco, Grad Program Chem & Chem Biol, San Francisco, CA 94158 USA.
   [Breslow, David K.; Collins, Sean R.; Weissman, Jonathan S.] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA.
   [Bodenmiller, Bernd; Aebersold, Ruedi] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Aebersold, Ruedi] Inst Syst Biol, Seattle, WA 98103 USA.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
   [Simons, Kai; Shevchenko, Andrej; Ejsing, Christer S.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Ejsing, Christer S.] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Swiss Federal Institutes of Technology Domain; ETH Zurich; Institute for Systems Biology (ISB); University of Zurich; Max Planck Society; University of Southern Denmark
RP Weissman, JS (corresponding author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, 1700 4th St, San Francisco, CA 94158 USA.
EM weissman@cmp.ucsf.edu
FU Deutsche Forschungsgemeinschaft [SFB/TR 13, A1, D1]; EUFP6 PRISM; ETH Zurich; National Heart, Lung, and Blood Institute, National Institute of Health [N01-HV-28179]; SystemsX.ch; Swiss initiative for systems biology; Boehringer Ingelheim Fonds; Swiss National Science Foundation; Howard Hughes Medical Institute; University of California, San Francisco Strategic Asthma Basic Research Center; National Science Foundation; Fannie and John Hertz Foundation
NR 50
TC 487
Z9 563
U1 1
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1048
EP U65
DI 10.1038/nature08787
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400029
PM 20182505
DA 2026-03-09
ER

PT J
AU Askarieh, G
   Hedhammar, M
   Nordling, K
   Saenz, A
   Casals, C
   Rising, A
   Johansson, J
   Knight, SD
AF Askarieh, Glareh
   Hedhammar, My
   Nordling, Kerstin
   Saenz, Alejandra
   Casals, Cristina
   Rising, Anna
   Johansson, Jan
   Knight, Stefan D.
TI Self-assembly of spider silk proteins is controlled by a pH-sensitive relay
SO NATURE
LA English
DT Article
ID dragline; fibroin; domain; phenix
AB Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains(1,2). Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity(3,4). How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider's spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH(5). We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH7. The X-ray structure of NT, determined to 1.7 angstrom resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider's silk extrusion duct.
C1 [Askarieh, Glareh; Knight, Stefan D.] SLU, Biomed Ctr, Uppsala BioCtr, Dept Mol Biol, SE-75124 Uppsala, Sweden.
   [Askarieh, Glareh] Univ Oslo, Dept Chem, N-0315 Oslo, Norway.
   [Hedhammar, My; Nordling, Kerstin; Rising, Anna; Johansson, Jan] SLU, Biomed Ctr, Dept Anat Physiol & Biochem, SE-75123 Uppsala, Sweden.
   [Saenz, Alejandra; Casals, Cristina] Univ Complutense Madrid, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain.
   [Saenz, Alejandra; Casals, Cristina] Univ Complutense Madrid, CIBER Enfermedades Resp, E-28040 Madrid, Spain.
C3 Swedish University of Agricultural Sciences; University of Oslo; Swedish University of Agricultural Sciences; Complutense University of Madrid; Complutense University of Madrid; CIBER - Centro de Investigacion Biomedica en Red; CIBERES
RP Knight, SD (corresponding author), SLU, Biomed Ctr, Uppsala BioCtr, Dept Mol Biol, SE-75124 Uppsala, Sweden.
EM jan.johansson@afb.slu.se; stefan.knight@molbio.slu.se
FU Swedish Research Council; FORMAS
NR 27
TC 392
Z9 470
U1 3
U2 320
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 13
PY 2010
VL 465
IS 7295
BP 236
EP U125
DI 10.1038/nature08962
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500039
PM 20463740
DA 2026-03-09
ER

PT J
AU Wu, M
   Pastor-Pareja, JC
   Xu, T
AF Wu, Ming
   Pastor-Pareja, Jose Carlos
   Xu, Tian
TI Interaction between RasV12 and scribbled clones induces tumour growth and invasion
SO NATURE
LA English
DT Article
ID drosophila jak/stat pathway; signaling pathway; cell polarity; jnk; cancer; activation; ras; overgrowth; expression; tissue
AB Human tumours have a large degree of cellular and genetic heterogeneity(1). Complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression(2). Furthermore, cooperation between oncogenic genetic lesions is required for tumour development(3); however, it is not known how cell interactions contribute to oncogenic cooperation. The genetic techniques available in the fruitfly Drosophila melanogaster allow analysis of the behaviour of cells with distinct mutations(4), making this the ideal model organism with which to study cell interactions and oncogenic cooperation. In Drosophila eye-antennal discs, cooperation between the oncogenic protein Ras(V12) (ref.5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib)(6,7) gives rise to metastatic tumours that display many characteristics observed in human cancers(8-11). Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the Ras(V12) and scrib(-) mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between Ras(V12) and scrib(-) clones involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines, a compensatory growth mechanism for tissue homeostasis. The development of Ras(V12) tumours can also be triggered by tissue damage, a stress condition that activates JNK signalling. Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers.
C1 [Wu, Ming; Pastor-Pareja, Jose Carlos; Xu, Tian] Yale Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, New Haven, CT 06519 USA.
   [Xu, Tian] Fudan Univ, Sch Life Sci, Inst Dev Biol & Mol Med, Fudan Yale Biomed Res Ctr, Shanghai 20043, Peoples R China.
C3 Howard Hughes Medical Institute; Yale University; Fudan University
RP Xu, T (corresponding author), Yale Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, 295 Congress Ave, New Haven, CT 06519 USA.
EM tian.xu@yale.edu
FU Spanish Ministry of Education; NIH/NCI
NR 30
TC 308
Z9 356
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 JAN 28
PY 2010
VL 463
IS 7280
BP 545
EP U165
DI 10.1038/nature08702
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100052
PM 20072127
DA 2026-03-09
ER

PT J
AU Say, RF
   Fuchs, G
AF Say, Rafael F.
   Fuchs, Georg
TI Fructose 1,6-bisphosphate aldolase/phosphatase may be an ancestral gluconeogenic enzyme
SO NATURE
LA English
DT Article
ID carbon-dioxide assimilation; thermococcus-kodakaraensis; purification; evolution; aldolase; metabolism; expression; cloning; genome; reductase
AB Most archaeal groups and deeply branching bacterial lineages harbour thermophilic organisms with a chemolithoautotrophic metabolism. They live at high temperatures in volcanic habitats at the expense of inorganic substances, often under anoxic conditions(1). These autotrophic organisms use diverse carbon dioxide fixation mechanisms generating acetyl-coenzyme A, from which gluconeogenesis must start(2-4). Here we show that virtually all archaeal groups as well as the deeply branching bacterial lineages contain a bifunctional fructose 1,6-bisphosphate (FBP) aldolase/phosphatase with both FBP aldolase and FBP phosphatase activity. This enzyme is missing inmost other Bacteria and in Eukaryota, and is heat-stabile even in mesophilic marine Crenarchaeota. Its bifunctionality ensures that heat-labile triosephosphates are quickly removed and trapped in stabile fructose 6-phosphate, rendering gluconeogenesis unidirectional. We propose that this highly conserved, heat-stabile and bifunctional FBP aldolase/phosphatase represents the pacemaking ancestral gluconeogenic enzyme, and that in evolution gluconeogenesis preceded glycolysis(5).
C1 [Say, Rafael F.; Fuchs, Georg] Univ Freiburg, Fak Biol, D-79104 Freiburg, Germany.
C3 University of Freiburg
RP Fuchs, G (corresponding author), Univ Freiburg, Fak Biol, Schanzlestr 1, D-79104 Freiburg, Germany.
EM georg.fuchs@biologie.uni-freiburg.de
FU Deutsche Forschungsgemeinschaft; Evonik-Degussa
NR 58
TC 161
Z9 200
U1 0
U2 56
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1077
EP U156
DI 10.1038/nature08884
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000046
PM 20348906
DA 2026-03-09
ER

PT J
AU Schmidt, AR
   Hamidian, MH
   Wahl, P
   Meier, F
   Balatsky, AV
   Garrett, JD
   Williams, TJ
   Luke, GM
   Davis, JC
AF Schmidt, A. R.
   Hamidian, M. H.
   Wahl, P.
   Meier, F.
   Balatsky, A. V.
   Garrett, J. D.
   Williams, T. J.
   Luke, G. M.
   Davis, J. C.
TI Imaging the Fano lattice to 'hidden order' transition in URu2Si2
SO NATURE
LA English
DT Article
ID quasi-particle interference; fermi-surface; magnetic excitations; electronic-structure; heavy; superconductivity; state; wave
AB Within a Kondo lattice, the strong hybridization between electrons localized in real space (r-space) and those delocalized in momentum-space (k-space) generates exotic electronic states called 'heavy fermions'. In URu2Si2 these effects begin at temperatures around 55 K but they are suddenly altered by an unidentified electronic phase transition at T-o=17.5 K. Whether this is conventional ordering of the k-space states, or a change in the hybridization of the r-space states at each U atom, is unknown. Here we use spectroscopic imaging scanning tunnelling microscopy (SI-STM) to image the evolution of URu2Si2 electronic structure simultaneously in r-space and k-space. Above T-o, the 'Fano lattice' electronic structure predicted for Kondo screening of a magnetic lattice is revealed. Below T-o, a partial energy gap without any associated density-wave signatures emerges from this Fano lattice. Heavy-quasiparticle interference imaging within this gap reveals its cause as the rapid splitting below T-o of a light k-space band into two new heavy fermion bands. Thus, the URu2Si2 'hidden order' state emerges directly from the Fano lattice electronic structure and exhibits characteristics, not of a conventional density wave, but of sudden alterations in both the hybridization at each U atom and the associated heavy fermion states.
C1 [Schmidt, A. R.; Hamidian, M. H.; Wahl, P.; Meier, F.; Davis, J. C.] Cornell Univ, Atom & Solid State Phys Lab, Dept Phys, Ithaca, NY 14853 USA.
   [Schmidt, A. R.; Hamidian, M. H.; Davis, J. C.] Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.
   [Wahl, P.] Max Planck Inst Festkorperforsch, D-70569 Stuttgart, Germany.
   [Balatsky, A. V.] Los Alamos Natl Lab, Div Theory, Los Alamos, NM 87545 USA.
   [Balatsky, A. V.] Los Alamos Natl Lab, Ctr Integrated Nanotechnol, Los Alamos, NM 87545 USA.
   [Garrett, J. D.] McMaster Univ, Brockhouse Inst Mat Res, Hamilton, ON L85 4M1, Canada.
   [Williams, T. J.; Luke, G. M.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Luke, G. M.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
   [Davis, J. C.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Davis, J. C.] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
C3 Cornell University; United States Department of Energy (DOE); Brookhaven National Laboratory; Max Planck Society; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory; McMaster University; McMaster University; Canadian Institute for Advanced Research (CIFAR); University of British Columbia; University of St Andrews
RP Davis, JC (corresponding author), Cornell Univ, Atom & Solid State Phys Lab, Dept Phys, Ithaca, NY 14853 USA.
EM jcdavis@ccmr.cornell.edu
FU US Department of Energy, Office of Basic Energy Sciences [DE-2009-BNL-PM015, DE-AC52-06NA25396]; NSERC; CIFAR; Center for Integrated Nanotechnology; LDRD; UCOP [TR01]; Humboldt Foundation; Physics and Astronomy Department at the University of British Columbia; German Academic Exchange Service; US Army Research Office
NR 47
TC 231
Z9 265
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 JUN 3
PY 2010
VL 465
IS 7298
BP 570
EP 576
DI 10.1038/nature09073
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000032
PM 20520706
DA 2026-03-09
ER

PT J
AU Jadamec, MA
   Billen, MI
AF Jadamec, Margarete A.
   Billen, Magali I.
TI Reconciling surface plate motions with rapid three-dimensional mantle flow around a slab edge
SO NATURE
LA English
DT Article
ID trench-parallel flow; seismic anisotropy; circulation; constraints; rheology; insights; strength; beneath; faults; field
AB The direction of tectonic plate motion at the Earth's surface and the flow field of the mantle inferred from seismic anisotropy are well correlated globally, suggesting large-scale coupling between the mantle and the surface plates(1,2). The fit is typically poor at subduction zones, however, where regional observations of seismic anisotropy suggest that the direction of mantle flow is not parallel to(3-7) and may be several times faster than(6) plate motions. Here we present three-dimensional numerical models of buoyancy-driven deformation with realistic slab geometry for the Alaska subduction-transform system and use them to determine the origin of this regional decoupling of flow. We find that near a subduction zone edge, mantle flow velocities can have magnitudes of more than ten times the surface plate motions, whereas surface plate velocities are consistent with plate motions(8) and the complex mantle flow field is consistent with observations from seismic anisotropy(5). The seismic anisotropy observations constrain the shape of the eastern slab edge and require non-Newtonian mantle rheology. The incorporation of the non-Newtonian viscosity(9,10) results in mantle viscosities of 10(17) to 10(18) Pa s in regions of high strain rate (10(-12) s(-1)), and this low viscosity enables the mantle flow field to decouple partially from the motion of the surface plates. These results imply local rapid transport of geochemical signatures through subduction zones and that the internal deformation of slabs decreases the slab-pull force available to drive subducting plates.
C1 [Jadamec, Margarete A.; Billen, Magali I.] Univ Calif Davis, Dept Geol, Davis, CA 95616 USA.
C3 University of California System; University of California Davis
RP Jadamec, MA (corresponding author), Monash Univ, Sch Math Sci, Clayton, Vic 3800, Australia.
EM majadamec@ucdavis.edu
FU US National Science Foundation [EAR-0537995]; Texas Advanced Computing Center [TG-EAR080015N]
NR 37
TC 211
Z9 246
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 338
EP U89
DI 10.1038/nature09053
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200038
PM 20485433
DA 2026-03-09
ER

PT J
AU Lin, SC
   Lo, YC
   Wu, H
AF Lin, Su-Chang
   Lo, Yu-Chih
   Wu, Hao
TI Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling
SO NATURE
LA English
DT Article
ID pyogenic bacterial-infections; nf-kappa-b; death domain; receptor superfamily; splice variant; toll; interleukin-1; myd88; irak-4; mechanism
AB MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex, which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.
C1 [Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA.
C3 Cornell University; Weill Cornell Medicine
RP Wu, H (corresponding author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA.
EM haowu@med.cornell.edu
FU NIH; Cancer Research Institute; American Heart Association
NR 58
TC 888
Z9 1093
U1 1
U2 135
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 885
EP U2
DI 10.1038/nature09121
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500029
PM 20485341
DA 2026-03-09
ER

PT J
AU Riedel, MF
   Böhi, P
   Li, Y
   Hänsch, TW
   Sinatra, A
   Treutlein, P
AF Riedel, Max F.
   Boehi, Pascal
   Li, Yun
   Haensch, Theodor W.
   Sinatra, Alice
   Treutlein, Philipp
TI Atom-chip-based generation of entanglement for quantum metrology
SO NATURE
LA English
DT Article
ID coherence; states; limit
AB Atom chips provide a versatile quantum laboratory for experiments with ultracold atomic gases(1). They have been used in diverse experiments involving low-dimensional quantum gases(2), cavity quantum electrodynamics(3), atom-surface interactions(4,5), and chip-based atomic clocks(6) and interferometers(7,8). However, a severe limitation of atom chips is that techniques to control atomic interactions and to generate entanglement have not been experimentally available so far. Such techniques enable chip-based studies of entangled many-body systems and are a key prerequisite for atom chip applications in quantum simulations(9), quantum information processing(10) and quantum metrology(11). Here we report the experimental generation of multi-particle entanglement on an atom chip by controlling elastic collisional interactions with a state-dependent potential(12). We use this technique to generate spin-squeezed states of a two-component Bose-Einstein condensate(13); such states are a useful resource for quantum metrology. The observed reduction in spin noise of -3.7 +/- 0.4 dB, combined with the spin coherence, implies four-partite entanglement between the condensate atoms(14); this could be used to improve an interferometric measurement by -2.5 +/- 0.6 dB over the standard quantum limit(15). Our data show good agreement with a dynamical multi-mode simulation(16) and allow us to reconstruct the Wigner function(17) of the spin-squeezed condensate. The techniques reported here could be directly applied to chip-based atomic clocks, currently under development(18).
C1 [Riedel, Max F.; Boehi, Pascal; Haensch, Theodor W.; Treutlein, Philipp] Univ Munich, Fak Phys, D-80799 Munich, Germany.
   [Riedel, Max F.; Boehi, Pascal; Haensch, Theodor W.; Treutlein, Philipp] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Li, Yun; Sinatra, Alice] ENS, Lab Kastler Brossel, F-75005 Paris, France.
   [Li, Yun] E China Normal Univ, Dept Phys, State Key Lab Precis Spect, Shanghai 200062, Peoples R China.
   [Treutlein, Philipp] Univ Basel, Dept Phys, CH-4056 Basel, Switzerland.
C3 University of Munich; Max Planck Society; Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; East China Normal University; University of Basel
RP Treutlein, P (corresponding author), Univ Munich, Fak Phys, Schellingstr 4, D-80799 Munich, Germany.
EM alice.sinatra@lkb.ens.fr; philipp.treutlein@unibas.ch
FU European Community [247687]; Max Planck Foundation
NR 30
TC 738
Z9 795
U1 3
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 22
PY 2010
VL 464
IS 7292
BP 1170
EP 1173
DI 10.1038/nature08988
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100032
PM 20357765
DA 2026-03-09
ER

PT J
AU Scheller, S
   Goenrich, M
   Boecher, R
   Thauer, RK
   Jaun, B
AF Scheller, Silvan
   Goenrich, Meike
   Boecher, Reinhard
   Thauer, Rudolf K.
   Jaun, Bernhard
TI The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane
SO NATURE
LA English
DT Article
ID coenzyme-m reductase; bacteria; archaea; f430; factor-f430; activation; consortia; sediment; protein
AB Large amounts (estimates range from 70 Tg per year to 300 Tg per year) of the potent greenhouse gas methane are oxidized to carbon dioxide in marine sediments by communities of methanotrophic archaea and sulphate-reducing bacteria(1-3), and thus are prevented from escaping into the atmosphere. Indirect evidence indicates that the anaerobic oxidation of methane might proceed as the reverse of archaeal methanogenesis from carbon dioxide with the nickel-containing methyl-coenzyme M reductase (MCR) as the methane-activating enzyme(4,5). However, experiments showing that MCR can catalyse the endergonic back reaction have been lacking. Here we report that purified MCR from Methanothermobacter marburgensis converts methane into methyl-coenzyme M under equilibrium conditions with apparent V-max (maximum rate) and Km (Michaelis constant) values consistent with the observed in vivo kinetics of the anaerobic oxidation of methane with sulphate(6-8). This result supports the hypothesis of 'reverse methanogenesis'(4,9) and is paramount to understanding the still-unknown mechanism of the last step of methanogenesis. The ability of MCR to cleave the particularly strong C-H bond of methane without the involvement of highly reactive oxygen-derived intermediates is directly relevant to catalytic C-H activation, currently an area of great interest in chemistry(10-13).
C1 [Scheller, Silvan; Jaun, Bernhard] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland.
   [Goenrich, Meike; Boecher, Reinhard; Thauer, Rudolf K.] Max Planck Inst Terr Microbiol, D-35043 Marburg, Germany.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Max Planck Society
RP Jaun, B (corresponding author), ETH, Organ Chem Lab, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland.
EM jaun@org.chem.ethz.ch
FU Swiss National Science Foundation [200020-119752]; Max Planck Society; Fonds der Chemischen Industrie; Swiss National Science Foundation (SNF) [200020-119752] Funding Source: Swiss National Science Foundation (SNF)
NR 32
TC 311
Z9 373
U1 1
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 JUN 3
PY 2010
VL 465
IS 7298
BP 606
EP U97
DI 10.1038/nature09015
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000039
PM 20520712
DA 2026-03-09
ER

PT J
AU Steen, EJ
   Kang, YS
   Bokinsky, G
   Hu, ZH
   Schirmer, A
   McClure, A
   del Cardayre, SB
   Keasling, JD
AF Steen, Eric J.
   Kang, Yisheng
   Bokinsky, Gregory
   Hu, Zhihao
   Schirmer, Andreas
   McClure, Amy
   del Cardayre, Stephen B.
   Keasling, Jay D.
TI Microbial production of fatty-acid-derived fuels and chemicals from plant biomass
SO NATURE
LA English
DT Article
ID escherichia-coli; acyl-coenzyme; biodiesel; ethanol; identification; biosynthesis; reductase; biofuels; genes; cdna
AB Increasing energy costs and environmental concerns have emphasized the need to produce sustainable renewable fuels and chemicals(1). Major efforts to this end are focused on the microbial production of high-energy fuels by cost-effective 'consolidated bioprocesses'(2). Fatty acids are composed of long alkyl chains and represent nature's 'petroleum', being a primary metabolite used by cells for both chemical and energy storage functions. These energy-rich molecules are today isolated from plant and animal oils for a diverse set of products ranging from fuels to oleochemicals. A more scalable, controllable and economic route to this important class of chemicals would be through the microbial conversion of renewable feedstocks, such as biomass-derived carbohydrates. Here we demonstrate the engineering of Escherichia coli to produce structurally tailored fatty esters (biodiesel), fatty alcohols, and waxes directly from simple sugars. Furthermore, we show engineering of the biodiesel-producing cells to express hemi-cellulases, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass.
C1 [Steen, Eric J.; Kang, Yisheng; Bokinsky, Gregory; Keasling, Jay D.] Joint BioEnergy Inst, Emeryville, CA 94608 USA.
   [Steen, Eric J.; Keasling, Jay D.] Synthet Biol Engn Res Ctr, Emeryville, CA 94608 USA.
   [Steen, Eric J.; Keasling, Jay D.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
   [Kang, Yisheng; Bokinsky, Gregory; Keasling, Jay D.] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94720 USA.
   [Keasling, Jay D.] Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA.
   [Hu, Zhihao; Schirmer, Andreas; McClure, Amy; del Cardayre, Stephen B.] LS9 Inc, San Francisco, CA 94080 USA.
   [Keasling, Jay D.] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
C3 United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Keasling, JD (corresponding author), Joint BioEnergy Inst, 5885 Hollis Ave, Emeryville, CA 94608 USA.
EM delc@ls9.com; keasling@berkeley.edu
FU Tien Scholar Environmental Fellowship; Synthetic Biology Engineering Research Center (SynBERC); LS9, Inc. (South San Francisco, California) through the University of California
NR 29
TC 1066
Z9 1421
U1 11
U2 898
PU NATURE PUBLISHING 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 28
PY 2010
VL 463
IS 7280
BP 559
EP U182
DI 10.1038/nature08721
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100055
PM 20111002
DA 2026-03-09
ER

PT J
AU Kollman, JM
   Polka, JK
   Zelter, A
   Davis, TN
   Agard, DA
AF Kollman, Justin M.
   Polka, Jessica K.
   Zelter, Alex
   Davis, Trisha N.
   Agard, David A.
TI Microtubule nucleating γ-TuSC assembles structures with 13-fold microtubule-like symmetry
SO NATURE
LA English
DT Article
ID tubulin ring complex; alpha-beta-tubulin; spindle pole body; electron-microscopy; centrosome; template; reconstitution; lattice
AB Microtubules are nucleated in vivo by gamma-tubulin complexes. The 300-kDa gamma-tubulin small complex (gamma-TuSC), consisting of two molecules of gamma-tubulin and one copy each of the accessory proteins Spc97 and Spc98, is the conserved, essential core of the microtubule nucleating machinery(1,2). In metazoa multiple gamma-TuSCs assemble with other proteins into gamma-tubulin ring complexes (gamma-TuRCs). The structure of gamma-TuRC indicated that it functions as a microtubule template(2-5). Because each gamma-TuSC contains two molecules of gamma-tubulin, it was assumed that the gamma-TuRC-specific proteins are required to organize gamma-TuSCs to match 13-fold microtubule symmetry. Here we show that Saccharomyces cerevisiae gamma-TuSC forms rings even in the absence of other gamma-TuRC components. The yeast adaptor protein Spc110 stabilizes the rings into extended filaments and is required for oligomer formation under physiological buffer conditions. The 8-angstrom cryo-electron microscopic reconstruction of the filament reveals 13 gamma-tubulins per turn, matching microtubule symmetry, with plus ends exposed for interaction with microtubules, implying that one turn of the filament constitutes a microtubule template. The domain structures of Spc97 and Spc98 suggest functions for conserved sequence motifs, with implications for the gamma-TuRC-specific proteins. The gamma-TuSC filaments nucleate microtubules at a low level, and the structure provides a strong hypothesis for how nucleation is regulated, converting this less active form to a potent nucleator.
C1 [Kollman, Justin M.; Agard, David A.] Univ Calif San Francisco, Dept Biochem & Biophys, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Kollman, Justin M.; Agard, David A.] Univ Calif San Francisco, Keck Adv Microscopy Ctr, San Francisco, CA 94158 USA.
   [Zelter, Alex; Davis, Trisha N.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of Washington; University of Washington Seattle
RP Agard, DA (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
EM agard@msg.ucsf.edu
FU National Institutes of Health (NIH) through the National Center for Research Resources'; NIH; Howard Hughes Medical Institute
NR 30
TC 205
Z9 284
U1 0
U2 25
PU 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 12
PY 2010
VL 466
IS 7308
BP 879
EP U114
DI 10.1038/nature09207
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100039
PM 20631709
DA 2026-03-09
ER

PT J
AU Kan, ZY
   Jaiswal, BS
   Stinson, J
   Janakiraman, V
   Bhatt, D
   Stern, HM
   Yue, P
   Haverty, PM
   Bourgon, R
   Zheng, JB
   Moorhead, M
   Chaudhuri, S
   Tomsho, LP
   Peters, BA
   Pujara, K
   Cordes, S
   Davis, DP
   Carlton, VEH
   Yuan, WL
   Li, L
   Wang, WR
   Eigenbrot, C
   Kaminker, JS
   Eberhard, DA
   Waring, P
   Schuster, SC
   Modrusan, Z
   Zhang, ZM
   Stokoe, D
   de Sauvage, FJ
   Faham, M
   Seshagiri, S
AF Kan, Zhengyan
   Jaiswal, Bijay S.
   Stinson, Jeremy
   Janakiraman, Vasantharajan
   Bhatt, Deepali
   Stern, Howard M.
   Yue, Peng
   Haverty, Peter M.
   Bourgon, Richard
   Zheng, Jianbiao
   Moorhead, Martin
   Chaudhuri, Subhra
   Tomsho, Lynn P.
   Peters, Brock A.
   Pujara, Kanan
   Cordes, Shaun
   Davis, David P.
   Carlton, Victoria E. H.
   Yuan, Wenlin
   Li, Li
   Wang, Weiru
   Eigenbrot, Charles
   Kaminker, Joshua S.
   Eberhard, David A.
   Waring, Paul
   Schuster, Stephan C.
   Modrusan, Zora
   Zhang, Zemin
   Stokoe, David
   de Sauvage, Frederic J.
   Faham, Malek
   Seshagiri, Somasekar
TI Diverse somatic mutation patterns and pathway alterations in human cancers
SO NATURE
LA English
DT Article
ID human breast; identification; melanoma; insights; reveals
AB The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics(1). Here we report the identification of 2,576 somatic mutations across similar to 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes. Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets. Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for G alpha subunits in multiple cancer types. Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a G alpha subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis. Our study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.
C1 [Kan, Zhengyan; Jaiswal, Bijay S.; Stinson, Jeremy; Janakiraman, Vasantharajan; Bhatt, Deepali; Chaudhuri, Subhra; Peters, Brock A.; Pujara, Kanan; Cordes, Shaun; Davis, David P.; Yuan, Wenlin; Modrusan, Zora; Stokoe, David; de Sauvage, Frederic J.; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Kan, Zhengyan; Yue, Peng; Haverty, Peter M.; Bourgon, Richard; Li, Li; Kaminker, Joshua S.; Zhang, Zemin] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
   [Stern, Howard M.; Eberhard, David A.; Waring, Paul] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Zheng, Jianbiao; Moorhead, Martin; Carlton, Victoria E. H.; Faham, Malek] Affymetrix Inc, Santa Clara, CA 95051 USA.
   [Tomsho, Lynn P.; Schuster, Stephan C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Wang, Weiru; Eigenbrot, Charles] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Affymetrix; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Roche Holding; Genentech; Roche Holding USA
RP Seshagiri, S (corresponding author), Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM sekar@gene.com
NR 43
TC 854
Z9 1026
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 AUG 12
PY 2010
VL 466
IS 7308
BP 869
EP U103
DI 10.1038/nature09208
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100037
PM 20668451
DA 2026-03-09
ER

PT J
AU Davis, ME
   Zuckerman, JE
   Choi, CHJ
   Seligson, D
   Tolcher, A
   Alabi, CA
   Yen, Y
   Heidel, JD
   Ribas, A
AF Davis, Mark E.
   Zuckerman, Jonathan E.
   Choi, Chung Hang J.
   Seligson, David
   Tolcher, Anthony
   Alabi, Christopher A.
   Yen, Yun
   Heidel, Jeremy D.
   Ribas, Antoni
TI Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
SO NATURE
LA English
DT Article
ID ribonucleotide reductase; gene-expression; in-vivo; interference; potent; mice; cell; pharmacokinetics; therapeutics; inhibition
AB Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients(1,2). Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans(3), and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response(4). We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind). Furthermore, a reduction was found in both the specific messenger RNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) levels when compared to pre-dosing tissue. Most notably, we detect the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action.
C1 [Davis, Mark E.; Zuckerman, Jonathan E.; Choi, Chung Hang J.; Alabi, Christopher A.] CALTECH, Pasadena, CA 91125 USA.
   [Seligson, David; Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Seligson, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
   [Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
   [Tolcher, Anthony] START LLC, San Antonio, TX 78229 USA.
   [Yen, Yun] City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
   [Heidel, Jeremy D.] Calando Pharmaceut, Pasadena, CA 91101 USA.
C3 California Institute of Technology; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; UCLA Jonsson Comprehensive Cancer 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 Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; City of Hope
RP Davis, ME (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM mdavis@cheme.caltech.edu
FU National Cancer Institute [CA U54 119347]; Daljit S. & Elaine Sarkaria Biomarker Laboratory Fund
NR 25
TC 2125
Z9 2533
U1 4
U2 999
PU 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 15
PY 2010
VL 464
IS 7291
BP 1067
EP U140
DI 10.1038/nature08956
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000044
PM 20305636
DA 2026-03-09
ER

PT J
AU Goulielmakis, E
   Loh, ZH
   Wirth, A
   Santra, R
   Rohringer, N
   Yakovlev, VS
   Zherebtsov, S
   Pfeifer, T
   Azzeer, AM
   Kling, MF
   Leone, SR
   Krausz, F
AF Goulielmakis, Eleftherios
   Loh, Zhi-Heng
   Wirth, Adrian
   Santra, Robin
   Rohringer, Nina
   Yakovlev, Vladislav S.
   Zherebtsov, Sergey
   Pfeifer, Thomas
   Azzeer, Abdallah M.
   Kling, Matthias F.
   Leone, Stephen R.
   Krausz, Ferenc
TI Real-time observation of valence electron motion
SO NATURE
LA English
DT Article
ID attosecond; dynamics; ionization
AB The superposition of quantum states drives motion on the atomic and subatomic scales, with the energy spacing of the states dictating the speed of the motion. In the case of electrons residing in the outer (valence) shells of atoms and molecules which are separated by electronvolt energies, this means that valence electron motion occurs on a subfemtosecond to few-femtosecond timescale (1 fs = 10(-15) s). In the absence of complete measurements, the motion can be characterized in terms of a complex quantity, the density matrix. Here we report an attosecond pump-probe measurement of the density matrix of valence electrons in atomic krypton ions(1). We generate the ions with a controlled few-cycle laser field(2) and then probe them through the spectrally resolved absorption of an attosecond extreme-ultraviolet pulse(3), which allows us to observe in real time the subfemtosecond motion of valence electrons over a multifemtosecond time span. We are able to completely characterize the quantum mechanical electron motion and determine its degree of coherence in the specimen of the ensemble. Although the present study uses a simple, prototypical open system, attosecond transient absorption spectroscopy should be applicable to molecules and solid-state materials to reveal the elementary electron motions that control physical, chemical and biological properties and processes.
C1 [Goulielmakis, Eleftherios; Wirth, Adrian; Yakovlev, Vladislav S.; Zherebtsov, Sergey; Kling, Matthias F.; Krausz, Ferenc] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Loh, Zhi-Heng; Pfeifer, Thomas; Leone, Stephen R.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Loh, Zhi-Heng; Pfeifer, Thomas; Leone, Stephen R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Loh, Zhi-Heng; Pfeifer, Thomas; Leone, Stephen R.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA.
   [Santra, Robin] Argonne Natl Lab, Argonne, IL 60439 USA.
   [Santra, Robin] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
   [Rohringer, Nina] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Yakovlev, Vladislav S.; Krausz, Ferenc] Univ Munich, Dept Phys, D-85748 Garching, Germany.
   [Azzeer, Abdallah M.] King Saud Univ, Dept Phys & Astron, Riyadh 11451, Saudi Arabia.
C3 Max Planck Society; 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; United States Department of Energy (DOE); Argonne National Laboratory; University of Chicago; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Munich; King Saud University
RP Goulielmakis, E (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM elgo@mpq.mpg.de; srl@berkeley.edu; krausz@lmu.de
FU Max Planck Society; King Saud University; DFG Cluster of Excellence: Munich Centre for Advanced Photonics; Marie-Curie Reintegration grant [MERG-CT-2007-208643]; DFG; Air Force Office of Scientific Research [FA9550-04-1-0242]; National Science Foundation [CHE-0742662, EEC-0310717]; Office of Science, Office of Basic Energy Sciences, US Department of Energy [DE-AC02-05-CH11231, DE-AC02-06CH11357]; MPG; US Department of Energy, Lawrence Livermore National Laboratory [DE-AC52-07NA27344]; Direct For Mathematical & Physical Scien [0742662] Funding Source: National Science Foundation; Division Of Chemistry [0742662] Funding Source: National Science Foundation
NR 30
TC 1097
Z9 1229
U1 8
U2 577
PU NATURE PUBLISHING 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 5
PY 2010
VL 466
IS 7307
BP 739
EP U7
DI 10.1038/nature09212
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500035
PM 20686571
DA 2026-03-09
ER

PT J
AU Secord, R
   Gingerich, PD
   Lohmann, KC
   MacLeod, KG
AF Secord, Ross
   Gingerich, Philip D.
   Lohmann, Kyger C.
   MacLeod, Kenneth G.
TI Continental warming preceding the Palaeocene-Eocene thermal maximum
SO NATURE
LA English
DT Article
ID bighorn basin; stable-isotopes; methane hydrate; climate-change; temperature; mammals; model; water; reconstruction; fractionation
AB Marine and continental records(1) show an abrupt negative shift in carbon isotope values at similar to 55.8 Myr ago. This carbon isotope excursion (CIE) is consistent with the release of a massive amount of isotopically light carbon into the atmosphere and was associated with a dramatic rise in global temperatures termed the Palaeocene-Eocene thermal maximum (PETM). Greenhouse gases released during the CIE, probably including methane, have often been considered the main cause of PETM warming. However, some evidence from the marine record suggests that warming directly preceded the CIE(2-4), raising the possibility that the CIE and PETM may have been linked to earlier warming with different origins. Yet pre-CIE warming is still uncertain. Disentangling the sequence of events before and during the CIE and PETM is important for understanding the causes of, and Earth system responses to, abrupt climate change. Here we show that continental warming of about 5 degrees C preceded the CIE in the Bighorn Basin, Wyoming. Our evidence, based on oxygen isotopes in mammal teeth (which reflect temperature-sensitive fractionation processes) and other proxies, reveals a marked temperature increase directly below the CIE, and again in the CIE. Pre-CIE warming is also supported by a negative amplification of delta(13)C values in soil carbonates below the CIE. Our results suggest that at least two sources of warming-the earlier of which is unlikely to have been methane-contributed to the PETM.
C1 [Secord, Ross] Univ Nebraska, Dept Earth & Atmospher Sci, Lincoln, NE 68588 USA.
   [Secord, Ross; Gingerich, Philip D.; Lohmann, Kyger C.] Univ Michigan, Dept Geol Sci, Ann Arbor, MI 48109 USA.
   [Secord, Ross] Florida Museum Nat Hist, Gainesville, FL 32611 USA.
   [MacLeod, Kenneth G.] Univ Missouri, Dept Geol Sci, Columbia, MO 65211 USA.
C3 University of Nebraska System; University of Nebraska Lincoln; University of Michigan System; University of Michigan; University of Missouri System; University of Missouri Columbia
RP Secord, R (corresponding author), Univ Nebraska, Dept Earth & Atmospher Sci, Lincoln, NE 68588 USA.
EM rsecord2@unl.edu
FU American Chemical Society; National Science Foundation; Geological Society of America; University of Michigan Department of Geological Sciences
NR 31
TC 72
Z9 94
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 OCT 21
PY 2010
VL 467
IS 7318
BP 955
EP 958
DI 10.1038/nature09441
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700036
PM 20962843
DA 2026-03-09
ER

PT J
AU Visel, A
   Zhu, YW
   May, D
   Afzal, V
   Gong, E
   Attanasio, C
   Blow, MJ
   Cohen, JC
   Rubin, EM
   Pennacchio, LA
AF Visel, Axel
   Zhu, Yiwen
   May, Dalit
   Afzal, Veena
   Gong, Elaine
   Attanasio, Catia
   Blow, Matthew J.
   Cohen, Jonathan C.
   Rubin, Edward M.
   Pennacchio, Len A.
TI Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice
SO NATURE
LA English
DT Article
ID chromosome 9p21; myocardial-infarction; tumor suppression; heart-disease; ink4a locus; association; atherosclerosis; expression; hypercholesterolemia; susceptibility
AB Sequence polymorphisms in a 58-kilobase (kb) interval on chromosome 9p21 confer a markedly increased risk of coronary artery disease (CAD), the leading cause of death worldwide(1,2). The variants have a substantial effect on the epidemiology of CAD and other life-threatening vascular conditions because nearly one-quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein-coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70-kb non-coding interval on mouse chromosome 4 affects cardiac expression of neighbouring genes, as well as proliferation properties of vascular cells. Chr4(Delta 70kb/Delta 70kb) mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the non-coding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4(Delta 70kb/Delta 70kb) mice, indicating that distant-acting gene regulatory functions are located in the non-coding CAD risk interval. Allele-specific expression of Cdkn2b transcripts in heterozygous mice showed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4(Delta 70kb/Delta 70kb) aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval has a pivotal role in regulation of cardiac Cdkn2a/b expression, and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.
C1 [Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Rubin, Edward M.; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA.
   [Visel, Axel; Blow, Matthew J.; Rubin, Edward M.; Pennacchio, Len A.] Joint Genome Inst, US DOE, Walnut Creek, CA 94598 USA.
   [Cohen, Jonathan C.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dept Mol Genet, Dallas, TX 75390 USA.
   [Cohen, Jonathan C.] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Pennacchio, LA (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, MS 84-171, Berkeley, CA 94720 USA.
EM LAPennacchio@lbl.gov
FU National Heart, Lung, and Blood Institute; EMBO; Department of Energy, University of California [DE-AC02-05CH11231]; MMPC [DK59630]; National Human Genome Research Institute [R01HG003988] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [U2CDK059630] Funding Source: NIH RePORTER
NR 31
TC 382
Z9 432
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 409
EP U103
DI 10.1038/nature08801
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100046
PM 20173736
DA 2026-03-09
ER

PT J
AU Mazin, II
AF Mazin, Igor I.
TI Superconductivity gets an iron boost
SO NATURE
LA English
DT Article
ID high-temperature superconductivity; pairing state; pnictides; symmetry
AB Superconductivity, the resistance-free flow of electrical charges, is one of the most exotic phenomena in solid-state physics. Even though it was discovered almost a century ago, many questions remain unanswered, in particular those concerning the physics of high-temperature superconductivity. The recent discovery of iron-based superconductors was arguably the most important breakthrough in this field for more than two decades and may provide new avenues for understanding this high-temperature phenomenon. Here I present my view of the recent developments in this field that have led to the current understanding of this important new class of superconductor.
C1 USN, Res Lab, Washington, DC 20375 USA.
C3 United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake
RP Mazin, II (corresponding author), USN, Res Lab, Code 6390,4555 Overlook Ave SW, Washington, DC 20375 USA.
EM mazin@dave.nrl.navy.mil
NR 15
TC 380
Z9 445
U1 1
U2 153
PU 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 11
PY 2010
VL 464
IS 7286
BP 183
EP 186
DI 10.1038/nature08914
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100030
PM 20220835
DA 2026-03-09
ER

PT J
AU Zipkes, C
   Palzer, S
   Sias, C
   Köhl, M
AF Zipkes, Christoph
   Palzer, Stefan
   Sias, Carlo
   Koehl, Michael
TI A trapped single ion inside a Bose-Einstein condensate
SO NATURE
LA English
DT Article
ID superconductivity; impurity; cavity
AB Improved control of the motional and internal quantum states of ultracold neutral atoms and ions has opened intriguing possibilities for quantum simulation and quantum computation. Many-body effects have been explored with hundreds of thousands of quantum-degenerate neutral atoms(1), and coherent light-matter interfaces have been built(2,3). Systems of single or a few trapped ions have been used to demonstrate universal quantum computing algorithms(4) and to search for variations of fundamental constants in precision atomic clocks(5). Until now, atomic quantum gases and single trapped ions have been treated separately in experiments. Here we investigate whether they can be advantageously combined into one hybrid system, by exploring the immersion of a single trapped ion into a Bose-Einstein condensate of neutral atoms. We demonstrate independent control over the two components of the hybrid system, study the fundamental interaction processes and observe sympathetic cooling of the single ion by the condensate. Our experiment calls for further research into the possibility of using this technique for the continuous cooling of quantum computers(6). We also anticipate that it will lead to explorations of entanglement in hybrid quantum systems and to fundamental studies of the decoherence of a single, locally controlled impurity particle coupled to a quantum environment(7,8).
C1 [Zipkes, Christoph; Palzer, Stefan; Sias, Carlo; 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 Engineering and Physical Sciences Research Council; European Research Council [240335]; Herchel Smith Fund; EPSRC [EP/H005676/1, EP/F016379/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F016379/1, EP/H005676/1] Funding Source: researchfish; European Research Council (ERC) [240335] Funding Source: European Research Council (ERC)
NR 33
TC 336
Z9 359
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 388
EP U79
DI 10.1038/nature08865
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100041
PM 20237565
DA 2026-03-09
ER

PT J
AU Johnson, RA
   Wright, KD
   Poppleton, H
   Mohankumar, KM
   Finkelstein, D
   Pounds, SB
   Rand, V
   Leary, SES
   White, E
   Eden, C
   Hogg, T
   Northcott, P
   Mack, S
   Neale, G
   Wang, YD
   Coyle, B
   Atkinson, J
   DeWire, M
   Kranenburg, TA
   Gillespie, Y
   Allen, JC
   Merchant, T
   Boop, FA
   Sanford, RA
   Gajjar, A
   Ellison, DW
   Taylor, MD
   Grundy, RG
   Gilbertson, RJ
AF Johnson, Robert A.
   Wright, Karen D.
   Poppleton, Helen
   Mohankumar, Kumarasamypet M.
   Finkelstein, David
   Pounds, Stanley B.
   Rand, Vikki
   Leary, Sarah E. S.
   White, Elsie
   Eden, Christopher
   Hogg, Twala
   Northcott, Paul
   Mack, Stephen
   Neale, Geoffrey
   Wang, Yong-Dong
   Coyle, Beth
   Atkinson, Jennifer
   DeWire, Mariko
   Kranenburg, Tanya A.
   Gillespie, Yancey
   Allen, Jeffrey C.
   Merchant, Thomas
   Boop, Fredrick A.
   Sanford, Robert. A.
   Gajjar, Amar
   Ellison, David W.
   Taylor, Michael D.
   Grundy, Richard G.
   Gilbertson, Richard J.
TI Cross-species genomics matches driver mutations and cell compartments to model ependymoma
SO NATURE
LA English
DT Article
ID lipid-binding protein; neural stem; radial glia; association; progression; expression
AB Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown(1-3). We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.
C1 [Johnson, Robert A.; Wright, Karen D.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; White, Elsie; Eden, Christopher; Hogg, Twala; Atkinson, Jennifer; Kranenburg, Tanya A.; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Wright, Karen D.; DeWire, Mariko; Gajjar, Amar; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Finkelstein, David; Neale, Geoffrey; Wang, Yong-Dong] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
   [Pounds, Stanley B.] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Rand, Vikki] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Leary, Sarah E. S.] Seattle Childrens Hosp, Seattle, WA 98105 USA.
   [Northcott, Paul; Mack, Stephen; Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M4N 1X8, Canada.
   [Coyle, Beth; Grundy, Richard G.] Univ Nottingham, Childrens Brain Tumour Res Ctr, Nottingham NG7 2RD, England.
   [Gillespie, Yancey] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
   [Allen, Jeffrey C.] NYU, Langone Med Ctr, New York, NY 10016 USA.
   [Merchant, Thomas] St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA.
   [Boop, Fredrick A.; Sanford, Robert. A.] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA.
   [Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, 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; Newcastle University - UK; Seattle Children's Hospital; University of Toronto; Hospital for Sick Children (SickKids); University of Nottingham; University of Alabama System; University of Alabama Birmingham; New York University; NYU Langone Medical Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital
RP Gilbertson, RJ (corresponding author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM richard.gilbertson@stjude.org
FU National Institutes of Health [R01CA129541, P01CA96832, P30CA021765]; Collaborative Ependymoma Research Network (CERN); American Lebanese Syrian Associated Charities (ALSAC); NRSA [T32 CA070089]; National Cancer Institute [P30CA021765, P01CA096832] Funding Source: NIH RePORTER
NR 30
TC 286
Z9 330
U1 0
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 632
EP 636
DI 10.1038/nature09173
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100055
PM 20639864
DA 2026-03-09
ER

PT J
AU Behar, DM
   Yunusbayev, B
   Metspalu, M
   Metspalu, E
   Rosset, S
   Parik, J
   Rootsi, S
   Chaubey, G
   Kutuev, I
   Yudkovsky, G
   Khusnutdinova, EK
   Balanovsky, O
   Semino, O
   Pereira, L
   Comas, D
   Gurwitz, D
   Bonne-Tamir, B
   Parfitt, T
   Hammer, MF
   Skorecki, K
   Villems, R
AF Behar, Doron M.
   Yunusbayev, Bayazit
   Metspalu, Mait
   Metspalu, Ene
   Rosset, Saharon
   Parik, Jueri
   Rootsi, Siiri
   Chaubey, Gyaneshwer
   Kutuev, Ildus
   Yudkovsky, Guennady
   Khusnutdinova, Elza K.
   Balanovsky, Oleg
   Semino, Ornella
   Pereira, Luisa
   Comas, David
   Gurwitz, David
   Bonne-Tamir, Batsheva
   Parfitt, Tudor
   Hammer, Michael F.
   Skorecki, Karl
   Villems, Richard
TI The genome-wide structure of the Jewish people
SO NATURE
LA English
DT Article
ID population stratification; european americans; middle-eastern; ancestry; individuals; association; genotype; patterns
AB Contemporary Jews comprise an aggregate of ethno-religious communities whose worldwide members identify with each other through various shared religious, historical and cultural traditions(1,2). Historical evidence suggests common origins in the Middle East, followed by migrations leading to the establishment of communities of Jews in Europe, Africa and Asia, in what is termed the Jewish Diaspora(3-5). This complex demographic history imposes special challenges in attempting to address the genetic structure of the Jewish people(6). Although many genetic studies have shed light on Jewish origins and on diseases prevalent among Jewish communities, including studies focusing on uniparentally and biparentally inherited markers(7-16), genome-wide patterns of variation across the vast geographic span of Jewish Diaspora communities and their respective neighbours have yet to be addressed. Here we use high-density bead arrays to genotype individuals from 14 Jewish Diaspora communities and compare these patterns of genome-wide diversity with those from 69 Old World non-Jewish populations, of which 25 have not previously been reported. These samples were carefully chosen to provide comprehensive comparisons between Jewish and non-Jewish populations in the Diaspora, as well as with non-Jewish populations from the Middle East and north Africa. Principal component and structure-like analyses identify previously unrecognized genetic substructure within the Middle East. Most Jewish samples form a remarkably tight subcluster that overlies Druze and Cypriot samples but not samples from other Levantine populations or paired Diaspora host populations. In contrast, Ethiopian Jews (Beta Israel) and Indian Jews (Bene Israel and Cochini) cluster with neighbouring autochthonous populations in Ethiopia and western India, respectively, despite a clear paternal link between the Bene Israel and the Levant. These results cast light on the variegated genetic architecture of the Middle East, and trace the origins of most Jewish Diaspora communities to the Levant.
C1 [Behar, Doron M.; Yudkovsky, Guennady; Skorecki, Karl] Mol Med Lab, IL-31096 Haifa, Israel.
   [Behar, Doron M.; Yunusbayev, Bayazit; Metspalu, Mait; Metspalu, Ene; Parik, Jueri; Rootsi, Siiri; Chaubey, Gyaneshwer; Kutuev, Ildus; Villems, Richard] Univ Tartu, Estonian Bioctr, EE-51010 Tartu, Estonia.
   [Behar, Doron M.; Yunusbayev, Bayazit; Metspalu, Mait; Metspalu, Ene; Parik, Jueri; Rootsi, Siiri; Chaubey, Gyaneshwer; Kutuev, Ildus; Villems, Richard] Univ Tartu, Dept Evolutionary Biol, EE-51010 Tartu, Estonia.
   [Yunusbayev, Bayazit; Kutuev, Ildus; Khusnutdinova, Elza K.] Russian Acad Sci, Ufa Res Ctr, Inst Biochem & Genet, Ufa 450054, Russia.
   [Rosset, Saharon] Tel Aviv Univ, Sch Math Sci, Dept Stat & Operat Res, IL-69978 Tel Aviv, Israel.
   [Yudkovsky, Guennady; Skorecki, Karl] Technion Israel Inst Technol, Rappaport Fac Med & Res Inst, IL-31096 Haifa, Israel.
   [Balanovsky, Oleg] Russian Acad Med Sci, Med Genet Res Ctr, Moscow 115478, Russia.
   [Semino, Ornella] Univ Pavia, Dipartimento Genet & Microbiol, I-27100 Pavia, Italy.
   [Pereira, Luisa] IPATIMUP, P-4200465 Oporto, Portugal.
   [Pereira, Luisa] Univ Porto, Fac Med, P-4200319 Oporto, Portugal.
   [Comas, David] CEXS UPF PRBB, Inst Evolutionary Biol, CSIC, Barcelona 08003, Spain.
   [Comas, David] CIBER Epidemiol & Salud Publ, Barcelona 08003, Spain.
   [Gurwitz, David; Bonne-Tamir, Batsheva] Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
   [Parfitt, Tudor] Univ London Sch Oriental & African Studies, Fac Languages & Cultures, Dept Languages & Cultures Near & Middle E, London WC1H 0XG, England.
   [Hammer, Michael F.] Univ Arizona, ARL Div Biotechnol, Tucson, AZ 85721 USA.
C3 Technion Israel Institute of Technology; Rambam Health Care Campus; Estonian Biocentre; University of Tartu; University of Tartu; Russian Academy of Sciences; Institute of Biochemistry & Genetics of Ufa Science Centre of the RAS; Tel Aviv University; Technion Israel Institute of Technology; Russian Academy of Medical Sciences; Research Centre for Medical Genetics; University of Pavia; Universidade do Porto; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Pompeu Fabra University; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; Tel Aviv University; Sackler Faculty of Medicine; University of London; University of London School Oriental & African Studies (SOAS); University of Arizona
RP Behar, DM (corresponding author), Mol Med Lab, Rambam Hlth Care Campus, IL-31096 Haifa, Israel.
EM behardm@usernet.com; skorecki@tx.technion.ac.il; rvillems@ebc.ee
FU European Commission [205419]; European Union through a Centre of Excellence in Genomics; Swedish Collegium for Advanced Studies; Estonian Science Foundation [7858, 7445]; Arthur and Rosalinde Gilbert Foundation; American Technion Society; European Union for Marie Curie International Reintegration [CT-2007-208019]; Israeli Science Foundation [1227/09]; Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education; Fundacao para a Ciencia ea Tecnologia; Portuguese Foundation for Science and Technology
NR 30
TC 319
Z9 348
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 JUL 8
PY 2010
VL 466
IS 7303
BP 238
EP U112
DI 10.1038/nature09103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800037
PM 20531471
DA 2026-03-09
ER

PT J
AU Mannini, M
   Pineider, F
   Danieli, C
   Totti, F
   Sorace, L
   Sainctavit, P
   Arrio, MA
   Otero, E
   Joly, L
   Cezar, JC
   Cornia, A
   Sessoli, R
AF Mannini, M.
   Pineider, F.
   Danieli, C.
   Totti, F.
   Sorace, L.
   Sainctavit, Ph.
   Arrio, M. -A.
   Otero, E.
   Joly, L.
   Cezar, J. C.
   Cornia, A.
   Sessoli, R.
TI Quantum tunnelling of the magnetization in a monolayer of oriented single-molecule magnets
SO NATURE
LA English
DT Article
ID anisotropy; dichroism; fe; spintronics; spectra; edge; gold
AB A fundamental step towards atomic- or molecular-scale spintronic devices has recently been made by demonstrating that the spin of an individual atom deposited on a surface(1), or of a small paramagnetic molecule embedded in a nanojunction(2), can be externally controlled. An appealing next step is the extension of such a capability to the field of information storage, by taking advantage of the magnetic bistability and rich quantum behaviour of single-molecule magnets(3-6) (SMMs). Recently, a proof of concept that the magnetic memory effect is retained when SMMs are chemically anchored to a metallic surface(7) was provided. However, control of the nanoscale organization of these complex systems is required for SMMs to be integrated into molecular spintronic devices(8,9). Here we show that a preferential orientation of Fe(4) complexes on a gold surface can be achieved by chemical tailoring. As a result, the most striking quantum feature of SMMs-their stepped hysteresis loop, which results from resonant quantum tunnelling of the magnetization(5,6)-can be clearly detected using synchrotron-based spectroscopic techniques. With the aid of multiple theoretical approaches, we relate the angular dependence of the quantum tunnelling resonances to the adsorption geometry, and demonstrate that molecules predominantly lie with their easy axes close to the surface normal. Our findings prove that the quantum spin dynamics can be observed in SMMs chemically grafted to surfaces, and offer a tool to reveal the organization of matter at the nanoscale.
C1 [Mannini, M.; Pineider, F.; Totti, F.; Sorace, L.; Sessoli, R.] Univ Florence, Dept Chem Ugo Schiff, I-50019 Sesto Fiorentino, Italy.
   [Mannini, M.; Pineider, F.; Totti, F.; Sorace, L.; Sessoli, R.] Univ Florence, INSTM Res Unit, I-50019 Sesto Fiorentino, Italy.
   [Mannini, M.] Univ Florence, ISTM CNR, URT Firenze, I-50019 Sesto Fiorentino, Italy.
   [Danieli, C.; Cornia, A.] Univ Modena & Reggio Emilia, Dept Chem, I-41100 Modena, Italy.
   [Danieli, C.; Cornia, A.] Univ Modena & Reggio Emilia, INSTM Res Unit, I-41100 Modena, Italy.
   [Sainctavit, Ph.; Arrio, M. -A.] Univ Paris 06, CNRS, UMR7590, Inst Mineral & Phys Milieux Condenses, F-75252 Paris, France.
   [Otero, E.] Synchrotron Soleil, F-91192 Gif Sur Yvette, France.
   [Joly, L.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Cezar, J. C.] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
C3 University of Florence; University of Florence; Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienze e Tecnologie Molecolari (ISTM-CNR); University of Florence; Universita di Modena e Reggio Emilia; Universita di Modena e Reggio Emilia; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; Universite Paris Cite; CNRS - Institute of Physics (INP); SOLEIL Synchrotron; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; European Synchrotron Radiation Facility (ESRF)
RP Sessoli, R (corresponding author), Univ Florence, Dept Chem Ugo Schiff, I-50019 Sesto Fiorentino, Italy.
EM roberta.sessoli@unifi.it
FU European Community [226716]; Italian CNR [PM.P05.012]; Italian MIUR; Ente CRF
NR 29
TC 568
Z9 586
U1 1
U2 314
PU 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 18
PY 2010
VL 468
IS 7322
BP 417
EP 421
DI 10.1038/nature09478
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100038
PM 20981008
DA 2026-03-09
ER

PT J
AU Stadtfeld, M
   Apostolou, E
   Akutsu, H
   Fukuda, A
   Follett, P
   Natesan, S
   Kono, T
   Shioda, T
   Hochedlinger, K
AF Stadtfeld, Matthias
   Apostolou, Effie
   Akutsu, Hidenori
   Fukuda, Atsushi
   Follett, Patricia
   Natesan, Sridaran
   Kono, Tomohiro
   Shioda, Toshi
   Hochedlinger, Konrad
TI Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID nuclear transfer; es cells; expression; mice; methylation; generation; cluster; differentiation; fibroblasts; cloning
AB Induced pluripotent stem cells (iPSCs) have been generated by enforced expression of defined sets of transcription factors in somatic cells. It remains controversial whether iPSCs are molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells. By comparing genetically identical mouse ES cells and iPSCs, we show here that their overall messenger RNA and microRNA expression patterns are indistinguishable with the exception of a few transcripts encoded within the imprinted Dlk1-Dio3 gene cluster on chromosome 12qF1, which were aberrantly silenced in most of the iPSC clones. Consistent with a developmental role of the Dlk1-Dio3 gene cluster, these iPSC clones contributed poorly to chimaeras and failed to support the development of entirely iPSC-derived animals ('all-iPSC mice'). In contrast, iPSC clones with normal expression of the Dlk1-Dio3 cluster contributed to high-grade chimaeras and generated viable all-iPSC mice. Notably, treatment of an iPSC clone that had silenced Dlk1-Dio3 with a histone deacetylase inhibitor reactivated the locus and rescued its ability to support full-term development of all-iPSC mice. Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells.
C1 [Stadtfeld, Matthias; Apostolou, Effie; Follett, Patricia; Hochedlinger, Konrad] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA.
   [Stadtfeld, Matthias; Apostolou, Effie; Shioda, Toshi; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
   [Stadtfeld, Matthias; Apostolou, Effie; Shioda, Toshi; Hochedlinger, Konrad] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   [Stadtfeld, Matthias; Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Stadtfeld, Matthias; Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   [Akutsu, Hidenori] Natl Inst Child Hlth & Dev, Dept Reprod Biol, Tokyo 1578535, Japan.
   [Fukuda, Atsushi; Kono, Tomohiro] Tokyo Univ Agr, Dept Biosci, Tokyo 1568502, Japan.
   [Natesan, Sridaran] Sanofi Aventis, Cambridge, MA 02139 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University; Harvard University; National Center for Child Health & Development - Japan; Tokyo University of Agriculture; Sanofi-Aventis; Sanofi USA
RP Hochedlinger, K (corresponding author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Harvard Stem Cell Inst, 185 Cambridge St, Boston, MA 02114 USA.
EM khochedlinger@helix.mgh.harvard.edu
FU Schering Foundation; Jane Coffin Childs postdoctoral fellowship; NIH; Harvard Stem Cell Institute; MGH; HHMI; Grants-in-Aid for Scientific Research [20062009] Funding Source: KAKEN
NR 50
TC 637
Z9 755
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 MAY 13
PY 2010
VL 465
IS 7295
BP 175
EP U55
DI 10.1038/nature09017
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500026
PM 20418860
DA 2026-03-09
ER

PT J
AU Xu, X
   Zheng, XT
   You, HL
AF Xu, Xing
   Zheng, Xiaoting
   You, Hailu
TI Exceptional dinosaur fossils show ontogenetic development of early feathers
SO NATURE
LA English
DT Article
ID evolutionary origin; china; diversification; morphogenesis; theropod; birds
AB Recent discoveries of feathered dinosaur specimens have greatly improved our understanding of the origin and early evolution of feathers, but little information is available on the ontogenetic development of early feathers(1-7). Here we describe an early-juvenile specimen and a late-juvenile specimen, both referable to the oviraptorosaur Similicaudipteryx(8), recovered from the Lower Cretaceous Yixian Formation of western Liaoning, China(9). The two specimens have strikingly different remiges and rectrices, suggesting that a radical morphological change occurred during feather development, as is the case for modern feathers(10). However, both the remiges and the rectrices are proximally ribbon-like in the younger specimen but fully pennaceous in the older specimen, a pattern not known in any modern bird(10). In combination with the wide distribution of proximally ribbon-like pennaceous feathers and elongate broad filamentous feathers among extinct theropods, this find suggests that early feathers were developmentally more diverse than modern ones and that some developmental features, and the resultant morphotypes, have been lost in feather evolution.
C1 [Xu, Xing] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Zheng, Xiaoting] Shandong Tianyu Museum Nat, Pingyi 273300, Shandong, Peoples R China.
   [You, Hailu] Chinese Acad Geol Sci, Inst Geol, Beijing 100037, Peoples R China.
C3 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
RP Xu, X (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, 142 Xiwai St, Beijing 100044, Peoples R China.
EM xingxu@vip.sina.com; ty4291666@163.com
FU Chinese Academy of Sciences; National Natural Science Foundation of China; Special Funds For Major State Basic Research Projects of China
NR 29
TC 114
Z9 137
U1 2
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 29
PY 2010
VL 464
IS 7293
BP 1338
EP 1341
DI 10.1038/nature08965
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000044
PM 20428169
DA 2026-03-09
ER

PT J
AU Zhang, Q
   Raoof, M
   Chen, Y
   Sumi, Y
   Sursal, T
   Junger, W
   Brohi, K
   Itagaki, K
   Hauser, CJ
AF Zhang, Qin
   Raoof, Mustafa
   Chen, Yu
   Sumi, Yuka
   Sursal, Tolga
   Junger, Wolfgang
   Brohi, Karim
   Itagaki, Kiyoshi
   Hauser, Carl J.
TI Circulating mitochondrial DAMPs cause inflammatory responses to injury
SO NATURE
LA English
DT Article
ID operated calcium influx; human neutrophils; trauma; shock; mobilization; chemotaxis; receptors; peptides; models; sirs
AB Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis(1). Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors(2). Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs) that activate innate immunity(3). Mitochondria are evolutionary endosymbionts that were derived from bacteria(4) and so might bear bacterial molecular motifs. Here we show that injury releases mitochondrial DAMPs (MTDs) into the circulation with functionally important immune consequences. MTDs include formyl peptides and mitochondrial DNA. These activate human polymorphonuclear neutrophils (PMNs) through formyl peptide receptor-1 and Toll-like receptor (TLR) 9, respectively. MTDs promote PMN Ca2+ flux and phosphorylation of mitogen-activated protein (MAP) kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTDs can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These signal through innate immune pathways identical to those activated in sepsis to create a sepsis-like state. The release of such mitochondrial 'enemies within' by cellular injury is a key link between trauma, inflammation and SIRS.
C1 [Zhang, Qin; Raoof, Mustafa; Chen, Yu; Sumi, Yuka; Sursal, Tolga; Junger, Wolfgang; Itagaki, Kiyoshi; Hauser, Carl J.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Trauma, Boston, MA 02215 USA.
   [Zhang, Qin; Raoof, Mustafa; Chen, Yu; Sumi, Yuka; Sursal, Tolga; Junger, Wolfgang; Itagaki, Kiyoshi; Hauser, Carl J.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Brohi, Karim] Univ London, Barts & London Sch Med & Dent, Trauma Clin Acad Unit, London E1 1BB, England.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; University of London; Queen Mary University London
RP Hauser, CJ (corresponding author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Trauma, 330 Brookline Ave, Boston, MA 02215 USA.
EM cjhauser@bidmc.harvard.edu
FU National Institute of General Medical Sciences; Department of Defense
NR 32
TC 3041
Z9 3465
U1 12
U2 449
PU NATURE PUBLISHING 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 4
PY 2010
VL 464
IS 7285
BP 104
EP U115
DI 10.1038/nature08780
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500042
PM 20203610
DA 2026-03-09
ER

PT J
AU Zhao, D
   McBride, D
   Nandi, S
   McQueen, HA
   McGrew, MJ
   Hocking, PM
   Lewis, PD
   Sang, HM
   Clinton, M
AF Zhao, D.
   McBride, D.
   Nandi, S.
   McQueen, H. A.
   McGrew, M. J.
   Hocking, P. M.
   Lewis, P. D.
   Sang, H. M.
   Clinton, M.
TI Somatic sex identity is cell autonomous in the chicken
SO NATURE
LA English
DT Article
ID dosage compensation; determining gene; differentiation; expression; embryos; birds; rnas; sry
AB In the mammalian model of sex determination, embryos are considered to be sexually indifferent until the transient action of a sex-determining gene initiates gonadal differentiation. Although this model is thought to apply to all vertebrates, this has yet to be established. Here we have examined three lateral gynandromorph chickens (a rare, naturally occurring phenomenon in which one side of the animal appears male and the other female) to investigate the sex-determining mechanism in birds. These studies demonstrated that gynandromorph birds are genuine male: female chimaeras, and indicated that male and female avian somatic cells may have an inherent sex identity. To test this hypothesis, we transplanted presumptive mesoderm between embryos of reciprocal sexes to generate embryos containing male: female chimaeric gonads. In contrast to the outcome for mammalian mixed-sex chimaeras, in chicken mixed-sex chimaeras the donor cells were excluded from the functional structures of the host gonad. In an example where female tissue was transplanted into a male host, donor cells contributing to the developing testis retained a female identity and expressed a marker of female function. Our study demonstrates that avian somatic cells possess an inherent sex identity and that, in birds, sexual differentiation is substantively cell autonomous.
C1 [Zhao, D.; McBride, D.; Nandi, S.; McGrew, M. J.; Sang, H. M.; Clinton, M.] Univ Edinburgh, Roslin Inst, Div Dev Biol, Roslin EH25 9PS, Midlothian, Scotland.
   [Hocking, P. M.] Univ Edinburgh, Roslin Inst, Div Genet & Genom, Roslin EH25 9PS, Midlothian, Scotland.
   [Hocking, P. M.] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland.
   [McQueen, H. A.] Univ Edinburgh, Inst Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
   [Lewis, P. D.] Univ KwaZulu Natal, Dept Anim & Poultry Sci, Pietermaritzburg, South Africa.
C3 University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of Edinburgh; University of Edinburgh; University of Kwazulu Natal
RP Clinton, M (corresponding author), Univ Edinburgh, Roslin Inst, Div Dev Biol, Roslin EH25 9PS, Midlothian, Scotland.
EM Michael.clinton@roslin.ed.ac.uk
FU DEFRA; BBSRC [BB/E015425/1]; BBSRC [BB/E011276/2, BB/E015425/1, BB/H012486/1, BBS/E/R/00001603, BB/E015425/2] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/R/00001603, BB/E015425/2, BB/E015425/1, BB/E011276/2, BB/H012486/1] Funding Source: researchfish
NR 43
TC 173
Z9 209
U1 2
U2 81
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 237
EP U115
DI 10.1038/nature08852
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100038
PM 20220842
DA 2026-03-09
ER

PT J
AU Carneiro, T
   Khair, L
   Reis, CC
   Borges, V
   Moser, BA
   Nakamura, TM
   Ferreira, MG
AF Carneiro, Tiago
   Khair, Lyne
   Reis, Clara C.
   Borges, Vanessa
   Moser, Bettina A.
   Nakamura, Toru M.
   Ferreira, Miguel Godinho
TI Telomeres avoid end detection by severing the checkpoint signal transduction pathway
SO NATURE
LA English
DT Article
ID fission yeast; dna-damage; cell-cycle; dysfunctional telomeres; protein crb2; rap1; recruitment; methylation; repair; breaks
AB Telomeres protect the normal ends of chromosomes from being recognized as deleterious DNA double-strand breaks. Recent studies have uncovered an apparent paradox: although DNA repair is prevented, several proteins involved in DNA damage processing and checkpoint responses are recruited to telomeres in every cell cycle and are required for end protection(1). It is currently not understood how telomeres prevent DNA damage responses from causing permanent cell cycle arrest. Here we show that fission yeast (Schizosaccharomyces pombe) cells lacking Taz1, an orthologue of human TRF1 and TRF2 (ref. 2), recruit DNA repair proteins (Rad22(RAD52) and Rhp51(RAD51), where the superscript indicates the human orthologue) and checkpoint sensors (RPA, Rad9, Rad26(ATRIP) and Cut5/Rad4(TOPBP1)) to telomeres. Despite this, telomeres fail to accumulate the checkpoint mediator Crb2(53BP1) and, consequently, do not activate Chk1-dependent cell cycle arrest. Artificially recruiting Crb2(53BP1) to taz1D telomeres results in a full checkpoint response and cell cycle arrest. Stable association of Crb2(53BP1) to DNA double-strand breaks requires two independent histone modifications: H4 dimethylation at lysine 20 (H4K20me2) and H2A carboxy-terminal phosphorylation (gamma H2A)(3-5). Whereas cH2A can be readily detected, telomeres lack H4K20me2, in contrast to internal chromosome locations. Blocking checkpoint signal transduction at telomeres requires Pot1 and Ccq1, and loss of either Pot1 or Ccq1 from telomeres leads to Crb2(53BP1) foci formation, Chk1 activation and cell cycle arrest. Thus, telomeres constitute a chromatin-privileged region of the chromosomes that lack essential epigenetic markers for DNA damage response amplification and cell cycle arrest. Because the protein kinases ATM and ATR must associate with telomeres in each S phase to recruit telomerase(6), exclusion of Crb2(53BP1) has a critical role in preventing telomeres from triggering cell cycle arrest.
C1 [Carneiro, Tiago; Reis, Clara C.; Borges, Vanessa; Ferreira, Miguel Godinho] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal.
   [Khair, Lyne; Moser, Bettina A.; Nakamura, Toru M.] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
C3 Instituto Gulbenkian de Ciencia; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Ferreira, MG (corresponding author), Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal.
EM mgferreira@igc.gulbenkian.pt
FU NIH [GM078253]; FCT [PTDC/BIA-BCM/67261/2006]; Association for International Cancer Research [06-396]; Fundação para a Ciência e a Tecnologia [PTDC/BIA-BCM/67261/2006] Funding Source: FCT
NR 33
TC 50
Z9 67
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 SEP 9
PY 2010
VL 467
IS 7312
BP 228
EP U124
DI 10.1038/nature09353
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300039
PM 20829797
DA 2026-03-09
ER

PT J
AU Jewitt, D
   Weaver, H
   Agarwal, J
   Mutchler, M
   Drahus, M
AF Jewitt, David
   Weaver, Harold
   Agarwal, Jessica
   Mutchler, Max
   Drahus, Michal
TI A recent disruption of the main-belt asteroid P/2010 A2
SO NATURE
LA English
DT Article
ID debris disks; origin; dust
AB Most inner main-belt asteroids are primitive rock and metal bodies in orbit about the Sun between Mars and Jupiter. Disruption, through high-velocity collisions or rotational spin-up, is believed to be the primary mechanism for the production and destruction of small asteroids(1,2) and a contributor to dust in the Sun's zodiacal cloud(3), while analogous collisions around other stars feed dust to their debris disks(4). Unfortunately, direct evidence about the mechanism or rate of disruption is lacking, owing to the rarity of the events. Here we report observations of P/2010 A2, a previously unknown inner-belt asteroid with a peculiar, comet-like morphology. The data reveal a nucleus of diameter approximately 120 metres with an associated tail of millimetre-sized dust particles. We conclude that it is most probably the remnant of a recent asteroidal disruption in February/March 2009, evolving slowly under the action of solar radiation pressure, in agreement with independent work(5).
C1 [Jewitt, David; Drahus, Michal] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
   [Jewitt, David] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA.
   [Jewitt, David] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Weaver, Harold] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Agarwal, Jessica] European Space Agcy, European Space Res & Technol Ctr, NL-2200 AG Noordwijk, Netherlands.
   [Mutchler, Max] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; European Space Agency; European Space Research & Technology Centre; Space Telescope Science Institute
RP Jewitt, D (corresponding author), Univ Calif Los Angeles, Dept Earth & Space Sci, 3713 Geol Bldg,595 Charles Young Dr E, Los Angeles, CA 90095 USA.
EM jewitt@ucla.edu
NR 18
TC 119
Z9 128
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 14
PY 2010
VL 467
IS 7317
BP 817
EP 819
DI 10.1038/nature09456
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700061
PM 20944743
DA 2026-03-09
ER

PT J
AU Kagey, MH
   Newman, JJ
   Bilodeau, S
   Zhan, Y
   Orlando, DA
   van Berkum, NL
   Ebmeier, CC
   Goossens, J
   Rahl, PB
   Levine, SS
   Taatjes, DJ
   Dekker, J
   Young, RA
AF Kagey, Michael H.
   Newman, Jamie J.
   Bilodeau, Steve
   Zhan, Ye
   Orlando, David A.
   van Berkum, Nynke L.
   Ebmeier, Christopher C.
   Goossens, Jesse
   Rahl, Peter B.
   Levine, Stuart S.
   Taatjes, Dylan J.
   Dekker, Job
   Young, Richard A.
TI Mediator and cohesin connect gene expression and chromatin architecture
SO NATURE
LA English
DT Article
ID embryonic stem-cells; de-lange-syndrome; transcriptional regulatory circuitry; integration host factor; nipped-b; coactivator; activation; proteins; complex; med12
AB Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.
C1 [Kagey, Michael H.; Newman, Jamie J.; Bilodeau, Steve; Orlando, David A.; Rahl, Peter B.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Newman, Jamie J.; Levine, Stuart S.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Zhan, Ye; van Berkum, Nynke L.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA.
   [Zhan, Ye; van Berkum, Nynke L.; Dekker, Job] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Ebmeier, Christopher C.; Goossens, Jesse; Taatjes, Dylan J.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; University of Colorado System; University of Colorado Boulder
RP Young, RA (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM Dylan.Taatjes@Colorado.EDU; young@wi.mit.edu
FU NIH [HG003143, HG002668]; Canadian Institutes of Health Research; American Cancer Society; Keck Distinguished young scholar award; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER
NR 50
TC 1502
Z9 1897
U1 1
U2 194
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 430
EP 435
DI 10.1038/nature09380
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200036
PM 20720539
DA 2026-03-09
ER

PT J
AU Hayes, M
   Östlin, G
   Schaerer, D
   Mas-Hesse, JM
   Leitherer, C
   Atek, H
   Kunth, D
   Verhamme, A
   de Barros, S
   Melinder, J
AF Hayes, Matthew
   Ostlin, Goran
   Schaerer, Daniel
   Miguel Mas-Hesse, J.
   Leitherer, Claus
   Atek, Hakim
   Kunth, Daniel
   Verhamme, Anne
   de Barros, Stephane
   Melinder, Jens
TI Escape of about five per cent of Lyman-α photons from high-redshift star-forming galaxies
SO NATURE
LA English
DT Article
ID ly-alpha; emitting galaxy; emission; emitters; populations; evolution; field; z=3.1
AB The Lyman-alpha (Ly alpha) emission line is the primary observational signature of star-forming galaxies at the highest redshifts(1), and has enabled the compilation of large samples of galaxies with which to study cosmic evolution(2-5). The resonant nature of the line, however, means that Ly alpha photons scatter in the neutral interstellar medium of their host galaxies, and their sensitivity to absorption by interstellar dust may therefore be greatly enhanced. This implies that the Ly alpha luminosity may be significantly reduced, or even completely suppressed. Hitherto, no unbiased empirical test of the escaping fraction (f(esc)) of Ly alpha photons has been performed at high redshifts. Here we report that the average f(esc) from star-forming galaxies at redshift z=2.2 is just 5 per cent by performing a blind narrowband survey in Ly alpha and H alpha. This implies that numerous conclusions based on Ly alpha-selected samples will require upwards revision by an order of magnitude and we provide a benchmark for this revision. We demonstrate that almost 90 per cent of star-forming galaxies emit insufficient Ly alpha to be detected by standard selection criteria(2-5). Both samples show an anti-correlation of f(esc) with dust content, and we show that Ly alpha- and H alpha-selection recovers populations that differ substantially in dust content and f(esc).
C1 [Hayes, Matthew; Schaerer, Daniel; de Barros, Stephane] Univ Geneva, Astron Observ, CH-1290 Sauverny, Switzerland.
   [Ostlin, Goran; Melinder, Jens] Stockholm Univ, AlbaNova Univ Ctr, Dept Astron, Oskar Klein Ctr, S-10691 Stockholm, Sweden.
   [Schaerer, Daniel] Univ Toulouse, CNRS, Lab Astrophys Toulouse Tarbes, F-31400 Toulouse, France.
   [Miguel Mas-Hesse, J.] Ctr Astrobiol CSIC INTA, Madrid 28691, Spain.
   [Leitherer, Claus] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Atek, Hakim; Kunth, Daniel] IAP, F-75014 Paris, France.
   [Verhamme, Anne] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
C3 University of Geneva; Oskar Klein Centre; Stockholm University; Universite de Toulouse; Centre National de la Recherche Scientifique (CNRS); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Astrobiologia (INTA); Space Telescope Science Institute; University of Oxford
RP Hayes, M (corresponding author), Univ Geneva, Astron Observ, 51 Chemin Maillettes, CH-1290 Sauverny, Switzerland.
EM matthew.hayes@unige.ch
FU Swiss National Science Foundation; Knut and Alice Wallenberg foundation; Swedish research council; Spanish MICINN [CSD2006-00070, AYA2007-67965];  [081.A-0932]
NR 30
TC 158
Z9 174
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 MAR 25
PY 2010
VL 464
IS 7288
BP 562
EP 565
DI 10.1038/nature08881
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 574FL
UT WOS:000275974200041
PM 20336139
DA 2026-03-09
ER

PT J
AU Reyes, A
   Haynes, M
   Hanson, N
   Angly, FE
   Heath, AC
   Rohwer, F
   Gordon, JI
AF Reyes, Alejandro
   Haynes, Matthew
   Hanson, Nicole
   Angly, Florent E.
   Heath, Andrew C.
   Rohwer, Forest
   Gordon, Jeffrey I.
TI Viruses in the faecal microbiota of monozygotic twins and their mothers
SO NATURE
LA English
DT Article
ID genomic analysis; viral community; diversity; protein; gene; identification; software; prophage; tool
AB Viral diversity and life cycles are poorly understood in the human gut and other body habitats. Phages and their encoded functions may provide informative signatures of a human microbiota and of microbial community responses to various disturbances, and may indicate whether community health or dysfunction is manifest after apparent recovery from a disease or therapeutic intervention. Here we report sequencing of the viromes (metagenomes) of virus-like particles isolated from faecal samples collected from healthy adult female monozygotic twins and their mothers at three time points over a one-year period. We compared these data sets with data sets of sequenced bacterial 16S ribosomal RNA genes and total-faecal-community DNA. Co-twins and their mothers share a significantly greater degree of similarity in their faecal bacterial communities than do unrelated individuals. In contrast, viromes are unique to individuals regardless of their degree of genetic relatedness. Despite remarkable interpersonal variations in viromes and their encoded functions, intrapersonal diversity is very low, with >95% of virotypes retained over the period surveyed, and with viromes dominated by a few temperate phages that exhibit remarkable genetic stability. These results indicate that a predatory viral-microbial dynamic, manifest in a number of other characterized environmental ecosystems, is notably absent in the very distal intestine.
C1 [Reyes, Alejandro; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Haynes, Matthew; Hanson, Nicole; Angly, Florent E.; Rohwer, Forest] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Angly, Florent E.] Univ Queensland, Adv Water Management Ctr, Brisbane, Qld 4072, Australia.
   [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63108 USA.
C3 Washington University (WUSTL); California State University System; San Diego State University; University of Queensland; 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 NIH [DK78669]; Crohn's and Colitis Foundation of America; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; International Fulbright Science and Technology Program; Crohn&apos;s & Colitis Foundation; Action Medical Research [2158] Funding Source: researchfish
NR 50
TC 889
Z9 1069
U1 1
U2 174
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 334
EP U81
DI 10.1038/nature09199
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100041
PM 20631792
DA 2026-03-09
ER

PT J
AU Ricci-Vitiani, L
   Pallini, R
   Biffoni, M
   Todaro, M
   Invernici, G
   Cenci, T
   Maira, G
   Parati, EA
   Stassi, G
   Larocca, LM
   De Maria, R
AF Ricci-Vitiani, Lucia
   Pallini, Roberto
   Biffoni, Mauro
   Todaro, Matilde
   Invernici, Gloria
   Cenci, Tonia
   Maira, Giulio
   Parati, Eugenio Agostino
   Stassi, Giorgio
   Larocca, Luigi Maria
   De Maria, Ruggero
TI Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells
SO NATURE
LA English
DT Article
ID vasculogenic mimicry; in-vivo; cancer; identification; angiogenesis; resistance; mechanisms; melanoma; niche
AB Glioblastoma is a highly angiogenetic malignancy, the neoformed vessels of which are thought to arise by sprouting of pre-existing brain capillaries. The recent demonstration that a population of glioblastoma stem-like cells (GSCs) maintains glioblastomas(1,2) indicates that the progeny of these cells may not be confined to the neural lineage(3). Normal neural stem cells are able to differentiate into functional endothelial cells(4). The connection between neural stem cells and the endothelial compartment seems to be critical in glioblastoma, where cancer stem cells closely interact with the vascular niche and promote angiogenesis through the release of vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (refs 5-9). Here we show that a variable number (range 20-90%, mean 60.7%) of endothelial cells in glioblastoma carry the same genomic alteration as tumour cells, indicating that a significant portion of the vascular endothelium has a neoplastic origin. The vascular endothelium contained a subset of tumorigenic cells that produced highly vascularized anaplastic tumours with areas of vasculogenic mimicry in immunocompromised mice. In vitro culture of GSCs in endothelial conditions generated progeny with phenotypic and functional features of endothelial cells. Likewise, orthotopic or subcutaneous injection of GSCs in immunocompromised mice produced tumour xenografts, the vessels of which were primarily composed of human endothelial cells. Selective targeting of endothelial cells generated by GSCs in mouse xenografts resulted in tumour reduction and degeneration, indicating the functional relevance of the GSC-derived endothelial vessels. These findings describe a new mechanism for tumour vasculogenesis and may explain the presence of cancer-derived endothelial-like cells in several malignancies.
C1 [Ricci-Vitiani, Lucia; Biffoni, Mauro; De Maria, Ruggero] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy.
   [Pallini, Roberto; Maira, Giulio] Univ Cattolica Sacro Cuore, Dept Neurosurg, I-00168 Rome, Italy.
   [Todaro, Matilde; Stassi, Giorgio] Univ Palermo, Dept Surg & Oncol Sci, I-90127 Palermo, Italy.
   [Invernici, Gloria; Parati, Eugenio Agostino] Neurol Inst Carlo Besta, Fdn IRCCS, UO Cerebrovasc Dis Cellular Neurobiol Lab, I-20133 Milan, Italy.
   [Cenci, Tonia; Larocca, Luigi Maria] Univ Cattolica Sacro Cuore, Inst Pathol, I-00168 Rome, Italy.
   [Stassi, Giorgio] Carattere Sci Fdn Salvatore Maugeri, Ist Ricovero & Cura, I-27100 Pavia, Italy.
   [De Maria, Ruggero] Mediterranean Inst Oncol, I-95029 Catania, Italy.
C3 Istituto Superiore di Sanita (ISS); Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; University of Palermo; Fondazione IRCCS Istituto Neurologico Carlo Besta; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Mediterranean Institute of Oncology
RP De Maria, R (corresponding author), Ist Super Sanita, Dept Hematol Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy.
EM pallini@rm.unicatt.it; demaria@iss.it
FU Associazione Italiana per la Ricerca sul Cancro
NR 23
TC 1086
Z9 1252
U1 2
U2 207
PU NATURE PUBLISHING 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 9
PY 2010
VL 468
IS 7325
BP 824
EP U121
DI 10.1038/nature09557
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700046
PM 21102434
DA 2026-03-09
ER

PT J
AU Zhang, APP
   Pigli, YZ
   Rice, PA
AF Zhang, Adrianna P. P.
   Pigli, Ying Z.
   Rice, Phoebe A.
TI Structure of the LexA-DNA complex and implications for SOS box measurement
SO NATURE
LA English
DT Article
ID noncontacted bases; crystal-structure; operator complex; binding domain; repressor; protein; affinity; identification; rotation; contacts
AB The eubacterial SOS system is a paradigm of cellular DNA damage and repair, and its activation can contribute to antibiotic resistance(1-3). Under normal conditions, LexA represses the transcription of many DNA repair proteins by binding to SOS 'boxes' in their operators. Under genotoxic stress, accumulating complexes of RecA, ATP and single-stranded DNA (ssDNA) activate LexA for autocleavage. To address how LexA recognizes its binding sites, we determined three crystal structures of Escherichia coli LexA in complex with SOS boxes. Here we report the structure of these LexA-DNA complexes. The DNA-binding domains of the LexA dimer interact with the DNA in the classical fashion of a winged helix-turn-helix motif. However, the wings of these two DNA-binding domains bind to the same minor groove of the DNA. These wing-wing contacts may explain why the spacing between the two half-sites of E. coli SOS boxes is invariant.
C1 [Pigli, Ying Z.; Rice, Phoebe A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Zhang, Adrianna P. P.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Rice, PA (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
EM price@uchicago.edu
FU National Institutes of Health [GM058827]
NR 39
TC 91
Z9 113
U1 1
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 883
EP U119
DI 10.1038/nature09200
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100040
PM 20703307
DA 2026-03-09
ER

PT J
AU Kertesz, M
   Wan, Y
   Mazor, E
   Rinn, JL
   Nutter, RC
   Chang, HY
   Segal, E
AF Kertesz, Michael
   Wan, Yue
   Mazor, Elad
   Rinn, John L.
   Nutter, Robert C.
   Chang, Howard Y.
   Segal, Eran
TI Genome-wide measurement of RNA secondary structure in yeast
SO NATURE
LA English
DT Article
ID messenger-rna; saccharomyces-cerevisiae; translation; site; prediction; transport; elements
AB The structures of RNA molecules are often important for their function and regulation(1-6), yet there are no experimental techniques for genome-scale measurement of RNA structure. Here we describe a novel strategy termed parallel analysis of RNA structure (PARS), which is based on deep sequencing fragments of RNAs that were treated with structure-specific enzymes, thus providing simultaneous in vitro profiling of the secondary structure of thousands of RNA species at single nucleotide resolution. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. Analysis of these profiles reveals several RNA structural properties of yeast transcripts, including the existence of more secondary structure over coding regions compared with untranslated regions, a three-nucleotide periodicity of secondary structure across coding regions and an anti-correlation between the efficiency with which an mRNA is translated and the structure over its translation start site. PARS is readily applicable to other organisms and to profiling RNA structure in diverse conditions, thus enabling studies of the dynamics of secondary structure at a genomic scale.
C1 [Wan, Yue; Chang, Howard Y.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Kertesz, Michael; Mazor, Elad; Segal, Eran] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Rinn, John L.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
   [Rinn, John L.] MIT, Cambridge, MA 02142 USA.
   [Nutter, Robert C.] Life Technol, Foster City, CA 94404 USA.
   [Segal, Eran] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
C3 Howard Hughes Medical Institute; Stanford University; Weizmann Institute of Science; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Thermo Fisher Scientific; Weizmann Institute of Science
RP Chang, HY (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Program Epithelial Biol, Stanford, CA 94305 USA.
EM howchang@stanford.edu; eran@weizmann.ac.il
FU National Institutes of Health [RO1HG004361]; Agency of Science, Technology and Research of Singapore
NR 20
TC 597
Z9 764
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 SEP 2
PY 2010
VL 467
IS 7311
BP 103
EP 107
DI 10.1038/nature09322
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200044
PM 20811459
DA 2026-03-09
ER

PT J
AU Nascimbène, S
   Navon, N
   Jiang, KJ
   Chevy, F
   Salomon, C
AF Nascimbene, S.
   Navon, N.
   Jiang, K. J.
   Chevy, F.
   Salomon, C.
TI Exploring the thermodynamics of a universal Fermi gas
SO NATURE
LA English
DT Article
ID phase-diagram
AB One of the greatest challenges in modern physics is to understand the behaviour of an ensemble of strongly interacting particles. A class of quantum many-body systems (such as neutron star matter and cold Fermi gases) share the same universal thermodynamic properties when interactions reach the maximum effective value allowed by quantum mechanics, the so-called unitary limit(1,2). This makes it possible in principle to simulate some astrophysical phenomena inside the highly controlled environment of an atomic physics laboratory. Previous work on the thermodynamics of a two-component Fermi gas led to thermodynamic quantities averaged over the trap(3-5), making comparisons with many-body theories developed for uniform gases difficult. Here we develop a general experimental method that yields the equation of state of a uniform gas, as well as enabling a detailed comparison with existing theories(6-15). The precision of our equation of state leads to new physical insights into the unitary gas. For the unpolarized gas, we show that the low-temperature thermodynamics of the strongly interacting normal phase is well described by Fermi liquid theory, and we localize the superfluid transition. For a spin-polarized system(16-18), our equation of state at zero temperature has a 2 per cent accuracy and extends work(19,20) on the phase diagram to a new regime of precision. We show in particular that, despite strong interactions, the normal phase behaves as a mixture of two ideal gases: a Fermi gas of bare majority atoms and a non-interacting gas of dressed quasi-particles, the fermionic polarons(10,18,20-22).
C1 [Nascimbene, S.; Navon, N.; Jiang, K. J.; Chevy, F.; Salomon, C.] UPMC, CNRS, Lab Kastler Brossel, Ecole Normale Super, F-75231 Paris, France.
C3 Universite PSL; College de France; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite
RP Nascimbène, S (corresponding author), UPMC, CNRS, Lab Kastler Brossel, Ecole Normale Super, 24 Rue Lhomond, F-75231 Paris, France.
EM sylvain.nascimbene@ens.fr
FU ESF (Euroquam); SCALA; ANR FABIOLA; Region Ile de France (IFRAF); ERC; Institut Universitaire de France
NR 34
TC 452
Z9 505
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 FEB 25
PY 2010
VL 463
IS 7284
BP 1057
EP U73
DI 10.1038/nature08814
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400031
PM 20182507
DA 2026-03-09
ER

PT J
AU Weber, TS
   Deutsch, C
AF Weber, Thomas S.
   Deutsch, Curtis
TI Ocean nutrient ratios governed by plankton biogeography
SO NATURE
LA English
DT Article
ID antarctic circumpolar current; glacial southern-ocean; elemental stoichiometry; marine-phytoplankton; community structure; nitrogen-fixation; pacific-ocean; co2; denitrification; phosphorus
AB The major nutrients nitrate and phosphate have one of the strongest correlations in the sea, with a slope similar to the average nitrogen (N) to phosphorus (P) content of plankton biomass (N/P = 16:1). The processes through which this global relationship emerges despite the wide range of N/P ratios at the organism level are not known. Here we use an ocean circulation model and observed nutrient distributions to show that the N/P ratio of biological nutrient removal varies across latitude in Southern Ocean surface waters, from 12: 1 in the polar ocean to 20: 1 in the sub-Antarctic zone. These variations are governed by regional differences in the species composition of the plankton community. The covariation of dissolved nitrate and phosphate is maintained by ocean circulation, which mixes the shallow subsurface nutrients between distinct biogeographic provinces. Climate-driven shifts in these marine biomes may alter the mean N/P ratio and the associated carbon export by Southern Ocean ecosystems.
C1 [Weber, Thomas S.; Deutsch, Curtis] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles
RP Weber, TS (corresponding author), Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
EM tweber@atmos.ucla.edu
FU National Science Foundation; Gordon and Betty Moore Foundation; UCLA; Directorate For Geosciences [0851483] Funding Source: National Science Foundation; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0747533] Funding Source: National Science Foundation; Division Of Ocean Sciences [0851483] Funding Source: National Science Foundation
NR 35
TC 232
Z9 274
U1 3
U2 199
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 550
EP 554
DI 10.1038/nature09403
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100030
PM 20882009
DA 2026-03-09
ER

PT J
AU Méndez-Ferrer, S
   Michurina, TV
   Ferraro, F
   Mazloom, AR
   MacArthur, BD
   Lira, SA
   Scadden, DT
   Ma'ayan, A
   Enikolopov, GN
   Frenette, PS
AF Mendez-Ferrer, Simon
   Michurina, Tatyana V.
   Ferraro, Francesca
   Mazloom, Amin R.
   MacArthur, Ben D.
   Lira, Sergio A.
   Scadden, David T.
   Ma'ayan, Avi
   Enikolopov, Grigori N.
   Frenette, Paul S.
TI Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
SO NATURE
LA English
DT Article
ID progenitor cells; self-renewal; neural stem; expression; differentiation; osteopontin; osteoblasts; cooperation; receptors; component
AB The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta 3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.
C1 [Mendez-Ferrer, Simon; Lira, Sergio A.; Frenette, Paul S.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
   [Mendez-Ferrer, Simon; Frenette, Paul S.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA.
   [Michurina, Tatyana V.; Enikolopov, Grigori N.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Ferraro, Francesca; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Mazloom, Amin R.; MacArthur, Ben D.; Ma'ayan, Avi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [Frenette, Paul S.] Yeshiva Univ Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Cold Spring Harbor Laboratory; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Icahn School of Medicine at Mount Sinai; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Frenette, PS (corresponding author), Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
EM simon.mendez-ferrer@cnic.es; paul.frenette@einstein.yu.edu
FU National Institutes of Health [DK056638, HL69438, HL097819]; Department of Defence [PC060271]; National Institute of Mental Health; Ira Hazan Fund; American Society of Hematology; National Heart Lung and Blood Institute [R01HL069438] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK056638] Funding Source: NIH RePORTER
NR 43
TC 2694
Z9 3127
U1 9
U2 422
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 829
EP U59
DI 10.1038/nature09262
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100028
PM 20703299
DA 2026-03-09
ER

PT J
AU Vamivakas, AN
   Lu, CY
   Matthiesen, C
   Zhao, Y
   Fält, S
   Badolato, A
   Atatüre, M
AF Vamivakas, A. N.
   Lu, C. -Y.
   Matthiesen, C.
   Zhao, Y.
   Falt, S.
   Badolato, A.
   Atatuere, M.
TI Observation of spin-dependent quantum jumps via quantum dot resonance fluorescence
SO NATURE
LA English
DT Article
ID single-electron spin; manipulation; dynamics
AB Reliable preparation, manipulation and measurement protocols are necessary to exploit a physical system as a quantum bit(1). Spins in optically active quantum dots offer one potential realization(2,3) and recent demonstrations have shown high-fidelity preparation(4,5) and ultrafast coherent manipulation(6-8). The final challenge-that is, single-shot measurement of the electron spin-has proved to be the most difficult of the three and so far only time-averaged optical measurements have been reported(9-12). The main obstacle to optical spin readout in single quantum dots is that the same laser that probes the spin state also flips the spin being measured. Here, by using a gate-controlled quantum dot molecule(13-15), we present the ability to measure the spin state of a single electron in real time via the intermittency of quantum dot resonance fluorescence(12,16). The quantum dot molecule, unlike its single quantum dot counterpart, allows separate and independent optical transitions for state preparation, manipulation and measurement, avoiding the dilemma of relying on the same transition to address the spin state of an electron.
C1 [Vamivakas, A. N.; Lu, C. -Y.; Matthiesen, C.; Zhao, Y.; Atatuere, M.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Lu, C. -Y.] Univ Sci & Technol China, Dept Modern Phys, Hefei 230026, Peoples R China.
   [Lu, C. -Y.] Univ Sci & Technol China, HFNL, Hefei 230026, Peoples R China.
   [Zhao, Y.] Heidelberg Univ, Inst Phys, D-69120 Heidelberg, Germany.
   [Falt, S.] Sol Volta AB, S-22370 Lund, Sweden.
   [Badolato, A.] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA.
C3 University of Cambridge; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Ruprecht Karls University Heidelberg; University of Rochester
RP Atatüre, M (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM anv21@cam.ac.uk; ma424@cam.ac.uk
FU University of Cambridge; EPSRC [EP/G000883/1]; QIPIRC; A. v. Humboldt Foundation; LGFG; Engineering and Physical Sciences Research Council [EP/G000883/1] Funding Source: researchfish; EPSRC [EP/G000883/1] Funding Source: UKRI
NR 32
TC 131
Z9 145
U1 2
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 297
EP 300
DI 10.1038/nature09359
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900032
PM 20844531
DA 2026-03-09
ER

PT J
AU Javaux, EJ
   Marshall, CP
   Bekker, A
AF Javaux, Emmanuelle J.
   Marshall, Craig P.
   Bekker, Andrey
TI Organic-walled microfossils in 3.2-billion-year-old shallow-marine siliciclastic deposits
SO NATURE
LA English
DT Article
ID barberton greenstone-belt; ga moodies group; south-africa; fossil evidence; pilbara craton; microbial mats; mountain land; onverwacht; cherts; carbon
AB Although the notion of an early origin and diversification of life on Earth during the Archaean eon has received increasing support in geochemical, sedimentological and palaeontological evidence, ambiguities and controversies persist regarding the biogenicity and syngeneity of the record older than Late Archaean(1-3). Non-biological processes are known to produce morphologies similar to some microfossils(4,5), and hydrothermal fluids have the potential to produce abiotic organic compounds with depleted carbon isotope values(6), making it difficult to establish unambiguous traces of life. Here we report the discovery of a population of large (up to about 300 mu m in diameter) carbonaceous spheroidal microstructures in Mesoarchaean shales and siltstones of the Moodies Group, South Africa, the Earth's oldest siliciclastic alluvial to tidal-estuarine deposits(7). These microstructures are interpreted as organic-walled microfossils on the basis of petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as a lack of abiotic explanation falsifying a biological origin. These are the oldest and largest Archaean organic-walled spheroidal microfossils reported so far. Our observations suggest that relatively large microorganisms cohabited with earlier reported benthic microbial mats(8) in the photic zone of marginal marine siliciclastic environments 3.2 billion years ago.
C1 [Javaux, Emmanuelle J.] Univ Liege, Dept Geol, B-4000 Liege, Belgium.
   [Marshall, Craig P.] Univ Kansas, Dept Geol, Lawrence, KS 66044 USA.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
C3 University of Liege; University of Kansas; University of Manitoba
RP Javaux, EJ (corresponding author), Univ Liege, Dept Geol, 17 Allee 6 Aout B18, B-4000 Liege, Belgium.
EM ej.javaux@ulg.ac.be
FU University of Liege Impulsion [CFRA0805]; University of Liege [RCFRA0036-J]; National Science Foundation [EAR-937 05-45484]; NASA Astrobiology Institute [NNA04CC09A]; Natural Sciences and Engineering Research Council of Canada; Australian Research Council
NR 31
TC 216
Z9 246
U1 1
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 934
EP U108
DI 10.1038/nature08793
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700043
PM 20139963
DA 2026-03-09
ER

PT J
AU Horiuchi, S
   Tokunaga, Y
   Giovannetti, G
   Picozzi, S
   Itoh, H
   Shimano, R
   Kumai, R
   Tokura, Y
AF Horiuchi, Sachio
   Tokunaga, Yusuke
   Giovannetti, Gianluca
   Picozzi, Silvia
   Itoh, Hirotake
   Shimano, Ryo
   Kumai, Reiji
   Tokura, Yoshinori
TI Above-room-temperature ferroelectricity in a single-component molecular crystal
SO NATURE
LA English
DT Article
ID croconic acid; polarization
AB Ferroelectrics are electro-active materials that can store and switch their polarity (ferroelectricity), sense temperature changes (pyroelectricity), interchange electric and mechanical functions (piezoelectricity), and manipulate light (through optical nonlinearities and the electro-optic effect): all of these functions have practical applications. Topological switching of pi-conjugation in organic molecules, such as the keto-enol transformation, has long been anticipated as a means of realizing these phenomena in molecular assemblies and crystals(1). Croconic acid, an ingredient of black dyes(2), was recently found to have a hydrogen-bonded polar structure in a crystalline state(3). Here we demonstrate that application of an electric field can coherently align the molecular polarities in crystalline croconic acid, as indicated by an increase of optical second harmonic generation, and produce a well-defined polarization hysteresis at room temperature. To make this simple pentagonal molecule ferroelectric, we switched the pi-bond topology using synchronized proton transfer instead of rigid-body rotation. Of the organic ferroelectrics, this molecular crystal exhibits the highest spontaneous polarization (similar to 20 mu C cm(-2)) in spite of its small molecular size, which is in accord with first-principles electronic-structure calculations. Such high polarization, which persists up to 400 K, may find application in active capacitor and nonlinear optics elements in future organic electronics.
C1 [Horiuchi, Sachio; Kumai, Reiji; Tokura, Yoshinori] Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058562, Japan.
   [Tokunaga, Yusuke; Itoh, Hirotake; Shimano, Ryo; Tokura, Yoshinori] Japan Sci & Technol Agcy, ERATO, Multiferro Project, Wako, Saitama 3510198, Japan.
   [Giovannetti, Gianluca; Picozzi, Silvia] CNR, INFM, CASTI Reg Lab, I-67100 Laquila, Italy.
   [Shimano, Ryo] Univ Tokyo, Dept Phys, Tokyo 1138656, Japan.
   [Giovannetti, Gianluca] Leiden Univ, Inst Lorenz Theoret Phys, NL-2300 RA Leiden, Netherlands.
   [Tokura, Yoshinori] Univ Tokyo, Dept Appl Phys, Tokyo 1138656, Japan.
C3 National Institute of Advanced Industrial Science & Technology (AIST); Japan Science & Technology Agency (JST); Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale per la Fisica della Materia (INFM-CNR); University of Tokyo; Leiden University - Excl LUMC; Leiden University; University of Tokyo
RP Horiuchi, S (corresponding author), Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058562, Japan.
EM s-horiuchi@aist.go.jp; tokura@ap.t.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [20110003]; European Research Council under the European Community [203523]
NR 29
TC 693
Z9 741
U1 8
U2 559
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 789
EP U97
DI 10.1038/nature08731
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300035
PM 20148035
DA 2026-03-09
ER

PT J
AU Sawamiphak, S
   Seidel, S
   Essmann, CL
   Wilkinson, GA
   Pitulescu, ME
   Acker, T
   Acker-Palmer, A
AF Sawamiphak, Suphansa
   Seidel, Sascha
   Essmann, Clara L.
   Wilkinson, George A.
   Pitulescu, Mara E.
   Acker, Till
   Acker-Palmer, Amparo
TI Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis
SO NATURE
LA English
DT Article
ID vascular morphogenesis; receptors; guidance; phosphorylation; astrocytes; ptp
AB The formation and guidance of specialized endothelial tip cells is essential for both developmental and pathological angiogenesis(1). Notch-1 signalling regulates the generation of tip cells, which respond to gradients of vascular endothelial growth factor (VEGF-A)(2). The molecular cues and signalling pathways that control the guidance of tip cells are poorly understood. Bidirectional signalling by Eph receptors and ephrin ligands represents one of the most important guidance cues involved in axon path finding(3). Here we show that ephrin-B2 reverse signalling involving PDZ interactions regulates endothelial tip cell guidance to control angiogenic sprouting and branching in physiological and pathological angiogenesis. In vivo, ephrin-B2 PDZ-signalling-deficient mice (ephrin-B2DV) exhibit a reduced number of tip cells with fewer filopodial extensions at the vascular front in the mouse retina. In pathological settings, impaired PDZ signalling decreases tumour vascularization and growth. Mechanistically, we show that ephrin-B2 controls VEGF receptor (VEGFR)-2 internalization and signalling. Importantly, internalization of VEGFR2 is necessary for activation and downstream signalling of the receptor and is required for VEGF-induced tip cell filopodial extension. Together, our results suggest that ephrin-B2 at the tip cell filopodia regulates the proper spatial activation of VEGFR2 endocytosis and signalling to direct filopodial extension. Blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis.
C1 [Sawamiphak, Suphansa; Essmann, Clara L.; Acker-Palmer, Amparo] Goethe Univ Frankfurt, Frankfurt Inst Mol Life Sci, D-60438 Frankfurt, Germany.
   [Sawamiphak, Suphansa; Essmann, Clara L.; Acker-Palmer, Amparo] Goethe Univ Frankfurt, Inst Cell Biol & Neurosci, D-60438 Frankfurt, Germany.
   [Seidel, Sascha; Acker, Till] Univ Giessen, Inst Neuropathol, D-35392 Giessen, Germany.
   [Wilkinson, George A.] Med Coll Wisconsin, Dev Vasc Biol Program, Milwaukee, WI 53226 USA.
   [Pitulescu, Mara E.] Univ Munster, Fac Med, D-48149 Munster, Germany.
   [Pitulescu, Mara E.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
C3 Goethe University Frankfurt; Goethe University Frankfurt; Justus Liebig University Giessen; Medical College of Wisconsin; University of Munster; Max Planck Society
RP Acker-Palmer, A (corresponding author), Goethe Univ Frankfurt, Frankfurt Inst Mol Life Sci, Max von Laue Str 9, D-60438 Frankfurt, Germany.
EM Acker-Palmer@bio.uni-frankfurt.de
FU Deutsche Forschungsgemeinschaft [AC110/3-1, 3-2, AC180/3-1, 3-2]; Deutsche Krebshilfe [107231]; Clusters of Excellence 'Macromolecular Complexes (CEF)' at University Frankfurt [EXC 115]; 'Cardio-Pulmonary System (ECCPS)' at the Universities of Giessen and Frankfurt [EXC 147]
NR 32
TC 441
Z9 533
U1 1
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 487
EP U115
DI 10.1038/nature08995
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700037
PM 20445540
DA 2026-03-09
ER

PT J
AU Sheard, LB
   Tan, X
   Mao, HB
   Withers, J
   Ben-Nissan, G
   Hinds, TR
   Kobayashi, Y
   Hsu, FF
   Sharon, M
   Browse, J
   He, SY
   Rizo, J
   Howe, GA
   Zheng, N
AF Sheard, Laura B.
   Tan, Xu
   Mao, Haibin
   Withers, John
   Ben-Nissan, Gili
   Hinds, Thomas R.
   Kobayashi, Yuichi
   Hsu, Fong-Fu
   Sharon, Michal
   Browse, John
   He, Sheng Yang
   Rizo, Josep
   Howe, Gregg A.
   Zheng, Ning
TI Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor
SO NATURE
LA English
DT Article
ID box protein tir1; regulated defense; isoleucine; receptor; coronatine; mechanism; acid; recognition; repression; software
AB Jasmonates are a family of plant hormones that regulate plant growth, development and responses to stress. The F-box protein CORONATINE INSENSITIVE 1 (COI1) mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JAZ proteins. Despite its importance, the mechanism of jasmonate perception remains unclear. Here we present structural and pharmacological data to show that the true Arabidopsis jasmonate receptor is a complex of both COI1 and JAZ. COI1 contains an open pocket that recognizes the bioactive hormone (3R, 7S)-jasmonoyl-L-isoleucine (JA-Ile) with high specificity. High-affinity hormone binding requires a bipartite JAZ degron sequence consisting of a conserved a-helix for COI1 docking and a loop region to trap the hormone in its binding pocket. In addition, we identify a third critical component of the jasmonate co-receptor complex, inositol pentakisphosphate, which interacts with both COI1 and JAZ adjacent to the ligand. Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs.
C1 [Sheard, Laura B.; Tan, Xu; Mao, Haibin; Hinds, Thomas R.; Zheng, Ning] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Withers, John; He, Sheng Yang; Howe, Gregg A.] Michigan State Univ, Dept Energy, Plant Res Lab, E Lansing, MI 48824 USA.
   [Withers, John; He, Sheng Yang] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.
   [Ben-Nissan, Gili; Sharon, Michal] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Kobayashi, Yuichi] Tokyo Inst Technol, Dept Biol Engn, Midori Ku, Yokohama, Kanagawa 2268501, Japan.
   [Hsu, Fong-Fu] Washington Univ, Sch Med, Dept Internal Med, Div Endocrinol Diabet Metab & Lipid Res, St Louis, MO 63110 USA.
   [Browse, John] Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA.
   [Rizo, Josep] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Howe, Gregg A.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA.
   [Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Michigan State University; Michigan State University; Weizmann Institute of Science; Institute of Science Tokyo; Tokyo Institute of Technology; Washington University (WUSTL); Washington State University; University of Texas System; University of Texas Southwestern Medical Center; Michigan State University; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
RP Zheng, N (corresponding author), Univ Washington, Dept Pharmacol, Box 357280, Seattle, WA 98195 USA.
EM nzheng@u.washington.edu
FU Howard Hughes Medical Institute; National Institutes of Health [R01 CA107134, T32 GM07270, R01GM57795, R01AI068718]; National Science Foundation [0929100]; US Department of Energy [DE-FG02-99ER20323, DE-FG02-91ER20021]; Michigan State University; Welch Foundation [I-1304]; European Research Council (ERC) under the European Community [239679]; U.S. Department of Energy (DOE) [DE-FG02-99ER20323] Funding Source: U.S. Department of Energy (DOE); National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056341] Funding Source: NIH RePORTER; European Research Council (ERC) [239679] Funding Source: European Research Council (ERC)
NR 38
TC 1198
Z9 1400
U1 8
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 NOV 18
PY 2010
VL 468
IS 7322
BP 400
EP U301
DI 10.1038/nature09430
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100035
PM 20927106
DA 2026-03-09
ER

PT J
AU Lopez-Mosqueda, J
   Maas, NL
   Jonsson, ZO
   DeFazio-Eli, LG
   Wohlschlegel, J
   Toczyski, DP
AF Lopez-Mosqueda, Jaime
   Maas, Nancy L.
   Jonsson, Zophonias O.
   DeFazio-Eli, Lisa G.
   Wohlschlegel, James
   Toczyski, David P.
TI Damage-induced phosphorylation of Sld3 is important to block late origin firing
SO NATURE
LA English
DT Article
ID protein identification technology; s-phase checkpoint; dna-replication; saccharomyces-cerevisiae; shotgun proteomics; budding yeast; mec1 kinase; complex; initiation; cdc7-dbf4
AB Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis(1-3) after gamma-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage(4). This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans)(5,6). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival.
C1 [Lopez-Mosqueda, Jaime; Maas, Nancy L.; DeFazio-Eli, Lisa G.; Toczyski, David P.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Jonsson, Zophonias O.; Wohlschlegel, James] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California Los Angeles
RP Toczyski, DP (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM toczyski@cc.ucsf.edu
FU Ford Foundation; National Institutes of Health [GM059691]; National Institute of General Medical Sciences [R01GM089778] Funding Source: NIH RePORTER
NR 39
TC 152
Z9 192
U1 0
U2 10
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 479
EP U133
DI 10.1038/nature09377
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200047
PM 20865002
DA 2026-03-09
ER

PT J
AU Bengtson, MH
   Joazeiro, CAP
AF Bengtson, Mario H.
   Joazeiro, Claudio A. P.
TI Role of a ribosome-associated E3 ubiquitin ligase in protein quality control
SO NATURE
LA English
DT Article
ID messenger-rna surveillance; yeast; translation; identification; proteasome; antibiotics; degradation; expression; mechanism; reveals
AB Messenger RNA lacking stop codons ('non-stop mRNA') can arise from errors in gene expression, and encode aberrant proteins whose accumulation could be deleterious to cellular function(1,2). In bacteria, these 'non-stop proteins' become co-translationally tagged with a peptide encoded by ssrA/tmRNA (transfer-messenger RNA), which signals their degradation by energy-dependent proteases(1,3). How eukaryotic cells eliminate non-stop proteins has remained unknown. Here we show that the Saccharomyces cerevisiae Ltn1 RING-domain-type E3 ubiquitin ligase acts in the quality control of non-stop proteins, in a process that is mechanistically distinct but conceptually analogous to that performed by ssrA: Ltn1 is predominantly associated with ribosomes, and it marks nascent non-stop proteins with ubiquitin to signal their proteasomal degradation. Ltn1-mediated ubiquitylation of non-stop proteins seems to be triggered by their stalling in ribosomes on translation through the poly(A) tail. The biological relevance of this process is underscored by the finding that loss of Ltn1 function confers sensitivity to stress caused by increased non-stop protein production. We speculate that defective protein quality control may underlie the neurodegenerative phenotype that results from mutation of the mouse Ltn1 homologue Listerin.
C1 [Bengtson, Mario H.; Joazeiro, Claudio A. P.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Joazeiro, CAP (corresponding author), Scripps Res Inst, Dept Cell Biol, CB168,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM joazeiro@scripps.edu
FU American Cancer Society [08-298-01-TBE]; National Institute of General Medical Sciences [R01GM083060]
NR 23
TC 393
Z9 472
U1 1
U2 60
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 470
EP 473
DI 10.1038/nature09371
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200045
PM 20835226
DA 2026-03-09
ER

PT J
AU Pironio, S
   Acín, A
   Massar, S
   de la Giroday, AB
   Matsukevich, DN
   Maunz, P
   Olmschenk, S
   Hayes, D
   Luo, L
   Manning, TA
   Monroe, C
AF Pironio, S.
   Acin, A.
   Massar, S.
   de la Giroday, A. Boyer
   Matsukevich, D. N.
   Maunz, P.
   Olmschenk, S.
   Hayes, D.
   Luo, L.
   Manning, T. A.
   Monroe, C.
TI Random numbers certified by Bell's theorem
SO NATURE
LA English
DT Article
AB Randomness is a fundamental feature of nature and a valuable resource for applications ranging from cryptography and gambling to numerical simulation of physical and biological systems. Random numbers, however, are difficult to characterize mathematically(1), and their generation must rely on an unpredictable physical process(2-6). Inaccuracies in the theoretical modelling of such processes or failures of the devices, possibly due to adversarial attacks, limit the reliability of random number generators in ways that are difficult to control and detect. Here, inspired by earlier work on non-locality-based(7-9) and device-independent(10-14) quantum information processing, we show that the non-local correlations of entangled quantum particles can be used to certify the presence of genuine randomness. It is thereby possible to design a cryptographically secure random number generator that does not require any assumption about the internal working of the device. Such a strong form of randomness generation is impossible classically and possible in quantum systems only if certified by a Bell inequality violation(15). We carry out a proof-of-concept demonstration of this proposal in a system of two entangled atoms separated by approximately one metre. The observed Bell inequality violation, featuring near perfect detection efficiency, guarantees that 42 new random numbers are generated with 99 per cent confidence. Our results lay the groundwork for future device-independent quantum information experiments and for addressing fundamental issues raised by the intrinsic randomness of quantum theory.
C1 [Acin, A.] ICREA, Barcelona 08010, Spain.
   [Acin, A.] ICFO, Barcelona 08860, Spain.
   [Pironio, S.; Massar, S.] Univ Libre Bruxelles, Lab Informat Quant, B-1050 Brussels, Belgium.
   [Pironio, S.] Univ Geneva, Appl Phys Grp, CH-1211 Geneva, Switzerland.
   [de la Giroday, A. Boyer] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Matsukevich, D. N.; Maunz, P.; Olmschenk, S.; Hayes, D.; Luo, L.; Manning, T. A.; Monroe, C.] Univ Maryland, Dept Phys, Joint Quantum Inst, College Pk, MD 20742 USA.
   [Matsukevich, D. N.; Maunz, P.; Olmschenk, S.; Hayes, D.; Luo, L.; Manning, T. A.; Monroe, C.] NIST, College Pk, MD 20742 USA.
C3 ICREA; Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); Universite Libre de Bruxelles; University of Geneva; University of Cambridge; University System of Maryland; University of Maryland College Park; National Institute of Standards & Technology (NIST) - USA
RP Acín, A (corresponding author), ICFO, Mediterranean Technol Pk, Barcelona 08860, Spain.
EM antonio.acin@icfo.es
FU Swiss NCCR Quantum Photonics; European ERC-AG QORE; European projects QAP and COM-PAS; Spanish MEC [FIS2007-60182]; Consolider-Ingenio QOIT projects; Generalitat de Catalunya; Caixa Manresa; Fundacio Cellex Barcelona; Interuniversity Attraction Poles Photonics@ be Programme (Belgian Science Policy); Brussels-Capital Region; BB2B Grant; US Army Research Office; IARPA; National Science Foundation (NSF), Physics Frontier Center; ICREA Funding Source: Custom
NR 29
TC 1141
Z9 1208
U1 3
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1021
EP 1024
DI 10.1038/nature09008
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000034
PM 20393558
DA 2026-03-09
ER

PT J
AU Fellay, J
   Thompson, AJ
   Ge, DL
   Gumbs, CE
   Urban, TJ
   Shianna, KV
   Little, LD
   Qiu, P
   Bertelsen, AH
   Watson, M
   Warner, A
   Muir, AJ
   Brass, C
   Albrecht, J
   Sulkowski, M
   McHutchison, JG
   Goldstein, DB
AF Fellay, Jacques
   Thompson, Alexander J.
   Ge, Dongliang
   Gumbs, Curtis E.
   Urban, Thomas J.
   Shianna, Kevin V.
   Little, Latasha D.
   Qiu, Ping
   Bertelsen, Arthur H.
   Watson, Mark
   Warner, Amelia
   Muir, Andrew J.
   Brass, Clifford
   Albrecht, Janice
   Sulkowski, Mark
   McHutchison, John G.
   Goldstein, David B.
TI ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C
SO NATURE
LA English
DT Article
ID triphosphate pyrophosphohydrolase deficiency; nonspherocytic hemolytic-anemia; whole-genome association; inosine triphosphatase; hexokinase deficiency; missense mutation; population; phenotype; ribavirin
AB Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality(1). The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects(2). One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV.
C1 [Fellay, Jacques; Ge, Dongliang; Gumbs, Curtis E.; Urban, Thomas J.; Shianna, Kevin V.; Little, Latasha D.; Goldstein, David B.] Duke Univ, Ctr Human Genome Variat, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Thompson, Alexander J.; Muir, Andrew J.; McHutchison, John G.] Duke Univ, Div Gastroenterol, Sch Med, Div Gastroenterol, Durham, NC 27705 USA.
   [Thompson, Alexander J.; Muir, Andrew J.; McHutchison, John G.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA.
   [Qiu, Ping; Bertelsen, Arthur H.; Watson, Mark; Warner, Amelia; Brass, Clifford; Albrecht, Janice] Schering Plough Res Inst, Kenilworth, NJ 07033 USA.
   [Sulkowski, Mark] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
C3 Duke University; Duke University; Duke University; Merck & Company; Schering-Plough Research Institute; Johns Hopkins University
RP Goldstein, DB (corresponding author), Duke Univ, Ctr Human Genome Variat, Inst Genome Sci & Policy, Durham, NC 27708 USA.
EM mchut001@mc.duke.edu; d.goldstein@duke.edu
FU Schering-Plough Research Institute, Kenilworth, New Jersey; National Health and Medical Research Council of Australia; Gastroenterological Society of Australia
NR 27
TC 387
Z9 416
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 18
PY 2010
VL 464
IS 7287
BP 405
EP 408
DI 10.1038/nature08825
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100045
PM 20173735
DA 2026-03-09
ER

PT J
AU Yachida, S
   Jones, S
   Bozic, I
   Antal, T
   Leary, R
   Fu, BJ
   Kamiyama, M
   Hruban, RH
   Eshleman, JR
   Nowak, MA
   Velculescu, VE
   Kinzler, KW
   Vogelstein, B
   Iacobuzio-Donahue, CA
AF Yachida, Shinichi
   Jones, Sian
   Bozic, Ivana
   Antal, Tibor
   Leary, Rebecca
   Fu, Baojin
   Kamiyama, Mihoko
   Hruban, Ralph H.
   Eshleman, James R.
   Nowak, Martin A.
   Velculescu, Victor E.
   Kinzler, Kenneth W.
   Vogelstein, Bert
   Iacobuzio-Donahue, Christine A.
TI Distant metastasis occurs late during the genetic evolution of pancreatic cancer
SO NATURE
LA English
DT Article
ID carcinoma; genome; tumors; model
AB Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated(1,2), is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy(3). Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.
C1 [Yachida, Shinichi; Fu, Baojin; Kamiyama, Mihoko; Hruban, Ralph H.; Eshleman, James R.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA.
   [Jones, Sian; Leary, Rebecca; Velculescu, Victor E.; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
   [Jones, Sian; Leary, Rebecca; Velculescu, Victor E.; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA.
   [Bozic, Ivana; Antal, Tibor; Nowak, Martin A.] Harvard Univ, Dept Organism & Evolutionary Biol, Dept Math, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Antal, Tibor] Univ Edinburgh, Sch Math, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Oncol, Baltimore, MD 21231 USA.
   [Iacobuzio-Donahue, Christine A.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21231 USA.
C3 Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Howard Hughes Medical Institute; Johns Hopkins University; Johns Hopkins Medicine; Harvard University; University of Edinburgh; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine
RP Iacobuzio-Donahue, CA (corresponding author), Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA.
EM ciacobu@jhmi.edu
FU National Institutes of Health [CA106610, CA62924, CA43460, CA57345, CA121113, GM078986]; Bill and Melinda Gates Foundation [37874]; Uehara Memorial Foundation; AACR-Barletta Foundation; John Templeton Foundation; Sol Goldman Pancreatic Cancer Research Center; Michael Rolfe Pancreatic Cancer Foundation; George Rubis Endowment for Pancreatic Cancer Research; Joseph C. Monastra Foundation for Pancreatic Cancer Research; Alfredo Scatena Memorial Fund; Virginia and the D. K. Ludwig Fund for Cancer Research; The Joint Programin Mathematical Biology and J. Epstein; National Cancer Institute [R01CA121113, P50CA062924] Funding Source: NIH RePORTER
NR 21
TC 2004
Z9 2414
U1 0
U2 268
PU 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 28
PY 2010
VL 467
IS 7319
BP 1114
EP U126
DI 10.1038/nature09515
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600049
PM 20981102
DA 2026-03-09
ER

PT J
AU Olszewski, KL
   Mather, MW
   Morrisey, JM
   Garcia, BA
   Vaidya, AB
   Rabinowitz, JD
   Llinás, M
AF Olszewski, Kellen L.
   Mather, Michael W.
   Morrisey, Joanne M.
   Garcia, Benjamin A.
   Vaidya, Akhil B.
   Rabinowitz, Joshua D.
   Llinas, Manuel
TI RETRACTED: Branched tricarboxylic acid metabolism in Plasmodium falciparum (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID cellular-metabolism; malaria parasites; dehydrogenase; purification; mitochondria; expression; pathways; histones; flux
AB A central hub of carbon metabolism is the tricarboxylic acid cycle 1, which serves to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid synthesis and other biosynthetic pathways. The protozoan intracellular malaria parasites (Plasmodium spp.), however, have long been suspected of possessing a significantly streamlined carbon metabolic network in which tricarboxylic acid metabolism plays a minor role(2). Blood-stage Plasmodium parasites rely almost entirely on glucose fermentation for energy and consume minimal amounts of oxygen(3), yet the parasite genome encodes all of the enzymes necessary for a complete tricarboxylic acid cycle(4). Here, by tracing C-13-labelled compounds using mass spectrometry(5), we show that tricarboxylic acid metabolism in the human malaria parasite Plasmodium falciparum is largely disconnected from glycolysis and is organized along a fundamentally different architecture from the canonical textbook pathway. We find that this pathway is not cyclic, but rather is a branched structure in which the major carbon sources are the amino acids glutamate and glutamine. As a consequence of this branched architecture, several reactions must run in the reverse of the standard direction, thereby generating two-carbon units in the form of acetyl-coenzyme A. We further show that glutamine-derived acetyl-coenzyme A is used for histone acetylation, whereas glucose-derived acetyl-coenzyme A is used to acetylate amino sugars. Thus, the parasite has evolved two independent production mechanisms for acetyl-coenzyme A with different biological functions. These results significantly clarify our understanding of the Plasmodium metabolic network and highlight the ability of altered variants of central carbon metabolism to arise in response to unique environments.
C1 [Olszewski, Kellen L.; Llinas, Manuel] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Olszewski, Kellen L.; Rabinowitz, Joshua D.; Llinas, Manuel] Princeton Univ, Lewis Sigler Inst Integrat Gen, Princeton, NJ 08544 USA.
   [Mather, Michael W.; Morrisey, Joanne M.; Vaidya, Akhil B.] Drexel Univ, Coll Med, Ctr Mol Parasitol, Philadelphia, PA 19129 USA.
   [Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Drexel University; Princeton University; Princeton University
RP Llinás, M (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
FU Burroughs Wellcome Fund; NIH [1DP2OD001315-01, R01 AI078063]; Beckman Young Investigators award; NSF [CBET-0941143]; Center for Quantitative Biology [P50 GM071508]; NIAID, NIH [AI028398]; National Institute of Allergy and Infectious Diseases [R01AI028398] Funding Source: NIH RePORTER
NR 48
TC 103
Z9 121
U1 1
U2 47
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 774
EP U16
DI 10.1038/nature09301
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500043
PM 20686576
DA 2026-03-09
ER

PT J
AU Stevenson, KB
   Harrington, J
   Nymeyer, S
   Madhusudhan, N
   Seager, S
   Bowman, WC
   Hardy, RA
   Deming, D
   Rauscher, E
   Lust, NB
AF Stevenson, Kevin B.
   Harrington, Joseph
   Nymeyer, Sarah
   Madhusudhan, Nikku
   Seager, Sara
   Bowman, William C.
   Hardy, Ryan A.
   Deming, Drake
   Rauscher, Emily
   Lust, Nate B.
TI Possible thermochemical disequilibrium in the atmosphere of the exoplanet GJ 436b
SO NATURE
LA English
DT Article
ID hot neptune; chemical-equilibrium; emission-spectrum; giant planets; dwarf; spitzer; temperature; transit; gj-436; carbon
AB The nearby extrasolar planet GJ 436b-which has been labelled as a 'hot Neptune'-reveals itself by the dimming of light as it crosses in front of and behind its parent star as seen from Earth. Respectively known as the primary transit and secondary eclipse, the former constrains the planet's radius and mass(1,2), and the latter constrains the planet's temperature(3,4) and, with measurements at multiple wavelengths, its atmospheric composition. Previous work(5) using transmission spectroscopy failed to detect the 1.4-mu m-water vapour band, leaving the planet's atmospheric composition poorly constrained. Here we report the detection of planetary thermal emission from the dayside of GJ 436b at multiple infrared wavelengths during the secondary eclipse. The best-fit compositional models contain a high CO abundance and a substantial methane (CH4) deficiency relative to thermochemical equilibrium models(6) for the predicted hydrogen-dominated atmosphere(7,8). Moreover, we report the presence of some H2O and traces of CO2. Because CH4 is expected to be the dominant carbon-bearing species, disequilibrium processes such as vertical mixing(9) and polymerization of methane(10) into substances such as ethylene may be required to explain the hot Neptune's small CH4-to-CO ratio, which is at least 10(5) times smaller than predicted(6).
C1 [Stevenson, Kevin B.; Harrington, Joseph; Nymeyer, Sarah; Bowman, William C.; Hardy, Ryan A.; Lust, Nate B.] Univ Cent Florida, Dept Phys, Planetary Sci Grp, Orlando, FL 32816 USA.
   [Madhusudhan, Nikku; Seager, Sara] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Madhusudhan, Nikku; Seager, Sara] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Deming, Drake] NASA, Goddard Space Flight Ctr, Planetary Syst Lab, Greenbelt, MD 20771 USA.
   [Rauscher, Emily] Columbia Univ, Dept Astron, New York, NY 10027 USA.
C3 State University System of Florida; University of Central Florida; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Columbia University
RP Stevenson, KB (corresponding author), Univ Cent Florida, Dept Phys, Planetary Sci Grp, Orlando, FL 32816 USA.
EM kevin218@knights.ucf.edu
FU US NSF; US NASA; JPL/Caltech
NR 30
TC 222
Z9 250
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 APR 22
PY 2010
VL 464
IS 7292
BP 1161
EP 1164
DI 10.1038/nature09013
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100030
PM 20414304
DA 2026-03-09
ER

PT J
AU Garaj, S
   Hubbard, W
   Reina, A
   Kong, J
   Branton, D
   Golovchenko, JA
AF Garaj, S.
   Hubbard, W.
   Reina, A.
   Kong, J.
   Branton, D.
   Golovchenko, J. A.
TI Graphene as a subnanometre trans-electrode membrane
SO NATURE
LA English
DT Article
ID carbon nanotubes; large-area; dna; nanopores; molecules; water
AB Isolated, atomically thin conducting membranes of graphite, called graphene, have recently been the subject of intense research with the hope that practical applications in fields ranging from electronics to energy science will emerge(1). The atomic thinness, stability and electrical sensitivity of graphene motivated us to investigate the potential use of graphene membranes and graphene nanopores to characterize single molecules of DNA in ionic solution. Here we show that when immersed in an ionic solution, a layer of graphene becomes a new electrochemical structure that we call a transelectrode. The trans-electrode's unique properties are the consequence of the atomic-scale proximity of its two opposing liquid-solid interfaces together with graphene's well known inplane conductivity. We show that several trans-electrode properties are revealed by ionic conductance measurements on a graphene membrane that separates two aqueous ionic solutions. Although our membranes are only one to two atomic layers(2,3) thick, we find they are remarkable ionic insulators with a very small stable conductance that depends on the ion species in solution. Electrical measurements on graphene membranes in which a single nanopore has been drilled show that the membrane's effective insulating thickness is less than one nanometre. This small effective thickness makes graphene an ideal substrate for very high resolution, high throughput nanopore-based single-molecule detectors. The sensitivity of graphene's in-plane electronic conductivity to its immediate surface environment and trans-membrane solution potentials will offer new insights into atomic surface processes and sensor development opportunities.
C1 [Garaj, S.; Golovchenko, J. A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Hubbard, W.; Golovchenko, J. A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Reina, A.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
   [Kong, J.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Branton, D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University
RP Golovchenko, JA (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM sgaraj@fas.harvard.edu; golovchenko@physics.harvard.edu
FU National Human Genome Research Institute, National Institutes of Health [R01 HG003703]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0845358] Funding Source: National Science Foundation
NR 21
TC 1268
Z9 1575
U1 11
U2 1171
PU 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 9
PY 2010
VL 467
IS 7312
BP 190
EP U73
DI 10.1038/nature09379
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300030
PM 20720538
DA 2026-03-09
ER

PT J
AU Zhang, Y
   Zhu, XL
   Torelli, AT
   Lee, M
   Dzikovski, B
   Koralewski, RM
   Wang, E
   Freed, J
   Krebs, C
   Ealick, SE
   Lin, HN
AF Zhang, Yang
   Zhu, Xuling
   Torelli, Andrew T.
   Lee, Michael
   Dzikovski, Boris
   Koralewski, Rachel M.
   Wang, Eileen
   Freed, Jack
   Krebs, Carsten
   Ealick, Steven E.
   Lin, Hening
TI Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme
SO NATURE
LA English
DT Article
ID toxin-resistant mutants; s-adenosylmethionine; crystal-structure; diphtheria-toxin; saccharomyces-cerevisiae; escherichia-coli; sam; proteins; synthase; localization
AB Archaeal and eukaryotic translation elongation factor 2 contain a unique post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide was proposed to involve three steps, with the first being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosyl-L-methionine (SAM). However, further details of the biosynthesis remain unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulphur-cluster enzyme, Dph2. Dph2 is a homodimer and each of its monomers can bind a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 59-deoxyadenosyl radical. Instead, it breaks the Cc, Met-S bond of SAM and generates a 3-amino-3-carboxypropyl radical. Our results suggest that P. horikoshii Dph2 represents a previously unknown, SAM-dependent, [4Fe-4S]-containing enzyme that catalyses unprecedented chemistry.
C1 [Zhang, Yang; Zhu, Xuling; Torelli, Andrew T.; Dzikovski, Boris; Koralewski, Rachel M.; Wang, Eileen; Freed, Jack; Ealick, Steven E.; Lin, Hening] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Lee, Michael; Krebs, Carsten] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Krebs, Carsten] Penn State Univ, Dept Chem, University Pk, PA 16802 USA.
C3 Cornell University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Lin, HN (corresponding author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
EM see3@cornell.edu; hl379@cornell.edu
FU Dreyfus Foundation; NIH/NIGMS [R01GM088276]; NIH/NCRR [P41-RR016292]; US National Center for Research Resources at the US National Institutes of Health [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [DE-AC02-06CH11357]
NR 47
TC 169
Z9 203
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 JUN 17
PY 2010
VL 465
IS 7300
BP 891
EP U4
DI 10.1038/nature09138
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500030
PM 20559380
DA 2026-03-09
ER

PT J
AU Tay, S
   Hughey, JJ
   Lee, TK
   Lipniacki, T
   Quake, SR
   Covert, MW
AF Tay, Savas
   Hughey, Jacob J.
   Lee, Timothy K.
   Lipniacki, Tomasz
   Quake, Stephen R.
   Covert, Markus W.
TI Single-cell NF-κB dynamics reveal digital activation and analogue information processing
SO NATURE
LA English
DT Article
ID variability; stability; responses
AB Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types(1). Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities(2). Here we use high-throughput microfluidic cell culture(3) and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-alpha, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kappa B. We measured NF-kappa B activity in thousands of live cells under TNF-alpha doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays(2), that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kappa B peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-alpha-induced NF-kappa B signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate.
C1 [Tay, Savas; Hughey, Jacob J.; Lee, Timothy K.; Quake, Stephen R.; Covert, Markus W.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Tay, Savas; Quake, Stephen R.] Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Lipniacki, Tomasz] Inst Fundamental Technol Res, PL-02106 Warsaw, Poland.
C3 Stanford University; Howard Hughes Medical Institute; Polish Academy of Sciences; Institute of Fundamental Technological Research of the Polish Academy of Sciences
RP Covert, MW (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM tlipnia@ippt.gov.pl; quake@stanford.edu; mcovert@stanford.edu
FU NIH; NCI [K99CA125994]; Foundation for Polish Science [TEAM 2009-3/6]; NSF/NIH [R01-GM086885]; Stanford Graduate Fellowship; Stanford Bio-X Graduate Fellowship
NR 28
TC 654
Z9 802
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 267
EP U149
DI 10.1038/nature09145
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800043
PM 20581820
DA 2026-03-09
ER

PT J
AU Bollag, G
   Hirth, P
   Tsai, J
   Zhang, JZ
   Ibrahim, PN
   Cho, HN
   Spevak, W
   Zhang, C
   Zhang, Y
   Habets, G
   Burton, E
   Wong, B
   Tsang, G
   West, BL
   Powell, B
   Shellooe, R
   Marimuthu, A
   Nguyen, H
   Zhang, KYJ
   Artis, DR
   Schlessinger, J
   Su, F
   Higgins, B
   Iyer, R
   D'Andrea, K
   Koehler, A
   Stumm, M
   Lin, PS
   Lee, RJ
   Grippo, J
   Puzanov, I
   Kim, KB
   Ribas, A
   McArthur, GA
   Sosman, JA
   Chapman, PB
   Flaherty, KT
   Xu, XW
   Nathanson, KL
   Nolop, K
AF Bollag, Gideon
   Hirth, Peter
   Tsai, James
   Zhang, Jiazhong
   Ibrahim, Prabha N.
   Cho, Hanna
   Spevak, Wayne
   Zhang, Chao
   Zhang, Ying
   Habets, Gaston
   Burton, ElizabethA.
   Wong, Bernice
   Tsang, Garson
   West, Brian L.
   Powell, Ben
   Shellooe, Rafe
   Marimuthu, Adhirai
   Nguyen, Hoa
   Zhang, Kam Y. J.
   Artis, Dean R.
   Schlessinger, Joseph
   Su, Fei
   Higgins, Brian
   Iyer, Raman
   D'Andrea, Kurt
   Koehler, Astrid
   Stumm, Michael
   Lin, Paul S.
   Lee, Richard J.
   Grippo, Joseph
   Puzanov, Igor
   Kim, Kevin B.
   Ribas, Antoni
   McArthur, Grant A.
   Sosman, Jeffrey A.
   Chapman, Paul B.
   Flaherty, Keith T.
   Xu, Xiaowei
   Nathanson, Katherine L.
   Nolop, Keith
TI Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
SO NATURE
LA English
DT Article
ID human cancer; braf(v600e); sorafenib; mutation; pathway; keratoacanthomas; sensitivity; progression; activation; senescence
AB B-RAF is the most frequently mutated protein kinase in human cancers(1). The finding that oncogenic mutations in BRAF are common in melanoma(2), followed by the demonstration that these tumours are dependent on the RAF/MEK/ERK pathway(3), offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity. Preclinical experiments demonstrated that PLX4032 selectively blocked the RAF/MEK/ERK pathway in BRAF mutant cells and caused regression of BRAF mutant xenografts(4). Toxicology studies confirmed a wide safety margin consistent with the high degree of selectivity, enabling Phase 1 clinical trials using a crystalline formulation of PLX4032 (ref. 5). In a subset of melanoma patients, pathway inhibition was monitored in paired biopsy specimens collected before treatment initiation and following two weeks of treatment. This analysis revealed substantial inhibition of ERK phosphorylation, yet clinical evaluation did not show tumour regressions. At higher drug exposures afforded by a new amorphous drug formulation(4,5), greater than 80% inhibition of ERK phosphorylation in the tumours of patients correlated with clinical response. Indeed, the Phase 1 clinical data revealed a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily(5). These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity.
C1 [Bollag, Gideon; Hirth, Peter; Tsai, James; Zhang, Jiazhong; Ibrahim, Prabha N.; Cho, Hanna; Spevak, Wayne; Zhang, Chao; Zhang, Ying; Habets, Gaston; Burton, ElizabethA.; Wong, Bernice; Tsang, Garson; West, Brian L.; Powell, Ben; Shellooe, Rafe; Marimuthu, Adhirai; Nguyen, Hoa; Zhang, Kam Y. J.; Artis, Dean R.; Lin, Paul S.; Nolop, Keith] Plexxikon Inc, Berkeley, CA 94710 USA.
   [Schlessinger, Joseph] Yale Univ, New Haven, CT 06520 USA.
   [Su, Fei; Higgins, Brian; Iyer, Raman; Koehler, Astrid; Stumm, Michael; Lee, Richard J.; Grippo, Joseph] Roche Pharmaceut, Nutley, NJ 07110 USA.
   [D'Andrea, Kurt; Flaherty, Keith T.; Xu, Xiaowei; Nathanson, Katherine L.] Univ Penn, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA.
   [D'Andrea, Kurt; Flaherty, Keith T.; Xu, Xiaowei; Nathanson, Katherine L.] Univ Penn, Abramson Canc Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Univ, Nashville, TN 37232 USA.
   [Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [McArthur, Grant A.] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
   [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
C3 Daiichi Sankyo Company Limited; Yale University; Roche Holding; Roche Holding USA; University of Pennsylvania; University of Pennsylvania; Vanderbilt University; University of Texas System; UTMD Anderson Cancer Center; University of California System; University of California Los Angeles; Peter Maccallum Cancer Center; Memorial Sloan Kettering Cancer Center
RP Bollag, G (corresponding author), Plexxikon Inc, 91 Bolivar Dr, Berkeley, CA 94710 USA.
EM gbollag@plexxikon.com
FU NIH; Cancer Council of Victoria
NR 28
TC 1491
Z9 1748
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 SEP 15
PY 2010
VL 467
IS 7315
BP 596
EP 599
DI 10.1038/nature09454
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100040
PM 20823850
DA 2026-03-09
ER

PT J
AU Karlas, A
   Machuy, N
   Shin, Y
   Pleissner, KP
   Artarini, A
   Heuer, D
   Becker, D
   Khalil, H
   Ogilvie, LA
   Hess, S
   Mäurer, AP
   Müller, E
   Wolff, T
   Rudel, T
   Meyer, TF
AF Karlas, Alexander
   Machuy, Nikolaus
   Shin, Yujin
   Pleissner, Klaus-Peter
   Artarini, Anita
   Heuer, Dagmar
   Becker, Daniel
   Khalil, Hany
   Ogilvie, Lesley A.
   Hess, Simone
   Maeurer, Andre P.
   Mueller, Elke
   Wolff, Thorsten
   Rudel, Thomas
   Meyer, Thomas F.
TI Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
SO NATURE
LA English
DT Article
ID ion-channel protein; a-virus; genes; export; interference; transcription; infection; complex; targets; atpase
AB Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health(1). High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective(2). In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON)(3) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1)(4) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses.
C1 [Karlas, Alexander; Machuy, Nikolaus; Shin, Yujin; Artarini, Anita; Heuer, Dagmar; Becker, Daniel; Khalil, Hany; Ogilvie, Lesley A.; Hess, Simone; Maeurer, Andre P.; Mueller, Elke; Rudel, Thomas; Meyer, Thomas F.] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany.
   [Pleissner, Klaus-Peter] Max Planck Inst Infect Biol, Core Facil Bioinformat, D-10117 Berlin, Germany.
   [Wolff, Thorsten] Robert Koch Inst, D-13353 Berlin, Germany.
C3 Max Planck Society; Max Planck Society; Robert Koch Institute
RP Meyer, TF (corresponding author), Max Planck Inst Infect Biol, Dept Mol Biol, Charitepl 1, D-10117 Berlin, Germany.
EM meyer@mpiib-berlin.mpg.de
FU EU [LSHB-CT-2004-005276]; ERA-Net Pathogenomics [0313938A]; FCI; RiNA network Berlin; German Government support via BMG; German Government support via BMBF
NR 33
TC 585
Z9 703
U1 2
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 818
EP U132
DI 10.1038/nature08760
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300042
PM 20081832
DA 2026-03-09
ER

PT J
AU Gracheva, EO
   Ingolia, NT
   Kelly, YM
   Cordero-Morales, JF
   Hollopeter, G
   Chesler, AT
   Sánchez, EE
   Perez, JC
   Weissman, JS
   Julius, D
AF Gracheva, Elena O.
   Ingolia, Nicholas T.
   Kelly, Yvonne M.
   Cordero-Morales, Julio F.
   Hollopeter, Gunther
   Chesler, Alexander T.
   Sanchez, Elda E.
   Perez, John C.
   Weissman, Jonathan S.
   Julius, David
TI Molecular basis of infrared detection by snakes
SO NATURE
LA English
DT Article
ID trigeminal system; ion channels; trpa1; neurons; pit; crotaline; projections; receptors; nucleus; thermosensation
AB Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a 'thermal image' of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibres of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibres that innervate the pit organ. TRPA1 orthologues from pit-bearing snakes (vipers, pythons and boas) are the most heat-sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of transient receptor potential (TRP) channels as thermosensors in the vertebrate nervous system.
C1 [Gracheva, Elena O.; Kelly, Yvonne M.; Cordero-Morales, Julio F.; Hollopeter, Gunther; Chesler, Alexander T.; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.; Julius, David] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Ingolia, Nicholas T.; Weissman, Jonathan S.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
   [Sanchez, Elda E.; Perez, John C.] Texas A&M Univ, 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; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; 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 julius@cmp.ucsf.edu
FU Ruth L. Kirschstein National Research Service Award [GM080853]; NIH; Howard Hughes Medical Institute; National Institutes of Health, including NCRR [P40 RR018300-06, P01 AG010770, NS047723, NS055299]
NR 48
TC 351
Z9 417
U1 12
U2 321
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1006
EP U66
DI 10.1038/nature08943
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000031
PM 20228791
DA 2026-03-09
ER

PT J
AU Sharma, CM
   Hoffmann, S
   Darfeuille, F
   Reignier, J
   Findeiss, S
   Sittka, A
   Chabas, S
   Reiche, K
   Hackermüller, J
   Reinhardt, R
   Stadler, PF
   Vogel, J
AF Sharma, Cynthia M.
   Hoffmann, Steve
   Darfeuille, Fabien
   Reignier, Jeremy
   Findeiss, Sven
   Sittka, Alexandra
   Chabas, Sandrine
   Reiche, Kristin
   Hackermueller, Joerg
   Reinhardt, Richard
   Stadler, Peter F.
   Vogel, Joerg
TI The primary transcriptome of the major human pathogen Helicobacter pylori
SO NATURE
LA English
DT Article
ID escherichia-coli; rna-polymerase; gene-expression; comparative genomics; messenger-rna; 6s rna; identification; promoter; sequence; bacteria
AB Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of similar to 60 small RNAs including the e-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.
C1 [Sharma, Cynthia M.; Sittka, Alexandra; Vogel, Joerg] Max Planck Inst Infect Biol, RNA Biol Grp, D-10117 Berlin, Germany.
   [Hoffmann, Steve; Findeiss, Sven; Stadler, Peter F.] Univ Leipzig, Dept Comp Sci, D-04107 Leipzig, Germany.
   [Hoffmann, Steve; Findeiss, Sven; Stadler, Peter F.] Univ Leipzig, Interdisciplinary Ctr Bioinformat, D-04107 Leipzig, Germany.
   [Darfeuille, Fabien; Reignier, Jeremy; Chabas, Sandrine] INSERM, U869, F-33076 Bordeaux, France.
   [Darfeuille, Fabien; Reignier, Jeremy; Chabas, Sandrine] Univ Bordeaux, F-33076 Bordeaux, France.
   [Reiche, Kristin; Hackermueller, Joerg; Stadler, Peter F.] Fraunhofer Inst Cell Therapy & Immunol, RNom Grp, D-04103 Leipzig, Germany.
   [Reinhardt, Richard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Stadler, Peter F.] Max Planck Inst Math Sci, D-04103 Leipzig, Germany.
   [Stadler, Peter F.] Univ Vienna, Inst Theoret Chem, A-1090 Vienna, Austria.
   [Stadler, Peter F.] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Vogel, Joerg] Univ Wurzburg, Inst Mol Infect Biol, D-97080 Wurzburg, Germany.
C3 Max Planck Society; Leipzig University; Leipzig University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Bordeaux; Fraunhofer Gesellschaft; Fraunhofer Germany; Fraunhofer Cell Therapy & Immunology; Max Planck Society; Max Planck Society; University of Vienna; The Santa Fe Institute; University of Wurzburg
RP Vogel, J (corresponding author), Max Planck Inst Infect Biol, RNA Biol Grp, D-10117 Berlin, Germany.
EM joerg.vogel@uni-wuerzburg.de
FU NGFN, BMBF, Germany; DFG [SPP1258]; Regulatory RNAs in Prokaryotes [VO8751/2, VO8751/4, STA850/7-1]; University of Leipzig; Freistaat Sachsen; German Research Foundation IZBI [BIZ6/1-4]; Volkswagen Stiftung [I/82 720]; French Agence Nationale de la Recherche [ANR-07-JCJC-0104-01]; French Association de la Recherche contre le Cancer (ARC); La Ligue Nationale contre le Cancer (LNCC); Agence Nationale de la Recherche (ANR) [ANR-07-JCJC-0104] Funding Source: Agence Nationale de la Recherche (ANR)
NR 50
TC 946
Z9 1067
U1 1
U2 181
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 250
EP 255
DI 10.1038/nature08756
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100040
PM 20164839
DA 2026-03-09
ER

PT J
AU Daffis, S
   Szretter, KJ
   Schriewer, J
   Li, JQ
   Youn, S
   Errett, J
   Lin, TY
   Schneller, S
   Zust, R
   Dong, HP
   Thiel, V
   Sen, GC
   Fensterl, V
   Klimstra, WB
   Pierson, TC
   Buller, RM
   Gale, M
   Shi, PY
   Diamond, MS
AF Daffis, Stephane
   Szretter, Kristy J.
   Schriewer, Jill
   Li, Jianqing
   Youn, Soonjeon
   Errett, John
   Lin, Tsai-Yu
   Schneller, Stewart
   Zust, Roland
   Dong, Hongping
   Thiel, Volker
   Sen, Ganes C.
   Fensterl, Volker
   Klimstra, William B.
   Pierson, Theodore C.
   Buller, R. Mark
   Gale, Michael, Jr.
   Shi, Pei-Yong
   Diamond, Michael S.
TI 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members
SO NATURE
LA English
DT Article
ID nile-virus-infection; proteins; genes; methyltransferase; translation; identification; initiation; induction; protects; alpha
AB Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability(1), the function of 2'-O methylation has remained uncertain since its discovery 35 years ago(2-4). Here we show that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was attenuated in wild-type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISGs) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and, specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of the 5' cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2'-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells.
C1 [Daffis, Stephane; Szretter, Kristy J.; Youn, Soonjeon; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Li, Jianqing; Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA.
   [Schriewer, Jill; Buller, R. Mark] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA.
   [Errett, John; Gale, Michael, Jr.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
   [Lin, Tsai-Yu; Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
   [Schneller, Stewart] Auburn Univ, Dept Chem & Biochem, Auburn, AL 36849 USA.
   [Zust, Roland; Thiel, Volker] Kantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland.
   [Thiel, Volker] Univ Zurich, Vetsuisse Fac, CH-8006 Zurich, Switzerland.
   [Dong, Hongping; Shi, Pei-Yong] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA.
   [Sen, Ganes C.; Fensterl, Volker] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Klimstra, William B.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
   [Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA.
   [Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Saint Louis University; University of Washington; University of Washington Seattle; National Institutes of Health (NIH) - USA; Auburn University System; Auburn University; Kantonsspital St. Gallen; Institute of Immunobiology, St. Gallen; University of Zurich; State University of New York (SUNY) System; Wadsworth Center; Cleveland Clinic Foundation; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Diamond, MS (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM diamond@borcim.wustl.edu
FU National Institutes of Health [U54 AI081680, U19 AI083019, R01 AI074973, R01 AI56540, U54 AI057160, U54 AI057158, R01 CA068782]; Swiss National Science Foundation [3100A0-118425/1]; Novartis Foundation
NR 25
TC 722
Z9 909
U1 3
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 452
EP 456
DI 10.1038/nature09489
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100046
PM 21085181
DA 2026-03-09
ER

PT J
AU Ding, L
   Ellis, MJ
   Li, SQ
   Larson, DE
   Chen, K
   Wallis, J
   Harris, CC
   McLellan, MD
   Fulton, RS
   Fulton, LL
   Abbott, RM
   Hoog, J
   Dooling, DJ
   Koboldt, DC
   Schmidt, H
   Kalicki, J
   Zhang, QY
   Chen, L
   Lin, L
   Wendl, MC
   McMichael, JF
   Magrini, VJ
   Cook, L
   McGrath, SD
   Vickery, TL
   Appelbaum, E
   DeSchryver, K
   Davies, S
   Guintoli, T
   Lin, L
   Crowder, R
   Tao, Y
   Snider, JE
   Smith, SM
   Dukes, AF
   Sanderson, GE
   Pohl, CS
   Delehaunty, KD
   Fronick, CC
   Pape, KA
   Reed, JS
   Robinson, JS
   Hodges, JS
   Schierding, W
   Dees, ND
   Shen, D
   Locke, DP
   Wiechert, ME
   Eldred, JM
   Peck, JB
   Oberkfell, BJ
   Lolofie, JT
   Du, FY
   Hawkins, AE
   O'Laughlin, MD
   Bernard, KE
   Cunningham, M
   Elliott, G
   Mason, MD
   Thompson, DM
   Ivanovich, JL
   Goodfellow, PJ
   Perou, CM
   Weinstock, GM
   Aft, R
   Watson, M
   Ley, TJ
   Wilson, RK
   Mardis, ER
AF Ding, Li
   Ellis, Matthew J.
   Li, Shunqiang
   Larson, David E.
   Chen, Ken
   Wallis, Johnw.
   Harris, Christopher C.
   McLellan, Michael D.
   Fulton, Robert S.
   Fulton, Lucinda L.
   Abbott, Rachel M.
   Hoog, Jeremy
   Dooling, David J.
   Koboldt, Daniel C.
   Schmidt, Heather
   Kalicki, Joelle
   Zhang, Qunyuan
   Chen, Lei
   Lin, Ling
   Wendl, Michael C.
   McMichael, Joshua F.
   Magrini, Vincent J.
   Cook, Lisa
   McGrath, Sean D.
   Vickery, Tammi L.
   Appelbaum, Elizabeth
   DeSchryver, Katherine
   Davies, Sherri
   Guintoli, Therese
   Lin, Li
   Crowder, Robert
   Tao, Yu
   Snider, Jacqueline E.
   Smith, Scott M.
   Dukes, Adam F.
   Sanderson, Gabriel E.
   Pohl, Craig S.
   Delehaunty, Kim D.
   Fronick, Catrina C.
   Pape, Kimberley A.
   Reed, Jerry S.
   Robinson, Jody S.
   Hodges, Jennifer S.
   Schierding, William
   Dees, Nathan D.
   Shen, Dong
   Locke, Devin P.
   Wiechert, Madeline E.
   Eldred, James M.
   Peck, Josh B.
   Oberkfell, Benjamin J.
   Lolofie, Justin T.
   Du, Feiyu
   Hawkins, Amy E.
   O'Laughlin, Michelle D.
   Bernard, Kelly E.
   Cunningham, Mark
   Elliott, Glendoria
   Mason, Mark D.
   Thompson, Dominic M., Jr.
   Ivanovich, Jennifer L.
   Goodfellow, Paul J.
   Perou, Charles M.
   Weinstock, George M.
   Aft, Rebecca
   Watson, Mark
   Ley, Timothy J.
   Wilson, Richard K.
   Mardis, Elaine R.
TI Genome remodelling in a basal-like breast cancer metastasis and xenograft
SO NATURE
LA English
DT Article
ID myeloid-leukemia genome; colorectal cancers; somatic mutations; tumor-suppressor; lung-cancer; differentiation; resolution; subtypes; taz
AB Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.
C1 [Ding, Li; Larson, David E.; Chen, Ken; Wallis, Johnw.; Harris, Christopher C.; McLellan, Michael D.; Fulton, Robert S.; Fulton, Lucinda L.; Abbott, Rachel M.; Dooling, David J.; Koboldt, Daniel C.; Schmidt, Heather; Kalicki, Joelle; Chen, Lei; Lin, Ling; Wendl, Michael C.; McMichael, Joshua F.; Magrini, Vincent J.; Cook, Lisa; McGrath, Sean D.; Vickery, Tammi L.; Appelbaum, Elizabeth; Smith, Scott M.; Dukes, Adam F.; Sanderson, Gabriel E.; Pohl, Craig S.; Delehaunty, Kim D.; Fronick, Catrina C.; Pape, Kimberley A.; Reed, Jerry S.; Robinson, Jody S.; Hodges, Jennifer S.; Schierding, William; Dees, Nathan D.; Shen, Dong; Locke, Devin P.; Wiechert, Madeline E.; Eldred, James M.; Peck, Josh B.; Oberkfell, Benjamin J.; Lolofie, Justin T.; Du, Feiyu; Hawkins, Amy E.; O'Laughlin, Michelle D.; Bernard, Kelly E.; Cunningham, Mark; Elliott, Glendoria; Mason, Mark D.; Weinstock, George M.; Ley, Timothy J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Genome Ctr, Sch Med, St Louis, MO 63108 USA.
   [Ding, Li; Wallis, Johnw.; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Zhang, Qunyuan; Wendl, Michael C.; Magrini, Vincent J.; Weinstock, George M.; Ley, Timothy J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Dept Genet, Sch Med, St Louis, MO 63108 USA.
   [Ellis, Matthew J.; Li, Shunqiang; Hoog, Jeremy; DeSchryver, Katherine; Davies, Sherri; Guintoli, Therese; Lin, Li; Crowder, Robert; Snider, Jacqueline E.; Ley, Timothy J.] Washington Univ, Dept Med, Sch Med, St Louis, MO 63108 USA.
   [Ellis, Matthew J.; Ley, Timothy J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Siteman Canc Ctr, Sch Med, St Louis, MO 63108 USA.
   [Zhang, Qunyuan] Washington Univ, Div Stat Genom, Sch Med, St Louis, MO 63108 USA.
   [Tao, Yu] Washington Univ, Div Biostat, Sch Med, St Louis, MO 63108 USA.
   [Thompson, Dominic M., Jr.; Ivanovich, Jennifer L.; Goodfellow, Paul J.; Aft, Rebecca] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63108 USA.
   [Thompson, Dominic M., Jr.; Ivanovich, Jennifer L.; Goodfellow, Paul J.; Aft, Rebecca] Washington Univ, Young Womens Breast Canc Program, Sch Med, St Louis, MO 63108 USA.
   [Watson, Mark] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63108 USA.
   [Perou, Charles M.] Univ N Carolina, Lineberger Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of North Carolina; University of North Carolina Chapel Hill
RP Wilson, RK (corresponding author), Washington Univ, Genome Ctr, Sch Med, St Louis, MO 63108 USA.
EM rwilson@wustl.edu
FU Washington University in St Louis; National Human Genome Research Institute (NHGRI) [U54 HG003079]; National Cancer Institute (NCI) [1 U01 CA114722-01]; Susan G Komen Breast Cancer Foundation [BCTR0707808]; Fashion Footwear Charitable Foundation, Inc. [NCI U10 CA076001, NCI 3P50 CA68438]; Breast Cancer Research Foundation; Institute of Clinical and Translational Sciences at Washington University [UL1 RR024992]; Illumina, Inc.
NR 30
TC 964
Z9 1123
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 999
EP 1005
DI 10.1038/nature08989
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000030
PM 20393555
DA 2026-03-09
ER

PT J
AU Sund, J
   Andér, M
   Åqvist, J
AF Sund, Johan
   Ander, Martin
   Aqvist, Johan
TI Principles of stop-codon reading on the ribosome
SO NATURE
LA English
DT Article
ID polypeptide release factors; different growth-rates; transfer-rna; escherichia-coli; translation termination; molecular-dynamics; crystal-structure; factor rf2; ggq motif; complex
AB In termination of protein synthesis, the bacterial release factors RF1 and RF2 bind to the ribosome through specific recognition of messenger RNA stop codons and trigger hydrolysis of the bond between the nascent polypeptide and the transfer RNA at the peptidyl-tRNA site, thereby releasing the newly synthesized protein. The release factors are highly specific for a U in the first stop-codon position 1 and recognize different combinations of purines in the second and third positions, with RF1 reading UAA and UAG and RF2 reading UAA and UGA. With recently determined crystal structures of termination complexes(2-4), it has become possible to decipher the energetics of stop-codon reading by computational analysis and to clarify the origin of the high release-factor binding accuracy. Here we report molecular dynamics free-energy calculations on different cognate and non-cognate termination complexes. The simulations quantitatively explain the basic principles of decoding in all three codon positions and reveal the key elements responsible for specificity of the release factors. The overall reading mechanism involves hitherto unidentified interactions and recognition switches that cannot be described in terms of a tripeptide anticodon model. Further simulations of complexes with tRNA(Trp), the tRNA recognizing the triplet codon for Trp, explain the observation of a 'leaky' stop codon 5 and highlight the fundamentally different third position reading by RF2, which leads to a high stop-codon specificity with strong discrimination against the Trp codon. The simulations clearly illustrate the versatility of codon reading by protein, which goes far beyond tRNA mimicry.
C1 [Sund, Johan; Ander, Martin; Aqvist, Johan] Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden.
C3 Uppsala University
RP Åqvist, J (corresponding author), Uppsala Univ, Biomed Ctr, Dept Cell & Mol Biol, Box 596, SE-75124 Uppsala, Sweden.
EM aqvist@xray.bmc.uu.se
FU Swedish Research Council
NR 33
TC 45
Z9 56
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 JUN 17
PY 2010
VL 465
IS 7300
BP 947
EP U12
DI 10.1038/nature09082
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500042
PM 20512119
DA 2026-03-09
ER

PT J
AU Junttila, MR
   Karnezis, AN
   Garcia, D
   Madriles, F
   Kortlever, RM
   Rostker, F
   Swigart, LB
   Pham, DM
   Seo, Y
   Evan, GI
   Martins, CP
AF Junttila, Melissa R.
   Karnezis, Anthony N.
   Garcia, Daniel
   Madriles, Francesc
   Kortlever, Roderik M.
   Rostker, Fanya
   Swigart, Lamorna Brown
   Pham, David M.
   Seo, Youngho
   Evan, Gerard I.
   Martins, Carla P.
TI Selective activation of p53-mediated tumour suppression in high-grade tumours
SO NATURE
LA English
DT Article
ID p53 restoration; mouse models; lung-cancer; in-vivo; k-ras; senescence; expression; oncogene; kras2
AB Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related death worldwide, with an overall 5-year survival rate of only 10-15%(1). Deregulation of the Ras pathway is a frequent hallmark of NSCLC, often through mutations that directly activate Kras(2). p53 is also frequently inactivated in NSCLC and, because oncogenic Ras can be a potent trigger of p53 (ref. 3), it seems likely that oncogenic Ras signalling has a major and persistent role in driving the selection against p53. Hence, pharmacological restoration of p53 is an appealing therapeutic strategy for treating this disease(4). Here we model the probable therapeutic impact of p53 restoration in a spontaneously evolving mouse model of NSCLC initiated by sporadic oncogenic activation of endogenous Kras(5). Surprisingly, p53 restoration failed to induce significant regression of established tumours, although it did result in a significant decrease in the relative proportion of high-grade tumours. This is due to selective activation of p53 only in the more aggressive tumour cells within each tumour. Such selective activation of p53 correlates with marked upregulation in Ras signal intensity and induction of the oncogenic signalling sensor p19(ARF) (ref. 6). Our data indicate that p53-mediated tumour suppression is triggered only when oncogenic Ras signal flux exceeds a critical threshold. Importantly, the failure of low-level oncogenic Kras to engage p53 reveals inherent limits in the capacity of p53 to restrain early tumour evolution and in the efficacy of therapeutic p53 restoration to eradicate cancers.
C1 [Junttila, Melissa R.; Karnezis, Anthony N.; Garcia, Daniel; Kortlever, Roderik M.; Rostker, Fanya; Swigart, Lamorna Brown; Evan, Gerard I.; Martins, Carla P.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Junttila, Melissa R.; Karnezis, Anthony N.; Garcia, Daniel; Kortlever, Roderik M.; Rostker, Fanya; Swigart, Lamorna Brown; Pham, David M.; Seo, Youngho; Evan, Gerard I.; Martins, Carla P.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Madriles, Francesc] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
   [Pham, David M.; Seo, Youngho] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Cancer Research UK; CRUK Cambridge Institute; University of California System; University of California San Francisco
RP Evan, GI (corresponding author), Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1GA, England.
EM gie20@cam.ac.uk
FU NCI [CA98018, CA100193]; AICR [09-0649]; Ellison Medical Foundation; Samuel R. Waxman Cancer Research Foundation
NR 30
TC 213
Z9 247
U1 1
U2 27
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 25
PY 2010
VL 468
IS 7323
BP 567
EP U244
DI 10.1038/nature09526
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200043
PM 21107427
DA 2026-03-09
ER

PT J
AU Kuba, H
   Oichi, Y
   Ohmori, H
AF Kuba, Hiroshi
   Oichi, Yuki
   Ohmori, Harunori
TI Presynaptic activity regulates Na+ channel distribution at the axon initial segment
SO NATURE
LA English
DT Article
ID stem auditory nuclei; action-potential initiation; afferent influences; pyramidal neurons; intrinsic excitability; n-magnocellularis; cochlea removal; sodium-channels; chicken; system
AB Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity(1). The axon initial segment (AIS) is the site at which neural signals arise(2,3), and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na+ channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na+ current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.
C1 [Kuba, Hiroshi; Oichi, Yuki] Kyoto Univ, Grad Sch Med, Career Path Promot Unit Young Life Scientists, Kyoto 6068501, Japan.
   [Ohmori, Harunori] Kyoto Univ, Grad Sch Med, Dept Physiol, Kyoto 6068501, Japan.
C3 Kyoto University; Kyoto University
RP Kuba, H (corresponding author), Kyoto Univ, Grad Sch Med, Career Path Promot Unit Young Life Scientists, Kyoto 6068501, Japan.
EM kuba@nbiol.med.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan; Grants-in-Aid for Scientific Research [20220008] Funding Source: KAKEN
NR 30
TC 347
Z9 406
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 JUN 24
PY 2010
VL 465
IS 7301
BP 1075
EP U136
DI 10.1038/nature09087
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900052
PM 20543825
DA 2026-03-09
ER

PT J
AU Stettenheim, J
   Thalakulam, M
   Pan, F
   Bal, M
   Ji, ZQ
   Xue, WW
   Pfeiffer, L
   West, KW
   Blencowe, MP
   Rimberg, AJ
AF Stettenheim, Joel
   Thalakulam, Madhu
   Pan, Feng
   Bal, Mustafa
   Ji, Zhonqing
   Xue, Weiwei
   Pfeiffer, Loren
   West, K. W.
   Blencowe, M. P.
   Rimberg, A. J.
TI A macroscopic mechanical resonator driven by mesoscopic electrical back-action
SO NATURE
LA English
DT Article
ID quantum point-contact; shot-noise; transistor; transport; junction; detector; motion; cavity
AB Systems with coupled mechanical and optical or electrical degrees of freedom(1,2) have fascinating dynamics that, through macroscopic manifestations of quantum behaviour(3), provide new insights into the transition between the classical and quantum worlds. Of particular interest is the back-action of electrons and photons on mechanical oscillators, which can lead to cooling and amplification of mechanical motion(4-6). Furthermore, feedback, which is naturally associated with back-action, has been predicted to have significant consequences for the noise of a detector coupled to a mechanical oscillator(7,8). Recently it has also been demonstrated that such feedback effects lead to strong coupling between single-electron transport and mechanical motion in carbon nanotube nanomechanical resonators(9,10). Here we present noise measurements which show that the mesoscopic back-action of electrons tunnelling through a radio-frequency quantum point contact(11) causes driven vibrations of the host crystal. This effect is a remarkable macroscopic manifestation of microscopic quantum behaviour, where the motion of a mechanical oscillator-the host crystal, which consists of on the order of 10(20) atoms-is determined by statistical fluctuations of tunnelling electrons.
C1 [Stettenheim, Joel; Pan, Feng; Bal, Mustafa; Xue, Weiwei; Blencowe, M. P.; Rimberg, A. J.] Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA.
   [Thalakulam, Madhu] Rice Univ, Rice Quantum Inst, Houston, TX 77005 USA.
   [Ji, Zhonqing] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
   [Pfeiffer, Loren; West, K. W.] Alcatel Lucent, Bell Labs, Murray Hill, NJ 07974 USA.
C3 Dartmouth College; Rice University; Rice University; AT&T; Alcatel-Lucent
RP Rimberg, AJ (corresponding author), Dartmouth Coll, Dept Phys & Astron, Hanover, NH 03755 USA.
EM ajrimberg@dartmouth.edu
FU NSF [DMR-0804488, DMR-0804477]; ARO [W911NF-06-1-0312, W911NF-06-1-0361]; NSA, LPS and ARO [W911-NF-08-1-0482]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0804488] Funding Source: National Science Foundation
NR 30
TC 28
Z9 32
U1 1
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 JUL 1
PY 2010
VL 466
IS 7302
BP 86
EP U100
DI 10.1038/nature09123
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800039
PM 20596016
DA 2026-03-09
ER

PT J
AU Buffett, BA
AF Buffett, Bruce A.
TI Tidal dissipation and the strength of the Earth's internal magnetic field
SO NATURE
LA English
DT Article
ID rotating spherical-shell; shear layers; torsional oscillations; core; nutation; constraints; precession; convection; geodynamo; dynamics
AB Magnetic fields at the Earth's surface represent only a fraction of the field inside the core(1). The strength and structure of the internal field are poorly known(2-5), yet the details are important for our understanding of the geodynamo. Here I obtain an indirect estimate for the field strength from measurements of tidal dissipation. Tidally driven flow in the Earth's liquid core develops internal shear layers, which distort the internal magnetic field and generate electric currents. Ohmic losses damp the tidal motions and produce detectable signatures in the Earth's nutations. Previously reported evidence of anomalous dissipation in nutations(3,6) can be explained with a core-averaged field of 2.5 mT, eliminating the need for high fluid viscosity(6) or a stronger magnetic field at the inner-core boundary(3). Estimates for the internal field constrain the power required for the geodynamo(7,8).
C1 Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Buffett, BA (corresponding author), Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
EM bbuffett@berkeley.edu
NR 26
TC 55
Z9 61
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 DEC 16
PY 2010
VL 468
IS 7326
BP 952
EP U345
DI 10.1038/nature09643
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600044
PM 21164483
DA 2026-03-09
ER

PT J
AU Lane, N
   Martin, W
AF Lane, Nick
   Martin, William
TI The energetics of genome complexity
SO NATURE
LA English
DT Article
ID mitochondrial gene-expression; eukaryotic genm; evolution; bacteria; origin; cell; oxygen; dna; compartmentalization; chromosm
AB All complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greater complexity. Why not? Prokaryotic genome size is constrained by bioenergetics. The endosymbiosis that gave rise to mitochondria restructured the distribution of DNA in relation to bioenergetic membranes, permitting a remarkable 200,000-fold expansion in the number of genes expressed. This vast leap in genomic capacity was strictly dependent on mitochondrial power, and prerequisite to eukaryote complexity: the key innovation en route to multicellular life.
C1 [Lane, Nick] UCL, Dept Genet Evolut & Environm, London W1E 6BT, England.
   [Martin, William] Univ Dusseldorf, Inst Bot 3, D-40225 Dusseldorf, Germany.
C3 University of London; University College London; Heinrich Heine University Dusseldorf
RP Lane, N (corresponding author), UCL, Dept Genet Evolut & Environm, Gower St, London W1E 6BT, England.
EM nick.lane@ucl.ac.uk
FU UCL; German Research Foundation; European Research Council (Networkorigins)
NR 74
TC 907
Z9 1066
U1 4
U2 331
PU 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 21
PY 2010
VL 467
IS 7318
BP 929
EP 934
DI 10.1038/nature09486
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700030
PM 20962839
DA 2026-03-09
ER

PT J
AU Calo, E
   Quintero-Estades, JA
   Danielian, PS
   Nedelcu, S
   Berman, SD
   Lees, JA
AF Calo, Eliezer
   Quintero-Estades, Jose A.
   Danielian, Paul S.
   Nedelcu, Simona
   Berman, Seth D.
   Lees, Jacqueline A.
TI Rb regulates fate choice and lineage commitment in vivo
SO NATURE
LA English
DT Article
ID adipocyte differentiation; osteoblast differentiation; retinoblastoma gene; tumor-suppressor; osteosarcoma; transcription; inactivation; expression; white; p53
AB Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma(1). Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb). The best known is pRb's ability to promote cell-cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell-cycle regulators(1). In addition, pRb has been shown in vitro to regulate several transcription factors that are master differentiation inducers(2). Depending on the differentiation factor and cellular context, pRb can either suppress or promote their transcriptional activity. For example, pRb binds to Runx2 and potentiates its ability to promote osteogenic differentiation in vitro(3). In contrast, pRb acts with E2F to suppress peroxisome proliferator-activated receptor gamma subunit (PPAR-gamma), the master activator of adipogenesis(4,5). Because osteoblasts and adipocytes can both arise from mesenchymal stem cells, these observations suggest that pRb might play a role in the choice between these two fates. However, so far, there is no evidence for this in vivo. Here we use mouse models to address this hypothesis in mesenchymal tissue development and tumorigenesis. Our data show that Rb status plays a key role in establishing fate choice between bone and brown adipose tissue in vivo.
C1 [Calo, Eliezer; Quintero-Estades, Jose A.; Danielian, Paul S.; Nedelcu, Simona; Berman, Seth D.; Lees, Jacqueline A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Lees, JA (corresponding author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jalees@mit.edu
FU National Cancer Institute/National Institutes of Health; National Cancer Institute [P01CA042063] Funding Source: NIH RePORTER
NR 20
TC 262
Z9 314
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1110
EP U126
DI 10.1038/nature09264
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600041
PM 20686481
DA 2026-03-09
ER

PT J
AU Valsecchi, F
   Glebbeek, E
   Farr, WM
   Fragos, T
   Willems, B
   Orosz, JA
   Liu, JF
   Kalogera, V
AF Valsecchi, Francesca
   Glebbeek, Evert
   Farr, Will M.
   Fragos, Tassos
   Willems, Bart
   Orosz, Jerome A.
   Liu, Jifeng
   Kalogera, Vassiliki
TI Formation of the black-hole binary M33 X-7 through mass exchange in a tight massive system
SO NATURE
LA English
DT Article
ID x-ray binary; eclipsing binary; evolution; stars; m-33; accretion; spin
AB The X-ray source M33 X-7 in the nearby galaxy Messier 33 is among the most massive X-ray binary stellar systems known, hosting a rapidly spinning, 15.65M(circle dot) black hole orbiting an underluminous, 70M(circle dot) main-sequence companion in a slightly eccentric 3.45-day orbit(1,2) (M-circle dot, solar mass). Although post-main-sequence mass transfer explains the masses and tight orbit(3), it leaves unexplained the observed X-ray luminosity, the star's underluminosity, the black hole's spin and the orbital eccentricity. A common envelope phase(1), or rotational mixing(4), could explain the orbit, but the former would lead to a merger and the latter to an overluminous companion. A merger would also ensue if mass transfer to the black hole were invoked for its spin-up(5). Here we report simulations of evolutionary tracks which reveal that if M33 X-7 started as a primary body of 85M(circle dot)-99M(circle dot) and a secondary body of 28M(circle dot)-32M(circle dot), in a 2.8-3.1-d orbit, its observed properties can be consistently explained. In this model, the main-sequence primary transfers part of its envelope to the secondary and loses the rest in a wind; it ends its life as a 16M(circle dot) helium star with an iron-nickel core that collapses to a black hole (with or without an accompanying supernova). The release of binding energy, and possibly collapse asymmetries, 'kick' the nascent black hole into an eccentric orbit. Wind accretion explains the X-ray luminosity, and the black-hole spin can be natal.
C1 [Valsecchi, Francesca; Farr, Will M.; Fragos, Tassos; Willems, Bart; Kalogera, Vassiliki] Northwestern Univ, CIERA, Evanston, IL 60208 USA.
   [Valsecchi, Francesca; Farr, Will M.; Fragos, Tassos; Willems, Bart; Kalogera, Vassiliki] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA.
   [Glebbeek, Evert] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Orosz, Jerome A.] San Diego State Univ, Dept Astron, San Diego, CA 92182 USA.
   [Liu, Jifeng] Chinese Acad Sci, Natl Astron Observ, Beijing 100012, Peoples R China.
   [Fragos, Tassos; Liu, Jifeng] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 Northwestern University; Northwestern University; McMaster University; California State University System; San Diego State University; Chinese Academy of Sciences; National Astronomical Observatory, CAS; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University
RP Valsecchi, F (corresponding author), Northwestern Univ, CIERA, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM francesca@u.northwestern.edu
FU Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908930] Funding Source: National Science Foundation
NR 25
TC 60
Z9 69
U1 0
U2 8
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 4
PY 2010
VL 468
IS 7320
BP 77
EP 79
DI 10.1038/nature09463
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674YF
UT WOS:000283786900038
PM 20962778
DA 2026-03-09
ER

PT J
AU Fujii, T
   Iwane, AH
   Yanagida, T
   Namba, K
AF Fujii, Takashi
   Iwane, Atsuko H.
   Yanagida, Toshio
   Namba, Keiichi
TI Direct visualization of secondary structures of F-actin by electron cryomicroscopy
SO NATURE
LA English
DT Article
ID tobacco-mosaic-virus; cryo-em structure; atomic model; microscopy; resolution; filament; complex; reconstruction; arrangement; chaperonin
AB F-actin is a helical assembly of actin, which is a component of muscle fibres essential for contraction and has a crucial role in numerous cellular processes, such as the formation of lamellipodia and filopodia(1,2), as the most abundant component and regulator of cytoskeletons by dynamic assembly and disassembly (from G-actin to F-actin and vice versa). Actin is a ubiquitous protein and is involved in important biological functions, but the definitive high-resolution structure of F-actin remains unknown. Although a recent atomic model well reproduced X-ray fibre diffraction intensity data from a highly oriented liquid-crystalline sol specimen(3), its refinement without experimental phase information has certain limitations. Direct visualization of the structure by electron cryomicroscopy, however, has been difficult because it is relatively thin and flexible. Here we report the F-actin structure at 6.6 angstrom resolution, made obtainable by recent advances in electron cryomicroscopy. The density map clearly resolves all the secondary structures of G-actin, such as alpha-helices, beta-structures and loops, and makes unambiguous modelling and refinement possible. Complex domain motions that open the nucleotide-binding pocket on F-actin formation, specific D-loop and terminal conformations, and relatively tight axial but markedly loose interprotofilament interactions hydrophilic in nature are revealed in the F-actin model, and all seem to be important for dynamic functions of actin.
C1 [Fujii, Takashi; Iwane, Atsuko H.; Yanagida, Toshio; Namba, Keiichi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
C3 University of Osaka
RP Namba, K (corresponding author), Osaka Univ, Grad Sch Frontier Biosci, 1-3 Yamadaoka, Suita, Osaka 5650871, Japan.
EM keiichi@fbs.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [16087207, 21227006]; Grants-in-Aid for Scientific Research [21227006] Funding Source: KAKEN
NR 35
TC 298
Z9 362
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 OCT 7
PY 2010
VL 467
IS 7316
BP 724
EP U117
DI 10.1038/nature09372
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 659NE
UT WOS:000282572500042
PM 20844487
DA 2026-03-09
ER

PT J
AU Canup, RM
AF Canup, Robin M.
TI Origin of Saturn's rings and inner moons by mass removal from a lost Titan-sized satellite
SO NATURE
LA English
DT Article
ID late heavy bombardment; planetary rings; evolution; viscosity; accretion; ganymede; systems; impact; disk
AB The origin of Saturn's rings has not been adequately explained. The current rings are more than 90 to 95 per cent water ice(1), which implies that initially they were almost pure ice because they are continually polluted by rocky meteoroids(2). In contrast, a half-rock, half-ice mixture (similar to the composition of many of the satellites in the outer Solar System) would generally be expected. Previous ring origin theories invoke the collisional disruption of a small moon(3,4), or the tidal disruption of a comet during a close passage by Saturn(5). These models are improbable and/or struggle to account for basic properties of the rings, including their icy composition. Saturn has only one large satellite, Titan, whereas Jupiter has four large satellites; additional large satellites probably existed originally but were lost as they spiralled into Saturn(6). Here I report numerical simulations of the tidal removal of mass from a differentiated, Titan-sized satellite as it migrates inward towards Saturn. Planetary tidal forces preferentially strip material from the satellite's outer icy layers, while its rocky core remains intact and is lost to collision with the planet. The result is a pure ice ring much more massive than Saturn's current rings. As the ring evolves, its mass decreases and icy moons are spawned from its outer edge(7) with estimated masses consistent with Saturn's ice-rich moons interior to and including Tethys.
C1 SW Res Inst, Planetary Sci Directorate, Boulder, CO 80302 USA.
RP Canup, RM (corresponding author), SW Res Inst, Planetary Sci Directorate, 1050 Walnut St,Suite 300, Boulder, CO 80302 USA.
EM robin@boulder.swri.edu
FU NASA
NR 30
TC 123
Z9 150
U1 1
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 16
PY 2010
VL 468
IS 7326
BP 943
EP 946
DI 10.1038/nature09661
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600042
PM 21151108
DA 2026-03-09
ER

PT J
AU Gehrke, S
   Imai, Y
   Sokol, N
   Lu, BW
AF Gehrke, Stephan
   Imai, Yuzuru
   Sokol, Nicholas
   Lu, Bingwei
TI Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression
SO NATURE
LA English
DT Article
ID let-7 microrna; distinct roles; cell-death; drosophila; mutations; 4e-bp; gene; identification; growth
AB Gain-of-function mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial as well as sporadic Parkinson's disease characterized by age-dependent degeneration of dopaminergic neurons(1,2). The molecular mechanism of LRRK2 action is not known. Here we show that LRRK2 interacts with the microRNA (miRNA) pathway to regulate protein synthesis. Drosophila e2f1 and dp messenger RNAs are translationally repressed by let-7 and miR-184*, respectively. Pathogenic LRRK2 antagonizes these miRNAs, leading to the overproduction of E2F1/DP, previously implicated in cell cycle and survival control 3 and shown here to be critical for LRRK2 pathogenesis. Genetic deletion of let-7, antagomir-mediated blockage of let-7 and miR-184* action, transgenic expression of dp target protector, or replacement of endogenous dp with a dp transgene non-responsive to let-7 each had toxic effects similar to those of pathogenic LRRK2. Conversely, increasing the level of let-7 or miR-184* attenuated pathogenic LRRK2 effects. LRRK2 associated with Drosophila Argonaute-1 (dAgo1) or human Argonaute-2 (hAgo2) of the RNA-induced silencing complex (RISC). In aged fly brain, dAgo1 protein level was negatively regulated by LRRK2. Further, pathogenic LRRK2 promoted the association of phospho-4E-BP1 with hAgo2. Our results implicate deregulated synthesis of E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2 pathogenesis and suggest novel miRNA-based therapeutic strategies.
C1 [Gehrke, Stephan; Lu, Bingwei] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
   [Imai, Yuzuru] Tohoku Univ, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan.
   [Sokol, Nicholas] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
C3 Stanford University; Tohoku University; Indiana University System; Indiana University Bloomington
RP Gehrke, S (corresponding author), Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
EM sgehrke@stanford.edu; bingwei@stanford.edu
FU National Institutes of Health [R01AR054926, R01MH080378, R21NS056878]; McKnight Foundation; Beckman Foundation; Sloan Foundation; MEXT in Japan; Asahi Glass Foundation
NR 30
TC 329
Z9 378
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 29
PY 2010
VL 466
IS 7306
BP 637
EP U9
DI 10.1038/nature09191
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100056
PM 20671708
DA 2026-03-09
ER

PT J
AU Kirkegaard, T
   Roth, AG
   Petersen, NHT
   Mahalka, AK
   Olsen, OD
   Moilanen, I
   Zylicz, A
   Knudsen, J
   Sandhoff, K
   Arenz, C
   Kinnunen, PKJ
   Nylandsted, J
   Jäättelä, M
AF Kirkegaard, Thomas
   Roth, Anke G.
   Petersen, Nikolaj H. T.
   Mahalka, Ajay K.
   Olsen, Ole Dines
   Moilanen, Irina
   Zylicz, Alicja
   Knudsen, Jens
   Sandhoff, Konrad
   Arenz, Christoph
   Kinnunen, Paavo K. J.
   Nylandsted, Jesper
   Jaattela, Marja
TI Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology
SO NATURE
LA English
DT Article
ID acid sphingomyelinase; heat-shock-protein-70 family; cell-death; stimulation; involvement; activation; cathepsins; apoptosis; membranes; proteins
AB Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization(1-5), a hallmark of stress-induced cell death(6-10). Clues to its molecular mechanism of action may lay in the recently reported stress-and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment(1,11). Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero) phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism(12-14). In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B-severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM(15)-is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.
C1 [Kirkegaard, Thomas; Petersen, Nikolaj H. T.; Olsen, Ole Dines; Nylandsted, Jesper; Jaattela, Marja] Danish Canc Soc, Inst Canc Biol, Apoptosis Dept, DK-2100 Copenhagen, Denmark.
   [Kirkegaard, Thomas; Petersen, Nikolaj H. T.; Olsen, Ole Dines; Nylandsted, Jesper; Jaattela, Marja] Danish Canc Soc, Inst Canc Biol, Ctr Genotox Stress Res, DK-2100 Copenhagen, Denmark.
   [Roth, Anke G.; Arenz, Christoph] Humboldt Univ, Inst Chem, D-10099 Berlin, Germany.
   [Mahalka, Ajay K.; Moilanen, Irina; Kinnunen, Paavo K. J.] Univ Helsinki, Inst Biomed, Helsinki Biophys & Biomembrane Grp, FIN-00014 Helsinki, Finland.
   [Olsen, Ole Dines; Knudsen, Jens] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark.
   [Zylicz, Alicja] Int Inst Mol & Cell Biol, PL-02109 Warsaw, Poland.
   [Sandhoff, Konrad] Univ Bonn, Kekule Inst Organ Chem & Biochem, LIMES, D-53121 Bonn, Germany.
C3 Danish Cancer Society; Danish Cancer Society; Humboldt University of Berlin; University of Helsinki; University of Southern Denmark; Miedzynarodowy Instytut Biologii Molekularnej i Komorkowej; University of Bonn
RP Jäättelä, M (corresponding author), Danish Canc Soc, Inst Canc Biol, Apoptosis Dept, DK-2100 Copenhagen, Denmark.
EM mj@cancer.dk
FU Danish Cancer Society; Danish National Research Foundation; Danish Medical Research Council; European Commission; Meyer Foundation; Novo Nordisk Foundation; Association for International Cancer Research; Finnish Academy; Sigrid Juselius Foundation; Volkswagenstiftung; Deutsche Forschungsgemeinschaft [SFB 645, SPP 1267]; EU; Polish Ministry of Science and High Education
NR 33
TC 420
Z9 490
U1 0
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 549
EP U171
DI 10.1038/nature08710
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100053
PM 20111001
DA 2026-03-09
ER

PT J
AU Pons, AJ
   Karma, A
AF Pons, Antonio J.
   Karma, Alain
TI Helical crack-front instability in mixed-mode fracture
SO NATURE
LA English
DT Article
ID pattern-formation; growth
AB Planar crack propagation under pure tension loading (mode I) is generally stable. However, it becomes universally unstable with the superposition of a shear stress parallel to the crack front (mode III). Under this mixed-mode (I + III) loading configuration, an initially flat parent crack segments into an array of daughter cracks that rotate towards a direction of maximum tensile stress(1). This segmentation produces stepped fracture surfaces with characteristic 'lance-shaped' markings observed in a wide range of engineering(2-7) and geological materials(1,8). The origin of this instability remains poorly understood and a theory with which to predict the surface roughness scale is lacking. Here we perform large-scale simulations of mixed-mode I + III brittle fracture using a continuum phase-field method(9-11) that describes the complete three-dimensional crack-front evolution. The simulations reveal that planar crack propagation is linearly unstable against helical deformations of the crack front, which evolve nonlinearly into a segmented array of finger-shaped daughter cracks. Furthermore, during their evolution, facets gradually coarsen owing to the growth competition of daughter cracks in striking analogy with the coarsening of finger patterns observed in nonequilibrium growth phenomena(12-14). We show that the dynamically preferred unstable wavelength is governed by the balance of the destabilizing effect of far-field stresses and the stabilizing effect of cohesive forces on the process zone scale, and we derive a theoretical estimate for this scale using a new propagation law for curved cracks in three dimensions. The rotation angles of coarsened facets are also compared to theoretical predictions and available experimental data.
C1 [Pons, Antonio J.; Karma, Alain] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
   [Pons, Antonio J.; Karma, Alain] Northeastern Univ, Ctr Interdisciplinary Res Complex Syst, Boston, MA 02115 USA.
C3 Northeastern University; Northeastern University
RP Karma, A (corresponding author), Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
EM a.karma@neu.edu
FU US DOE [DE-FG02-07ER46400]; Spanish Ministry of Science and Innovation;  [EX2005-0085];  [FIS2009-13360-C03-02]; U.S. Department of Energy (DOE) [DE-FG02-07ER46400] Funding Source: U.S. Department of Energy (DOE)
NR 29
TC 177
Z9 190
U1 13
U2 139
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 4
PY 2010
VL 464
IS 7285
BP 85
EP 89
DI 10.1038/nature08862
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500038
PM 20203607
DA 2026-03-09
ER

PT J
AU Drake, JM
   Griffen, BD
AF Drake, John M.
   Griffen, Blaine D.
TI Early warning signals of extinction in deteriorating environments
SO NATURE
LA English
DT Article
ID regime shifts; populations; stochasticity; ecosystems; system; times
AB During the decline to extinction, animal populations may present dynamical phenomena not exhibited by robust populations(1,2). Some of these phenomena, such as the scaling of demographic variance, are related to small size(3-6) whereas others result from density-dependent nonlinearities(7). Although understanding the causes of population extinction has been a central problem in theoretical biology for decades(8), the ability to anticipate extinction has remained elusive(9). Here we argue that the causes of a population's decline are central to the predictability of its extinction. Specifically, environmental degradation may cause a tipping point in population dynamics, corresponding to a bifurcation in the underlying population growth equations, beyond which decline to extinction is almost certain. In such cases, imminent extinction will be signalled by critical slowing down (CSD). We conducted an experiment with replicate laboratory populations of Daphnia magna to test this hypothesis. We show that populations crossing a transcritical bifurcation, experimentally induced by the controlled decline in environmental conditions, show statistical signatures of CSD after the onset of environmental deterioration and before the critical transition. Populations in constant environments did not have these patterns. Four statistical indicators all showed evidence of the approaching bifurcation as early as 110 days (similar to 8 generations) before the transition occurred. Two composite indices improved predictability, and comparative analysis showed that early warning signals based solely on observations in deteriorating environments without reference populations for standardization were hampered by the presence of transient dynamics before the onset of deterioration, pointing to the importance of reliable baseline data before environmental deterioration begins. The universality of bifurcations in models of population dynamics suggests that this phenomenon should be general(10-12).
C1 [Drake, John M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
   [Griffen, Blaine D.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
C3 University System of Georgia; University of Georgia; University of South Carolina System; University of South Carolina Columbia
RP Drake, JM (corresponding author), Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
EM jdrake@uga.edu
FU Odum School of Ecology, University of Georgia; University of South Carolina
NR 30
TC 448
Z9 516
U1 8
U2 272
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 456
EP 459
DI 10.1038/nature09389
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200042
PM 20827269
DA 2026-03-09
ER

PT J
AU Cerf, M
   Thiruvengadam, N
   Mormann, F
   Kraskov, A
   Quiroga, RQ
   Koch, C
   Fried, I
AF Cerf, Moran
   Thiruvengadam, Nikhil
   Mormann, Florian
   Kraskov, Alexander
   Quiroga, Rodrigo Quian
   Koch, Christof
   Fried, Itzhak
TI On-line, voluntary control of human temporal lobe neurons
SO NATURE
LA English
DT Article
ID single neurons; human hippocampus; representation; attention; computer; explicit
AB Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition(1-4). Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons(5-9), here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.
C1 [Cerf, Moran; Thiruvengadam, Nikhil; Mormann, Florian; Kraskov, Alexander; Quiroga, Rodrigo Quian; Koch, Christof] CALTECH, Pasadena, CA 91125 USA.
   [Cerf, Moran; Fried, Itzhak] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA.
   [Cerf, Moran] NYU, Stern Sch Business, New York, NY 10012 USA.
   [Thiruvengadam, Nikhil] Carnegie Mellon Univ, Sch Comp Sci, Pittsburgh, PA 15213 USA.
   [Mormann, Florian] Univ Bonn, Dept Epileptol, D-53105 Bonn, Germany.
   [Quiroga, Rodrigo Quian] Univ Leicester, Dept Engn, Leicester LE1 7RH, Leics, England.
   [Koch, Christof] Korea Univ, Dept Brain & Cognit Engn, Seoul 136713, South Korea.
   [Fried, Itzhak] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
   [Fried, Itzhak] Tel Aviv Med Ctr & Sch Med, Funct Neurosurg Unit, IL-64239 Tel Aviv, Israel.
   [Fried, Itzhak] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
C3 California Institute of Technology; University of California System; University of California Los Angeles; New York University; Carnegie Mellon University; University of Bonn; University of Leicester; Korea University; University of California System; University of California Los Angeles; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv University; Sackler Faculty of Medicine
RP Cerf, M (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM moran@klab.caltech.edu; koch@klab.caltech.edu; ifried@mednet.ucla.edu
FU National Institute of Neurological Disorders and Stroke (NINDS); National Institute of Mental Health (NIMH); G. Harold & Leila Y. Mathers Charitable Foundation; Ministry of Education, Science and Technology [R31-2008-000-10008-0]; MRC [G0701038] Funding Source: UKRI; Direct For Biological Sciences; Div Of Biological Infrastructure [0922982] Funding Source: National Science Foundation
NR 23
TC 121
Z9 134
U1 0
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 28
PY 2010
VL 467
IS 7319
BP 1104
EP U115
DI 10.1038/nature09510
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600047
PM 20981100
DA 2026-03-09
ER

PT J
AU Nicoli, S
   Standley, C
   Walker, P
   Hurlstone, A
   Fogarty, KE
   Lawson, ND
AF Nicoli, Stefania
   Standley, Clive
   Walker, Paul
   Hurlstone, Adam
   Fogarty, Kevin E.
   Lawson, Nathan D.
TI MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis
SO NATURE
LA English
DT Article
ID developing zebrafish; tip cells; forces; expression
AB Within the circulatory system, blood flow regulates vascular remodelling(1), stimulates blood stem cell formation(2), and has a role in the pathology of vascular disease(3). During vertebrate embryogenesis, vascular patterning is initially guided by conserved genetic pathways that act before circulation(4). Subsequently, endothelial cells must incorporate the mechanosensory stimulus of blood flow with these early signals to shape the embryonic vascular system(4). However, few details are known about how these signals are integrated during development. To investigate this process, we focused on the aortic arch (AA) blood vessels, which are known to remodel in response to blood flow(1). By using two-photon imaging of live zebrafish embryos, we observe that flow is essential for angiogenesis during AA development. We further find that angiogenic sprouting of AA vessels requires a flow-induced genetic pathway in which the mechano-sensitive zinc finger transcription factor klf2a(5-7) induces expression of an endothelial-specific microRNA, mir-126, to activate Vegf signalling. Taken together, our work describes a novel genetic mechanism in which a microRNA facilitates integration of a physiological stimulus with growth factor signalling in endothelial cells to guide angiogenesis.
C1 [Nicoli, Stefania; Lawson, Nathan D.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
   [Standley, Clive; Fogarty, Kevin E.] Univ Massachusetts, Sch Med, Program Mol Med, Biomed Imaging Grp, Worcester, MA 01605 USA.
   [Walker, Paul; Hurlstone, Adam] Univ Manchester, Fac Life Sci, Mol Canc Studies Grp, Manchester M13 9PT, Lancs, England.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; University of Manchester
RP Lawson, ND (corresponding author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM nathan.lawson@umassmed.edu
FU National Heart, Lung, and Blood Institute and National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Endocrinology Research Center (DERC) [DK32520]
NR 30
TC 353
Z9 428
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 22
PY 2010
VL 464
IS 7292
BP 1196
EP U118
DI 10.1038/nature08889
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100038
PM 20364122
DA 2026-03-09
ER

PT J
AU Lv, S
   Dudek, DM
   Cao, Y
   Balamurali, MM
   Gosline, J
   Li, HB
AF Lv, Shanshan
   Dudek, Daniel M.
   Cao, Yi
   Balamurali, M. M.
   Gosline, John
   Li, Hongbin
TI Designed biomaterials to mimic the mechanical properties of muscles
SO NATURE
LA English
DT Article
ID cardiac-muscle; protein titin; elastin; resilin; connectin/titin; myofibrils; molecules; filaments; domains; tension
AB The passive elasticity of muscle is largely governed by the I-band part of the giantmuscle protein titin(1-4), a complex molecular spring composed of a series of individually folded immunoglobulin-like domains as well as largely unstructured unique sequences(5). These mechanical elements have distinct mechanical properties, and when combined, they provide the desired passive elastic properties of muscle(6-11), which are a unique combination of strength, extensibility and resilience. Single-molecule atomic force microscopy (AFM) studies demonstrated that the macroscopic behaviour of titin in intact myofibrils can be reconstituted by combining the mechanical properties of these mechanical elements measured at the single-molecule level(8). Here we report artificial elastomeric proteins that mimic the molecular architecture of titin through the combination of well-characterized protein domains GB1(12) and resilin(13). We show that these artificial elastomeric proteins can be photochemically crosslinked and cast into solid biomaterials. These biomaterials behave as rubber-like materials showing high resilience at low strain and as shock-absorber-like materials at high strain by effectively dissipating energy. These properties are comparable to the passive elastic properties of muscles within the physiological range of sarcomere length(14) and so these materials represent a new muscle-mimetic biomaterial. The mechanical properties of these biomaterials can be fine-tuned by adjusting the composition of the elastomeric proteins, providing the opportunity to develop biomaterials that are mimetic of different types of muscles. We anticipate that these biomaterials will find applications in tissue engineering(15) as scaffold and matrix for artificial muscles.
C1 [Lv, Shanshan; Cao, Yi; Balamurali, M. M.; Li, Hongbin] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
   [Dudek, Daniel M.; Gosline, John] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z1, Canada.
C3 University of British Columbia; University of British Columbia
RP Li, HB (corresponding author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
EM gosline@zoology.ubc.ca; hongbin@chem.ubc.ca
FU Canadian Institutes of Health Research; Canada Research Chairs program; Canada Foundation for Innovation; Michael Smith Foundation for Health Research; Natural Sciences and Engineering Research Council of Canada
NR 33
TC 497
Z9 557
U1 10
U2 536
PU 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 6
PY 2010
VL 465
IS 7294
BP 69
EP 73
DI 10.1038/nature09024
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900032
PM 20445626
DA 2026-03-09
ER

PT J
AU Petukhova, L
   Duvic, M
   Hordinsky, M
   Norris, D
   Price, V
   Shimomura, Y
   Kim, H
   Singh, P
   Lee, A
   Chen, WV
   Meyer, KC
   Paus, R
   Jahoda, CAB
   Amos, CI
   Gregersen, PK
   Christiano, AM
AF Petukhova, Lynn
   Duvic, Madeleine
   Hordinsky, Maria
   Norris, David
   Price, Vera
   Shimomura, Yutaka
   Kim, Hyunmi
   Singh, Pallavi
   Lee, Annette
   Chen, Wei V.
   Meyer, Katja C.
   Paus, Ralf
   Jahoda, Colin A. B.
   Amos, Christopher I.
   Gregersen, Peter K.
   Christiano, Angela M.
TI Genome-wide association study in alopecia areata implicates both innate and adaptive immunity
SO NATURE
LA English
DT Article
ID autoimmune-disease; hair follicle; nkg2d ligand; risk locus; expression; cancer; genes; cells; peroxiredoxin-5; susceptibility
AB Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack(1,2). The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P <= 5 x 10(-7)). Here we show an association with genomic regions containing several genes controlling the activation and proliferation of regulatory T cells (T-reg cells), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), interleukin (IL)-2/IL-21, IL-2 receptor A (IL-2RA; CD25) and Eos (also known as Ikaros family zinc finger 4; IKZF4), as well as the human leukocyte antigen (HLA) region. We also find association evidence for regions containing genes expressed in the hair follicle itself (PRDX5 and STX17). A region of strong association resides within the ULBP (cytomegalovirus UL16-binding protein) gene cluster on chromosome 6q25.1, encoding activating ligands of the natural killer cell receptor NKG2D that have not previously been implicated in an autoimmune disease. By probing the role of ULBP3 in disease pathogenesis, we also show that its expression in lesional scalp from patients with AA is markedly upregulated in the hair follicle dermal sheath during active disease. This study provides evidence for the involvement of both innate and acquired immunity in the pathogenesis of AA. We have defined the genetic underpinnings of AA, placing it within the context of shared pathways among autoimmune diseases, and implicating a novel disease mechanism, the upregulation of ULBP ligands, in triggering autoimmunity.
C1 [Petukhova, Lynn; Shimomura, Yutaka; Kim, Hyunmi; Singh, Pallavi; Christiano, Angela M.] Columbia Univ, Dept Dermatol, New York, NY 10032 USA.
   [Duvic, Madeleine] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA.
   [Hordinsky, Maria] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA.
   [Norris, David] Univ Colorado, Dept Dermatol, Denver, CO 80010 USA.
   [Price, Vera] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA.
   [Lee, Annette; Gregersen, Peter K.] N Shore LIJHS, Feinstein Inst Med Res, Manhasset, NY 11030 USA.
   [Chen, Wei V.; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Meyer, Katja C.; Paus, Ralf] Univ Lubeck, Dept Dermatol, D-23538 Lubeck, Germany.
   [Paus, Ralf] Univ Manchester, Sch Translat Med, Manchester M13 9PT, Lancs, England.
   [Jahoda, Colin A. B.] Univ Durham, Dept Biol Sci, Durham DH1 3LE, England.
   [Christiano, Angela M.] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA.
C3 Columbia University; University of Texas System; UTMD Anderson Cancer Center; University of Minnesota System; University of Minnesota Twin Cities; University of Colorado System; University of Colorado Denver; University of California System; University of California San Francisco; Northwell Health; University of Texas System; UTMD Anderson Cancer Center; University of Lubeck; University of Manchester; Durham University; Columbia University
RP Christiano, AM (corresponding author), Columbia Univ, Dept Dermatol, New York, NY 10032 USA.
EM amc65@columbia.edu
FU National Alopecia Areata Foundation (NAAF); DFG Cluster of Excellence, Inflammation at Interfaces; National Institutes of Health [R01AR44422, R01CA133996, P30CA016772, R01AR52579, R01AR56016]
NR 39
TC 607
Z9 722
U1 2
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 1
PY 2010
VL 466
IS 7302
BP 113
EP U129
DI 10.1038/nature09114
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800045
PM 20596022
DA 2026-03-09
ER

PT J
AU Fratini, M
   Poccia, N
   Ricci, A
   Campi, G
   Burghammer, M
   Aeppli, G
   Bianconi, A
AF Fratini, Michela
   Poccia, Nicola
   Ricci, Alessandro
   Campi, Gaetano
   Burghammer, Manfred
   Aeppli, Gabriel
   Bianconi, Antonio
TI Scale-free structural organization of oxygen interstitials in La2CuO4+y
SO NATURE
LA English
DT Article
ID phase-separation; strain
AB It is well known that the microstructures of the transition-metal oxides(1-3), including the high-transition-temperature (high-T-c) copper oxide superconductors(4-7), are complex. This is particularly so when there are oxygen interstitials or vacancies 8, which influence the bulk properties. For example, the oxygen interstitials in the spacer layers separating the superconducting CuO2 planes undergo ordering phenomena in Sr2O1+yCuO2 (ref.9), YBa2Cu3O6+y (ref.10) and La2CuO4+y (refs 11-15) that induce enhancements in the transition temperatures with no changes in hole concentrations. It is also known that complex systems often have a scale-invariant structural organization 16, but hitherto none had been found in high-T-c materials. Here we report that the ordering of oxygen interstitials in the La2O2+y spacer layers of La2CuO4+y high-T-c superconductors is characterized by a fractal distribution up to a maximum limiting size of 400 mu m. Intriguingly, these fractal distributions of dopants seem to enhance superconductivity at high temperature.
C1 [Fratini, Michela; Poccia, Nicola; Ricci, Alessandro; Campi, Gaetano; Bianconi, Antonio] Univ Roma La Sapienza, Dept Phys, I-00185 Rome, Italy.
   [Campi, Gaetano] CNR, Inst Crystallog, I-00016 Monterotondo, Italy.
   [Burghammer, Manfred] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
   [Aeppli, Gabriel] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Aeppli, Gabriel] UCL, Dept Phys & Astron, London WC1H 0AH, England.
C3 Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto Di Cristallografia (IC-CNR); European Synchrotron Radiation Facility (ESRF); University of London; University College London; University of London; University College London
RP Bianconi, A (corresponding author), Univ Roma La Sapienza, Dept Phys, Piazzale Aldo Moro 2, I-00185 Rome, Italy.
EM antonio.bianconi@uniroma1.it
FU European STREP [517039]; Sapienza University of Rome
NR 29
TC 252
Z9 275
U1 3
U2 142
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 12
PY 2010
VL 466
IS 7308
BP 841
EP 844
DI 10.1038/nature09260
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636TT
UT WOS:000280766100030
PM 20703301
DA 2026-03-09
ER

PT J
AU Han, ZF
   Niu, TH
   Chang, JB
   Lei, XG
   Zhao, MY
   Wang, Q
   Cheng, W
   Wang, JJ
   Feng, Y
   Chai, JJ
AF Han, Zhifu
   Niu, Tianhui
   Chang, Junbiao
   Lei, Xiaoguang
   Zhao, Mingyan
   Wang, Qiang
   Cheng, Wei
   Wang, Jinjing
   Feng, Yi
   Chai, Jijie
TI Crystal structure of the FTO protein reveals basis for its substrate specificity
SO NATURE
LA English
DT Article
ID uracil-dna glycosylase; repair enzyme alkb; oxidative demethylation; escherichia-coli; alkylation damage; adult obesity; rna; gene; methylation; mitochondrial
AB Recent studies(1-5) have unequivocally associated the fat mass and obesity-associated (FTO) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNA demethylase with a strong preference for 3-methylthymidine (3-meT) in single-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA(6-8). Here we report the crystal structure of FTO in complex with the mononucleotide 3-meT. FTO comprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with a novel fold. Biochemical assays show that these two domains interact with each other, which is required for FTO catalytic activity. In contrast with the structures of other AlkB members, FTO possesses an extra loop covering one side of the conserved jelly-roll motif. Structural comparison shows that this loop selectively competes with the unmethylated strand of the DNA duplex for binding to FTO, suggesting that it has an important role in FTO selection against double-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meU from other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors.
C1 [Han, Zhifu; Niu, Tianhui; Lei, Xiaoguang; Zhao, Mingyan; Cheng, Wei; Wang, Jinjing; Feng, Yi; Chai, Jijie] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Niu, Tianhui] China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China.
   [Chang, Junbiao; Wang, Qiang] Zhengzhou Univ, Dept Chem, Zhengzhou 450001, Peoples R China.
   [Lei, Xiaoguang] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China.
   [Chai, Jijie] Tsinghua Univ, Dept Biol Sci & Biotechnol, Beijing 100084, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; China Agricultural University; Zhengzhou University; Tianjin University; Tsinghua University
RP Chai, JJ (corresponding author), Natl Inst Biol Sci, 7 Sci Pk Rd, Beijing 102206, Peoples R China.
EM chaijijie@nibs.ac.cn
FU Chinese Ministry of Science and Technology [2008AA022305, 2006CB806704, 2008AA022317]; National Natural Science Foundation of China [30825043]
NR 30
TC 360
Z9 411
U1 5
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 APR 22
PY 2010
VL 464
IS 7292
BP 1205
EP U129
DI 10.1038/nature08921
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100040
PM 20376003
DA 2026-03-09
ER

PT J
AU Song, Y
   Altarejos, J
   Goodarzi, MO
   Inoue, H
   Guo, XQ
   Berdeaux, R
   Kim, JH
   Goode, J
   Igata, M
   Paz, JC
   Hogan, MF
   Singh, PK
   Goebel, N
   Vera, L
   Miller, N
   Cui, JR
   Jones, MR
   Chen, YDI
   Taylor, KD
   Hsueh, WA
   Rotter, JI
   Montminy, M
AF Song, Youngsup
   Altarejos, Judith
   Goodarzi, Mark O.
   Inoue, Hiroshi
   Guo, Xiuqing
   Berdeaux, Rebecca
   Kim, Jeong-Ho
   Goode, Jason
   Igata, Motoyuki
   Paz, Jose C.
   Hogan, Meghan F.
   Singh, Pankaj K.
   Goebel, Naomi
   Vera, Lili
   Miller, Nina
   Cui, Jinrui
   Jones, Michelle R.
   Chen, Yii-Der I.
   Taylor, Kent D.
   Hsueh, Willa A.
   Rotter, Jerome I.
   Montminy, Marc
TI CRTC3 links catecholamine signalling to energy balance
SO NATURE
LA English
DT Article
ID creb coactivator crtc2; brown adipose-tissue; adenylyl-cyclase; insulin-resistance; lipoprotein-lipase; mexican-americans; obesity; gene; transcription; cells
AB The adipose-derived hormone leptin maintains energy balance in part through central nervous system-mediated increases in sympathetic outflow that enhance fat burning. Triggering of beta-adrenergic receptors in adipocytes stimulates energy expenditure by cyclic AMP (cAMP)-dependent increases in lipolysis and fatty-acid oxidation. Although the mechanism is unclear, catecholamine signalling is thought to be disrupted in obesity, leading to the development of insulin resistance. Here we show that the cAMP response element binding (CREB) coactivator Crtc3 promotes obesity by attenuating beta-adrenergic receptor signalling in adipose tissue. Crtc3 was activated in response to catecholamine signals, when it reduced adenyl cyclase activity by upregulating the expression of Rgs2, a GTPase-activating protein that also inhibits adenyl cyclase activity. As a common human CRTC3 variant with increased transcriptional activity is associated with adiposity in two distinct Mexican-American cohorts, these results suggest that adipocyte CRTC3 may play a role in the development of obesity in humans.
C1 [Song, Youngsup; Altarejos, Judith; Inoue, Hiroshi; Berdeaux, Rebecca; Kim, Jeong-Ho; Goode, Jason; Igata, Motoyuki; Paz, Jose C.; Hogan, Meghan F.; Singh, Pankaj K.; Goebel, Naomi; Vera, Lili; Miller, Nina; Montminy, Marc] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Goodarzi, Mark O.; Jones, Michelle R.] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
   [Guo, Xiuqing; Cui, Jinrui; Chen, Yii-Der I.; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Hsueh, Willa A.] Methodist Hosp, Res Inst, Diabet Res Ctr, Div Diabet Obes & Lipids, Houston, TX 77030 USA.
C3 Salk Institute; Cedars Sinai Medical Center; Cedars Sinai Medical Center; Houston Methodist
RP Montminy, M (corresponding author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM montminy@salk.edu
FU National Institutes of Health [R01-DK049777, R01-DK083834, P30-DK063491, R01-HL088457, R01-DK79888, R01-HL071205, N01-HC95159, N02-HL64278, M01-RR00425]; Cedars-Sinai Board of Governor's Chair in Medical Genetics; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK063491, R01DK083834] Funding Source: NIH RePORTER
NR 48
TC 131
Z9 154
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 DEC 16
PY 2010
VL 468
IS 7326
BP 933
EP U329
DI 10.1038/nature09564
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600040
PM 21164481
DA 2026-03-09
ER

PT J
AU Schnorrer, F
   Schönbauer, C
   Langer, CCH
   Dietzl, G
   Novatchkova, M
   Schernhuber, K
   Fellner, M
   Azaryan, A
   Radolf, M
   Stark, A
   Keleman, K
   Dickson, BJ
AF Schnorrer, Frank
   Schoenbauer, Cornelia
   Langer, Christoph C. H.
   Dietzl, Georg
   Novatchkova, Maria
   Schernhuber, Katharina
   Fellner, Michaela
   Azaryan, Anna
   Radolf, Martin
   Stark, Alexander
   Keleman, Krystyna
   Dickson, Barry J.
TI Systematic genetic analysis of muscle morphogenesis and function in Drosophila
SO NATURE
LA English
DT Article
ID encodes; protein; melanogaster; expression; mutants
AB Systematic genetic approaches have provided deep insight into the molecular and cellular mechanisms that operate in simple unicellular organisms. For multicellular organisms, however, the pleiotropy of gene function has largely restricted such approaches to the study of early embryogenesis. With the availability of genome-wide transgenic RNA interference (RNAi) libraries in Drosophila(1,2), it is now possible to perform a systematic genetic dissection of any cell or tissue type at any stage of the lifespan. Here we apply these methods to define the genetic basis for formation and function of the Drosophila muscle. We identify a role inmuscle for 2,785 genes, many of which we assign to specific functions in the organization of muscles, myofibrils or sarcomeres. Many of these genes are phylogenetically conserved, including genes implicated in mammalian sarcomere organization and human muscle diseases.
C1 [Schnorrer, Frank; Schoenbauer, Cornelia; Langer, Christoph C. H.] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
   [Schnorrer, Frank; Dietzl, Georg; Novatchkova, Maria; Schernhuber, Katharina; Fellner, Michaela; Azaryan, Anna; Radolf, Martin; Stark, Alexander; Keleman, Krystyna; Dickson, Barry J.] Res Inst Mol Pathol, A-1030 Vienna, Austria.
C3 Max Planck Society; 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; dickson@imp.ac.at
FU Boehringer Ingelheim GmbH; Max-Planck Society; Human Frontier Science Program; European Union; Austrian Ministry for Science and Research; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF)
NR 27
TC 236
Z9 273
U1 0
U2 30
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 287
EP 291
DI 10.1038/nature08799
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100049
PM 20220848
DA 2026-03-09
ER

PT J
AU Liu, WM
   Li, YY
   Learn, GH
   Rudicell, RS
   Robertson, JD
   Keele, BF
   Ndjango, JBN
   Sanz, CM
   Morgan, DB
   Locatelli, S
   Gonder, MK
   Kranzusch, PJ
   Walsh, PD
   Delaporte, E
   Mpoudi-Ngole, E
   Georgiev, AV
   Muller, MN
   Shaw, GM
   Peeters, M
   Sharp, PM
   Rayner, JC
   Hahn, BH
AF Liu, Weimin
   Li, Yingying
   Learn, Gerald H.
   Rudicell, Rebecca S.
   Robertson, Joel D.
   Keele, Brandon F.
   Ndjango, Jean-Bosco N.
   Sanz, Crickette M.
   Morgan, David B.
   Locatelli, Sabrina
   Gonder, Mary K.
   Kranzusch, Philip J.
   Walsh, Peter D.
   Delaporte, Eric
   Mpoudi-Ngole, Eitel
   Georgiev, Alexander V.
   Muller, Martin N.
   Shaw, George M.
   Peeters, Martine
   Sharp, Paul M.
   Rayner, Julian C.
   Hahn, Beatrice H.
TI Origin of the human malaria parasite Plasmodium falciparum in gorillas
SO NATURE
LA English
DT Article
ID infection; hiv-1; diversification; evolutionary; phylogeny; reservoirs; multiple; acid; gene; apes
AB Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.
C1 [Liu, Weimin; Li, Yingying; Learn, Gerald H.; Robertson, Joel D.; Keele, Brandon F.; Shaw, George M.; Rayner, Julian C.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
   [Rudicell, Rebecca S.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
   [Ndjango, Jean-Bosco N.] Univ Kisangani, Dept Ecol & Management Plant & Anim Resources, Fac Sci, Kisangani, DEM REP CONGO.
   [Sanz, Crickette M.] Washington Univ, Dept Anthropol, St Louis, MO 63130 USA.
   [Sanz, Crickette M.; Morgan, David B.] Wildlife Conservat Soc, Congo Program, Brazzaville, Rep Congo.
   [Morgan, David B.] Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL 60614 USA.
   [Locatelli, Sabrina; Gonder, Mary K.] SUNY Albany, Dept Biol Sci, Albany, NY 12222 USA.
   [Kranzusch, Philip J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   [Walsh, Peter D.] VaccinApe, Bethesda, MD USA.
   [Delaporte, Eric; Peeters, Martine] Univ Montpellier I, F-34394 Montpellier, France.
   [Delaporte, Eric; Peeters, Martine] Inst Rech Dev, F-34394 Montpellier, France.
   [Mpoudi-Ngole, Eitel] Ctr Rech Med, Inst Rech Med & Etud Plantes Med Prevent Sida Cam, Yaounde, Cameroon.
   [Georgiev, Alexander V.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Muller, Martin N.] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA.
   [Sharp, Paul M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Sharp, Paul M.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Rayner, Julian C.] Wellcome Trust Sanger Inst, Sanger Inst, Malaria Programme, Cambridge CB10 1SA, England.
C3 University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham; University of Kisangani; Washington University (WUSTL); State University of New York (SUNY) System; University at Albany, SUNY; Harvard University; Harvard Medical School; Universite de Montpellier; Institut de Recherche pour le Developpement (IRD); Harvard University; University of New Mexico; University of Edinburgh; University of Edinburgh; Wellcome Trust Sanger Institute
RP Hahn, BH (corresponding author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
EM bhahn@uab.edu
FU National Institutes of Health [R01 AI50529, R01 AI58715, U19 AI 067854, R03 AI074778, T32 GM008111, T32 AI007245, P30 AI 27767]; BillAMP;Melinda Gates Foundation [37874]; National Science Foundation [0755823]; Agence Nationale de Recherche sur le Sida [12152/12182]; US Fish and Wildlife Service; Arthur L. Greene Fund; Wallace Global Fund; Bristol Myers Freedom to Discover Program; Wellcome Trust; Howard Hughes Medical Institute; 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 Dental and Craniofacial Research; National Cancer Institute; National Institute of Nursing Research; National Institute on Aging; National Institute on Drug Abuse; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Minority Health and Health Disparities [P30AI027767] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI050529, T32AI007245] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008111] Funding Source: NIH RePORTER; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [0755823] Funding Source: National Science Foundation
NR 37
TC 406
Z9 495
U1 3
U2 193
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 420
EP +
DI 10.1038/nature09442
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200034
PM 20864995
DA 2026-03-09
ER

PT J
AU Haller, E
   Hart, R
   Mark, MJ
   Danzl, JG
   Reichsöllner, L
   Gustavsson, M
   Dalmonte, M
   Pupillo, G
   Nägerl, HC
AF Haller, Elmar
   Hart, Russell
   Mark, Manfred J.
   Danzl, Johann G.
   Reichsoellner, Lukas
   Gustavsson, Mattias
   Dalmonte, Marcello
   Pupillo, Guido
   Naegerl, Hanns-Christoph
TI Pinning quantum phase transition for a Luttinger liquid of strongly interacting bosons
SO NATURE
LA English
DT Article
ID atoms; gas; insulator; fermions
AB Quantum many-body systems can have phase transitions(1) even at zero temperature; fluctuations arising from Heisenberg's uncertainty principle, as opposed to thermal effects, drive the system from one phase to another. Typically, during the transition the relative strength of two competing terms in the system's Hamiltonian changes across a finite critical value. A well-known example is the Mott-Hubbard quantum phase transition from a superfluid to an insulating phase(2,3), which has been observed for weakly interacting bosonic atomic gases. However, for strongly interacting quantum systems confined to lower-dimensional geometry, a novel type(4,5) of quantum phase transition may be induced and driven by an arbitrarily weak perturbation to the Hamiltonian. Here we observe such an effect-the sine-Gordon quantum phase transition from a superfluid Luttinger liquid to a Mott insulator(6,7)-in a one-dimensional quantum gas of bosonic caesium atoms with tunable interactions. For sufficiently strong interactions, the transition is induced by adding an arbitrarily weak optical lattice commensurate with the atomic granularity, which leads to immediate pinning of the atoms. We map out the phase diagram and find that our measurements in the strongly interacting regime agree well with a quantum field description based on the exactly solvable sine-Gordon model(8). We trace the phase boundary all the way to the weakly interacting regime, where we find good agreement with the predictions of the one-dimensional Bose-Hubbard model. Our results open up the experimental study of quantum phase transitions, criticality and transport phenomena beyond Hubbard-type models in the context of ultracold gases.
C1 [Haller, Elmar; Hart, Russell; Mark, Manfred J.; Danzl, Johann G.; Reichsoellner, Lukas; Gustavsson, Mattias; Naegerl, Hanns-Christoph] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Haller, Elmar; Hart, Russell; Mark, Manfred J.; Danzl, Johann G.; Reichsoellner, Lukas; Gustavsson, Mattias; Naegerl, Hanns-Christoph] Univ Innsbruck, Zentrum Quantenphys, A-6020 Innsbruck, Austria.
   [Dalmonte, Marcello; Pupillo, Guido] Univ Innsbruck, Inst Theoret Phys, A-6020 Innsbruck, Austria.
   [Dalmonte, Marcello; Pupillo, Guido] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Dalmonte, Marcello] Univ Bologna, Dipartimento Fis, I-40127 Bologna, Italy.
   [Dalmonte, Marcello] Ist Nazl Fis Nucl, I-40127 Bologna, Italy.
C3 University of Innsbruck; University of Innsbruck; University of Innsbruck; Austrian Academy of Sciences; University of Bologna; Istituto Nazionale di Fisica Nucleare (INFN)
RP Nägerl, HC (corresponding author), Univ Innsbruck, Inst Expt Phys, Tech Str 25, A-6020 Innsbruck, Austria.
EM christoph.naegerl@uibk.ac.at
FU Austrian Ministry of Science and Research (Bundesministerium fur Wissenschaft und Forschung); Austrian Science Fund (Fonds zur Forderung der wissenschaftlichen Forschung); European Union [FP7-ICT-2007-C]; Marie Curie International Incoming Fellowship
NR 30
TC 203
Z9 224
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 29
PY 2010
VL 466
IS 7306
BP 597
EP U1
DI 10.1038/nature09259
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 632HA
UT WOS:000280412100047
PM 20671704
DA 2026-03-09
ER

PT J
AU Gómez, JM
   Verdú, M
   Perfectti, F
AF Gomez, Jose M.
   Verdu, Miguel
   Perfectti, Francisco
TI Ecological interactions are evolutionarily conserved across the entire tree of life
SO NATURE
LA English
DT Article
ID phylogenetic signal; patterns
AB Ecological interactions are crucial to understanding both the ecology and the evolution of organisms(1,2). Because the phenotypic traits regulating species interactions are largely a legacy of their ancestors, it is widely assumed that ecological interactions are phylogenetically conserved, with closely related species interacting with similar partners(2). However, the existing empirical evidence is inadequate to appropriately evaluate the hypothesis of phylogenetic conservatism in ecological interactions, because it is both ecologically and taxonomically biased. In fact, most studies on the evolution of ecological interactions have focused on specialized organisms, such as some parasites or insect herbivores(3-7), belonging to a limited subset of the overall tree of life. Here we study the evolution of host use in a large and diverse group of interactions comprising both specialist and generalist acellular, unicellular and multicellular organisms. We show that, as previously found for specialized interactions, generalized interactions can be evolutionarily conserved. Significant phylogenetic conservatism of interaction patterns was equally likely to occur in symbiotic and non-symbiotic interactions, as well as in mutualistic and antagonistic interactions. Host-use differentiation among species was higher in phylogenetically conserved clades, irrespective of their generalization degree and taxonomic position within the tree of life. Our findings strongly suggest a shared pattern in the organization of biological systems through evolutionary time, mediated by marked conservatism of ecological interactions among taxa.
C1 [Gomez, Jose M.] Univ Granada, Dept Ecol, E-18071 Granada, Spain.
   [Verdu, Miguel] Univ Valencia Generalitat Valenciana, CSIC, Ctr Invest Desertificac, E-46470 Valencia, Spain.
   [Perfectti, Francisco] Univ Granada, Dept Genet, E-18071 Granada, Spain.
C3 University of Granada; Consejo Superior de Investigaciones Cientificas (CSIC); University of Valencia; CSIC-GV-UV - Centro de Investigaciones sobre Desertificacion (CIDE); University of Granada
RP Gómez, JM (corresponding author), Univ Granada, Dept Ecol, E-18071 Granada, Spain.
EM jmgreyes@ugr.es
FU Spanish Ministry of Science; Junta de Andalucia
NR 29
TC 196
Z9 212
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 JUN 17
PY 2010
VL 465
IS 7300
BP 918
EP U6
DI 10.1038/nature09113
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500036
PM 20520609
DA 2026-03-09
ER

PT J
AU Schwenk, J
   Metz, M
   Zolles, G
   Turecek, R
   Fritzius, T
   Bildl, W
   Tarusawa, E
   Kulik, A
   Unger, A
   Ivankova, K
   Seddik, R
   Tiao, JY
   Rajalu, M
   Trojanova, J
   Rohde, V
   Gassmann, M
   Schulte, U
   Fakler, B
   Bettler, B
AF Schwenk, Jochen
   Metz, Michaela
   Zolles, Gerd
   Turecek, Rostislav
   Fritzius, Thorsten
   Bildl, Wolfgang
   Tarusawa, Etsuko
   Kulik, Akos
   Unger, Andreas
   Ivankova, Klara
   Seddik, Riad
   Tiao, Jim Y.
   Rajalu, Mathieu
   Trojanova, Johana
   Rohde, Volker
   Gassmann, Martin
   Schulte, Uwe
   Fakler, Bernd
   Bettler, Bernhard
TI Native GABAB receptors are heteromultimers with a family of auxiliary subunits
SO NATURE
LA English
DT Article
ID k+ channels; ampa receptors; cultured-cells; hcn channels; protein; rat; expression; responses; inhibition; complexes
AB GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. They are expressed in almost all neurons of the brain, where they regulate synaptic transmission and signal propagation by controlling the activity of voltage-gated calcium (Ca-v) and inward-rectifier potassium (K-ir) channels(1). Molecular cloning revealed that functional GABA(B) receptors are formed by the heteromeric assembly of GABA(B1) with GABA(B2) subunits(2-5). However, cloned GABA(B(1,2)) receptors failed to reproduce the functional diversity observed with native GABA(B) receptors(6-8). Here we show by functional proteomics that GABA(B) receptors in the brain are high-molecular-mass complexes of GABA(B1), GABA(B2) and members of a subfamily of the KCTD (potassium channel tetramerization domain-containing) proteins. KCTD proteins 8, 12, 12b and 16 show distinct expression profiles in the brain and associate tightly with the carboxy terminus of GABA(B2) as tetramers. This co-assembly changes the properties of the GABA(B(1,2)) core receptor: the KCTD proteins increase agonist potency and markedly alter the G-protein signalling of the receptors by accelerating onset and promoting desensitization in a KCTD-subtype-specific manner. Taken together, our results establish the KCTD proteins as auxiliary subunits of GABA(B) receptors that determine the pharmacology and kinetics of the receptor response.
C1 [Schwenk, Jochen; Zolles, Gerd; Bildl, Wolfgang; Schulte, Uwe; Fakler, Bernd] Univ Freiburg, Inst Physiol 2, D-79108 Freiburg, Germany.
   [Metz, Michaela; Turecek, Rostislav; Fritzius, Thorsten; Ivankova, Klara; Seddik, Riad; Tiao, Jim Y.; Rajalu, Mathieu; Gassmann, Martin; Bettler, Bernhard] Univ Basel, Inst Physiol, Pharmazentrum, Dept Biomed, CH-4056 Basel, Switzerland.
   [Rohde, Volker; Schulte, Uwe] Logopharm GmbH, D-79108 Freiburg, Germany.
   [Tarusawa, Etsuko; Kulik, Akos; Unger, Andreas] Univ Freiburg, Inst Anat & Cell Biol, D-79104 Freiburg, Germany.
   [Fakler, Bernd] Ctr Biol Signaling Studies Bioss, D-79104 Freiburg, Germany.
   [Turecek, Rostislav; Trojanova, Johana] Acad Sci Czech Republic, Inst Expt Med, Prague 14220 4, Czech Republic.
C3 University of Freiburg; University of Basel; University of Freiburg; Czech Academy of Sciences; Institute of Experimental Medicine of the Czech Academy of Sciences
RP Fakler, B (corresponding author), Univ Freiburg, Inst Physiol 2, Engesserstr 4, D-79108 Freiburg, Germany.
EM bernd.fakler@physiologie.uni-freiburg.de; bernhard.bettler@unibas.ch
FU Deutsche Forschungsgemeinschaft [SFB 746/TP16, SFB 780/A3, EXC294, SFB 780/A2]; Wellcome Trust (ISRF); EU Synapse; GACR [309/06/1304]; Swiss Science Foundation [3100A0-117816]; Fridericus Stiftung; European Community [FP7/2007-2013, 201714]
NR 35
TC 262
Z9 304
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 MAY 13
PY 2010
VL 465
IS 7295
BP 231
EP U121
DI 10.1038/nature08964
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500038
PM 20400944
DA 2026-03-09
ER

PT J
AU Togan, E
   Chu, Y
   Trifonov, AS
   Jiang, L
   Maze, J
   Childress, L
   Dutt, MVG
   Sorensen, AS
   Hemmer, PR
   Zibrov, AS
   Lukin, MD
AF Togan, E.
   Chu, Y.
   Trifonov, A. S.
   Jiang, L.
   Maze, J.
   Childress, L.
   Dutt, M. V. G.
   Sorensen, A. S.
   Hemmer, P. R.
   Zibrov, A. S.
   Lukin, M. D.
TI Quantum entanglement between an optical photon and a solid-state spin qubit
SO NATURE
LA English
DT Article
ID single-photon; atomic ensembles; diamond; excitation; interface; violation; matter; light
AB Quantum entanglement is among the most fascinating aspects of quantum theory(1). Entangled optical photons are now widely used for fundamental tests of quantum mechanics(2) and applications such as quantum cryptography(1). Several recent experiments demonstrated entanglement of optical photons with trapped ions(3), atoms(4,5) and atomic ensembles(6-8), which are then used to connect remote long-term memory nodes in distributed quantum networks(9-11). Here we realize quantum entanglement between the polarization of a single optical photon and a solid-state qubit associated with the single electronic spin of a nitrogen vacancy centre in diamond. Our experimental entanglement verification uses the quantum eraser technique(5,12), and demonstrates that a high degree of control over interactions between a solid-state qubit and the quantum light field can be achieved. The reported entanglement source can be used in studies of fundamental quantum phenomena and provides a key building block for the solid-state realization of quantum optical networks(13,14).
C1 [Togan, E.; Chu, Y.; Trifonov, A. S.; Jiang, L.; Maze, J.; Childress, L.; Dutt, M. V. G.; Zibrov, A. S.; Lukin, M. D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Jiang, L.] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
   [Jiang, L.] CALTECH, Inst Quantum Informat, Pasadena, CA 91125 USA.
   [Childress, L.] Bates Coll, Dept Phys & Astron, Lewiston, ME 04240 USA.
   [Dutt, M. V. G.] Univ Pittsburgh, Dept Phys & Astron, Pittsburgh, PA 15260 USA.
   [Sorensen, A. S.] Univ Copenhagen, Niels Bohr Inst, QUANTOP, DK-2100 Copenhagen, Denmark.
   [Hemmer, P. R.] Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX 77843 USA.
C3 Harvard University; California Institute of Technology; California Institute of Technology; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Copenhagen; Niels Bohr Institute; Texas A&M University System; Texas A&M University College Station
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM lukin@fas.harvard.edu
FU Defense Advanced Research Projects Agency; NSF; Harvard-MIT CUA; NDSEG Fellowship; Packard Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0969816] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [0847195] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0855599] Funding Source: National Science Foundation
NR 30
TC 1041
Z9 1212
U1 6
U2 369
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 730
EP U4
DI 10.1038/nature09256
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500033
PM 20686569
DA 2026-03-09
ER

PT J
AU Suzuki, J
   Umeda, M
   Sims, PJ
   Nagata, S
AF Suzuki, Jun
   Umeda, Masato
   Sims, Peter J.
   Nagata, Shigekazu
TI Calcium-dependent phospholipid scrambling by TMEM16F
SO NATURE
LA English
DT Article
ID scott-syndrome; blood-coagulation; apoptotic cells; expression cloning; phosphatidylserine; family; phosphatidylethanolamine; lymphocytes; disorder; exposure
AB In all animal cells, phospholipids are asymmetrically distributed between the outer and inner leaflets of the plasma membrane(1). This asymmetrical phospholipid distribution is disrupted in various biological systems. For example, when blood platelets are activated, they expose phosphatidylserine (PtdSer) to trigger the clotting system(2,3). The PtdSer exposure is believed to be mediated by Ca2+-dependent phospholipid scramblases that transport phospholipids bidirectionally(1,4), but its molecular mechanism is still unknown. Here we show that TMEM16F (transmembrane protein 16F) is an essential component for the Ca2+-dependent exposure of PtdSer on the cell surface. When a mouse B-cell line, Ba/F3, was treated with a Ca2+ ionophore under low-Ca2+ conditions, it reversibly exposed PtdSer. Using this property, we established a Ba/F3 subline that strongly exposed PtdSer by repetitive fluorescence-activated cell sorting. A complementary DNA library was constructed from the subline, and a cDNA that caused Ba/F3 to expose PtdSer spontaneously was identified by expression cloning. The cDNA encoded a constitutively active mutant of TMEM16F, a protein with eight transmembrane segments(5). Wild-type TMEM16F was localized on the plasma membrane and conferred Ca2+-dependent scrambling of phospholipids. A patient with Scott syndrome(6,7), which results from a defect in phospholipid scrambling activity(8,9), was found to carry a mutation at a splice-acceptor site of the gene encoding TMEM16F, causing the premature termination of the protein.
C1 [Suzuki, Jun; Nagata, Shigekazu] Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan.
   [Suzuki, Jun; Nagata, Shigekazu] Japan Sci & Technology Corp, Core Res Evolut Sci & Technol, Kyoto 6068501, Japan.
   [Umeda, Masato] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Nishikyo Ku, Kyoto 6158510, Japan.
   [Sims, Peter J.] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
C3 Kyoto University; Japan Science & Technology Agency (JST); Kyoto University; University of Rochester
RP Nagata, S (corresponding author), Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan.
EM snagata@mfour.med.kyoto-u.ac.jp
FU Japan Society for the Promotion of Science; National Institutes of Health, USA; Grants-in-Aid for Scientific Research [22390014] Funding Source: KAKEN
NR 36
TC 757
Z9 872
U1 4
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 DEC 9
PY 2010
VL 468
IS 7325
BP 834
EP U135
DI 10.1038/nature09583
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 691PQ
UT WOS:000285093700048
PM 21107324
DA 2026-03-09
ER

PT J
AU Fuller, RA
   McDonald-Madden, E
   Wilson, KA
   Carwardine, J
   Grantham, HS
   Watson, JEM
   Klein, CJ
   Green, DC
   Possingham, HP
AF Fuller, Richard A.
   McDonald-Madden, Eve
   Wilson, Kerrie A.
   Carwardine, Josie
   Grantham, Hedley S.
   Watson, James E. M.
   Klein, Carissa J.
   Green, David C.
   Possingham, Hugh P.
TI Replacing underperforming protected areas achieves better conservation outcomes
SO NATURE
LA English
DT Article
ID property-rights; global-network; gap analysis; thailand; reserve; priority; diversity; world; costs; save
AB Protected areas vary enormously in their contribution to conserving biodiversity, and the inefficiency of protected area systems is widely acknowledged(1-3). However, conservation plans focus overwhelmingly on adding new sites to current protected area estates(4). Here we show that the conservation performance of a protected area system can be radically improved, without extra expenditure, by replacing a small number of protected areas with new ones that achieve more for conservation. Replacing the least cost-effective 1% of Australia's 6,990 strictly protected areas could increase the number of vegetation types that have 15% or more of their original extent protected from 18 to 54, of a maximum possible of 58. Moreover, it increases markedly the area that can be protected, with no increase in overall spending. This new paradigm for protected area system expansion could yield huge improvements to global conservation at a time when competition for land is increasingly intense.
C1 [Fuller, Richard A.; McDonald-Madden, Eve; Wilson, Kerrie A.; Carwardine, Josie; Grantham, Hedley S.; Watson, James E. M.; Klein, Carissa J.; Possingham, Hugh P.] Univ Queensland, Ctr Ecol, St Lucia, Qld 4072, Australia.
   [Fuller, Richard A.; McDonald-Madden, Eve; Carwardine, Josie] CSIRO Climate Adaptat Flagship, St Lucia, Qld 4072, Australia.
   [Fuller, Richard A.; McDonald-Madden, Eve; Carwardine, Josie] CSIRO Sustainable Ecosyst, St Lucia, Qld 4072, Australia.
   [Green, David C.] Univ Queensland, Informat Technol Serv, St Lucia, Qld 4072, Australia.
C3 University of Queensland; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Queensland
RP Fuller, RA (corresponding author), Univ Queensland, Ctr Ecol, St Lucia, Qld 4072, Australia.
EM r.a.fuller@dunelm.org.uk
FU Centre for Applied Environmental Decision Analysis, an Australian Commonwealth Environment Research Facility
NR 27
TC 198
Z9 236
U1 2
U2 232
PU 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 15
PY 2010
VL 466
IS 7304
BP 365
EP 367
DI 10.1038/nature09180
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100048
PM 20592729
DA 2026-03-09
ER

PT J
AU Carey, AF
   Wang, GR
   Su, CY
   Zwiebel, LJ
   Carlson, JR
AF Carey, Allison F.
   Wang, Guirong
   Su, Chih-Ying
   Zwiebel, Laurence J.
   Carlson, John R.
TI Odorant reception in the malaria mosquito Anopheles gambiae
SO NATURE
LA English
DT Article
ID volatile organic-compounds; human skin emanations; drosophila-antenna; aedes-aegypti; molecular-basis; cellular basis; identification; attractants; olfaction; behavior
AB The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan Africa. It locates its human hosts primarily through olfaction, but little is known about the molecular basis of this process. Here we functionally characterize the Anopheles gambiae odorant receptor (AgOr) repertoire. We identify receptors that respond strongly to components of human odour and that may act in the process of human recognition. Some of these receptors are narrowly tuned, and some salient odorants elicit strong responses from only one or a few receptors, suggesting a central role for specific transmission channels in human host-seeking behaviour. This analysis of the Anopheles gambiae receptors permits a comparison with the corresponding Drosophila melanogaster odorant receptor repertoire. We find that odorants are differentially encoded by the two species in ways consistent with their ecological needs. Our analysis of the Anopheles gambiae repertoire identifies receptors that may be useful targets for controlling the transmission of malaria.
C1 [Carey, Allison F.; Su, Chih-Ying; Carlson, John R.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Wang, Guirong; Zwiebel, Laurence J.] Vanderbilt Univ, Global Hlth & Program Dev Biol, Nashville, TN 37235 USA.
   [Wang, Guirong; Zwiebel, Laurence J.] Vanderbilt Univ, Inst Biol Chem, Ctr Mol Neurosci, Dept Biol Sci, Nashville, TN 37235 USA.
C3 Yale University; Vanderbilt University; Vanderbilt University
RP Carlson, JR (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM john.carlson@yale.edu
FU Foundation for the National Institutes of Health (NIH); NIH [2T32GM07205]; National Institute on Deafness and Other Communication Disorders [R01DC004729, R01DC002174] Funding Source: NIH RePORTER
NR 47
TC 447
Z9 530
U1 4
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 MAR 4
PY 2010
VL 464
IS 7285
BP 66
EP U77
DI 10.1038/nature08834
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500034
PM 20130575
DA 2026-03-09
ER

PT J
AU Thorne, RM
   Ni, BB
   Tao, X
   Horne, RB
   Meredith, NP
AF Thorne, Richard M.
   Ni, Binbin
   Tao, Xin
   Horne, Richard B.
   Meredith, Nigel P.
TI Scattering by chorus waves as the dominant cause of diffuse auroral precipitation
SO NATURE
LA English
DT Article
ID pitch-angle; electrostatic-waves; radiation; distributions; cyclotron; driven
AB Earth's diffuse aurora occurs over a broad latitude range(1) and is primarily caused by the precipitation of low-energy (0.1-30-keV) electrons originating in the central plasma sheet(2), which is the source region for hot electrons in the nightside outer magnetosphere. Although generally not visible, the diffuse auroral precipitation provides the main source of energy for the high-latitude nightside upper atmosphere(3), leading to enhanced ionization and chemical changes. Previous theoretical studies have indicated that two distinct classes of magnetospheric plasma wave, electrostatic electron cyclotron harmonic waves(4,5) and whistler-mode chorus waves(6,7), could be responsible for the electron scattering that leads to diffuse auroral precipitation, but it has hitherto not been possible to determine which is the more important. Here we report an analysis of satellite wave data and Fokker-Planck diffusion calculations which reveals that scattering by chorus is the dominant cause of the most intense diffuse auroral precipitation. This resolves a long-standing controversy. Furthermore, scattering by chorus can remove most electrons as they drift around Earth's magnetosphere, leading to the development of observed pancake distributions(8), and can account for the global morphology of the diffuse aurora(1,3).
C1 [Thorne, Richard M.; Ni, Binbin; Tao, Xin] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
   [Horne, Richard B.; Meredith, Nigel P.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Horne, Richard B.] Univ Sheffield, Dept Automat Control & Syst Engn, Sheffield S1 3JD, S Yorkshire, England.
C3 University of California System; University of California Los Angeles; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of Sheffield
RP Thorne, RM (corresponding author), Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, 405 Hilgard Ave, Los Angeles, CA 90095 USA.
EM rmt@atmos.ucla.edu
FU NSF [ATM 0802843]; UK Natural Environment Research Council; Natural Environment Research Council [bas0100025, bas0100023] Funding Source: researchfish; NERC [bas0100025, bas0100023] Funding Source: UKRI
NR 16
TC 514
Z9 559
U1 3
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 OCT 21
PY 2010
VL 467
IS 7318
BP 943
EP 946
DI 10.1038/nature09467
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700033
PM 20962841
DA 2026-03-09
ER

PT J
AU Muraki, N
   Nomata, J
   Ebata, K
   Mizoguchi, T
   Shiba, T
   Tamiaki, H
   Kurisu, G
   Fujita, Y
AF Muraki, Norifumi
   Nomata, Jiro
   Ebata, Kozue
   Mizoguchi, Tadashi
   Shiba, Tomoo
   Tamiaki, Hitoshi
   Kurisu, Genji
   Fujita, Yuichi
TI X-ray crystal structure of the light-independent protochlorophyllide reductase
SO NATURE
LA English
DT Article
ID pyrococcus-furiosus; bchn-bchb; l-protein; in-vitro; oxidoreductase; biosynthesis; ligand; enzyme; identification; ferredoxin
AB Photosynthetic organisms adopt two different strategies for the reduction of the C17=C18 double bond of protochlorophyllide (Pchlide) to form chlorophyllide a, the direct precursor of chlorophyll a (refs 1-4). The first involves the activity of the light-dependent Pchlide oxidoreductase(5-9), and the second involves the light-independent (dark-operative) Pchlide oxidoreductase(10) (DPOR). DPOR is a nitrogenase-like enzyme consisting of two components, L-protein (a BchL dimer) and NB-protein (a BchN-BchB heterotetramer), which are structurally related to nitrogenase Fe protein and MoFe protein, respectively(10,11). Here we report the crystal structure of the NB-protein of DPOR from Rhodobacter capsulatus at a resolution of 2.3 angstrom. As expected, the overall structure is similar to that of nitrogenase MoFe protein: each catalytic BchN-BchB unit contains one Pchlide and one iron-sulphur cluster (NB-cluster) coordinated uniquely by one aspartate and three cysteines. Unique aspartate ligation is not necessarily needed for the cluster assembly but is essential for the catalytic activity. Specific Pchlide-binding accompanies the partial unwinding of an a-helix that belongs to the next catalytic BchN-BchB unit. We propose a unique trans-specific reduction mechanism in which the distorted C17-propionate of Pchlide and an aspartate from BchB serve as proton donors for C18 and C17 of Pchlide, respectively. Intriguingly, the spatial arrangement of the NB-cluster and Pchlide is almost identical to that of the P-cluster and FeMo-cofactor in nitrogenase MoFe-protein, illustrating that a common architecture exists to reduce chemically stable multibonds of porphyrin and dinitrogen.
C1 [Muraki, Norifumi; Kurisu, Genji] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan.
   [Muraki, Norifumi; Shiba, Tomoo] Univ Tokyo, Dept Life Sci, Meguro Ku, Tokyo 1538902, Japan.
   [Nomata, Jiro; Ebata, Kozue; Fujita, Yuichi] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Mizoguchi, Tadashi; Tamiaki, Hitoshi] Ritsumeikan Univ, Dept Biosci & Biotechnol, Shiga 5258577, Japan.
   [Fujita, Yuichi] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan.
C3 University of Osaka; University of Tokyo; Nagoya University; Ritsumeikan University; Japan Science & Technology Agency (JST)
RP Kurisu, G (corresponding author), Osaka Univ, Inst Prot Res, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM gkurisu@protein.osaka-u.ac.jp; fujita@agr.nagoya-u.ac.jp
FU Japan Society for the Promotion of Science (JSPS) [17687008, 18054308, 19570036, 20200063, 19750148, 19350088, 19010733, 2110614]; Japan Science and Technology Agency (JST); Kato Memorial Science Foundation; Toyoaki Scholarship Foundation; Japan Securities Scholarship Foundation; Grants-in-Aid for Scientific Research [19750148, 17687008] Funding Source: KAKEN
NR 33
TC 163
Z9 193
U1 4
U2 83
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 110
EP U124
DI 10.1038/nature08950
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900041
PM 20400946
DA 2026-03-09
ER

PT J
AU Li, L
   Jose, J
   Xiang, Y
   Kuhn, RJ
   Rossmann, MG
AF Li, Long
   Jose, Joyce
   Xiang, Ye
   Kuhn, Richard J.
   Rossmann, Michael G.
TI Structural changes of envelope proteins during alphavirus fusion
SO NATURE
LA English
DT Article
ID semliki-forest-virus; ph-dependent fusion; class-ii virus; sindbis virus; conformational-change; dynamic envelope; membrane-fusion; glycoprotein; precursor; e3
AB Alphaviruses are enveloped RNA viruses that have a diameter of about 700 angstrom and can be lethal human pathogens(1). Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2-E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface(1,2), 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T 54 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion(3,4). The E2 protein is responsible for receptor binding(5,6) and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm(3,4). Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2-E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino-and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.
C1 [Li, Long; Jose, Joyce; Xiang, Ye; Kuhn, Richard J.; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University
RP Rossmann, MG (corresponding author), Purdue Univ, Dept Biol Sci, 915 W State St, W Lafayette, IN 47907 USA.
EM mr@purdue.edu
FU NIH [P01 AI055672]
NR 45
TC 271
Z9 335
U1 2
U2 36
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 2
PY 2010
VL 468
IS 7324
BP 705
EP U131
DI 10.1038/nature09546
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700043
PM 21124457
DA 2026-03-09
ER

PT J
AU Currie, TE
   Greenhill, SJ
   Gray, RD
   Hasegawa, T
   Mace, R
AF Currie, Thomas E.
   Greenhill, Simon J.
   Gray, Russell D.
   Hasegawa, Toshikazu
   Mace, Ruth
TI Rise and fall of political complexity in island South-East Asia and the Pacific
SO NATURE
LA English
DT Article
ID evolution
AB There is disagreement about whether human political evolution has proceeded through a sequence of incremental increases in complexity, or whether larger, non-sequential increases have occurred. The extent to which societies have decreased in complexity is also unclear. These debates have continued largely in the absence of rigorous, quantitative tests. We evaluated six competing models of political evolution in Austronesian-speaking societies using phylogenetic methods. Here we show that in the best-fitting model political complexity rises and falls in a sequence of small steps. This is closely followed by another model in which increases are sequential but decreases can be either sequential or in bigger drops. The results indicate that large, non-sequential jumps in political complexity have not occurred during the evolutionary history of these societies. This suggests that, despite the numerous contingent pathways of human history, there are regularities in cultural evolution that can be detected using computational phylogenetic methods.
C1 [Currie, Thomas E.; Hasegawa, Toshikazu] Univ Tokyo, Grad Sch Arts & Sci, Evolutionary Cognit Sci Res Ctr, Tokyo 1538902, Japan.
   [Currie, Thomas E.; Mace, Ruth] UCL, Dept Anthropol, Human Evolutionary Ecol Grp, London WC1H 0BW, England.
   [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 University of Tokyo; University of London; University College London; University of Auckland; University of Auckland
RP Currie, TE (corresponding author), Univ Tokyo, Grad Sch Arts & Sci, Evolutionary Cognit Sci Res Ctr, Tokyo 1538902, Japan.
EM t.currie@ucl.ac.uk
FU ESRC/NERC; Japan Society for the Promotion of Science; Royal Society of New Zealand; European Research Council
NR 30
TC 144
Z9 156
U1 3
U2 65
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 801
EP 804
DI 10.1038/nature09461
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700057
PM 20944739
DA 2026-03-09
ER

PT J
AU Rosing, MT
   Bird, DK
   Sleep, NH
   Bjerrum, CJ
AF Rosing, Minik T.
   Bird, Dennis K.
   Sleep, Norman H.
   Bjerrum, Christian J.
TI No climate paradox under the faint early Sun
SO NATURE
LA English
DT Article
ID continental-crust; atmospheric co2; evolution; oxygen; earth; models; ch4; greenhouse; paleosols; greenland
AB Environmental niches in which life first emerged and later evolved on the Earth have undergone dramatic changes in response to evolving tectonic/geochemical cycles and to biologic interventions(1-3), as well as increases in the Sun's luminosity of about 25 to 30 per cent over the Earth's history(4). It has been inferred that the greenhouse effect of atmospheric CO2 and/or CH4 compensated for the lower solar luminosity and dictated an Archaean climate in which liquid water was stable in the hydrosphere(5-8). Here we demonstrate, however, that the mineralogy of Archaean sediments, particularly the ubiquitous presence of mixed-valence Fe(II-III) oxides (magnetite) in banded iron formations(9) is inconsistent with such high concentrations of greenhouse gases and the metabolic constraints of extant methanogens. Prompted by this, and the absence of geologic evidence for very high greenhouse-gas concentrations(10-13), we hypothesize that a lower albedo on the Earth, owing to considerably less continental area and to the lack of biologically induced cloud condensation nuclei(14), made an important contribution to moderating surface temperature in the Archaean eon. Our model calculations suggest that the lower albedo of the early Earth provided environmental conditions above the freezing point of water, thus alleviating the need for extreme greenhouse-gas concentrations to satisfy the faint early Sun paradox.
C1 [Rosing, Minik T.; Bird, Dennis K.; Bjerrum, Christian J.] Univ Copenhagen, Nord Ctr Earth Evolut, DK-1350 Copenhagen K, Denmark.
   [Rosing, Minik T.] Univ Copenhagen, Nat Hist Museum Denmark, DK-1350 Copenhagen K, Denmark.
   [Bjerrum, Christian J.] Univ Copenhagen, Dept Geog & Geol, DK-1350 Copenhagen K, Denmark.
   [Rosing, Minik T.; Bird, Dennis K.] Stanford Univ, Dept Geol & Environm Sci, Stanford, CA 94305 USA.
   [Sleep, Norman H.] Stanford Univ, Dept Geophys, Stanford, CA 94305 USA.
C3 University of Copenhagen; University of Copenhagen; University of Copenhagen; Stanford University; Stanford University
RP Rosing, MT (corresponding author), Univ Copenhagen, Nord Ctr Earth Evolut, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
EM minik@snm.ku.dk
FU Danish National Research Foundation; Allan C. Cox Professorship; Department of Geological and Environmental Sciences, Stanford University; NSF
NR 51
TC 178
Z9 204
U1 0
U2 134
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 744
EP U117
DI 10.1038/nature08955
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000042
PM 20360739
DA 2026-03-09
ER

PT J
AU Garcia-Perez, JL
   Morell, M
   Scheys, JO
   Kulpa, DA
   Morell, S
   Carter, CC
   Hammer, GD
   Collins, KL
   O'Shea, KS
   Menendez, P
   Moran, JV
AF Garcia-Perez, Jose L.
   Morell, Maria
   Scheys, Joshua O.
   Kulpa, Deanna A.
   Morell, Santiago
   Carter, Christoph C.
   Hammer, Gary D.
   Collins, Kathleen L.
   O'Shea, K. Sue
   Menendez, Pablo
   Moran, John V.
TI Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells
SO NATURE
LA English
DT Article
ID stem-cells; line-1 retrotransposition; somatic mosaicism; protein; mouse; expression; patterns; virus
AB Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution(1,2). L1s can retrotranspose in the germline, during early development and in select somatic cells(3-8); however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.
C1 [Garcia-Perez, Jose L.; Moran, John V.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Garcia-Perez, Jose L.; Morell, Maria; Morell, Santiago; Menendez, Pablo] Univ Granada, Ctr Biomed Res, Consejeria Salud Junta Andalucia, Andalusian Stem Cell Bank, Granada 18100, Spain.
   [Morell, Maria; Hammer, Gary D.; O'Shea, K. Sue] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Scheys, Joshua O.; Carter, Christoph C.; Hammer, Gary D.; Collins, Kathleen L.; Moran, John V.] Univ Michigan, Sch Med, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA.
   [Kulpa, Deanna A.; Hammer, Gary D.; Collins, Kathleen L.; Moran, John V.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Hammer, Gary D.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
   [Collins, Kathleen L.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Moran, John V.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 University of Michigan System; University of Michigan; University of Granada; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Howard Hughes Medical Institute
RP Moran, JV (corresponding author), Univ Michigan, Sch Med, Dept Human Genet, 1241 E Catherine St, Ann Arbor, MI 48109 USA.
EM josel.garcia.perez@juntadeandalucia.es; moranj@umich.edu
FU National Institutes of Health (NIH) [GM060518, GM082970, NS-048187, GM-069985, AI051198]; Howard Hughes Medical Institute; Instituto de Salud Carlos III - Consejeria de Salud Junta de Andalucia (ISCIII-CSJA) [EMER07/056]; Marie Curie International Reintegration Grant action [FP7-PEOPLE-2007-4-3-IRG]; Junta de Andalucia (Spain) [P09-CTS-4980, PI0002/2009, P08-CTS-3678]; Spanish Ministry of Health [FIS PI08171, CP07/00065, FIS PI070026]; Spanish Ministry of Science and Innovation MICINN-PLANE [PLE-2009-0111]; Burroughs Wellcome Foundation; National Institute of Diabetes and Digestive and Kidney Diseases NIH [R01 (DK62027)]; Cellular and Molecular Approaches to Systems and Integrative Biology Training Grant [T32-GM08322]; Cancer Research Institute; University of Michigan; University of Michigan's Cancer Center [NIH 5 P30 CA46592]; National Cancer Institute [P30CA046592] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK062027] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007315, R01GM060518] Funding Source: NIH RePORTER
NR 30
TC 129
Z9 148
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 AUG 5
PY 2010
VL 466
IS 7307
BP 769
EP 773
DI 10.1038/nature09209
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500042
PM 20686575
DA 2026-03-09
ER

PT J
AU Schwickart, M
   Huang, XD
   Lill, JR
   Liu, JF
   Ferrando, R
   French, DM
   Maecker, H
   O'Rourke, K
   Bazan, F
   Eastham-Anderson, J
   Yue, P
   Dornan, D
   Huang, DCS
   Dixit, VM
AF Schwickart, Martin
   Huang, XiaoDong
   Lill, Jennie R.
   Liu, Jinfeng
   Ferrando, Ronald
   French, Dorothy M.
   Maecker, Heather
   O'Rourke, Karen
   Bazan, Fernando
   Eastham-Anderson, Jeffrey
   Yue, Peng
   Dornan, David
   Huang, David C. S.
   Dixit, Vishva M.
TI Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival
SO NATURE
LA English
DT Article
ID multiple-myeloma; bcl-2 family; ubiquitin ligase; breast-cancer; in-vitro; apoptosis; expression; proteins; pathway; activation
AB MCL1 is essential for the survival of stem and progenitor cells of multiple lineages(1,2), and is unique among pro-survival BCL2 family members in that it is rapidly turned over through the action of ubiquitin ligases(3-6). B-and mantle-cell lymphomas, chronic myeloid leukaemia, and multiple myeloma(7-9), however, express abnormally high levels of MCL1, contributing to chemoresistance and disease relapse. The mechanism of MCL1 overexpression in cancer is not well understood. Here we show that the deubiquitinase USP9X stabilizes MCL1 and thereby promotes cell survival. USP9X binds MCL1 and removes the Lys 48-linked polyubiquitin chains that normally mark MCL1 for proteasomal degradation. Increased USP9X expression correlates with increased MCL1 protein in human follicular lymphomas and diffuse large B-cell lymphomas. Moreover, patients with multiple myeloma overexpressing USP9X have a poor prognosis. Knockdown of USP9X increases MCL1 polyubiquitination, which enhances MCL1 turnover and cell killing by the BH3 mimetic ABT-737. These results identify USP9X as a prognostic and therapeutic target, and they show that deubiquitinases may stabilize labile oncoproteins in human malignancies.
C1 [Schwickart, Martin; Huang, XiaoDong; O'Rourke, Karen; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
   [Lill, Jennie R.] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Liu, Jinfeng; Yue, Peng] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA.
   [Ferrando, Ronald; French, Dorothy M.; Eastham-Anderson, Jeffrey] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Bazan, Fernando] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA.
   [Maecker, Heather] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA.
   [Dornan, David] Genentech Inc, Dept Res Oncol Diagnost, San Francisco, CA 94080 USA.
   [Huang, David C. S.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Walter & Eliza Hall Institute; Melbourne Health; Royal Melbourne Hospital
RP Dixit, VM (corresponding author), Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA.
EM dixit@gene.com
NR 31
TC 534
Z9 631
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 JAN 7
PY 2010
VL 463
IS 7277
BP 103
EP U114
DI 10.1038/nature08646
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900039
PM 20023629
DA 2026-03-09
ER

PT J
AU Kinchen, JM
   Ravichandran, KS
AF Kinchen, Jason M.
   Ravichandran, Kodi S.
TI Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells
SO NATURE
LA English
DT Article
ID c-elegans; caenorhabditis-elegans; phagosome maturation; death; degradation; receptor; endocytosis; mechanisms; proteins; pathway
AB Engulfment of apoptotic cells occurs throughout life in multicellular organisms. Impaired apoptotic cell clearance (due to defective recognition, internalization or degradation) results in autoimmune disease(1,2). One fundamental challenge in understanding how defects in corpse removal translate into diseased states is the identification of critical components orchestrating the different stages of engulfment. Here we use genetic, cell biological and molecular studies in Caenorhabditis elegans and mammalian cells to identify SAND-1 and its partner CCZ-1 as new factors in corpse removal. In worms deficient in either sand-1 or ccz-1, apoptotic cells are internalized and the phagosomes recruit the small GTPase RAB-5 but fail to progress to the subsequent RAB-7(+) stage. The mammalian orthologues of SAND-1, namely Mon1a and Mon1b, were similarly required for phagosome maturation. Mechanistically, Mon1 interacts with GTP-bound Rab5, identifying Mon1 as a previously unrecognized Rab5 effector. Moreover, a Mon1-Ccz1 complex (but not either protein alone) could bind Rab7 and could also influence Rab7 activation, suggesting Mon1-Ccz1 as an important link in progression from the Rab5-positive stage to the Rab7-positive stage of phagosome maturation. Taken together, these data identify SAND-1 (Mon1) and CCZ-1 (Ccz1) as critical and evolutionarily conserved components regulating the processing of ingested apoptotic cell corpses.
C1 [Kinchen, Jason M.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Ravichandran, Kodi S.] Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Kinchen, Jason M.; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
EM kinchen@virginia.edu; ravi@virginia.edu
FU NIH; American Heart Association; NIGMS/NIH
NR 35
TC 192
Z9 243
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 APR 1
PY 2010
VL 464
IS 7289
BP 778
EP U157
DI 10.1038/nature08853
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000049
PM 20305638
DA 2026-03-09
ER

PT J
AU Carvajal-Vergara, X
   Sevilla, A
   D'Souza, SL
   Ang, YS
   Schaniel, C
   Lee, DF
   Yang, L
   Kaplan, AD
   Adler, ED
   Rozov, R
   Ge, YC
   Cohen, N
   Edelmann, LJ
   Chang, B
   Waghray, A
   Su, J
   Pardo, S
   Lichtenbelt, KD
   Tartaglia, M
   Gelb, BD
   Lemischka, IR
AF Carvajal-Vergara, Xonia
   Sevilla, Ana
   D'Souza, Sunita L.
   Ang, Yen-Sin
   Schaniel, Christoph
   Lee, Dung-Fang
   Yang, Lei
   Kaplan, Aaron D.
   Adler, Eric D.
   Rozov, Roye
   Ge, YongChao
   Cohen, Ninette
   Edelmann, Lisa J.
   Chang, Betty
   Waghray, Avinash
   Su, Jie
   Pardo, Sherly
   Lichtenbelt, Klaske D.
   Tartaglia, Marco
   Gelb, Bruce D.
   Lemischka, Ihor R.
TI Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome
SO NATURE
LA English
DT Article
ID somatic ptpn11 mutations; shp2 mutations; human es; differentiation; hematopoiesis; expression; leukemia
AB The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems(1,2). The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.
C1 [Carvajal-Vergara, Xonia; Sevilla, Ana; D'Souza, Sunita L.; Ang, Yen-Sin; Schaniel, Christoph; Lee, Dung-Fang; Yang, Lei; Rozov, Roye; Chang, Betty; Waghray, Avinash; Su, Jie; Lemischka, Ihor R.] Mt Sinai Sch Med, Black Family Stem Cell Inst, Dept Dev & Regenerat Biol, Dept Gene & Cell Med, New York, NY 10029 USA.
   [Carvajal-Vergara, Xonia] Ctr Nacl Invest Cardiovasc, Dept Regenerat Cardiol, Madrid 28029, Spain.
   [Kaplan, Aaron D.; Adler, Eric D.] Mt Sinai Sch Med, Dept Med, Cardiovasc Inst, New York, NY 10029 USA.
   [Ge, YongChao] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
   [Cohen, Ninette; Edelmann, Lisa J.; Pardo, Sherly; Gelb, Bruce D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Pardo, Sherly; Gelb, Bruce D.] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY 10029 USA.
   [Lichtenbelt, Klaske D.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 EA Utrecht, Netherlands.
   [Tartaglia, Marco] Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy.
   [Gelb, Bruce D.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA.
C3 Icahn School of Medicine at Mount Sinai; Centro Nacional de Investigaciones Cardiovasculares (CNIC); Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Utrecht University; Utrecht University Medical Center; Istituto Superiore di Sanita (ISS); Icahn School of Medicine at Mount Sinai
RP Carvajal-Vergara, X (corresponding author), Mt Sinai Sch Med, Black Family Stem Cell Inst, Dept Dev & Regenerat Biol, Dept Gene & Cell Med, New York, NY 10029 USA.
FU National Institutes of Health (NIH) [5R01GM078465]; New York State Department of Health (NYSTEM) [C024410, C024176, C024407]; American College of Cardiology/Pfizer; ERA; Ministerio de Ciencia e Innovacion/Instituto de Salud Carlos III; New York Stem Cell Foundation; Ruth L. Kirschstein National Research Service Award (NRSA) [T32]
NR 31
TC 536
Z9 641
U1 0
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 808
EP U12
DI 10.1038/nature09005
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800051
PM 20535210
DA 2026-03-09
ER

PT J
AU Osi, A
   Butler, RJ
   Weishampel, DB
AF Osi, Attila
   Butler, Richard J.
   Weishampel, David B.
TI A Late Cretaceous ceratopsian dinosaur from Europe with Asian affinities
SO NATURE
LA English
DT Article
ID neoceratopsian dinosaur; early evolution; remains; hungary; china
AB Ceratopsians (horned dinosaurs) represent a highly diverse and abundant radiation of non-avian dinosaurs(1-5) known primarily from the Cretaceous period (65-145 million years ago). This radiation has been considered to be geographically limited to Asia and western North America(1-3), with only controversial remains reported from other continents. Here we describe new ceratopsian cranial material from the Late Cretaceous of Iharkut, Hungary(6), from a coronosaurian ceratopsian, Ajkaceratops kozmai. Ajkaceratops is most similar to 'bagaceratopsids' such as Bagaceratops and Magnirostris, previously known only from Late Cretaceous east Asia(3,5,7,8). The new material unambiguously demonstrates that ceratopsians occupied Late Cretaceous Europe and, when considered with the recent discovery of possible leptoceratopsid teeth from Sweden(9), indicates that the clade may have reached Europe on at least two independent occasions. European Late Cretaceous dinosaur faunas have been characterized as consisting of a mix of endemic 'relictual' taxa and 'Gondwanan' taxa, with typical Asian and North American groups largely absent(10,11). Ajkaceratops demonstrates that this prevailing biogeographical hypothesis is overly simplified and requires reassessment. Iharkut was part of the western Tethyan archipelago, a tectonically complex series of island chains between Africa and Europe(12), and the occurrence of a coronosaurian ceratopsian in this locality may represent an early Late Cretaceous 'island-hopping' dispersal across the Tethys Ocean.
C1 [Osi, Attila] Hungarian Acad Sci, Res Grp Paleontol, Hungarian Nat Hist Museum, H-1083 Budapest, Hungary.
   [Butler, Richard J.] Bayer Staatssammlung Palaontol & Geol, D-80333 Munich, Germany.
   [Weishampel, David B.] Johns Hopkins Univ, Ctr Funct Anat & Evolut, Baltimore, MD 21205 USA.
C3 Hungarian Academy of Sciences; Johns Hopkins University
RP Osi, A (corresponding author), Hungarian Acad Sci, Res Grp Paleontol, Hungarian Nat Hist Museum, Ludovika Ter 2, H-1083 Budapest, Hungary.
EM hungaros@freemail.hu
FU Hungarian Scientific Research Fund (OTKA) [PD 73021]; Hantken Foundation; Humboldt Postdoctoral Fellowship
NR 30
TC 53
Z9 58
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 466
EP 468
DI 10.1038/nature09019
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700032
PM 20505726
DA 2026-03-09
ER

PT J
AU Collinet, C
   Stöter, M
   Bradshaw, CR
   Samusik, N
   Rink, JC
   Kenski, D
   Habermann, B
   Buchholz, F
   Henschel, R
   Mueller, MS
   Nagel, WE
   Fava, E
   Kalaidzidis, Y
   Zerial, M
AF Collinet, Claudio
   Stoeter, Martin
   Bradshaw, Charles R.
   Samusik, Nikolay
   Rink, Jochen C.
   Kenski, Denise
   Habermann, Bianca
   Buchholz, Frank
   Henschel, Robert
   Mueller, Matthias S.
   Nagel, Wolfgang E.
   Fava, Eugenio
   Kalaidzidis, Yannis
   Zerial, Marino
TI Systems survey of endocytosis by multiparametric image analysis
SO NATURE
LA English
DT Article
ID mediated endocytosis; signal-transduction; cell biology; endosm; cytokinesis; specificity; mechanisms; proteins; gradient; screen
AB Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.
C1 [Collinet, Claudio; Bradshaw, Charles R.; Samusik, Nikolay; Habermann, Bianca; Buchholz, Frank; Kalaidzidis, Yannis; Zerial, Marino] MPI CBG, Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Henschel, Robert; Mueller, Matthias S.; Nagel, Wolfgang E.] Tech Univ Dresden, Ctr Informat Serv & High Performance Comp ZIH, D-01062 Dresden, Germany.
   [Kalaidzidis, Yannis] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia.
C3 Max Planck Society; Technische Universitat Dresden; Lomonosov Moscow State University
RP Zerial, M (corresponding author), MPI CBG, Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
EM zerial@mpi-cbg.de
FU Max Planck Society (MPG); HepatoSys of the German Ministry for Education and Research BMBF; DFG; Gottlieb Daimler und Karl Benz Stiftung; European Community
NR 44
TC 351
Z9 406
U1 0
U2 57
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 243
EP U123
DI 10.1038/nature08779
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100039
PM 20190736
DA 2026-03-09
ER

PT J
AU Liao, YA
   Rittner, ASC
   Paprotta, T
   Li, WH
   Partridge, GB
   Hulet, RG
   Baur, SK
   Mueller, EJ
AF Liao, Yean-an
   Rittner, Ann Sophie C.
   Paprotta, Tobias
   Li, Wenhui
   Partridge, Guthrie B.
   Hulet, Randall G.
   Baur, Stefan K.
   Mueller, Erich J.
TI Spin-imbalance in a one-dimensional Fermi gas
SO NATURE
LA English
DT Article
ID delta-function interaction; phase-separation; superconductivity
AB Superconductivity and magnetism generally do not coexist. Changing the relative number of up and down spin electrons disrupts the basic mechanism of superconductivity, where atoms of opposite momentum and spin form Cooper pairs. Nearly forty years ago Fulde and Ferrell(1) and Larkin and Ovchinnikov(2) (FFLO) proposed an exotic pairing mechanism in which magnetism is accommodated by the formation of pairs with finite momentum. Despite intense theoretical and experimental efforts, however, polarized superconductivity remains largely elusive(3). Unlike the three-dimensional (3D) case, theories predict that in one dimension (1D) a state with FFLO correlations occupies a major part of the phase diagram(4-12). Here we report experimental measurements of density profiles of a two-spin mixture of ultracold Li-6 atoms trapped in an array of 1D tubes (a system analogous to electrons in 1D wires). At finite spin imbalance, the system phase separates with an inverted phase profile, as compared to the 3D case. In 1D, we find a partially polarized core surrounded by wings which, depending on the degree of polarization, are composed of either a completely paired or a fully polarized Fermi gas. Our work paves the way to direct observation and characterization of FFLO pairing.
C1 [Liao, Yean-an; Rittner, Ann Sophie C.; Paprotta, Tobias; Li, Wenhui; Partridge, Guthrie B.; Hulet, Randall G.] Rice Univ, Dept Phys & Astron, Houston, TX 77251 USA.
   [Liao, Yean-an; Rittner, Ann Sophie C.; Paprotta, Tobias; Li, Wenhui; Partridge, Guthrie B.; Hulet, Randall G.] Rice Univ, Rice Quantum Inst, Houston, TX 77251 USA.
   [Baur, Stefan K.; Mueller, Erich J.] Cornell Univ, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
   [Li, Wenhui] Natl Univ Singapore, Ctr Quantum Technol, Singapore 117543, Singapore.
C3 Rice University; Rice University; Cornell University; National University of Singapore
RP Hulet, RG (corresponding author), Rice Univ, Dept Phys & Astron, Houston, TX 77251 USA.
EM randy@rice.edu
FU DARPAOLE programme [W911NF-07-1-0464]; NSF; ONR; Welch Foundation [C-1133]; Keck Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0801457] Funding Source: National Science Foundation
NR 40
TC 460
Z9 510
U1 2
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 567
EP U86
DI 10.1038/nature09393
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100033
PM 20882011
DA 2026-03-09
ER

PT J
AU Wang, LM
   Anderson, DJ
AF Wang, Liming
   Anderson, David J.
TI Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila
SO NATURE
LA English
DT Article
ID behavioral-responses; sensitive neurons; melanogaster; acetate; protein; fly
AB Aggression is regulated by pheromones in many animal species(1-3). However, in no system have aggression pheromones, their cognate receptors and corresponding sensory neurons been identified. Here we show that 11-cis-vaccenyl acetate (cVA), a male-specific volatile pheromone, robustly promotes male-male aggression in the vinegar fly Drosophila melanogaster. The aggression-promoting effect of synthetic cVA requires olfactory sensory neurons (OSNs) expressing the receptor Or67d(4-6), as well as the receptor itself. Activation of Or67d-expressing OSNs, either by genetic manipulation of their excitability or by exposure to male pheromones in the absence of other classes of OSNs, is sufficient to promote aggression. High densities of male flies can promote aggression by the release of volatile cVA. In turn, cVA-promoted aggression can promote male fly dispersal from a food resource, in a manner dependent on Or67d-expressing OSNs. These data indicate that cVA may mediate negative-feedback control of male population density, through its effect on aggression. Identification of a pheromone-OSN pair controlling aggression in a genetic organism opens the way to unravelling the neurobiology of this evolutionarily conserved behaviour.
C1 [Wang, Liming; Anderson, David J.] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA.
   [Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
C3 California Institute of Technology; Howard Hughes Medical Institute; California Institute of Technology
RP Anderson, DJ (corresponding author), CALTECH, Div Biol 216 76, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM lmwang@caltech.edu; wuwei@caltech.edu
FU NSF [EF-0623527, MCB-0418479]; Howard Hughes Medical Institute
NR 30
TC 236
Z9 297
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 JAN 14
PY 2010
VL 463
IS 7278
BP 227
EP U114
DI 10.1038/nature08678
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700035
PM 19966787
DA 2026-03-09
ER

PT J
AU Efremov, RG
   Baradaran, R
   Sazanov, LA
AF Efremov, Rouslan G.
   Baradaran, Rozbeh
   Sazanov, Leonid A.
TI The architecture of respiratory complex I
SO NATURE
LA English
DT Article
ID nadh-quinone oxidoreductase; escherichia-coli ndh-1; ubiquinone oxidoreductase; membrane domain; electron-transfer; binding-site; subunit; mitochondrial; topology; nuom
AB Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the alpha-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 angstrom resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-angstrom long amphipathic alpha-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 angstrom resolution. The L-shaped assembly consists of the alpha-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic alpha-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.
C1 [Efremov, Rouslan G.; Baradaran, Rozbeh; Sazanov, Leonid A.] Wellcome Trust Res Labs, MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
C3 Wellcome Trust Sanger Institute
RP Sazanov, LA (corresponding author), Wellcome Trust Res Labs, MRC, Mitochondrial Biol Unit, MRC Bldg,Hills Rd, Cambridge CB2 0XY, England.
EM sazanov@mrc-mbu.cam.ac.uk
FU Medical Research Council; MRC [MC_U105674180] Funding Source: UKRI; Medical Research Council [MC_U105674180] Funding Source: researchfish
NR 57
TC 501
Z9 598
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 27
PY 2010
VL 465
IS 7297
BP 441
EP U61
DI 10.1038/nature09066
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700026
PM 20505720
DA 2026-03-09
ER

PT J
AU Mulitza, S
   Heslop, D
   Pittauerova, D
   Fischer, HW
   Meyer, I
   Stuut, JB
   Zabel, M
   Mollenhauer, G
   Collins, JA
   Kuhnert, H
   Schulz, M
AF Mulitza, Stefan
   Heslop, David
   Pittauerova, Daniela
   Fischer, Helmut W.
   Meyer, Inka
   Stuut, Jan-Berend
   Zabel, Matthias
   Mollenhauer, Gesine
   Collins, James A.
   Kuhnert, Henning
   Schulz, Michael
TI Increase in African dust flux at the onset of commercial agriculture in the Sahel region
SO NATURE
LA English
DT Article
ID desertification; desert; reinterpretation; vegetation; transport; atlantic; rainfall; drought; erosion; load
AB The Sahara Desert is the largest source of mineral dust in the world(1). Emissions of African dust increased sharply in the early 1970s (ref. 2), a change that has been attributed mainly to drought in the Sahara/Sahel region(2) caused by changes in the global distribution of sea surface temperature(3,4). The human contribution to land degradation and dust mobilization in this region remains poorly understood(5-11), owing to the paucity of data that would allow the identification of long-term trends in desertification(12). Direct measurements of airborne African dust concentrations only became available in the mid-1960s from a station on Barbados(2) and subsequently from satellite imagery since the late 1970s: they do not cover the onset of commercial agriculture in the Sahel region similar to 170 years ago(11,13,14). Here we construct a 3,200-year record of dust deposition off northwest Africa by investigating the chemistry and grain-size distribution of terrigenous sediments deposited at a marine site located directly under the West African dust plume. With the help of our dust record and a proxy record for West African precipitation(15) we find that, on the century scale, dust deposition is related to precipitation in tropical West Africa until the seventeenth century. At the beginning of the nineteenth century, a sharp increase in dust deposition parallels the advent of commercial agriculture in the Sahel region. Our findings suggest that human-induced dust emissions from the Sahel region have contributed to the atmospheric dust load for about 200 years.
C1 [Mulitza, Stefan; Heslop, David; Meyer, Inka; Stuut, Jan-Berend; Zabel, Matthias; Mollenhauer, Gesine; Collins, James A.; Kuhnert, Henning; Schulz, Michael] Univ Bremen, Ctr Marine Environm Sci, MARUM, D-28359 Bremen, Germany.
   [Pittauerova, Daniela; Fischer, Helmut W.] Univ Bremen, Inst Environm Phys, D-28359 Bremen, Germany.
   [Stuut, Jan-Berend] Royal Netherlands Inst Sea Res, NL-1790 AB Den Burg, Texel, Netherlands.
   [Mollenhauer, Gesine] Alfred Wegener Inst Polar & Marine Res, D-27515 Bremerhaven, Germany.
C3 University of Bremen; University of Bremen; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Mulitza, S (corresponding author), Univ Bremen, Ctr Marine Environm Sci, MARUM, Leobener Str, D-28359 Bremen, Germany.
EM smulitza@uni-bremen.de
FU DFG Research Center/Cluster of Excellence
NR 27
TC 209
Z9 229
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 JUL 8
PY 2010
VL 466
IS 7303
BP 226
EP 228
DI 10.1038/nature09213
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800034
PM 20613839
DA 2026-03-09
ER

PT J
AU El Albani, A
   Bengtson, S
   Canfield, DE
   Bekker, A
   Macchiarelli, R
   Mazurier, A
   Hammarlund, EU
   Boulvais, P
   Dupuy, JJ
   Fontaine, C
   Fürsich, FT
   Gauthier-Lafaye, F
   Janvier, P
   Javaux, E
   Ossa, FO
   Pierson-Wickmann, AC
   Riboulleau, A
   Sardini, P
   Vachard, D
   Whitehouse, M
   Meunier, A
AF El Albani, Abderrazak
   Bengtson, Stefan
   Canfield, Donald E.
   Bekker, Andrey
   Macchiarelli, Roberto
   Mazurier, Arnaud
   Hammarlund, Emma U.
   Boulvais, Philippe
   Dupuy, Jean-Jacques
   Fontaine, Claude
   Fuersich, Franz T.
   Gauthier-Lafaye, Francois
   Janvier, Philippe
   Javaux, Emmanuelle
   Ossa, Frantz Ossa
   Pierson-Wickmann, Anne-Catherine
   Riboulleau, Armelle
   Sardini, Paul
   Vachard, Daniel
   Whitehouse, Martin
   Meunier, Alain
TI Large colonial organisms with coordinated growth in oxygenated environments 2.1 Gyr ago
SO NATURE
LA English
DT Article
ID nuclear-fission reactors; gabon; deposits; uranium; eukaryotes; fossils; carbon; oklo
AB The evidence for macroscopic life during the Palaeoproterozoic era (2.5-1.6 Gyr ago) is controversial(1-5). Except for the nearly 2-Gyr-old coil-shaped fossil Grypania spiralis(6,7), which may have been eukaryotic, evidence for morphological and taxonomic bio-diversification of macroorganisms only occurs towards the beginning of the Mesoproterozoic era (1.6-1.0 Gyr)(8). Here we report the discovery of centimetre-sized structures from the 2.1-Gyr-old black shales of the Palaeoproterozoic Francevillian B Formation in Gabon, which we interpret as highly organized and spatially discrete populations of colonial organisms. The structures are up to 12 cm in size and have characteristic shapes, with a simple but distinct ground pattern of flexible sheets and, usually, a permeating radial fabric. Geochemical analyses suggest that the sediments were deposited under an oxygenated water column. Carbon and sulphur isotopic data indicate that the structures were distinct biogenic objects, fossilized by pyritization early in the formation of the rock. The growth patterns deduced from the fossil morphologies suggest that the organisms showed cell-to-cell signalling and coordinated responses, as is commonly associated with multicellular organization(9). The Gabon fossils, occurring after the 2.45-2.32-Gyr increase in atmospheric oxygen concentration(10), may be seen as ancient representatives of multicellular life, which expanded so rapidly 1.5 Gyr later, in the Cambrian explosion.
C1 [El Albani, Abderrazak; Fontaine, Claude; Ossa, Frantz Ossa; Sardini, Paul; Meunier, Alain] Univ Poitiers, CNRS, UMR INSU 6269, Lab HYDRASA, F-86022 Poitiers, France.
   [Bengtson, Stefan; Hammarlund, Emma U.] Swedish Museum Nat Hist, Dept Palaeozool, SE-10405 Stockholm, Sweden.
   [Canfield, Donald E.; Hammarlund, Emma U.] Nord Ctr Earth Evolut, DK-5230 Odense M, Denmark.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
   [Macchiarelli, Roberto] Univ Poitiers, Dept Geosci, Ctr Microtomog, F-86022 Poitiers, France.
   [Macchiarelli, Roberto] Museum Natl Hist Nat, CNRS, UMR 7194, Dept Prehist, F-75005 Paris, France.
   [Mazurier, Arnaud] CRI Biopole, Soc Etud Rech Mat, F-86000 Poitiers, France.
   [Hammarlund, Emma U.] Stockholm Univ, Dept Geol Sci, S-10691 Stockholm, Sweden.
   [Boulvais, Philippe; Pierson-Wickmann, Anne-Catherine] Univ Rennes, UMR 6118, Dept Geosci, F-35042 Rennes, France.
   [Dupuy, Jean-Jacques] Bur Rech Geol & Minieres, F-45060 Orleans, France.
   [Fuersich, Franz T.] Univ Erlangen Nurnberg, GeoZentrum Nordbayern, Fachgrp Palaoumwelt, D-91054 Erlangen, Germany.
   [Gauthier-Lafaye, Francois] CNRS, UMR 7517, Lab Hydrol & Geochim Strasbourg, F-67084 Strasbourg, France.
   [Janvier, Philippe] Museum Natl Hist Nat, CNRS, UMR 7207, Dept Hist Terre, F-75005 Paris, France.
   [Javaux, Emmanuelle] Univ Liege, Dept Geol, Unite Rech Paleobot Paleopalynol Micropaleontol, B-4000 Sart Tilman Par Liege, Belgium.
   [Riboulleau, Armelle; Vachard, Daniel] Univ Lille 1, CNRS, FRE 3298, Lab Geosyst, F-59655 Villeneuve Dascq, France.
   [Whitehouse, Martin] Swedish Museum Nat Hist, Lab Isotope Geol, SE-10405 Stockholm, Sweden.
C3 Universite de Poitiers; Centre National de la Recherche Scientifique (CNRS); Swedish Museum of Natural History; University of Manitoba; Universite de Poitiers; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Poitiers; Stockholm University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Rennes; Bureau de Recherches Geologiques et Minieres (BRGM); University of Erlangen Nuremberg; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Museum National d'Histoire Naturelle (MNHN); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University of Liege; Centre National de la Recherche Scientifique (CNRS); Universite de Lille; Swedish Museum of Natural History
RP El Albani, A (corresponding author), Univ Poitiers, CNRS, UMR INSU 6269, Lab HYDRASA, F-86022 Poitiers, France.
EM abder.albani@univ-poitiers.fr
FU French Embassy at Libreville; French Ministry for Foreign Affairs; Knut and Alice Wallenberg Foundation; French CNRS-INSU; Bureau de Recherches Geologiques et Minieres (BRGM); Danish National Research Foundation; Swedish Research Council
NR 30
TC 184
Z9 196
U1 1
U2 144
PU 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 1
PY 2010
VL 466
IS 7302
BP 100
EP 104
DI 10.1038/nature09166
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618HW
UT WOS:000279343800042
PM 20596019
DA 2026-03-09
ER

PT J
AU Grashoff, C
   Hoffman, BD
   Brenner, MD
   Zhou, RB
   Parsons, M
   Yang, MT
   McLean, MA
   Sligar, SG
   Chen, CS
   Ha, T
   Schwartz, MA
AF Grashoff, Carsten
   Hoffman, Brenton D.
   Brenner, Michael D.
   Zhou, Ruobo
   Parsons, Maddy
   Yang, Michael T.
   McLean, Mark A.
   Sligar, Stephen G.
   Chen, Christopher S.
   Ha, Taekjip
   Schwartz, Martin A.
TI Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
SO NATURE
LA English
DT Article
ID cell-matrix adhesions; force; actin; talin; mechanosensors; complex; switch
AB Mechanical forces are central to developmental, physiological and pathological processes(1). However, limited understanding of force transmission within sub-cellular structures is a major obstacle to unravelling molecular mechanisms. Here we describe the development of a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity, as demonstrated by single molecule fluorescence force spectroscopy(2). The method is applied to vinculin, a protein that connects integrins to actin filaments and whose recruitment to focal adhesions (FAs) is force-dependent(3). We show that tension across vinculin in stable FAs is similar to 2.5 pN and that vinculin recruitment to FAs and force transmission across vinculin are regulated separately. Highest tension across vinculin is associated with adhesion assembly and enlargement. Conversely, vinculin is under low force in disassembling or sliding FAs at the trailing edge of migrating cells. Furthermore, vinculin is required for stabilizing adhesions under force. Together, these data reveal that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently.
C1 [Grashoff, Carsten; Hoffman, Brenton D.; Schwartz, Martin A.] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Grashoff, Carsten; Hoffman, Brenton D.; Schwartz, Martin A.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Brenner, Michael D.; Zhou, Ruobo; Ha, Taekjip] Univ Illinois, Ctr Phys Living Cells, Urbana, IL 61801 USA.
   [Brenner, Michael D.; Zhou, Ruobo; Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Brenner, Michael D.; Ha, Taekjip] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Parsons, Maddy] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England.
   [Yang, Michael T.; Chen, Christopher S.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
   [McLean, Mark A.; Sligar, Stephen G.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
   [Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Schwartz, Martin A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; 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 London; King's College London; University of Pennsylvania; University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; University of Virginia
RP Schwartz, MA (corresponding author), Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
EM tjha@illinois.edu; maschwartz@virginia.edu
FU USPHS [U54 GM64346, 5T32-HL007284, R21 RR025341]; Deutsche Forschungsgemeinschaft (DFG) [GR3399/1-1]; AHA; US National Science Foundation Physics Frontier Center [0822613]; Royal Society; National Science Foundation [DGE-0221664]; National Heart Lung and Blood Institute [T32HL007284] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Physics [0822613] Funding Source: National Science Foundation
NR 30
TC 1224
Z9 1554
U1 6
U2 412
PU 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 8
PY 2010
VL 466
IS 7303
BP 263
EP U143
DI 10.1038/nature09198
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800042
PM 20613844
DA 2026-03-09
ER

PT J
AU Ahn, YY
   Bagrow, JP
   Lehmann, S
AF Ahn, Yong-Yeol
   Bagrow, James P.
   Lehmann, Sune
TI Link communities reveal multiscale complexity in networks
SO NATURE
LA English
DT Article
ID hierarchical organization
AB Networks have become a key approach to understanding systems of interacting objects, unifying the study of diverse phenomena including biological organisms and human society(1-3). One crucial step when studying the structure and dynamics of networks is to identify communities(4,5): groups of related nodes that correspond to functional subunits such as protein complexes(6,7) or social spheres(8-10). Communities in networks often overlap(9,10) such that nodes simultaneously belong to several groups. Meanwhile, many networks are known to possess hierarchical organization, where communities are recursively grouped into a hierarchical structure(11-13). However, the fact that many real networks have communities with pervasive overlap, where each and every node belongs to more than one group, has the consequence that a global hierarchy of nodes cannot capture the relationships between overlapping groups. Here we reinvent communities as groups of links rather than nodes and show that this unorthodox approach successfully reconciles the antagonistic organizing principles of overlapping communities and hierarchy. In contrast to the existing literature, which has entirely focused on grouping nodes, link communities naturally incorporate overlap while revealing hierarchical organization. We find relevant link communities in many networks, including major biological networks such as protein-protein interaction(6,7,14) and metabolic networks(11,15,16), and show that a large social network(10,17,18) contains hierarchically organized community structures spanning inner-city to regional scales while maintaining pervasive overlap. Our results imply that link communities are fundamental building blocks that reveal overlap and hierarchical organization in networks to be two aspects of the same phenomenon.
C1 [Lehmann, Sune] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
   [Ahn, Yong-Yeol; Bagrow, James P.] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Ahn, Yong-Yeol; Bagrow, James P.] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
   [Lehmann, Sune] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA.
C3 Harvard University; Northeastern University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Northeastern University
RP Lehmann, S (corresponding author), Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
EM sune.lehmann@gmail.com
FU James S. McDonnell Foundation; NSF-DDDAS [CNS-0540348]; NSF-ITR [DMR-0426737]; US ONR [N00014-07-C]; NIH [U01 A1070499-01, 111620-2]; DTRA [BRBAA07-J-2-0035]; US ARL [W911NF-09-2-0053]; NKTH NAP [KCKHA005]; Danish Natural Science Research Council;  [NSF-IIS-0513650]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0837678] Funding Source: National Science Foundation; Academy of Finland (AKA) [111620] Funding Source: Academy of Finland (AKA)
NR 30
TC 1356
Z9 1679
U1 6
U2 358
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 761
EP U11
DI 10.1038/nature09182
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500040
PM 20562860
DA 2026-03-09
ER

PT J
AU Agarwal, S
   Loh, YH
   McLoughlin, EM
   Huang, JJ
   Park, IH
   Miller, JD
   Huo, HG
   Okuka, M
   dos Reis, RM
   Loewer, S
   Ng, HH
   Keefe, DL
   Goldman, FD
   Klingelhutz, AJ
   Liu, L
   Daley, GQ
AF Agarwal, Suneet
   Loh, Yuin-Han
   McLoughlin, Erin M.
   Huang, Junjiu
   Park, In-Hyun
   Miller, Justine D.
   Huo, Hongguang
   Okuka, Maja
   dos Reis, Rosana Maria
   Loewer, Sabine
   Ng, Huck-Hui
   Keefe, David L.
   Goldman, Frederick D.
   Klingelhutz, Aloysius J.
   Liu, Lin
   Daley, George Q.
TI Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
SO NATURE
LA English
DT Article
ID life-span; gene-expression; rna component; maintenance; mutations; disease; lymphocytes; extension; delivery; htert
AB Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer degeneration of multiple tissues(1-3). Patient-specific induced pluripotent stem (iPS) cells(4) represent invaluable in vitro models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, which is accompanied by induction of the telomerase reverse transcriptase gene (TERT)(5-7). We investigated whether defects in telomerase function would limit derivation and maintenance of iPS cells from patients with DC. Here we show that reprogrammed DC cells overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal. We discovered that TERC upregulation is a feature of the pluripotent state, that several telomerase components are targeted by pluripotency-associated transcription factors, and that in autosomal dominant DC, transcriptional silencing accompanies a 3' deletion at the TERC locus. Our results demonstrate that reprogramming restores telomere elongation in DC cells despite genetic lesions affecting telomerase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC patients.
C1 [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Agarwal, Suneet; Loh, Yuin-Han; McLoughlin, Erin M.; Park, In-Hyun; Miller, Justine D.; Huo, Hongguang; Loewer, Sabine; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
   [Huang, Junjiu; Okuka, Maja; dos Reis, Rosana Maria; Keefe, David L.; Liu, Lin] Univ S Florida, Coll Med, Dept Obstet & Gynecol, MDC 3125, Tampa, FL 33612 USA.
   [Huang, Junjiu] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Guangdong, Peoples R China.
   [Ng, Huck-Hui] Genome Inst Singapore, Gene Regulatory Lab, Singapore 138672, Singapore.
   [Ng, Huck-Hui] Natl Univ Singapore, Dept Biol Sci, Singapore 138672, Singapore.
   [Goldman, Frederick D.] Childrens Hosp Alabama, Dept Pediat, Birmingham, AL 35233 USA.
   [Klingelhutz, Aloysius J.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
   [Liu, Lin] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
   [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; State University System of Florida; University of South Florida; Sun Yat Sen University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); National University of Singapore; University of Iowa; Nankai University; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Daley, GQ (corresponding author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
FU National Institutes of Health (NIH) [K08HL089150, R01AG0227388]; Manton Center for Orphan Disease Research; Amy Clare Potter Fellowship; Agency of Science, Technology and Research; Institute of Medical Biology, Singapore; James and Esther King Biomedical Research Program; MOST 973 project [2009CB941000]
NR 38
TC 247
Z9 285
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 292
EP U176
DI 10.1038/nature08792
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100050
PM 20164838
DA 2026-03-09
ER

PT J
AU Cavazzana-Calvo, M
   Payen, E
   Negre, O
   Wang, G
   Hehir, K
   Fusil, F
   Down, J
   Denaro, M
   Brady, T
   Westerman, K
   Cavallesco, R
   Gillet-Legrand, B
   Caccavelli, L
   Sgarra, R
   Maouche-Chrétien, L
   Bernaudin, F
   Girot, R
   Dorazio, R
   Mulder, GJ
   Polack, A
   Bank, A
   Soulier, J
   Larghero, J
   Kabbara, N
   Dalle, B
   Gourmel, B
   Socie, G
   Chrétien, S
   Cartier, N
   Aubourg, P
   Fischer, A
   Cornetta, K
   Galacteros, F
   Beuzard, Y
   Gluckman, E
   Bushman, F
   Hacein-Bey-Abina, S
   Leboulch, P
AF Cavazzana-Calvo, Marina
   Payen, Emmanuel
   Negre, Olivier
   Wang, Gary
   Hehir, Kathleen
   Fusil, Floriane
   Down, Julian
   Denaro, Maria
   Brady, Troy
   Westerman, Karen
   Cavallesco, Resy
   Gillet-Legrand, Beatrix
   Caccavelli, Laure
   Sgarra, Riccardo
   Maouche-Chretien, Leila
   Bernaudin, Francoise
   Girot, Robert
   Dorazio, Ronald
   Mulder, Geert-Jan
   Polack, Axel
   Bank, Arthur
   Soulier, Jean
   Larghero, Jerome
   Kabbara, Nabil
   Dalle, Bruno
   Gourmel, Bernard
   Socie, Gerard
   Chretien, Stany
   Cartier, Nathalie
   Aubourg, Patrick
   Fischer, Alain
   Cornetta, Kenneth
   Galacteros, Frederic
   Beuzard, Yves
   Gluckman, Eliane
   Bushman, Frederick
   Hacein-Bey-Abina, Salima
   Leboulch, Philippe
TI Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
SO NATURE
LA English
DT Article
ID globin lentiviral vector; hematopoietic stem-cells; locus-control region; in-vivo; expression; insulator; disease; sites; long; localization
AB The beta-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of beta-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound beta(E)/beta(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas(1,2). The beta(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated beta(E)-globin with partial instability(1,2). When this is compounded with a non-functional beta(0) allele, a profound decrease in beta-globin synthesis results, and approximately half of beta(E)/beta(0)-thalassaemia patients are transfusion-dependent(1,2). The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral beta-globin gene transfer, an adult patient with severe beta(E)/beta(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded beta-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result froma hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.
C1 [Payen, Emmanuel; Negre, Olivier; Fusil, Floriane; Maouche-Chretien, Leila; Chretien, Stany; Beuzard, Yves; Leboulch, Philippe] CEA, Inst Emerging Dis & Innovat Therapies iMETI, F-92265 Fontenay Aux Roses, France.
   [Cavazzana-Calvo, Marina; Caccavelli, Laure; Hacein-Bey-Abina, Salima] Grp Hosp Univ Ouest, AP HP, INSERM, Clin Invest Ctr Biotherapy, F-75015 Paris, France.
   [Cavazzana-Calvo, Marina; Caccavelli, Laure; Fischer, Alain; Hacein-Bey-Abina, Salima] Univ Paris 05, F-75005 Paris, France.
   [Payen, Emmanuel; Negre, Olivier; Fusil, Floriane; Maouche-Chretien, Leila; Chretien, Stany; Beuzard, Yves; Leboulch, Philippe] Univ Paris 11, CEA, iMETI, F-92265 Fontenay Aux Roses, France.
   [Payen, Emmanuel; Negre, Olivier; Fusil, Floriane; Maouche-Chretien, Leila; Chretien, Stany; Beuzard, Yves; Leboulch, Philippe] INSERM, U962, F-92265 Fontenay Aux Roses, France.
   [Payen, Emmanuel; Negre, Olivier; Fusil, Floriane; Soulier, Jean; Larghero, Jerome; Kabbara, Nabil; Dalle, Bruno; Gourmel, Bernard; Socie, Gerard; Beuzard, Yves; Gluckman, Eliane] Univ Paris 07, Hop St Louis, Inst Hematol,AP HP, Dept Hematol Bone Marrow Transplantat & Biochem, F-75010 Paris, France.
   [Negre, Olivier; Gillet-Legrand, Beatrix] CEA, iMETI, F-92265 Fontenay Aux Roses, France.
   [Wang, Gary; Brady, Troy; Bushman, Frederick] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Hehir, Kathleen; Down, Julian; Denaro, Maria; Westerman, Karen; Dorazio, Ronald; Mulder, Geert-Jan; Polack, Axel] Genetix Pharmaceut, Cambridge, MA 02139 USA.
   [Westerman, Karen; Cavallesco, Resy; Chretien, Stany; Leboulch, Philippe] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Westerman, Karen; Cavallesco, Resy; Chretien, Stany; Leboulch, Philippe] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Sgarra, Riccardo] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy.
   [Bernaudin, Francoise] Ctr Hosp Intercommunal Creteil, F-94000 Creteil, France.
   [Girot, Robert] Hop Tenon, Dept Biol, F-75020 Paris, France.
   [Bank, Arthur] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
   [Bank, Arthur] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
   [Cartier, Nathalie; Aubourg, Patrick] Univ Paris 05, INSERM, UMR745, F-75005 Paris, France.
   [Cornetta, Kenneth] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
   [Galacteros, Frederic] Hop Henri Mondor, AP HP, F-94000 Creteil, France.
C3 CEA; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Universite Paris Saclay; CEA; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Universite Paris Saclay; CEA; University of Pennsylvania; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Trieste; Universite Paris-Est-Creteil-Val-de-Marne (UPEC); CHI Creteil; Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; Hopital Universitaire Tenon - APHP; Columbia University; Columbia University; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Indiana University System; Indiana University Indianapolis; Assistance Publique Hopitaux Paris (APHP); Universite Paris-Est-Creteil-Val-de-Marne (UPEC); Hopital Universitaire Henri-Mondor - APHP
RP Leboulch, P (corresponding author), CEA, Inst Emerging Dis & Innovat Therapies iMETI, F-92265 Fontenay Aux Roses, France.
EM pleboulch@rics.bwh.harvard.edu
FU NIH [HL090921, AI52845, AI082020]; L'Association francaise contre les myopathies
NR 32
TC 1082
Z9 1285
U1 3
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 318
EP U94
DI 10.1038/nature09328
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900037
PM 20844535
DA 2026-03-09
ER

PT J
AU Schiller, D
   Monfils, MH
   Raio, CM
   Johnson, DC
   LeDoux, JE
   Phelps, EA
AF Schiller, Daniela
   Monfils, Marie-H.
   Raio, Candace M.
   Johnson, David C.
   LeDoux, Joseph E.
   Phelps, Elizabeth A.
TI Preventing the return of fear in humans using reconsolidation update mechanisms
SO NATURE
LA English
DT Article
ID posttraumatic-stress-disorder; memory stabilization; conditioned fear; extinction; consolidation; retrieval; amygdala; context; propranolol; recall
AB Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear.
C1 [Schiller, Daniela; Monfils, Marie-H.; LeDoux, Joseph E.; Phelps, Elizabeth A.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Schiller, Daniela; Raio, Candace M.; Johnson, David C.; Phelps, Elizabeth A.] NYU, Dept Psychol, New York, NY 10003 USA.
   [Monfils, Marie-H.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
C3 New York University; New York University; University of Texas System; University of Texas Austin
RP Phelps, EA (corresponding author), NYU, Ctr Neural Sci, New York, NY 10003 USA.
EM liz.phelps@nyu.edu
FU James S. McDonnell Foundation; National Institutes of Health (NIH) [R21 MH072279, R37 MH038774, P50 MH058911, RO1 MH046516, K05 MH067048]; NSERC; CIHR; AHFMR; Fulbright award
NR 31
TC 945
Z9 1112
U1 4
U2 263
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 49
EP U51
DI 10.1038/nature08637
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900027
PM 20010606
DA 2026-03-09
ER

PT J
AU Pang, SS
   Berry, R
   Chen, ZJ
   Kjer-Nielsen, L
   Perugini, MA
   King, GF
   Wang, C
   Chew, SH
   La Gruta, NL
   Williams, NK
   Beddoe, T
   Tiganis, T
   Cowieson, NP
   Godfrey, DI
   Purcell, AW
   Wilce, MCJ
   McCluskey, J
   Rossjohn, J
AF Pang, Siew Siew
   Berry, Richard
   Chen, Zhenjun
   Kjer-Nielsen, Lars
   Perugini, Matthew A.
   King, Glenn F.
   Wang, Christina
   Chew, Sock Hui
   La Gruta, Nicole L.
   Williams, Neal K.
   Beddoe, Travis
   Tiganis, Tony
   Cowieson, Nathan P.
   Godfrey, Dale I.
   Purcell, Anthony W.
   Wilce, Matthew C. J.
   McCluskey, James
   Rossjohn, Jamie
TI The structural basis for autonomous dimerization of the pre-T-cell antigen receptor
SO NATURE
LA English
DT Article
ID analytical ultracentrifugation; sedimentation-velocity; alpha; tcr; beta; selection; angstrom; opinion; chains; phenix
AB The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR beta-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent ab T-cell lineage differentiation(1-3). Whereas alpha beta TCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling(4), preTCR-induced signalling occurs by means of a ligand-independent dimerization event(5). The pre-TCR comprises an invariant a-chain (pre-T alpha) that pairs with any TCR beta-chain (TCR beta) following successful TCR beta-gene rearrangement(6). Here we provide the basis of pre-T alpha-TCR beta assembly and pre-TCR dimerization. The pre-T alpha chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR alpha-chain(7); nevertheless, the mode of association between pre-T alpha and TCRb mirrored that mediated by the C alpha-C beta domains of the abTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-T alpha domain to interact with the variable (V) beta domain through residues that are highly conserved across the V beta and joining (J) beta gene families, thus mimicking the interactions at the core of the alpha beta TCR's V alpha-V beta interface. Disruption of this pre-T alpha-V beta dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-T alpha chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR beta-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-T alpha represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.
C1 [Chen, Zhenjun; Kjer-Nielsen, Lars; La Gruta, Nicole L.; Godfrey, Dale I.; McCluskey, James] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
   [Pang, Siew Siew; Berry, Richard; Wang, Christina; Chew, Sock Hui; Williams, Neal K.; Beddoe, Travis; Tiganis, Tony; Cowieson, Nathan P.; Wilce, Matthew C. J.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Prot Crystallog Unit, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Perugini, Matthew A.; Purcell, Anthony W.] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.
   [Perugini, Matthew A.; Purcell, Anthony W.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3010, Australia.
   [King, Glenn F.] Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, St Lucia, Qld 4072, Australia.
C3 University of Melbourne; Monash University; University of Melbourne; University of Melbourne; University of Queensland
RP McCluskey, J (corresponding author), Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
EM jamesm1@unimelb.edu.au; jamie.rossjohn@monash.edu
FU Australian Research Council; National Health and Medical Research Council of Australia
NR 30
TC 66
Z9 83
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 844
EP U110
DI 10.1038/nature09448
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700067
PM 20944746
DA 2026-03-09
ER

PT J
AU Tsuchimatsu, T
   Suwabe, K
   Shimizu-Inatsugi, R
   Isokawa, S
   Pavlidis, P
   Städler, T
   Suzuki, G
   Takayama, S
   Watanabe, M
   Shimizu, KK
AF Tsuchimatsu, Takashi
   Suwabe, Keita
   Shimizu-Inatsugi, Rie
   Isokawa, Sachiyo
   Pavlidis, Pavlos
   Staedler, Thomas
   Suzuki, Go
   Takayama, Seiji
   Watanabe, Masao
   Shimizu, Kentaro K.
TI Evolution of self-compatibility in Arabidopsis by a mutation in the male specificity gene
SO NATURE
LA English
DT Article
ID s-locus genes; brassica-napus; incompatibility; thaliana; haplotypes; transition; breakdown; distance; rna
AB Ever since Darwin's pioneering research, the evolution of self-fertilisation (selfing) has been regarded as one of the most prevalent evolutionary transitions in flowering plants(1,2). A major mechanism to prevent selfing is the self-incompatibility (SI) recognition system, which consists of male and female specificity genes at the S-locus and SI modifier genes(2-4). Under conditions that favour selfing, mutations disabling the male recognition component are predicted to enjoy a relative advantage over those disabling the female component, because male mutations would increase through both pollen and seeds whereas female mutations would increase only through seeds(5,6). Despite many studies on the genetic basis of loss of SI in the predominantly selfing plant Arabidopsis thaliana(7-15), it remains unknown whether selfing arose through mutations in the female specificity gene (S-receptor kinase, SRK), male specificity gene (S-locus cysteine-rich protein, SCR; also known as S-locus protein 11, SP11) or modifier genes, and whether any of them rose to high frequency across large geographic regions. Here we report that a disruptive 213-base-pair (bp) inversion in the SCR gene (or its derivative haplotypes with deletions encompassing the entire SCR-A and a large portion of SRK-A) is found in 95% of European accessions, which contrasts with the genome-wide pattern of polymorphism in European A. thaliana(16,17). Importantly, interspecific crossings using Arabidopsis halleri as a pollen donor reveal that some A. thaliana accessions, including Wei-1, retain the female SI reaction, suggesting that all female components including SRK are still functional. Moreover, when the 213-bp inversion in SCR was inverted and expressed in transgenic Wei-1 plants, the functional SCR restored the SI reaction. The inversion within SCR is the first mutation disrupting SI shown to be nearly fixed in geographically wide samples, and its prevalence is consistent with theoretical predictions regarding the evolutionary advantage of mutations in male components.
C1 [Tsuchimatsu, Takashi; Shimizu-Inatsugi, Rie; Shimizu, Kentaro K.] Univ Zurich, Inst Plant Biol, Univ Res Prior Program Syst Biol, Funct Genom & Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland.
   [Tsuchimatsu, Takashi] Univ Tokyo, Dept Gen Syst Studies, Meguro Ku, Tokyo 1538902, Japan.
   [Suwabe, Keita; Isokawa, Sachiyo; Watanabe, Masao] Tohoku Univ, Grad Sch Life Sci, Sendai, Miyagi 9808577, Japan.
   [Suwabe, Keita] Mie Univ, Grad Sch Bioresources, Tsu, Mie 5148507, Japan.
   [Isokawa, Sachiyo; Watanabe, Masao] Tohoku Univ, Fac Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan.
   [Pavlidis, Pavlos] Univ Munich LMU, Bioctr, Sect Evolutionary Biol, D-82152 Planegg Martinsried, Germany.
   [Staedler, Thomas] ETH, Inst Integrat Biol, CH-8092 Zurich, Switzerland.
   [Suzuki, Go] Osaka Kyoiku Univ, Div Nat Sci, Kashiwara 5828582, Japan.
   [Takayama, Seiji] Nara Inst Sci & Technol, Grad Sch Biol Sci, Ikoma 6300101, Japan.
C3 University of Zurich; University of Tokyo; Tohoku University; Mie University; Tohoku University; University of Munich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Osaka University of Education; Nara Institute of Science & Technology
RP Shimizu, KK (corresponding author), Univ Zurich, Inst Plant Biol, Univ Res Prior Program Syst Biol, Funct Genom & Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland.
EM nabe@ige.tohoku.ac.jp; shimizu@botinst.uzh.ch
FU University of Zurich; Swiss National Science Foundation (SNF); Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT); Japan Society for the Promotion of Science (JSPS); Volkswagen Foundation; Deutscher Akademischer Austauschdienst (DAAD); Grants-in-Aid for Scientific Research [20678001] Funding Source: KAKEN
NR 37
TC 117
Z9 140
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 APR 29
PY 2010
VL 464
IS 7293
BP 1342
EP 1346
DI 10.1038/nature08927
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 589LI
UT WOS:000277149000045
PM 20400945
DA 2026-03-09
ER

PT J
AU Werner, T
   Koshikawa, S
   Williams, TM
   Carroll, SB
AF Werner, Thomas
   Koshikawa, Shigeyuki
   Williams, Thomas M.
   Carroll, Sean B.
TI Generation of a novel wing colour pattern by the Wingless morphogen
SO NATURE
LA English
DT Article
ID segment-polarity gene; pigment patterns; neural crest; yellow gene; drosophila; zebrafish; evolution; elements; specification; expression
AB The complex, geometric colour patterns of many animal bodies have important roles in behaviour and ecology. The generation of certain patterns has been the subject of considerable theoretical exploration, however, very little is known about the actual mechanisms underlying colour pattern formation or evolution. Here we have investigated the generation and evolution of the complex, spotted wing pattern of Drosophila guttifera. We show that wing spots are induced by the Wingless morphogen, which is expressed at many discrete sites that are specified by pre-existing positional information that governs the development of wing structures. Furthermore, we demonstrate that the elaborate spot pattern evolved from simpler schemes by co-option of Wingless expression at new sites. This example of a complex design developing and evolving by the layering of new patterns on pre-patterns is likely to be a general theme in other animals.
C1 [Werner, Thomas; Koshikawa, Shigeyuki; Williams, Thomas M.; Carroll, Sean B.] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA.
   [Werner, Thomas; Koshikawa, Shigeyuki; Williams, Thomas M.; Carroll, Sean B.] Univ Wisconsin, Mol Biol Lab, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Howard Hughes Medical Institute; University of Wisconsin System; University of Wisconsin Madison
RP Carroll, SB (corresponding author), Univ Wisconsin, Howard Hughes Med Inst, 1525 Linden Dr, Madison, WI 53706 USA.
EM sbcarrol@wisc.edu
FU Human Frontiers Science Program Fellowship [LT00640/2005-L]; JSPS; National Institutes of Health [GM076935]; Howard Hughes Medical Institute
NR 49
TC 172
Z9 215
U1 5
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 22
PY 2010
VL 464
IS 7292
BP 1143
EP U57
DI 10.1038/nature08896
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100027
PM 20376004
DA 2026-03-09
ER

PT J
AU Martin, F
   Kohler, A
   Murat, C
   Balestrini, R
   Coutinho, PM
   Jaillon, O
   Montanini, B
   Morin, E
   Noel, B
   Percudani, R
   Porcel, B
   Rubini, A
   Amicucci, A
   Amselem, J
   Anthouard, V
   Arcioni, S
   Artiguenave, F
   Aury, JM
   Ballario, P
   Bolchi, A
   Brenna, A
   Brun, A
   Buée, M
   Cantarel, B
   Chevalier, G
   Couloux, A
   Da Silva, C
   Denoeud, F
   Duplessis, S
   Ghignone, S
   Hilselberger, B
   Iotti, M
   Marcais, B
   Mello, A
   Miranda, M
   Pacioni, G
   Quesneville, H
   Riccioni, C
   Ruotolo, R
   Splivallo, R
   Stocchi, V
   Tisserant, E
   Viscomi, AR
   Zambonelli, A
   Zampieri, E
   Henrissat, B
   Lebrun, MH
   Paolocci, F
   Bonfante, P
   Ottonello, S
   Wincker, P
AF Martin, Francis
   Kohler, Annegret
   Murat, Claude
   Balestrini, Raffaella
   Coutinho, Pedro M.
   Jaillon, Olivier
   Montanini, Barbara
   Morin, Emmanuelle
   Noel, Benjamin
   Percudani, Riccardo
   Porcel, Bettina
   Rubini, Andrea
   Amicucci, Antonella
   Amselem, Joelle
   Anthouard, Veronique
   Arcioni, Sergio
   Artiguenave, Francois
   Aury, Jean-Marc
   Ballario, Paola
   Bolchi, Angelo
   Brenna, Andrea
   Brun, Annick
   Buee, Marc
   Cantarel, Brandi
   Chevalier, Gerard
   Couloux, Arnaud
   Da Silva, Corinne
   Denoeud, France
   Duplessis, Sebastien
   Ghignone, Stefano
   Hilselberger, Benoit
   Iotti, Mirco
   Marcais, Benoit
   Mello, Antonietta
   Miranda, Michele
   Pacioni, Giovanni
   Quesneville, Hadi
   Riccioni, Claudia
   Ruotolo, Roberta
   Splivallo, Richard
   Stocchi, Vilberto
   Tisserant, Emilie
   Viscomi, Arturo Roberto
   Zambonelli, Alessandra
   Zampieri, Elisa
   Henrissat, Bernard
   Lebrun, Marc-Henri
   Paolocci, Francesco
   Bonfante, Paola
   Ottonello, Simone
   Wincker, Patrick
TI Perigord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis
SO NATURE
LA English
DT Article
ID fungal; insights
AB The Perigord black truffle (Tuber melanosporum Vittad.) and the Piedmont white truffle dominate today's truffle market(1,2). The hypogeous fruiting body of T. melanosporum is a gastronomic delicacy produced by an ectomycorrhizal symbiont(3) endemic to calcareous soils in southern Europe. The worldwide demand for this truffle has fuelled intense efforts at cultivation. Identification of processes that condition and trigger fruit body and symbiosis formation, ultimately leading to efficient crop production, will be facilitated by a thorough analysis of truffle genomic traits. In the ectomycorrhizal Laccaria bicolor, the expansion of gene families may have acted as a 'symbiosis toolbox'(4). This feature may however reflect evolution of this particular taxon and not a general trait shared by all ectomycorrhizal species(5). To get a better understanding of the biology and evolution of the ectomycorrhizal symbiosis, we report here the sequence of the haploid genome of T. melanosporum, which at similar to 125 megabases is the largest and most complex fungal genome sequenced so far. This expansion results from a proliferation of transposable elements accounting for similar to 58% of the genome. In contrast, this genome only contains similar to 7,500 protein-coding genes with very rare multigene families. It lacks large sets of carbohydrate cleaving enzymes, but a few of them involved in degradation of plant cell walls are induced in symbiotic tissues. The latter feature and the upregulation of genes encoding for lipases and multicopper oxidases suggest that T. melanosporum degrades its host cell walls during colonization. Symbiosis induces an increased expression of carbohydrate and amino acid transporters in both L. bicolor and T. melanosporum, but the comparison of genomic traits in the two ectomycorrhizal fungi showed that genetic predispositions for symbiosis-'the symbiosis toolbox'-evolved along different ways in ascomycetes and basidiomycetes.
C1 [Martin, Francis; Kohler, Annegret; Murat, Claude; Morin, Emmanuelle; Brun, Annick; Buee, Marc; Duplessis, Sebastien; Marcais, Benoit; Tisserant, Emilie] Nancy Univ, UMR 1136, INRA, F-54280 Champenoux, France.
   [Balestrini, Raffaella; Ghignone, Stefano; Mello, Antonietta; Zampieri, Elisa; Bonfante, Paola] Univ Turin, Dipartimento Biol Vegetale, I-10125 Turin, Italy.
   [Balestrini, Raffaella; Ghignone, Stefano; Mello, Antonietta; Zampieri, Elisa; Bonfante, Paola] Univ Turin, CNR, Ist Protez Piante, Sez Torino, I-10125 Turin, Italy.
   [Coutinho, Pedro M.; Cantarel, Brandi; Henrissat, Bernard] Univ Aix Marseille 1, CNRS, UMR6098, F-13288 Marseille, France.
   [Coutinho, Pedro M.; Cantarel, Brandi; Henrissat, Bernard] Univ Aix Marseille 2, CNRS, UMR6098, F-13288 Marseille, France.
   [Jaillon, Olivier; Noel, Benjamin; Porcel, Bettina; Anthouard, Veronique; Artiguenave, Francois; Aury, Jean-Marc; Couloux, Arnaud; Da Silva, Corinne; Denoeud, France; Wincker, Patrick] CEA, IG, F-91057 Evry, France.
   [Jaillon, Olivier; Noel, Benjamin; Porcel, Bettina; Anthouard, Veronique; Artiguenave, Francois; Aury, Jean-Marc; Couloux, Arnaud; Da Silva, Corinne; Denoeud, France; Wincker, Patrick] CNRS, UMR 8030, F-91057 Evry, France.
   [Jaillon, Olivier; Noel, Benjamin; Porcel, Bettina; Anthouard, Veronique; Artiguenave, Francois; Aury, Jean-Marc; Couloux, Arnaud; Da Silva, Corinne; Denoeud, France; Wincker, Patrick] Univ Evry, F-91057 Evry, France.
   [Montanini, Barbara; Percudani, Riccardo; Bolchi, Angelo; Ruotolo, Roberta; Viscomi, Arturo Roberto; Ottonello, Simone] Univ Parma, Dipartmento Biochim & Biol Mol, I-43100 Parma, Italy.
   [Rubini, Andrea; Arcioni, Sergio; Riccioni, Claudia; Paolocci, Francesco] CNR, IGV, Unita Organizzat Supporto Perugia, I-06128 Perugia, Italy.
   [Amicucci, Antonella] Univ Urbino, Dipartimento Sci Biomol, I-61029 Urbino, PU, Italy.
   [Amselem, Joelle; Hilselberger, Benoit; Quesneville, Hadi] INRA, Unite Rech Genom Info, F-78000 Versailles, France.
   [Ballario, Paola; Brenna, Andrea] Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy.
   [Ballario, Paola; Brenna, Andrea] Univ Roma La Sapienza, CNR, IBPM, I-00185 Rome, Italy.
   [Chevalier, Gerard] Univ Blaise Pascal, INRA Clermont Theix, INRA, UMR Ameliorat & Sante Plantes, F-63122 St Genes Champanelle, France.
   [Iotti, Mirco; Zambonelli, Alessandra] Univ Bologna, Dipartimento Protez Valorizzaz Agroalimentare, I-40126 Bologna, Italy.
   [Miranda, Michele] Univ Aquila, Dipartimento Biol Base & Applicata, I-67100 Laquila, Italy.
   [Pacioni, Giovanni] Univ Aquila, Dipartimento Sci Ambientali, I-67100 Laquila, Italy.
   [Splivallo, Richard] Univ Gottingen, D-37077 Gottingen, Germany.
   [Lebrun, Marc-Henri] INRA Grignon, INRA, UMR BIOGER CPP, F-78850 Thiverval Grignon, France.
C3 INRAE; Universite de Lorraine; University of Turin; Consiglio Nazionale delle Ricerche (CNR); University of Turin; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CEA; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); Universite Paris Saclay; University of Parma; Consiglio Nazionale delle Ricerche (CNR); University of Urbino; INRAE; Universite Paris Saclay; Sapienza University Rome; Sapienza University Rome; Consiglio Nazionale delle Ricerche (CNR); Istituto di Biologia e Patologia Molecolari (IBPM-CNR); Universite Clermont Auvergne (UCA); INRAE; University of Bologna; University of L'Aquila; University of L'Aquila; University of Gottingen; INRAE; AgroParisTech; Universite Paris Saclay
RP Martin, F (corresponding author), Nancy Univ, UMR 1136, INRA, F-54280 Champenoux, France.
EM fmartin@nancy.inra.fr
FU Genoscope, Institut de Genomique, CEA; Agence Nationale de la Recherche (ANR); European FP6 Network of Excellence EVOLTREE, Region Lorraine; Fondazione Cariparma, Compagnia di San Paolo-Torino; Italian Ministry of Education, University and Research (MIUR), Regione Umbria; Instituto Pasteur Fondazione Cenci Bolognetti
NR 19
TC 525
Z9 602
U1 3
U2 192
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1033
EP 1038
DI 10.1038/nature08867
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000037
PM 20348908
DA 2026-03-09
ER

PT J
AU Shuman, ES
   Barry, JF
   DeMille, D
AF Shuman, E. S.
   Barry, J. F.
   DeMille, D.
TI Laser cooling of a diatomic molecule
SO NATURE
LA English
DT Article
ID polar-molecules; temperatures; monohalides; chemistry; atoms; field; srf
AB It has been roughly three decades since laser cooling techniques produced ultracold atoms(1-3), leading to rapid advances in a wide array of fields. Laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for a wide range of applications(4). For example, heteronuclear molecules possess permanent electric dipole moments that lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures makes ultracold molecules attractive candidates for use in quantum simulations of condensed-matter systems(5) and in quantum computation(6). Also, ultracold molecules could provide unique opportunities for studying chemical dynamics(7,8) and for tests of fundamental symmetries(9-11). Here we experimentally demonstrate laser cooling of the polar molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers(12), we have observed both Sisyphus and Doppler cooling forces that reduce the transverse temperature of a SrF molecular beam substantially, to a few millikelvin or less. At present, the only technique for producing ultracold molecules is to bind together ultracold alkali atoms through Feshbach resonance(13) or photoassociation(14). However, proposed applications for ultracold molecules require a variety of molecular energy-level structures (for example unpaired electronic spin(5,9,11,15), Omega doublets(16) and so on). Our method provides an alternative route to ultracold molecules. In particular, it bridges the gap between ultracold (submillikelvin) temperatures and the similar to 1-K temperatures attainable with directly cooled molecules (for example with cryogenic buffer-gas cooling(17) or decelerated supersonic beams(18)). Ultimately, our technique should allow the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.
C1 [Shuman, E. S.; Barry, J. F.; DeMille, D.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
C3 Yale University
RP Shuman, ES (corresponding author), Yale Univ, Dept Phys, POB 208120, New Haven, CT 06520 USA.
EM edward.shuman@yale.edu
FU ARO; NSF; AFOSR [FA9550-09-1-0588]
NR 30
TC 678
Z9 780
U1 2
U2 205
PU 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 14
PY 2010
VL 467
IS 7317
BP 820
EP 823
DI 10.1038/nature09443
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700062
PM 20852614
DA 2026-03-09
ER

PT J
AU Bhutani, N
   Brady, JJ
   Damian, M
   Sacco, A
   Corbel, SY
   Blau, HM
AF Bhutani, Nidhi
   Brady, Jennifer J.
   Damian, Mara
   Sacco, Alessandra
   Corbel, Stephane Y.
   Blau, Helen M.
TI Reprogramming towards pluripotency requires AID-dependent DNA demethylation
SO NATURE
LA English
DT Article
ID class switch recombination; stem-cells; gene-expression; somatic-cells; activation; differentiation; fibroblasts; heterokaryons; generation; deaminase
AB Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (<0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons ( fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly ( 1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase ( AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide the first evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.
C1 [Bhutani, Nidhi; Brady, Jennifer J.; Damian, Mara; Sacco, Alessandra; Corbel, Stephane Y.; Blau, Helen M.] Stanford Univ, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Inst Stem Cell Biol & Regenerat Med,Sch Med, Stanford, CA 94305 USA.
   [Damian, Mara] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Blau, HM (corresponding author), Stanford Univ, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Inst Stem Cell Biol & Regenerat Med,Sch Med, Stanford, CA 94305 USA.
EM hblau@stanford.edu
FU National Science Foundation; National Institutes of Health (NIH) [AI007328, AG009521, AG024987]; Baxter Foundation; National Institute of Allergy and Infectious Diseases [T32AI007328] Funding Source: NIH RePORTER
NR 49
TC 558
Z9 674
U1 0
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1042
EP U57
DI 10.1038/nature08752
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400028
PM 20027182
DA 2026-03-09
ER

PT J
AU Boudsocq, M
   Willmann, MR
   McCormack, M
   Lee, H
   Shan, LB
   He, P
   Bush, J
   Cheng, SH
   Sheen, J
AF Boudsocq, Marie
   Willmann, Matthew R.
   McCormack, Matthew
   Lee, Horim
   Shan, Libo
   He, Ping
   Bush, Jenifer
   Cheng, Shu-Hua
   Sheen, Jen
TI Differential innate immune signalling via Ca2+ sensor protein kinases
SO NATURE
LA English
DT Article
ID gene-expression analysis; plant defense; molecular-patterns; arabidopsis; calcium; perception; resistance; flagellin; identification; transduction
AB Innate immunity represents the first line of inducible defence against microbial infection in plants and animals(1-3). In both kingdoms, recognition of pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs, respectively), such as flagellin, initiates convergent signalling pathways involving mitogen-activated protein kinase ( MAPK) cascades and global transcriptional changes to boost immunity(1-4). Although Ca2+ has long been recognized as an essential and conserved primary mediator in plant defence responses, how Ca2+ signals are sensed and relayed into early MAMP signalling is unknown(5,6). Using a functional genomic screen and genome-wide gene expression profiling, here we show that four calcium-dependent protein kinases (CDPKs) are Ca2+-sensor protein kinases critical for transcriptional reprogramming in plant innate immune signalling. Unexpectedly, CDPKs and MAPK cascades act differentially in four MAMP-mediated regulatory programs to control early genes involved in the synthesis of defence peptides and metabolites, cell wall modifications and redox signalling. Transcriptome profile comparison suggests that CDPKs are the convergence point of signalling triggered by most MAMPs. Double, triple and quadruple cpk mutant plants display progressively diminished oxidative burst and gene activation induced by the 22-amino-acid peptide flg22, as well as compromised pathogen defence. In contrast to negative roles of calmodulin and a calmodulin-activated transcription factor in plant defence(7,8), the present study reveals Ca2+ signalling complexity and demonstrates key positive roles of specific CDPKs in initial MAMP signalling.
C1 [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
   [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Boudsocq, Marie; Willmann, Matthew R.; McCormack, Matthew; Lee, Horim; Shan, Libo; He, Ping; Bush, Jenifer; Cheng, Shu-Hua; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Boudsocq, M (corresponding author), CNRS, UPR2355, Inst Sci Vegetal, 1 Ave Terrasse, F-91198 Gif Sur Yvette, France.
EM boudsocq@molbio.mgh.harvard.edu; willmann@sas.upenn.edu
FU European Community; NSF; National Science Foundation; National Institute of Health; MGH CCIB; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0843244] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM097247, R01GM092893] Funding Source: NIH RePORTER
NR 38
TC 689
Z9 791
U1 8
U2 295
PU 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 18
PY 2010
VL 464
IS 7287
BP 418
EP U116
DI 10.1038/nature08794
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570FG
UT WOS:000275657100048
PM 20164835
DA 2026-03-09
ER

PT J
AU Draghi, JA
   Parsons, TL
   Wagner, GP
   Plotkin, JB
AF Draghi, Jeremy A.
   Parsons, Todd L.
   Wagner, Guenter P.
   Plotkin, Joshua B.
TI Mutational robustness can facilitate adaptation
SO NATURE
LA English
DT Article
ID gene networks; promotes evolvability; digital organisms; evolution; innovation; selection; rna
AB Robustness seems to be the opposite of evolvability. If phenotypes are robust against mutation, we might expect that a population will have difficulty adapting to an environmental change, as several studies have suggested(1-4). However, other studies contend that robust organisms are more adaptable(5-8). A quantitative understanding of the relationship between robustness and evolvability will help resolve these conflicting reports and will clarify outstanding problems in molecular and experimental evolution, evolutionary developmental biology and protein engineering. Here we demonstrate, using a general population genetics model, that mutational robustness can either impede or facilitate adaptation, depending on the population size, the mutation rate and the structure of the fitness landscape. In particular, neutral diversity in a robust population can accelerate adaptation as long as the number of phenotypes accessible to an individual by mutation is smaller than the total number of phenotypes in the fitness landscape. These results provide a quantitative resolution to a significant ambiguity in evolutionary theory.
C1 [Draghi, Jeremy A.; Parsons, Todd L.; Plotkin, Joshua B.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Plotkin, Joshua B.] Univ Penn, Program Appl Math & Computat Sci, Philadelphia, PA 19104 USA.
   [Wagner, Guenter P.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
C3 University of Pennsylvania; University of Pennsylvania; Yale University
RP Plotkin, JB (corresponding author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
EM jplotkin@sas.upenn.edu
FU Burroughs Wellcome Fund; David and Lucile Packard Foundation; James S. McDonnell Foundation; Alfred P. Sloan Foundation; Defense Advanced Research Projects Agency [HR0011-05-1-0057]; US National Institute of Allergy and Infectious Diseases [2U54AI057168]; John Templeton Foundation; Perinatology Research Branch of the US National Institutes of Health
NR 30
TC 254
Z9 304
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 JAN 21
PY 2010
VL 463
IS 7279
BP 353
EP 355
DI 10.1038/nature08694
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100043
PM 20090752
DA 2026-03-09
ER

PT J
AU Brumm, A
   Jensen, GM
   van den Bergh, GD
   Morwood, MJ
   Kurniawan, I
   Aziz, F
   Storey, M
AF Brumm, Adam
   Jensen, Gitte M.
   van den Bergh, Gert D.
   Morwood, Michael J.
   Kurniawan, Iwan
   Aziz, Fachroel
   Storey, Michael
TI Hominins on Flores, Indonesia, by one million years ago
SO NATURE
LA English
DT Article
ID homo-floresiensis; late pleistocene; stone technology; southeast-asia; liang-bua; artifacts; mengeruda; evolution; island; ages
AB Previous excavations at Mata Menge and Boa Lesa in the Soa Basin of Flores, Indonesia, recovered stone artefacts in association with fossilized remains of the large-bodied Stegodon florensis florensis(1-9). Zircon fission-track ages from these sites indicated that hominins had colonized the island by 0.88 +/- 0.07 million years (Myr) ago(6). Here we describe the contents, context and age of Wolo Sege, a recently discovered archaeological site in the Soa Basin that has in situ stone artefacts and that lies stratigraphically below Mata Menge and immediately above the basement breccias of the basin. We show using 40Ar/39Ar dating that an ignimbrite overlying the artefact layers at Wolo Sege was erupted 1.02 +/- 0.02 Myr ago, providing a new minimum age for hominins on Flores. This predates the disappearance from the Soa Basin of 'pygmy' Stegodon sondaari and Geochelone spp. (giant tortoise), as evident at the nearby site of Tangi Talo, which has been dated to 0.90 +/- 0.07 Myr ago(10). It now seems that this extirpation or possible extinction event and the associated faunal turnover were the result of natural processes rather than the arrival of hominins(9). It also appears that the volcanic and fluvio-lacustrine deposits infilling the Soa Basin may not be old enough to register the initial arrival of hominins on the island.
C1 [Jensen, Gitte M.; Storey, Michael] Roskilde Univ, Dept Environm Social & Spatial Change, Quaternary Dating Lab, DK-4000 Roskilde, Denmark.
   [Brumm, Adam; van den Bergh, Gert D.; Morwood, Michael J.] Univ Wollongong, Sch Earth & Environm Sci, Ctr Archaeol Sci, Wollongong, NSW 2522, Australia.
   [Kurniawan, Iwan; Aziz, Fachroel] Geol Survey Inst, Bandung 40122, Indonesia.
   [van den Bergh, Gert D.] Natl Museum Nat Hist, NL-2333 CR Leiden, Netherlands.
C3 Roskilde University; University of Wollongong
RP Storey, M (corresponding author), Roskilde Univ, Dept Environm Social & Spatial Change, Quaternary Dating Lab, POB 260, DK-4000 Roskilde, Denmark.
EM abrumm@uow.edu.au; storey@ruc.dk
FU Australian Research Council (ARC); Australian National University; McDonald Institute for Archaeological Research, University of Cambridge; D. M. McDonald Grants and Awards Fund; Villum Kann Rasmussen Foundation; Villum Kann Rasmussen Foundation, Roskilde University; Danish Agency for Science, Technology and Innovation
NR 30
TC 138
Z9 153
U1 0
U2 72
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 748
EP U123
DI 10.1038/nature08844
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000043
PM 20237472
DA 2026-03-09
ER

PT J
AU Sendoel, A
   Kohler, I
   Fellmann, C
   Lowe, SW
   Hengartner, MO
AF Sendoel, Ataman
   Kohler, Ines
   Fellmann, Christof
   Lowe, Scott W.
   Hengartner, Michael O.
TI HIF-1 antagonizes p53-mediated apoptosis through a secreted neuronal tyrosinase
SO NATURE
LA English
DT Article
ID hypoxia-inducible factor; damage-induced apoptosis; caenorhabditis-elegans; c-elegans; cell-lines; protein; p53; pathway; cancer; gene
AB Hypoxia-inducible factor (HIF) is a transcription factor that regulates fundamental cellular processes in response to changes in oxygen concentration. HIF alpha protein levels are increased in most solid tumours and correlate with patient prognosis. The link between HIF and apoptosis, a major determinant of cancer progression and treatment outcome, is poorly understood. Here we show that Caenorhabditis elegans HIF-1 protects against DNA-damage-induced germ cell apoptosis by antagonizing the function of CEP-1, the homologue of the tumour suppressor p53. The antiapoptotic property of HIF-1 is mediated by means of transcriptional upregulation of the tyrosinase family member TYR-2 in the ASJ sensory neurons. TYR-2 is secreted by ASJ sensory neurons to antagonize CEP-1-dependent germline apoptosis. Knock down of the TYR-2 homologue TRP2 (also called DCT) in human melanoma cells similarly increases apoptosis, indicating an evolutionarily conserved function. Our findings identify a novel link between hypoxia and programmed cell death, and provide a paradigm for HIF-1 dictating apoptotic cell fate at a distance.
C1 [Sendoel, Ataman; Kohler, Ines; Fellmann, Christof; Hengartner, Michael O.] Univ Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland.
   [Sendoel, Ataman] Univ Zurich, PhD Program Canc Biol, CH-8057 Zurich, Switzerland.
   [Sendoel, Ataman] Univ Zurich, MD PhD Program, CH-8057 Zurich, Switzerland.
   [Lowe, Scott W.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Fellmann, Christof] Univ Zurich, PhD Program Mol Life Sci, CH-8057 Zurich, Switzerland.
C3 University of Zurich; University of Zurich; University of Zurich; Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; University of Zurich
RP Hengartner, MO (corresponding author), Univ Zurich, Inst Mol Life Sci, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM michael.hengartner@imls.uzh.ch
FU Swiss National Science Foundation; Kanton of Zurich; Josef-Steiner Foundation; Oncosuisse; NIH National Center for Research Resources (NCRR)
NR 46
TC 151
Z9 196
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 577
EP U69
DI 10.1038/nature09141
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000033
PM 20520707
DA 2026-03-09
ER

PT J
AU Parker, CV
   Aynajian, P
   Neto, EHD
   Pushp, A
   Ono, S
   Wen, JS
   Xu, ZJ
   Gu, GD
   Yazdani, A
AF Parker, Colin V.
   Aynajian, Pegor
   da Silva Neto, Eduardo H.
   Pushp, Aakash
   Ono, Shimpei
   Wen, Jinsheng
   Xu, Zhijun
   Gu, Genda
   Yazdani, Ali
TI Fluctuating stripes at the onset of the pseudogap in the high-Tc superconductor Bi2Sr2CaCu2O8+x
SO NATURE
LA English
DT Article
ID high-temperature superconductors; quasi-particle interference; symmetry-breaking; mott insulator; atomic-scale; states; phase
AB Doped Mott insulators have a strong propensity to form patterns of holes and spins often referred to as stripes(1-5). In copper oxides, doping also gives rise to the pseudogap state(6), which can be transformed into a high-temperature superconducting state with sufficient doping or by reducing the temperature. A long-standing issue has been the interplay between the pseudogap, which is generic to all hole-doped copper oxide superconductors, and stripes, whose static form occurs in only one family of copper oxides over a narrow range of the phase diagram(2,7). Here we report observations of the spatial reorganization of electronic states with the onset of the pseudogap state in the high-temperature superconductor Bi2Sr2CaCu2O8+x, using spectroscopic mapping with a scanning tunnelling microscope. We find that the onset of the pseudogap phase coincides with the appearance of electronic patterns that have the predicted characteristics of fluctuating stripes(8). As expected, the stripe patterns are strongest when the hole concentration in the CuO2 planes is close to 1/8 (per copper atom)(2-5,8). Although they demonstrate that the fluctuating stripes emerge with the onset of the pseudogap state and occur over a large part of the phase diagram, our experiments indicate that the stripes are a consequence of pseudogap behaviour rather than its cause.
C1 [Parker, Colin V.; Aynajian, Pegor; da Silva Neto, Eduardo H.; Pushp, Aakash; Yazdani, Ali] Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
   [Parker, Colin V.; Aynajian, Pegor; da Silva Neto, Eduardo H.; Pushp, Aakash; Yazdani, Ali] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Ono, Shimpei] Cent Res Inst Elect Power Ind, Tokyo 2018511, Japan.
   [Wen, Jinsheng; Xu, Zhijun; Gu, Genda] Brookhaven Natl Lab, Upton, NY 11973 USA.
C3 Princeton University; Princeton University; Central Research Institute of Electric Power Industry - Japan; United States Department of Energy (DOE); Brookhaven National Laboratory
RP Yazdani, A (corresponding author), Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
EM yazdani@princeton.edu
FU DOE-BES; NSF-DMR; NSF-MRSEC through the Princeton Centre for Complex Materials; W. M. Keck Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [0819860] Funding Source: National Science Foundation
NR 31
TC 209
Z9 236
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 DEC 2
PY 2010
VL 468
IS 7324
BP 677
EP 680
DI 10.1038/nature09597
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 688GB
UT WOS:000284836700037
PM 21124453
DA 2026-03-09
ER

PT J
AU Lee, BH
   Lee, MJ
   Park, S
   Oh, DC
   Elsasser, S
   Chen, PC
   Gartner, C
   Dimova, N
   Hanna, J
   Gygi, SP
   Wilson, SM
   King, RW
   Finley, D
AF Lee, Byung-Hoon
   Lee, Min Jae
   Park, Soyeon
   Oh, Dong-Chan
   Elsasser, Suzanne
   Chen, Ping-Chung
   Gartner, Carlos
   Dimova, Nevena
   Hanna, John
   Gygi, Steven P.
   Wilson, Scott M.
   King, Randall W.
   Finley, Daniel
TI Enhancement of proteasome activity by a small-molecule inhibitor of USP14
SO NATURE
LA English
DT Article
ID deubiquitinating enzyme usp14; 26s proteasome; ataxia mice; ubiquitin; degradation; proteins; subunit; survival; system; stress
AB Proteasomes, the primary mediators of ubiquitin-protein conjugate degradation, are regulated through complex and poorly understood mechanisms. Here we show that USP14, a proteasome-associated deubiquitinating enzyme, can inhibit the degradation of ubiquitin-protein conjugates both in vitro and in cells. A catalytically inactive variant of USP14 has reduced inhibitory activity, indicating that inhibition is mediated by trimming of the ubiquitin chain on the substrate. A high-throughput screen identified a selective small-molecule inhibitor of the deubiquitinating activity of human USP14. Treatment of cultured cells with this compound enhanced degradation of several proteasome substrates that have been implicated in neurodegenerative disease. USP14 inhibition accelerated the degradation of oxidized proteins and enhanced resistance to oxidative stress. Enhancement of proteasome activity through inhibition of USP14 may offer a strategy to reduce the levels of aberrant proteins in cells under proteotoxic stress.
C1 [Lee, Byung-Hoon; Lee, Min Jae; Park, Soyeon; Elsasser, Suzanne; Gartner, Carlos; Dimova, Nevena; Hanna, John; Gygi, Steven P.; King, Randall W.; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Oh, Dong-Chan] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Oh, Dong-Chan] Seoul Natl Univ, Coll Pharm, Inst Nat Prod Res, Seoul 151742, South Korea.
   [Chen, Ping-Chung; Wilson, Scott M.] Univ Alabama, Civitan Int Res Ctr, Evelyn F McKnight Brain Inst, Dept Neurobiol, Birmingham, AL 35294 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Seoul National University (SNU); University of Alabama System; University of Alabama Birmingham
RP King, RW (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM randy_king@hms.harvard.edu; daniel_finley@hms.harvard.edu
FU National Institutes of Health [DK082906, GM65592, GM66492, NS047533]; Harvard Technology Development Accelerator Fund; Merck Co.; Johnson Johnson; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER
NR 64
TC 804
Z9 967
U1 0
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 9
PY 2010
VL 467
IS 7312
BP 179
EP U63
DI 10.1038/nature09299
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 647KB
UT WOS:000281616300028
PM 20829789
DA 2026-03-09
ER

PT J
AU Dalgliesh, GL
   Furge, K
   Greenman, C
   Chen, LN
   Bignell, G
   Butler, A
   Davies, H
   Edkins, S
   Hardy, C
   Latimer, C
   Teague, J
   Andrews, J
   Barthorpe, S
   Beare, D
   Buck, G
   Campbell, PJ
   Forbes, S
   Jia, MM
   Jones, D
   Knott, H
   Kok, CY
   Lau, KW
   Leroy, C
   Lin, ML
   McBride, DJ
   Maddison, M
   Maguire, S
   McLay, K
   Menzies, A
   Mironenko, T
   Mulderrig, L
   Mudie, L
   O'Meara, S
   Pleasance, E
   Rajasingham, A
   Shepherd, R
   Smith, R
   Stebbings, L
   Stephens, P
   Tang, G
   Tarpey, PS
   Turrell, K
   Dykema, KJ
   Khoo, SK
   Petillo, D
   Wondergem, B
   Anema, J
   Kahnoski, RJ
   Teh, B
   Stratton, MR
   Futreal, PA
AF Dalgliesh, Gillian L.
   Furge, Kyle
   Greenman, Chris
   Chen, Lina
   Bignell, Graham
   Butler, Adam
   Davies, Helen
   Edkins, Sarah
   Hardy, Claire
   Latimer, Calli
   Teague, Jon
   Andrews, Jenny
   Barthorpe, Syd
   Beare, Dave
   Buck, Gemma
   Campbell, Peter J.
   Forbes, Simon
   Jia, Mingming
   Jones, David
   Knott, Henry
   Kok, Chai Yin
   Lau, King Wai
   Leroy, Catherine
   Lin, Meng-Lay
   McBride, David J.
   Maddison, Mark
   Maguire, Simon
   McLay, Kirsten
   Menzies, Andrew
   Mironenko, Tatiana
   Mulderrig, Lee
   Mudie, Laura
   O'Meara, Sarah
   Pleasance, Erin
   Rajasingham, Arjunan
   Shepherd, Rebecca
   Smith, Raffaella
   Stebbings, Lucy
   Stephens, Philip
   Tang, Gurpreet
   Tarpey, Patrick S.
   Turrell, Kelly
   Dykema, Karl J.
   Khoo, Sok Kean
   Petillo, David
   Wondergem, Bill
   Anema, John
   Kahnoski, Richard J.
   Teh, Bin Tean
   Stratton, Michael R.
   Futreal, P. Andrew
TI Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
SO NATURE
LA English
DT Article
ID cell carcinoma; prognostic-significance; somatic mutations; cancer genm; p600
AB Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer, characterized by the presence of inactivating mutations in the VHL gene in most cases(1,2), and by infrequent somatic mutations in known cancer genes. To determine further the genetics of ccRCC, we have sequenced 101 cases through 3,544 protein-coding genes. Here we report the identification of inactivating mutations in two genes encoding enzymes involved in histone modification-SETD2, a histone H3 lysine 36 methyltransferase, and JARID1C (also known as KDM5C), a histone H3 lysine 4 demethylase-as well as mutations in the histone H3 lysine 27 demethylase, UTX (KMD6A), that we recently reported(3). The results highlight the role of mutations in components of the chromatin modification machinery in human cancer. Furthermore, NF2 mutations were found in non-VHL mutated ccRCC, and several other probable cancer genes were identified. These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer.
C1 [Khoo, Sok Kean; Petillo, David; Teh, Bin Tean] Van Andel Res Inst, Lab Canc Genert, Grand Rapids, MI 49503 USA.
   [Anema, John; Kahnoski, Richard J.] Spectrum Hlth Hosp, Dept Urol, Grand Rapids, MI 49503 USA.
   [Teh, Bin Tean] Natl Canc Ctr, NCCS VARI Translat Canc Res Lab, Singapore 169610, Singapore.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
   [Furge, Kyle; Dykema, Karl J.; Wondergem, Bill] Van Andel Res Inst, Lab Computat Biol, Grand Rapids, MI 49503 USA.
   [Dalgliesh, Gillian L.; Greenman, Chris; Chen, Lina; Bignell, Graham; Butler, Adam; Davies, Helen; Edkins, Sarah; Hardy, Claire; Latimer, Calli; Teague, Jon; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J.; Forbes, Simon; Jia, Mingming; Jones, David; Knott, Henry; Kok, Chai Yin; Lau, King Wai; Leroy, Catherine; Lin, Meng-Lay; McBride, David J.; Maddison, Mark; Maguire, Simon; McLay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Mulderrig, Lee; Mudie, Laura; O'Meara, Sarah; Pleasance, Erin; Rajasingham, Arjunan; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S.; Turrell, Kelly; Stratton, Michael R.; Futreal, P. Andrew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
C3 Van Andel Institute; Van Andel Research Institute; National Cancer Centre Singapore (NCCS); University of London; Institute of Cancer Research - UK; Van Andel Institute; Van Andel Research Institute; Wellcome Trust Sanger Institute
RP Teh, B (corresponding author), Van Andel Res Inst, Lab Canc Genert, Grand Rapids, MI 49503 USA.
EM Bin.Teh@vai.org; mrs@sanger.ac.uk; paf@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; Hauenstein and Gerber Foundations
NR 27
TC 958
Z9 1127
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 JAN 21
PY 2010
VL 463
IS 7279
BP 360
EP 363
DI 10.1038/nature08672
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100045
PM 20054297
DA 2026-03-09
ER

PT J
AU Guichard, A
   McGillivray, SM
   Cruz-Moreno, B
   van Sorge, NM
   Nizet, V
   Bier, E
AF Guichard, Annabel
   McGillivray, Shauna M.
   Cruz-Moreno, Beatriz
   van Sorge, Nina M.
   Nizet, Victor
   Bier, Ethan
TI Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst
SO NATURE
LA English
DT Article
ID lethal factor; edema factor; wing vein; sec15; rab11; morphogenesis; pathogenesis; components; endosm; effector
AB Bacillus anthracis is the causative agent of anthrax in humans and other mammals(1,2). In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mitogen-activated protein-kinase kinases) and EF (cAMP-dependent processes)(3) have been implicated in the initial phase of anthrax(1,2), less is understood about toxin action during the final stage of infection. Here we use Drosophila melanogaster to identify the Rab11/Sec15 exocyst, which acts at the last step of endocytic recycling, as a novel target of both EF and LF. EF reduces levels of apically localized Rab11 and indirectly blocks vesicle formation by its binding partner and effector Sec15 (Sec15-GFP), whereas LF acts more directly to reduce Sec15-GFP vesicles. Convergent effects of EF and LF on Rab11/Sec15 inhibit expression of and signalling by the Notch ligand Delta and reduce DE-cadherin levels at adherens junctions. In human endothelial cells, the two toxins act in a conserved fashion to block formation of Sec15 vesicles, inhibit Notch signalling, and reduce cadherin expression at adherens junctions. This coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during B. anthracis infection.
C1 [Guichard, Annabel; Cruz-Moreno, Beatriz; Bier, Ethan] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
   [McGillivray, Shauna M.; van Sorge, Nina M.; Nizet, Victor] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [McGillivray, Shauna M.] Texas Christian Univ, Dept Biol, Ft Worth, TX 76129 USA.
   [Nizet, Victor] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Texas Christian University; University of California System; University of California San Diego
RP Bier, E (corresponding author), Univ Calif San Diego, Sect Cell & Dev Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM ebier@ucsd.edu
FU National Institutes of Health (NIH) [AI070654, NS29870, AI077780]; IRACDA NIH [GM068524]; Hartwell Foundation; National Institute of General Medical Sciences [K12GM068524] Funding Source: NIH RePORTER
NR 33
TC 89
Z9 103
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 14
PY 2010
VL 467
IS 7317
BP 854
EP U123
DI 10.1038/nature09446
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 663PB
UT WOS:000282898700069
PM 20944747
DA 2026-03-09
ER

PT J
AU Lam, CK
   Yoo, T
   Hiner, B
   Liu, ZQ
   Grutzendler, J
AF Lam, Carson K.
   Yoo, Taehwan
   Hiner, Bennett
   Liu, Zhiqiang
   Grutzendler, Jaime
TI Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization
SO NATURE
LA English
DT Article
ID blood-brain-barrier; tissue-plasminogen activator; matrix metalloproteinases; alzheimers-disease; in-vivo; vessels; stroke; capillary; ischemia; decline
AB Cerebral microvascular occlusion is a common phenomenon throughout life 1,2 that might require greater recognition as a mechanism of brain pathology. Failure to recanalize microvessels promptly may lead to the disruption of brain circuits and significant functional deficits(3). Haemodynamic forces and the fibrinolytic system(4) are considered to be the principal mechanisms responsible for recanalization of occluded cerebral capillaries and terminal arterioles. Here we identify a previously unrecognized cellular mechanism that may also be critical for this recanalization. By using high-resolution fixed-tissue microscopy and two-photon imaging in living mice we observed that a large fraction of microemboli infused through the internal carotid artery failed to be lysed or washed out within 48 h. Instead, emboli were found to translocate outside the vessel lumen within 2-7 days, leading to complete re-establishment of blood flow and sparing of the vessel. Recanalization occurred by a previously unknown mechanism of microvascular plasticity involving the rapid envelopment of emboli by endothelial membrane projections that subsequently form a new vessel wall. This was followed by the formation of an endothelial opening through which emboli translocated into the perivascular parenchyma. The rate of embolus extravasation was significantly decreased by pharmacological inhibition of matrix metalloproteinase 2/9 activity. In aged mice, extravasation was markedly delayed, resulting in persistent tissue hypoxia, synaptic damage and cell death. Alterations in the efficiency of the protective mechanism that we have identified may have important implications in microvascular pathology, stroke recovery and age-related cognitive decline.
C1 [Lam, Carson K.; Yoo, Taehwan; Hiner, Bennett; Liu, Zhiqiang; Grutzendler, Jaime] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
C3 Northwestern University; Feinberg School of Medicine
RP Grutzendler, J (corresponding author), Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
EM grutzj@northwestern.edu
FU National Institutes of Health/National Institute on Aging [AG027855]; Howard Hughes Medical Institute
NR 30
TC 140
Z9 155
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 MAY 27
PY 2010
VL 465
IS 7297
BP 478
EP U101
DI 10.1038/nature09001
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700035
PM 20505729
DA 2026-03-09
ER

PT J
AU Kim, J
   Lee, JE
   Heynen-Genel, S
   Suyama, E
   Ono, K
   Lee, K
   Ideker, T
   Aza-Blanc, P
   Gleeson, JG
AF Kim, Joon
   Lee, Ji Eun
   Heynen-Genel, Susanne
   Suyama, Eigo
   Ono, Keiichiro
   Lee, KiYoung
   Ideker, Trey
   Aza-Blanc, Pedro
   Gleeson, Joseph G.
TI Functional genomic screen for modulators of ciliogenesis and cilium length
SO NATURE
LA English
DT Article
ID phospholipase a(2); fibroblasts; dissection; mutations; proteins; complex
AB Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways(1,2). Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities(3). Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance(4). However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.
C1 [Kim, Joon; Lee, Ji Eun; Gleeson, Joseph G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci, Inst Genom Med, La Jolla, CA 92093 USA.
   [Kim, Joon; Lee, Ji Eun; Gleeson, Joseph G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Pediat, Inst Genom Med, La Jolla, CA 92093 USA.
   [Heynen-Genel, Susanne; Suyama, Eigo; Aza-Blanc, Pedro] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Ono, Keiichiro; Lee, KiYoung; Ideker, Trey] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Ono, Keiichiro; Lee, KiYoung; Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Lee, KiYoung] Ajou Univ, Sch Med, Dept Biomed Informat, Suwon 443749, South Korea.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; Howard Hughes Medical Institute; Sanford Burnham Prebys Medical Discovery Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Ajou University
RP Gleeson, JG (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci, Inst Genom Med, La Jolla, CA 92093 USA.
EM jogleeson@ucsd.edu
FU UCSD Microscopy Core [P30 NS047101, P30 CA23100]; NARSAD; NINDS [RO1 NS052455]; NIH [GM070743]; Korea Food and Drug Administration [10182KFDA992]; Brain Research Center [M103KV010008-07K2201-00810]; Howard Hughes Medical Institute; National Cancer Institute [P30CA023100] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 25
TC 431
Z9 514
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 15
PY 2010
VL 464
IS 7291
BP 1048
EP U114
DI 10.1038/nature08895
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000040
PM 20393563
DA 2026-03-09
ER

PT J
AU Ito, T
   Woloszyn, M
   Mazloff, M
AF Ito, T.
   Woloszyn, M.
   Mazloff, M.
TI Anthropogenic carbon dioxide transport in the Southern Ocean driven by Ekman flow
SO NATURE
LA English
DT Article
ID recent climate-change; co2; circulation; model; sink
AB The Southern Ocean, with its large surface area and vigorous overturning circulation, is potentially a substantial sink of anthropogenic CO(2) (refs 1-4). Despite its importance, the mechanism and pathways of anthropogenic CO(2) uptake and transport are poorly understood. Regulation of the Southern Ocean carbon sink by the wind-driven Ekman flow, mesoscale eddies and their interaction is under debate(5-8). Here we use a high-resolution ocean circulation and carbon cycle model to address the mechanisms controlling the Southern Ocean sink of anthropogenic CO(2). The focus of our study is on the intra-annual variability in anthropogenic CO(2) over a two-year time period. We show that the pattern of carbon uptake is correlated with the oceanic vertical exchange. Zonally integrated carbon uptake peaks at the Antarctic polar front. The carbon is then advected away from the uptake regions by the circulation of the Southern Ocean, which is controlled by the interplay among Ekman flow, ocean eddies and subduction of water masses. Although lateral carbon fluxes are locally dominated by the imprint of mesoscale eddies, the Ekman transport is the primary mechanism for the zonally integrated, cross-frontal transport of anthropogenic CO(2). Intra-annual variability of the cross-frontal transport is dominated by the Ekman flow with little compensation from eddies. A budget analysis in the density coordinate highlights the importance of wind-driven transport across the polar front and subduction at the subtropical front. Our results suggest intimate connections between oceanic carbon uptake and climate variability through the temporal variability of Ekman transport.
C1 [Ito, T.; Woloszyn, M.] Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
   [Mazloff, M.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
C3 Colorado State University System; Colorado State University Fort Collins; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Ito, T (corresponding author), Colorado State Univ, Dept Atmospher Sci, 1371 Campus Delivery, Ft Collins, CO 80523 USA.
EM ito@atmos.colostate.edu
FU US National Aeronautics and Space Administration (NASA) [NNX08AL72G]; US National Oceanic and Atmospheric Administration [NA08OAR4320893]
NR 30
TC 130
Z9 156
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 7
PY 2010
VL 463
IS 7277
BP 80
EP U85
DI 10.1038/nature08687
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900034
PM 20054394
DA 2026-03-09
ER

PT J
AU Snellen, IAG
   de Kok, RJ
   de Mooij, EJW
   Albrecht, S
AF Snellen, Ignas A. G.
   de Kok, Remco J.
   de Mooij, Ernst J. W.
   Albrecht, Simon
TI The orbital motion, absolute mass and high-altitude winds of exoplanet HD 209458b
SO NATURE
LA English
DT Article
ID dayside spectrum; water; atmosphere; methane
AB For extrasolar planets discovered using the radial velocity method 1, the spectral characterization of the host star leads to a mass estimate of the star and subsequently of the orbiting planet. If the orbital velocity of the planet could be determined, the masses of both star and planet could be calculated using Newton's law of gravity, just as in the case of stellar double-line eclipsing binaries. Here we report high-dispersion ground-based spectroscopy of a transit of the extrasolar planet HD 209458b. We see a significant wavelength shift in absorption lines from carbon monoxide in the planet's atmosphere, which we conclude arises from a change in the radial component of the planet's orbital velocity. The masses of the star and planet are 1.00 +/- 0.22M(Sun) and 0.64 +/- 0.09M(Jup) respectively. A blueshift of the carbon monoxide signal of approximately 2 km s(-1) with respect to the systemic velocity of the host star suggests the presence of a strong wind flowing from the irradiated dayside to the non-irradiated nightside of the planet within the 0.01-0.1 mbar atmospheric pressure range probed by these observations. The strength of the carbon monoxide signal suggests a carbon monoxide mixing ratio of (1-3) x 10(-3) in this planet's upper atmosphere.
C1 [Snellen, Ignas A. G.; de Mooij, Ernst J. W.; Albrecht, Simon] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [de Kok, Remco J.] SRON, NL-3584 CA Utrecht, Netherlands.
   [Albrecht, Simon] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Albrecht, Simon] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Leiden University; Leiden University - Excl LUMC; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Snellen, IAG (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM snellen@strw.leidenuniv.nl
FU Netherlands Organisation for Scientific Research (NWO)
NR 21
TC 636
Z9 715
U1 0
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1049
EP 1051
DI 10.1038/nature09111
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900046
PM 20577209
DA 2026-03-09
ER

PT J
AU Irvine, WTM
   Vitelli, V
   Chaikin, PM
AF Irvine, William T. M.
   Vitelli, Vincenzo
   Chaikin, Paul M.
TI Pleats in crystals on curved surfaces
SO NATURE
LA English
DT Article
ID grain-boundary scars; order
AB Hexagons can easily tile a flat surface, but not a curved one. Introducing heptagons and pentagons (defects with topological charge) makes it easier to tile curved surfaces; for example, soccer balls based on the geodesic domes(1) of Buckminster Fuller have exactly 12 pentagons (positive charges). Interacting particles that invariably form hexagonal crystals on a plane exhibit fascinating scarred defect patterns on a sphere(2-4). Here we show that, for more general curved surfaces, curvature may be relaxed by pleats: uncharged lines of dislocations (topological dipoles) that vanish on the surface and play the same role as fabric pleats. We experimentally investigate crystal order on surfaces with spatially varying positive and negative curvature. On cylindrical capillary bridges, stretched to produce negative curvature, we observe a sequence of transitions-consistent with our energetic calculations-from no defects to isolated dislocations, which subsequently proliferate and organize into pleats; finally, scars and isolated heptagons (previously unseen) appear. This fine control of crystal order with curvature will enable explorations of general theories of defects in curved spaces(5-11). From a practical viewpoint, it may be possible to engineer structures with curvature (such as waisted nanotubes and vaulted architecture) and to develop novel methods for soft lithography(12) and directed self-assembly(13).
C1 [Irvine, William T. M.; Chaikin, Paul M.] NYU, Dept Phys, Ctr Soft Matter Res, New York, NY 10003 USA.
   [Vitelli, Vincenzo] Leiden Univ, Inst Lorentz Theoret Phys, NL-2333 CA Leiden, Netherlands.
C3 New York University; Leiden University - Excl LUMC; Leiden University
RP Irvine, WTM (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM wtmirvine@uchicago.edu; chaikin@nyu.edu
FU Rhodia; English Speaking Union; MRSEC [DMR-0820341]; NASA [NNX08AK04G]; NASA [99476, NNX08AK04G] Funding Source: Federal RePORTER
NR 29
TC 302
Z9 342
U1 3
U2 194
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 16
PY 2010
VL 468
IS 7326
BP 947
EP 951
DI 10.1038/nature09620
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600043
PM 21164482
DA 2026-03-09
ER

PT J
AU Zakamska, NL
AF Zakamska, Nadia L.
TI H2 emission arises outside photodissociation regions in ultraluminous infrared galaxies
SO NATURE
LA English
DT Article
ID shocked molecular-hydrogen; excitation; features; sings; dust; agns; irs
AB Ultraluminous infrared galaxies are among the most luminous objects in the local Universe and are thought to be powered by intense star formation(1,2). It has been shown that in these objects the rotational spectral lines of molecular hydrogen observed at mid-infrared wavelengths are not affected by dust obscuration(3), but left unresolved was the source of excitation for this emission. Here I report an analysis of archival Spitzer Space Telescope data on ultraluminous infrared galaxies and demonstrate that dust obscuration affects star formation indicators but not molecular hydrogen. I thereby establish that the emission of H-2 is not co-spatial with the buried starburst activity and originates outside the obscured regions. This is unexpected in light of the standard view that H-2 emission is directly associated with star-formation activity(3-5). I propose the alternative view that H-2 emission in these objects traces shocks in the surrounding material that are excited by interactions with nearby galaxies. Large-scale shocks cooling by means of H-2 emission may accordingly be more common than previously thought. In the early Universe, a boost in H-2 emission by this process may have accelerated the cooling of matter as it collapsed to form the first stars and galaxies, and would make these first structures more readily observable(6).
C1 Inst Adv Study, Princeton, NJ 08540 USA.
C3 Institute for Advanced Study - USA
RP Zakamska, NL (corresponding author), Inst Adv Study, Einstein Dr, Princeton, NJ 08540 USA.
EM zakamska@ias.edu
FU NASA; John N. Bahcall Fellowship at the Institute for Advanced Study; NSF [AST-0807444]
NR 30
TC 35
Z9 42
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 MAY 6
PY 2010
VL 465
IS 7294
BP 60
EP 63
DI 10.1038/nature09037
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900030
PM 20445624
DA 2026-03-09
ER

PT J
AU Cheloufi, S
   Dos Santos, CO
   Chong, MMW
   Hannon, GJ
AF Cheloufi, Sihem
   Dos Santos, Camila O.
   Chong, Mark M. W.
   Hannon, Gregory J.
TI A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis
SO NATURE
LA English
DT Article
ID crystal-structure; argonaute family; small rnas; slicer; risc; identification; micrornas; sirnas; gene; recruits
AB The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely required for viability, and only this family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, we engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anaemia. Examination of microRNAs and their potential targets revealed a loss of miR-451, a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha (also known as Rnasen), its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic centre to generate an intermediate 39 end, which is then further trimmed. Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development.
C1 [Cheloufi, Sihem; Dos Santos, Camila O.; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Cheloufi, Sihem] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
   [Chong, Mark M. W.] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY 10016 USA.
   [Chong, Mark M. W.] Walter & Eliza Hall Inst Med Res Parkville, Parkville, Vic 3052, Australia.
C3 Cold Spring Harbor Laboratory; Howard Hughes Medical Institute; State University of New York (SUNY) System; Stony Brook University; New York University; Walter & Eliza Hall Institute
RP Hannon, GJ (corresponding author), Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
EM hannon@cshl.edu
FU NIH; National Cancer Institute [P01CA013106] Funding Source: NIH RePORTER
NR 55
TC 869
Z9 1120
U1 0
U2 138
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 584
EP U76
DI 10.1038/nature09092
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000034
PM 20424607
DA 2026-03-09
ER

PT J
AU Marteyn, B
   West, NP
   Browning, DF
   Cole, JA
   Shaw, JG
   Palm, F
   Mounier, J
   Prévost, MC
   Sansonetti, P
   Tang, CM
AF Marteyn, Benoit
   West, Nicholas P.
   Browning, Douglas F.
   Cole, Jeffery A.
   Shaw, Jonathan G.
   Palm, Fredrik
   Mounier, Joelle
   Prevost, Marie-Christine
   Sansonetti, Philippe
   Tang, Christoph M.
TI Modulation of Shigella virulence in response to available oxygen in vivo
SO NATURE
LA English
DT Article
ID iii secretion machinery; escherichia-coli k-12; chromosomal genes; flexneri; proteins; expression; invasion; cells; ipac; construction
AB Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence(1). In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.
C1 [Marteyn, Benoit; West, Nicholas P.; Tang, Christoph M.] Univ London Imperial Coll Sci Technol & Med, Dept Microbiol, Ctr Mol Microbiol & Infect, London SW7 2AZ, England.
   [Browning, Douglas F.; Cole, Jeffery A.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
   [Shaw, Jonathan G.] Univ Sheffield, Sch Med, Div Genom Med, Sheffield S10 2RX, S Yorkshire, England.
   [Palm, Fredrik] Uppsala Univ, Biomed Ctr, Dept Med Cell Biol, S-75123 Uppsala, Sweden.
   [Mounier, Joelle; Sansonetti, Philippe] Inst Pasteur, INSERM, U786, F-75724 Paris 15, France.
   [Mounier, Joelle; Sansonetti, Philippe] Inst Pasteur, Unite Pathogenie Microbienne Mol, F-75724 Paris 15, France.
   [Sansonetti, Philippe] Coll France, F-75231 Paris 05, France.
C3 Imperial College London; University of Birmingham; University of Sheffield; Uppsala University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Institut National de la Sante et de la Recherche Medicale (Inserm); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite PSL; College de France
RP Tang, CM (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Microbiol, Ctr Mol Microbiol & Infect, Flowers Bldg, London SW7 2AZ, England.
EM psanson@pasteur.fr; c.tang@imperial.ac.uk
FU Fondation pour la Recherche Medicale; Royal Society; ERC; European Union [QLRT-1999-00938]; Wellcome Trust; Medical Research Council
NR 35
TC 267
Z9 312
U1 1
U2 73
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 20
PY 2010
VL 465
IS 7296
BP 355
EP U113
DI 10.1038/nature08970
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598IO
UT WOS:000277829200042
PM 20436458
DA 2026-03-09
ER

PT J
AU Mayer, M
   Depken, M
   Bois, JS
   Jülicher, F
   Grill, SW
AF Mayer, Mirjam
   Depken, Martin
   Bois, Justin S.
   Juelicher, Frank
   Grill, Stephan W.
TI Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows
SO NATURE
LA English
DT Article
ID c-elegans embryos; caenorhabditis-elegans; early embryogenesis; proteins rga-3; cell-division; par proteins; germ-line; cytokinesis; microfilaments; morphogenesis
AB Asymmetric cell divisions are essential for the development of multicellular organisms. To proceed, they require an initially symmetric cell to polarize(1). In Caenorhabditis elegans zygotes, anteroposterior polarization is facilitated by a large-scale flow of the actomyosin cortex(2-4), which directs the asymmetry of the first mitotic division. Cortical flows appear in many contexts of development(5), but their underlying forces and physical principles remain poorly understood. How actomyosin contractility and cortical tension interact to generate large-scale flow is unclear. Here we report on the subcellular distribution of cortical tension in the polarizing C. elegans zygote, which we determined using position- and direction-sensitive laser ablation. We demonstrate that cortical flow is associated with anisotropies in cortical tension and is not driven by gradients in cortical tension, which contradicts previous proposals(5). These experiments, in conjunction with a theoretical description of active cortical mechanics, identify two prerequisites for large-scale cortical flow: a gradient in actomyosin contractility to drive flow and a sufficiently large viscosity of the cortex to allow flow to be long-ranged. We thus reveal the physical requirements of large-scale intracellular cortical flow that ensure the efficient polarization of the C. elegans zygote.
C1 [Mayer, Mirjam; Depken, Martin; Bois, Justin S.; Grill, Stephan W.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Mayer, Mirjam; Depken, Martin; Bois, Justin S.; Juelicher, Frank; Grill, Stephan W.] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
C3 Max Planck Society; Max Planck Society
RP Grill, SW (corresponding author), Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
EM grill@mpi-cbg.de
FU Boehringer Ingelheim Fonds; Human Frontier Science Program
NR 47
TC 377
Z9 432
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 617
EP U150
DI 10.1038/nature09376
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100045
PM 20852613
DA 2026-03-09
ER

PT J
AU Sherson, JF
   Weitenberg, C
   Endres, M
   Cheneau, M
   Bloch, I
   Kuhr, S
AF Sherson, Jacob F.
   Weitenberg, Christof
   Endres, Manuel
   Cheneau, Marc
   Bloch, Immanuel
   Kuhr, Stefan
TI Single-atom-resolved fluorescence imaging of an atomic Mott insulator
SO NATURE
LA English
DT Article
ID tonks-girardeau gas; 3d optical lattice; quantum gas; transition
AB The reliable detection of single quantum particles has revolutionized the field of quantum optics and quantum information processing. For several years, researchers have aspired to extend such detection possibilities to larger-scale, strongly correlated quantum systems(1,2) in order to record in situ images of a quantum fluid in which each underlying quantum particle is detected. Here we report fluorescence imaging of strongly interacting bosonic Mott insulators in an optical lattice with single-atom and single-site resolution. From our images, we fully reconstruct the atom distribution on the lattice and identify individual excitations with high fidelity. A comparison of the radial density and variance distributions with theory provides a precise in situ temperature and entropy measurement from single images. We observe Mott-insulating plateaus with near-zero entropy and clearly resolve the high-entropy rings separating them, even though their width is of the order of just a single lattice site. Furthermore, we show how a Mott insulator melts with increasing temperature, owing to a proliferation of local defects. The ability to resolve individual lattice sites directly opens up new avenues for the manipulation, analysis and applications of strongly interacting quantum gases on a lattice. For example, one could introduce local perturbations or access regions of high entropy, a crucial requirement for the implementation of novel cooling schemes(3).
C1 [Sherson, Jacob F.; Weitenberg, Christof; Endres, Manuel; Cheneau, Marc; 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-Pfalz fur Innovation; Carl-Zeiss Stiftung; EU
NR 30
TC 1137
Z9 1281
U1 2
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 SEP 2
PY 2010
VL 467
IS 7311
BP 68
EP U97
DI 10.1038/nature09378
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200036
PM 20720540
DA 2026-03-09
ER

PT J
AU Yu, L
   McPhee, CK
   Zheng, LX
   Mardones, GA
   Rong, YG
   Peng, JY
   Mi, N
   Zhao, Y
   Liu, ZH
   Wan, FY
   Hailey, DW
   Oorschot, V
   Klumperman, J
   Baehrecke, EH
   Lenardo, MJ
AF Yu, Li
   McPhee, Christina K.
   Zheng, Lixin
   Mardones, Gonzalo A.
   Rong, Yueguang
   Peng, Junya
   Mi, Na
   Zhao, Ying
   Liu, Zhihua
   Wan, Fengyi
   Hailey, Dale W.
   Oorschot, Viola
   Klumperman, Judith
   Baehrecke, Eric H.
   Lenardo, Michael J.
TI Termination of autophagy and reformation of lysosomes regulated by mTOR
SO NATURE
LA English
DT Article
ID cell-death; maturation; survival; program; tor
AB Autophagy is an evolutionarily conserved process by which cytoplasmic proteins and organelles are catabolized(1,2). During starvation, the protein TOR (target of rapamycin), a nutrient-responsive kinase, is inhibited, and this induces autophagy. In autophagy, double-membrane autophagosomes envelop and sequester intracellular components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients. Current models of autophagy terminate with the degradation of the autophagosome cargo in autolysosomes(3-5), but the regulation of autophagy in response to nutrients and the subsequent fate of the autolysosome are poorly understood. Here we show that mTOR signalling in rat kidney cells is inhibited during initiation of autophagy, but reactivated by prolonged starvation. Reactivation of mTOR is autophagy-dependent and requires the degradation of autolysosomal products. Increased mTOR activity attenuates autophagy and generates proto-lysosomal tubules and vesicles that extrude from autolysosomes and ultimately mature into functional lysosomes, thereby restoring the full complement of lysosomes in the cell-a process we identify in multiple animal species. Thus, an evolutionarily conserved cycle in autophagy governs nutrient sensing and lysosome homeostasis during starvation.
C1 [Yu, Li; Zheng, Lixin; Liu, Zhihua; Wan, Fengyi; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Yu, Li; Rong, Yueguang; Peng, Junya; Mi, Na] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
   [Yu, Li; Rong, Yueguang; Peng, Junya; Mi, Na] State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [McPhee, Christina K.; Baehrecke, Eric H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
   [McPhee, Christina K.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
   [Mardones, Gonzalo A.; Hailey, Dale W.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
   [Mardones, Gonzalo A.] Univ Austral Chile, Dept Physiol, Valdivia 5099200, Chile.
   [Zhao, Ying] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China.
   [Oorschot, Viola; Klumperman, Judith] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Tsinghua University; University of Massachusetts System; University of Massachusetts Worcester; University System of Maryland; University of Maryland College Park; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Universidad Austral de Chile; Peking University; Utrecht University; Utrecht University Medical Center
RP Lenardo, MJ (corresponding author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
FU Division of Intramural Research of the NIAID, NIH, Department of Health and Human Services; NIH [GM079431]; 973 program [2010CB833704]; NSF [20091300700]; Tsinghua University [20091081391]; Netherlands Organisation for Scientific Research (NWO) [918.56.611]; National Institute of Allergy and Infectious Diseases [ZIAAI000718] Funding Source: NIH RePORTER
NR 17
TC 1267
Z9 1496
U1 1
U2 227
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 17
PY 2010
VL 465
IS 7300
BP 942
EP U11
DI 10.1038/nature09076
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611HN
UT WOS:000278804500041
PM 20526321
DA 2026-03-09
ER

PT J
AU Neumann, B
   Walter, T
   Heriche, JK
   Bulkescher, J
   Erfle, H
   Conrad, C
   Rogers, P
   Poser, I
   Held, M
   Liebel, U
   Cetin, C
   Sieckmann, F
   Pau, G
   Kabbe, R
   Wünsche, A
   Satagopam, V
   Schmitz, MHA
   Chapuis, C
   Gerlich, DW
   Schneider, R
   Eils, R
   Huber, W
   Peters, JM
   Hyman, AA
   Durbin, R
   Pepperkok, R
   Ellenberg, J
AF Neumann, Beate
   Walter, Thomas
   Heriche, Jean-Karim
   Bulkescher, Jutta
   Erfle, Holger
   Conrad, Christian
   Rogers, Phill
   Poser, Ina
   Held, Michael
   Liebel, Urban
   Cetin, Cihan
   Sieckmann, Frank
   Pau, Gregoire
   Kabbe, Rolf
   Wuensche, Annelie
   Satagopam, Venkata
   Schmitz, Michael H. A.
   Chapuis, Catherine
   Gerlich, Daniel W.
   Schneider, Reinhard
   Eils, Roland
   Huber, Wolfgang
   Peters, Jan-Michael
   Hyman, Anthony A.
   Durbin, Richard
   Pepperkok, Rainer
   Ellenberg, Jan
TI Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes
SO NATURE
LA English
DT Article
ID tissue-culture cells; rna interference; identification; organization; arrays
AB Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the similar to 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.
C1 [Wuensche, Annelie; Ellenberg, Jan] European Mol Biol Lab, Gene Express Unit, D-69117 Heidelberg, Germany.
   [Neumann, Beate; Walter, Thomas; Bulkescher, Jutta; Erfle, Holger; Conrad, Christian; Rogers, Phill; Held, Michael; Liebel, Urban] European Mol Biol Lab, MitoCheck Project Grp, D-69117 Heidelberg, Germany.
   [Erfle, Holger; Conrad, Christian; Cetin, Cihan; Chapuis, Catherine; Pepperkok, Rainer] European Mol Biol Lab, Cell Biol Biophys Unit, D-69117 Heidelberg, Germany.
   [Satagopam, Venkata; Schneider, Reinhard] European Mol Biol Lab, Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Heriche, Jean-Karim; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Poser, Ina; Hyman, Anthony A.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Schmitz, Michael H. A.; Gerlich, Daniel W.] Swiss Fed Inst Technol Zurich ETHZ, Inst Biochem, CH-8093 Zurich, Switzerland.
   [Sieckmann, Frank] Leica Microsyst CMS GmbH, D-68165 Mannheim, Germany.
   [Pau, Gregoire; Huber, Wolfgang] European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Kabbe, Rolf; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Peters, Jan-Michael] Inst Mol Pathol, A-1030 Vienna, Austria.
C3 European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Wellcome Trust Sanger Institute; Max Planck Society; Swiss Federal Institutes of Technology Domain; ETH Zurich; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Helmholtz Association; German Cancer Research Center (DKFZ); Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Ellenberg, J (corresponding author), European Mol Biol Lab, Gene Express Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM jan.ellenberg@embl.de
FU European Commission [LSHG-CT-2004-503464]; Federal Ministry of Education and Research (BMBF) [FKZ01GR0403, FKZ01GR0423]; Wellcome Trust
NR 22
TC 677
Z9 751
U1 0
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 1
PY 2010
VL 464
IS 7289
BP 721
EP 727
DI 10.1038/nature08869
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000037
PM 20360735
DA 2026-03-09
ER

PT J
AU Lee, HH
   Molla, MN
   Cantor, CR
   Collins, JJ
AF Lee, Henry H.
   Molla, Michael N.
   Cantor, Charles R.
   Collins, James J.
TI Bacterial charity work leads to population-wide resistance
SO NATURE
LA English
DT Article
ID escherichia-coli; antibiotic-resistance; induced mutagenesis; evolution; indole; death; adaptation; expression; mutations; strains
AB Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates(1-7). Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population's less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells(8). We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection(9) whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.
C1 [Lee, Henry H.; Molla, Michael N.; Collins, James J.] Howard Hughes Med Inst, Ctr BioDynam, Boston, MA 02115 USA.
   [Lee, Henry H.; Molla, Michael N.; Cantor, Charles R.; Collins, James J.] Boston Univ, Dept Biomed Engn, Ctr Adv Biotechnol, Boston, MA 02215 USA.
   [Collins, James J.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02215 USA.
C3 Howard Hughes Medical Institute; Boston University; Harvard University
RP Collins, JJ (corresponding author), Howard Hughes Med Inst, Ctr BioDynam, Boston, MA 02115 USA.
EM jcollins@bu.edu
FU National Institutes of Health [DP1OD003644]; National Science Foundation [DMS-0602204]; Howard Hughes Medical Institute
NR 30
TC 476
Z9 578
U1 1
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 2
PY 2010
VL 467
IS 7311
BP 82
EP U113
DI 10.1038/nature09354
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645MB
UT WOS:000281461200039
PM 20811456
DA 2026-03-09
ER

PT J
AU Perocchi, F
   Gohil, VM
   Girgis, HS
   Bao, XR
   McCombs, JE
   Palmer, AE
   Mootha, VK
AF Perocchi, Fabiana
   Gohil, Vishal M.
   Girgis, Hany S.
   Bao, X. Robert
   McCombs, Janet E.
   Palmer, Amy E.
   Mootha, Vamsi K.
TI MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
SO NATURE
LA English
DT Article
ID rat kidney mitochondria; calcium-uptake; yeast mitochondria; inner membrane; uniporter; transport; cell; phosphorylation; glycoprotein; oscillations
AB Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.
C1 [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA.
   [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [McCombs, Janet E.; Palmer, Amy E.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; University of Colorado System; University of Colorado Boulder
RP Mootha, VK (corresponding author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM vamsi@hms.harvard.edu
FU National Institutes of Health [GM084027, TR2 GM08759, GM0077465, DK080261]; HHMI
NR 48
TC 725
Z9 830
U1 2
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 16
PY 2010
VL 467
IS 7313
BP 291
EP U67
DI 10.1038/nature09358
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 650CF
UT WOS:000281824900031
PM 20693986
DA 2026-03-09
ER

PT J
AU Yang, JY
   Reth, M
AF Yang, Jianying
   Reth, Michael
TI Oligomeric organization of the B-cell antigen receptor on resting cells
SO NATURE
LA English
DT Article
ID chronic lymphocytic-leukemia; ig-alpha/ig-beta; living cells; protein interactions; activation; visualization; initiation; itam; bcr
AB B lymphocytes are activated by many different antigens to produce specific antibodies protecting higher organisms from infection. To detect its cognate antigen, each B cell contains up to 120,000 B-cell antigen receptor (BCR) complexes on its cell surface. How these abundant receptors stay silent on resting B cells and how they can be activated by a molecularly diverse set of ligands is poorly understood(1). Here we show, with the use of a quantitative bifluorescence complementation assay (BiFC)(2,3), that the BCR has an intrinsic ability to form oligomers on the surface of living cells. A BCR mutant that fails to form oligomers is more active and cannot be expressed stably on the B-cell surface, whereas BiFC-stabilized BCR oligomers are less active and more strongly expressed on the surface. We propose that oligomers are the autoinhibited form of the BCR and that it is the shift from closed BCR oligomers to clustered monomers that drives B-cell activation in a way that is independent of the structural input from the antigen.
C1 [Yang, Jianying; Reth, Michael] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, Dept Mol Immunol, Fac Biol, D-79108 Freiburg, Germany.
   [Yang, Jianying; Reth, Michael] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany.
C3 University of Freiburg; Max Planck Society
RP Reth, M (corresponding author), Univ Freiburg, Ctr Biol Signalling Studies BIOSS, Dept Mol Immunol, Fac Biol, Stubeweg 51, D-79108 Freiburg, Germany.
EM michael.reth@bioss.uni-freiburg.de
FU Excellence Initiative of the German Federal and State Governments [EXC 294]; Deutsche Forschungsgemeinschaft [SFB746]; FRISYS
NR 31
TC 150
Z9 185
U1 1
U2 36
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 23
PY 2010
VL 467
IS 7314
BP 465
EP U117
DI 10.1038/nature09357
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 653KO
UT WOS:000282090200044
PM 20818374
DA 2026-03-09
ER

PT J
AU Serabyn, E
   Mawet, D
   Burruss, R
AF Serabyn, E.
   Mawet, D.
   Burruss, R.
TI An image of an exoplanet separated by two diffraction beamwidths from a star
SO NATURE
LA English
DT Article
ID optical vortex coronagraph; phase-mask coronagraph; hr 8799; telescope; planets
AB Three exoplanets around the star HR8799 have recently been discovered by means of differential imaging with large telescopes(1). Bright scattered starlight limits high-contrast imaging to large angular offsets, currently of the order of ten diffraction beamwidths, 10 lambda/D, of the star (where lambda is the wavelength and D is the aperture diameter(1-5)). Imaging faint planets at smaller angles calls for reducing the starlight and associated photon and speckle noise before detection, while efficiently transmitting nearby planet light. To carry out initial demonstrations of reduced-angle high-contrast coronagraphy, we installed a vortex coronagraph(6-9) capable of reaching small angles behind a small, well-corrected telescope subaperture that provides low levels of scattered starlight(10,11). Here we report the detection of all three HR8799 planets with the resultant small-aperture (1.5 m) system, for which only 2 lambda/D separate the innermost planet from the star, with a final noise level within a factor of two of that given by photon statistics. Similar well-corrected small-angle coronagraphs should thus be able to detect exoplanets located even closer to their host stars with larger ground-based telescopes(12-15), and also allow a reduction in the size of potential space telescopes aimed at the imaging of very faint terrestrial planets.
C1 [Serabyn, E.; Mawet, D.; Burruss, R.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology
RP Serabyn, E (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM gene.serabyn@jpl.nasa.gov
NR 23
TC 167
Z9 183
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1018
EP 1020
DI 10.1038/nature09007
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000033
PM 20393557
DA 2026-03-09
ER

PT J
AU Burke, MK
   Dunham, JP
   Shahrestani, P
   Thornton, KR
   Rose, MR
   Long, AD
AF Burke, Molly K.
   Dunham, Joseph P.
   Shahrestani, Parvin
   Thornton, Kevin R.
   Rose, Michael R.
   Long, Anthony D.
TI Genome-wide analysis of a long-term evolution experiment with Drosophila
SO NATURE
LA English
DT Article
ID selection; adaptation; genetics; locus
AB Experimental evolution systems allow the genomic study of adaptation, and so far this has been done primarily in asexual systems with small genomes, such as bacteria and yeast(1-3). Here we present whole-genome resequencing data from Drosophila melanogaster populations that have experienced over 600 generations of laboratory selection for accelerated development. Flies in these selected populations develop from egg to adult similar to 20% faster than flies of ancestral control populations, and have evolved a number of other correlated phenotypes. On the basis of 688,520 intermediate-frequency, high-quality single nucleotide polymorphisms, we identify several dozen genomic regions that show strong allele frequency differentiation between a pooled sample of five replicate populations selected for accelerated development and pooled controls. On the basis of resequencing data from a single replicate population with accelerated development, as well as single nucleotide polymorphism data from individual flies from each replicate population, we infer little allele frequency differentiation between replicate populations within a selection treatment. Signatures of selection are qualitatively different than what has been observed in asexual species; in our sexual populations, adaptation is not associated with 'classic' sweeps whereby newly arising, unconditionally advantageous mutations become fixed. More parsimonious explanations include 'incomplete' sweep models, in which mutations have not had enough time to fix, and 'soft' sweep models, in which selection acts on pre-existing, common genetic variants. We conclude that, at least for life history characters such as development time, unconditionally advantageous alleles rarely arise, are associated with small net fitness gains or cannot fix because selection coefficients change over time.
C1 [Burke, Molly K.; Shahrestani, Parvin; Thornton, Kevin R.; Rose, Michael R.; Long, Anthony D.] Univ Calif Irvine, Irvine, CA 92697 USA.
   [Dunham, Joseph P.] Univ So Calif, Los Angeles, CA 90098 USA.
C3 University of California System; University of California Irvine; University of Southern California
RP Burke, MK (corresponding author), Univ Calif Irvine, 321 Steinhaus Hall, Irvine, CA 92697 USA.
EM burkem@uci.edu; tdlong@uci.edu
FU UCI; NSF [DEB-0614429, DGE-0638751]
NR 22
TC 336
Z9 412
U1 1
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 15
PY 2010
VL 467
IS 7315
BP 587
EP U111
DI 10.1038/nature09352
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100038
PM 20844486
DA 2026-03-09
ER

PT J
AU Cvetkovic, A
   Menon, AL
   Thorgersen, MP
   Scott, JW
   Poole, FL
   Jenney, FE
   Lancaster, WA
   Praissman, JL
   Shanmukh, S
   Vaccaro, BJ
   Trauger, SA
   Kalisiak, E
   Apon, JV
   Siuzdak, G
   Yannone, SM
   Tainer, JA
   Adams, MWW
AF Cvetkovic, Aleksandar
   Menon, Angeli Lal
   Thorgersen, Michael P.
   Scott, Joseph W.
   Poole, Farris L., II
   Jenney, Francis E., Jr.
   Lancaster, W. Andrew
   Praissman, Jeremy L.
   Shanmukh, Saratchandra
   Vaccaro, Brian J.
   Trauger, Sunia A.
   Kalisiak, Ewa
   Apon, Junefredo V.
   Siuzdak, Gary
   Yannone, Steven M.
   Tainer, John A.
   Adams, Michael W. W.
TI Microbial metalloproteomes are largely uncharacterized
SO NATURE
LA English
DT Article
ID archaeon pyrococcus-furiosus; hyperthermophilic archaeon; mass-spectrometry; trace-elements; key role; proteins; metabolism; rubredoxin; insights; database
AB Metal ion cofactors afford proteins virtually unlimited catalytic potential, enable electron transfer reactions and have a great impact on protein stability(1,2). Consequently, metalloproteins have key roles in most biological processes, including respiration (iron and copper), photosynthesis (manganese) and drug metabolism (iron). Yet, predicting from genome sequence the numbers and types of metal an organism assimilates from its environment or uses in its metalloproteome is currently impossible because metal coordination sites are diverse and poorly recognized(2-4). We present here a robust, metal-based approach to determine all metals an organism assimilates and identify its metalloproteins on a genome-wide scale. This shifts the focus from classical protein-based purification to metal-based identification and purification by liquid chromatography, high-throughput tandem mass spectrometry (HT-MS/MS) and inductively coupled plasma mass spectrometry (ICP-MS) to characterize cytoplasmic metalloproteins from an exemplary microorganism (Pyrococcus furiosus). Of 343 metal peaks in chromatography fractions, 158 did not match any predicted metalloprotein. Unassigned peaks included metals known to be used (cobalt, iron, nickel, tungsten and zinc; 83 peaks) plus metals the organism was not thought to assimilate (lead, manganese, molybdenum, uranium and vanadium; 75 peaks). Purification of eight of 158 unexpected metal peaks yielded four novel nickel- and molybdenum-containing proteins, whereas four purified proteins contained sub-stoichiometric amounts of misincorporated lead and uranium. Analyses of two additional microorganisms (Escherichia coli and Sulfolobus solfataricus) revealed species-specific assimilation of yet more unexpected metals. Metalloproteomes are therefore much more extensive and diverse than previously recognized, and promise to provide key insights for cell biology, microbial growth and toxicity mechanisms.
C1 [Cvetkovic, Aleksandar; Menon, Angeli Lal; Thorgersen, Michael P.; Scott, Joseph W.; Poole, Farris L., II; Jenney, Francis E., Jr.; Lancaster, W. Andrew; Praissman, Jeremy L.; Shanmukh, Saratchandra; Vaccaro, Brian J.; Adams, Michael W. W.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
   [Trauger, Sunia A.; Kalisiak, Ewa; Apon, Junefredo V.; Siuzdak, Gary] Scripps Res Inst, Scripps Ctr Mass Spectrometry, La Jolla, CA 92037 USA.
   [Trauger, Sunia A.; Kalisiak, Ewa; Apon, Junefredo V.; Siuzdak, Gary] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Trauger, Sunia A.; Kalisiak, Ewa; Apon, Junefredo V.; Siuzdak, Gary] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Yannone, Steven M.; Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
C3 University System of Georgia; University of Georgia; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Adams, MWW (corresponding author), Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
EM adams@bmb.uga.edu
FU Department of Energy [DE-FG0207ER64326]
NR 37
TC 316
Z9 367
U1 1
U2 240
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 779
EP U18
DI 10.1038/nature09265
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500044
PM 20639861
DA 2026-03-09
ER

PT J
AU Faccenna, C
   Becker, TW
AF Faccenna, Claudio
   Becker, Thorsten W.
TI Shaping mobile belts by small-scale convection
SO NATURE
LA English
DT Article
ID dynamic topography; subduction; kinematics; tectonics; east; slab
AB Mobile belts are long-lived deformation zones composed of an ensemble of crustal fragments, distributed over hundreds of kilometres inside continental convergent margins(1,2). The Mediterranean represents a remarkable example of this tectonic setting(3): the region hosts a diffuse boundary between the Nubia and Eurasia plates comprised of a mosaic of microplates that move and deform independently from the overall plate convergence(4). Surface expressions of Mediterranean tectonics include deep, subsiding backarc basins, intraplate plateaux and uplifting orogenic belts. Although the kinematics of the area are now fairly well defined, the dynamical origins of many of these active features are controversial and usually attributed to crustal and lithospheric interactions. However, the effects of mantle convection, well established for continental interiors(5-7), should be particularly relevant in a mobile belt, and modelling may constrain important parameters such as slab coherence and lithospheric strength. Here we compute global mantle flow on the basis of recent, high-resolution seismic tomography to investigate the role of buoyancy-driven and plate-motion-induced mantle circulation for the Mediterranean. We show that mantle flow provides an explanation for much of the observed dynamic topography and microplate motion in the region. More generally, vigorous small-scale convection in the uppermost mantle may also underpin other complex mobile belts such as the North American Cordillera or the Himalayan-Tibetan collision zone.
C1 [Faccenna, Claudio] Univ Roma TRE, Dipartimento Sci Geol, I-00146 Rome, Italy.
   [Faccenna, Claudio] CNR IGAG, I-00016 Monterotondo, Italy.
   [Becker, Thorsten W.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
C3 Roma Tre University; Consiglio Nazionale delle Ricerche (CNR); Istituto di Geologia Ambientale e Geoingegneria (IGAG-CNR); University of Southern California
RP Faccenna, C (corresponding author), Univ Roma TRE, Dipartimento Sci Geol, I-00146 Rome, Italy.
EM faccenna@uniroma3.it
FU University of Southern California (USC); Consiglio Nazionale Ricerche; TOPOEUROPE; MEDUSA [NSF-EAR 0451952]; Directorate For Geosciences; Division Of Earth Sciences [0910985] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0809023] Funding Source: National Science Foundation
NR 30
TC 208
Z9 224
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 JUN 3
PY 2010
VL 465
IS 7298
BP 602
EP 605
DI 10.1038/nature09064
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000038
PM 20520711
DA 2026-03-09
ER

PT J
AU Li, XY
   Wei, YJ
   Lu, L
   Lu, K
   Gao, HJ
AF Li, Xiaoyan
   Wei, Yujie
   Lu, Lei
   Lu, Ke
   Gao, Huajian
TI Dislocation nucleation governed softening and maximum strength in nano-twinned metals
SO NATURE
LA English
DT Article
ID mechanical-property; deformation; plasticity; ductility; copper; scale
AB In conventional metals, there is plenty of space for dislocations-line defects whose motion results in permanent material deformation-to multiply, so that the metal strengths are controlled by dislocation interactions with grain boundaries(1,2) and other obstacles(3,4). For nano-structured materials, in contrast, dislocation multiplication is severely confined by the nanometre-scale geometries so that continued plasticity can be expected to be source-controlled. Nano-grained polycrystalline materials were found to be strong but brittle(5-9), because both nucleation and motion of dislocations are effectively suppressed by the nanoscale crystallites. Here we report a dislocation-nucleation-controlled mechanism in nano-twinned metals(10,11) in which there are plenty of dislocation nucleation sites but dislocation motion is not confined. We show that dislocation nucleation governs the strength of such materials, resulting in their softening below a critical twin thickness. Large-scale molecular dynamics simulations and a kinetic theory of dislocation nucleation in nano-twinned metals show that there exists a transition in deformation mechanism, occurring at a critical twin-boundary spacing for which strength is maximized. At this point, the classical Hall-Petch type of strengthening due to dislocation pile-up and cutting through twin planes switches to a dislocation-nucleation-controlled softening mechanism with twin-boundary migration resulting from nucleation and motion of partial dislocations parallel to the twin planes. Most previous studies(12,13) did not consider a sufficient range of twin thickness and therefore missed this strength-softening regime. The simulations indicate that the critical twin-boundary spacing for the onset of softening in nano-twinned copper and the maximum strength depend on the grain size: the smaller the grain size, the smaller the critical twin-boundary spacing, and the higher the maximum strength of the material.
C1 [Li, Xiaoyan; Gao, Huajian] Brown Univ, Div Engn, Providence, RI 02912 USA.
   [Wei, Yujie] Univ Alabama, Dept Mech Engn, Tuscaloosa, AL 35487 USA.
   [Lu, Lei; Lu, Ke] Chinese Acad Sci, Shenyang Natl Lab Mat Sci, Inst Met Res, Shenyang 110016, Peoples R China.
C3 Brown University; University of Alabama System; University of Alabama Tuscaloosa; Chinese Academy of Sciences; Institute of Metal Research, CAS
RP Wei, YJ (corresponding author), Chinese Acad Sci, Inst Mech, State Key Lab Nonlinear Mech, Beijing 100190, Peoples R China.
EM yujie_wei@lnm.imech.ac.cn; huajian_gao@brown.edu
FU NSF [DMR-0520651]; Brown University [CMMI-0758535]; NSFC [50621091, 50725103, 50890171]; MOST of China [2005CB623604]; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0758535] Funding Source: National Science Foundation
NR 32
TC 1130
Z9 1243
U1 33
U2 1674
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 877
EP 880
DI 10.1038/nature08929
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300034
PM 20376146
DA 2026-03-09
ER

PT J
AU Okada, Y
   Yamagata, K
   Hong, K
   Wakayama, T
   Zhang, Y
AF Okada, Yuki
   Yamagata, Kazuo
   Hong, Kwonho
   Wakayama, Teruhiko
   Zhang, Yi
TI A role for the elongator complex in zygotic paternal genome demethylation
SO NATURE
LA English
DT Article
ID dna demethylation; preimplantation embryos; s-adenosylmethionine; mouse; gene; methylation; protein; glycosylase; arabidopsis; subunit
AB The life cycle of mammals begins when a sperm enters an egg. Immediately after fertilization, both the maternal and paternal genomes undergo dramatic reprogramming to prepare for the transition from germ cell to somatic cell transcription programs(1). One of the molecular events that takes place during this transition is the demethylation of the paternal genome(2,3). Despite extensive efforts, the factors responsible for paternal DNA demethylation have not been identified(4). To search for such factors, we developed a live cell imaging system that allows us to monitor the paternal DNA methylation state in zygotes. Through short-interfering-RNA-mediated knockdown in mouse zygotes, we identified Elp3 (also called KAT9), a component of the elongator complex(5), to be important for paternal DNA demethylation. We demonstrate that knockdown of Elp3 impairs paternal DNA demethylation as indicated by reporter binding, immunostaining and bisulphite sequencing. Similar results were also obtained when other elongator components, Elp1 and Elp4, were knocked down. Importantly, injection of messenger RNA encoding the Elp3 radical SAM domain mutant, but not the HAT domain mutant, into MII oocytes before fertilization also impaired paternal DNA demethylation, indicating that the SAM radical domain is involved in the demethylation process. Our study not only establishes a critical role for the elongator complex in zygotic paternal genome demethylation, but also indicates that the demethylation process may be mediated through a reaction that requires an intact radical SAM domain.
C1 [Okada, Yuki; Hong, Kwonho; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
   [Okada, Yuki; Hong, Kwonho; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   [Yamagata, Kazuo; Wakayama, Teruhiko] RIKEN, Ctr Dev Biol, Lab Genom Reprogramming, Chuo Ku, Kobe, Hyogo 6500047, Japan.
C3 Howard Hughes Medical Institute; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; RIKEN
RP Zhang, Y (corresponding author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
EM yi_zhang@med.unc.edu
FU Howard Hughes Medical Institute Funding Source: Medline; NIGMS NIH HHS [R01 GM068804] Funding Source: Medline
NR 30
TC 231
Z9 264
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 JAN 28
PY 2010
VL 463
IS 7280
BP 554
EP U177
DI 10.1038/nature08732
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100054
PM 20054296
DA 2026-03-09
ER

PT J
AU Nowak, MA
   Tarnita, CE
   Wilson, EO
AF Nowak, Martin A.
   Tarnita, Corina E.
   Wilson, Edward O.
TI The evolution of eusociality
SO NATURE
LA English
DT Article
ID division-of-labor; group-selection; kin selection; social interactions; inclusive fitness; cooperation; altruism; polymorphism; hymenoptera; multilevel
AB Eusociality, in which some individuals reduce their own lifetime reproductive potential to raise the offspring of others, underlies the most advanced forms of social organization and the ecologically dominant role of social insects and humans. For the past four decades kin selection theory, based on the concept of inclusive fitness, has been the major theoretical attempt to explain the evolution of eusociality. Here we show the limitations of this approach. We argue that standard natural selection theory in the context of precise models of population structure represents a simpler and superior approach, allows the evaluation of multiple competing hypotheses, and provides an exact framework for interpreting empirical observations.
C1 [Nowak, Martin A.; Tarnita, Corina E.] Harvard Univ, Dept Math, Dept Organism & Evolutionary Biol, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Wilson, Edward O.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Nowak, MA (corresponding author), Harvard Univ, Dept Math, Dept Organism & Evolutionary Biol, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
EM martin_nowak@harvard.edu
FU John Templeton Foundation; NSF/NIH [R01GM078986]; Bill and Melinda Gates Foundation [37874]
NR 61
TC 807
Z9 1016
U1 5
U2 1095
PU NATURE PUBLISHING 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 26
PY 2010
VL 466
IS 7310
BP 1057
EP 1062
DI 10.1038/nature09205
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600030
PM 20740005
DA 2026-03-09
ER

PT J
AU Humbard, MA
   Miranda, HV
   Lim, JM
   Krause, DJ
   Pritz, JR
   Zhou, GY
   Chen, SX
   Wells, L
   Maupin-Furlow, JA
AF Humbard, Matthew A.
   Miranda, Hugo V.
   Lim, Jae-Min
   Krause, David J.
   Pritz, Jonathan R.
   Zhou, Guangyin
   Chen, Sixue
   Wells, Lance
   Maupin-Furlow, Julie A.
TI Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii
SO NATURE
LA English
DT Article
ID proteasome-activating nucleotidase; rhodanese-like protein; molybdenum cofactor; dependent degradation; sulfur carrier; system; chains; pup; deubiquitination; metalloprotease
AB Archaea, one of three major evolutionary lineages of life, encode proteasomes highly related to those of eukaryotes. In contrast, archaeal ubiquitin-like proteins are less conserved and not known to function in protein conjugation. This has complicated our understanding of the origins of ubiquitination and its connection to proteasomes. Here we report two small archaeal modifier proteins, SAMP1 and SAMP2, with a beta-grasp fold and carboxy-terminal diglycine motif similar to ubiquitin, that form protein conjugates in the archaeon Haloferax volcanii. The levels of SAMP-conjugates were altered by nitrogen-limitation and proteasomal gene knockout and spanned various functions including components of the Urm1 pathway. LC-MS/MS-based collision-induced dissociation demonstrated isopeptide bonds between the C-terminal glycine of SAMP2 and the epsilon-amino group of lysines from a number of protein targets and Lys58 of SAMP2 itself, revealing poly-SAMP chains. The widespread distribution and diversity of pathways modified by SAMPylation suggest that this type of protein conjugation is central to the archaeal lineage.
C1 [Humbard, Matthew A.; Miranda, Hugo V.; Krause, David J.; Pritz, Jonathan R.; Zhou, Guangyin; Maupin-Furlow, Julie A.] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA.
   [Chen, Sixue] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
   [Chen, Sixue] Univ Florida, Interdisciplinary Ctr Biotechnol Res, Gainesville, FL 32611 USA.
   [Lim, Jae-Min; Wells, Lance] Univ Georgia, Dept Biochem & Mol Biol, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
C3 State University System of Florida; University of Florida; State University System of Florida; University of Florida; State University System of Florida; University of Florida; University System of Georgia; University of Georgia
RP Maupin-Furlow, JA (corresponding author), Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA.
EM jmaupin@ufl.edu
FU NIH [1S10 RR025418-01, NCRR P41 RR018502, R01 GM057498]; DOE [DE-FG02-05ER15650]; National Institute of General Medical Sciences [R01GM057498] Funding Source: NIH RePORTER
NR 44
TC 157
Z9 194
U1 1
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 JAN 7
PY 2010
VL 463
IS 7277
BP 54
EP U60
DI 10.1038/nature08659
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 540OV
UT WOS:000273344900028
PM 20054389
DA 2026-03-09
ER

PT J
AU Malmgren, RD
   Ottino, JM
   Amaral, LAN
AF Malmgren, R. Dean
   Ottino, Julio M.
   Amaral, Luis A. Nunes
TI The role of mentorship in protege performance
SO NATURE
LA English
DT Article
ID organizational commitment; longitudinal examination; perspective; selection
AB The role of mentorship in protege performance is a matter of importance to academic, business and governmental organizations. Although the benefits of mentorship for proteges, mentors and their organizations are apparent(1-9), the extent to which proteges mimic their mentors' career choices and acquire their mentorship skills is unclear(10-16). The importance of a science, technology, engineering and mathematics workforce to economic growth and the role of effective mentorship in maintaining a 'healthy' such workforce demand the study of the role of mentorship in academia. Here we investigate one aspect of mentor emulation by studying mentorship fecundity-the number of proteges a mentor trains-using data from the Mathematics Genealogy Project(17), which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further discover three significant correlations in mentorship fecundity. First, mentors with low mentorship fecundities train proteges that go on to have mentorship fecundities 37% higher than expected. Second, in the first third of their careers, mentors with high fecundities train proteges that go on to have fecundities 29% higher than expected. Finally, in the last third of their careers, mentors with high fecundities train proteges that go on to have fecundities 31% lower than expected.
C1 [Malmgren, R. Dean; Ottino, Julio M.; Amaral, Luis A. Nunes] Northwestern Univ, Dept Biol & Chem Engn, Evanston, IL 60208 USA.
   [Malmgren, R. Dean] Datascope Analyt, Evanston, IL 60201 USA.
   [Ottino, Julio M.; Amaral, Luis A. Nunes] Northwestern Univ, NW Inst Complex Syst, Evanston, IL 60208 USA.
   [Amaral, Luis A. Nunes] Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA.
C3 Northwestern University; Northwestern University; Northwestern University; Howard Hughes Medical Institute
RP Ottino, JM (corresponding author), Northwestern Univ, Dept Biol & Chem Engn, Evanston, IL 60208 USA.
EM jm-ottino@northwestern.edu; amaral@northwestern.edu
FU US National Science Foundation [SBE 0830388, IIS 0838564]
NR 30
TC 126
Z9 155
U1 5
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 622
EP U117
DI 10.1038/nature09040
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000043
PM 20520715
DA 2026-03-09
ER

PT J
AU Asselin-Labat, ML
   Vaillant, F
   Sheridan, JM
   Pal, B
   Wu, D
   Simpson, ER
   Yasuda, H
   Smyth, GK
   Martin, TJ
   Lindeman, GJ
   Visvader, JE
AF Asselin-Labat, Marie-Liesse
   Vaillant, Francois
   Sheridan, Julie M.
   Pal, Bhupinder
   Wu, Di
   Simpson, Evan R.
   Yasuda, Hisataka
   Smyth, Gordon K.
   Martin, T. John
   Lindeman, Geoffrey J.
   Visvader, Jane E.
TI Control of mammary stem cell function by steroid hormone signalling
SO NATURE
LA English
DT Article
ID estrogen-receptor-alpha; breast-cancer; progesterone-receptor; gland morphogenesis; mice lacking; proliferation; ligand; risk; differentiation; activator
AB The ovarian hormones oestrogen and progesterone profoundly influence breast cancer risk(1-3), underpinning the benefit of endocrine therapies in the treatment of breast cancer(4). Modulation of their effects through ovarian ablation or chemoprevention strategies also significantly decreases breast cancer incidence(5,6). Conversely, there is an increased risk of breast cancer associated with pregnancy in the short term(7). The cellular mechanisms underlying these observations, however, are poorly defined. Here we demonstrate that mouse mammary stem cells (MaSCs)(8,9) are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors(10). Ovariectomy markedly diminished MaSC number and outgrowth potential in vivo, whereas MaSC activity increased in mice treated with oestrogen plus progesterone. Notably, even three weeks of treatment with the aromatase inhibitor letrozole was sufficient to reduce the MaSC pool. In contrast, pregnancy led to a transient 11-fold increase in MaSC numbers, probably mediated through paracrine signalling from RANK ligand. The augmented MaSC pool indicates a cellular basis for the short-term increase in breast cancer incidence that accompanies pregnancy. These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.
C1 [Asselin-Labat, Marie-Liesse; Vaillant, Francois; Sheridan, Julie M.; Pal, Bhupinder; Wu, Di; Smyth, Gordon K.; Lindeman, Geoffrey J.; Visvader, Jane E.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Wu, Di; Smyth, Gordon K.; Visvader, Jane E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
   [Simpson, Evan R.] Monash Med Ctr, Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia.
   [Yasuda, Hisataka] Oriental Yeast Co, Nagahama Inst Biochem Sci, Shiga 5260804, Japan.
   [Martin, T. John] St Vincents Inst, Fitzroy, Vic 3065, Australia.
   [Lindeman, Geoffrey J.] Royal Melbourne Hosp, Dept Med Oncol, Parkville, Vic 3050, Australia.
   [Lindeman, Geoffrey J.] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia.
C3 Walter & Eliza Hall Institute; University of Melbourne; Hudson Institute of Medical Research; Monash Health; Monash Medical Centre; Monash University; Oriental Yeast Co., Ltd.; St. Vincent's Institute of Medical Research; Melbourne Health; Royal Melbourne Hospital; University of Melbourne
RP Lindeman, GJ (corresponding author), Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
EM lindeman@wehi.edu.au; visvader@wehi.edu.au
FU Australian Research Council; Victorian Breast Cancer Research Consortium; National Health and Medical Research Council (Australia); Susan G. Komen Foundation; National Breast Cancer Foundation; Australian Cancer Research Foundation
NR 37
TC 562
Z9 667
U1 1
U2 67
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 10
PY 2010
VL 465
IS 7299
BP 798
EP 802
DI 10.1038/nature09027
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AM
UT WOS:000278551800049
PM 20383121
DA 2026-03-09
ER

PT J
AU Bonfanti, P
   Claudinot, S
   Amici, AW
   Farley, A
   Blackburn, CC
   Barrandon, Y
AF Bonfanti, Paola
   Claudinot, Stephanie
   Amici, Alessandro W.
   Farley, Alison
   Blackburn, C. Clare
   Barrandon, Yann
TI Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells
SO NATURE
LA English
DT Article
ID hair-follicles; progenitor cells; clonal analysis; tolerance; identification; organogenesis; regeneration; keratinocyte; generation; aire
AB The thymus develops from the third pharyngeal pouch of the anterior gut and provides the necessary environment for thymopoiesis (the process by which thymocytes differentiate into mature T lymphocytes) and the establishment and maintenance of self-tolerance(1-3). It contains thymic epithelial cells (TECs) that form a complex three-dimensional network organized in cortical and medullary compartments, the organization of which is notably different from simple or stratified epithelia(4). TECs have an essential role in the generation of self-tolerant thymocytes through expression of the autoimmune regulator Aire(5,6), but the mechanisms involved in the specification and maintenance of TECs remain unclear(7-9). Despite the different embryological origins of thymus and skin (endodermal and ectodermal, respectively), some cells of the thymic medulla express stratified-epithelium markers(10-12), interpreted as promiscuous gene expression. Here we show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured while conserving the capacity to integrate in a thymic epithelial network and to express major histocompatibility complex class II (MHC II) molecules and Aire. These cells can irreversibly adopt the fate of hair follicle multipotent stem cells when exposed to an inductive skin microenvironment; this change in fate is correlated with robust changes in gene expression. Hence, microenvironmental cues are sufficient here to re-direct epithelial cell fate, allowing crossing of primitive germ layer boundaries and an increase in potency(13).
C1 [Bonfanti, Paola; Claudinot, Stephanie; Amici, Alessandro W.; Barrandon, Yann] Ecole Polytech Fed Lausanne, Sch Life Sci, Lab Stem Cell Dynam, CH-1015 Lausanne, Switzerland.
   [Bonfanti, Paola; Claudinot, Stephanie; Amici, Alessandro W.; Barrandon, Yann] CHU Vaudois, Univ Lausanne Hosp, Dept Expt Surg, CH-1011 Lausanne, Switzerland.
   [Farley, Alison; Blackburn, C. Clare] Univ Edinburgh, Sch Biol Sci, MRC, Ctr Regenerat Med,Inst Stem Cell Res, Edinburgh EH16 4SB, Midlothian, Scotland.
C3 Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Edinburgh
RP Barrandon, Y (corresponding author), Ecole Polytech Fed Lausanne, Sch Life Sci, Lab Stem Cell Dynam, CH-1015 Lausanne, Switzerland.
EM Yann.Barrandon@epfl.ch
FU Swiss National Science Foundation [3100A0-104160]; Juvenile Diabetes Research Foundation; EPFL; CHUV; Leukaemia Research Fund; European Union (EU); Heiwa Nakajima Foundation; Medical Research Council [G0700711B] Funding Source: researchfish
NR 33
TC 114
Z9 129
U1 0
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 AUG 19
PY 2010
VL 466
IS 7309
BP 978
EP U105
DI 10.1038/nature09269
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640ED
UT WOS:000281030300035
PM 20725041
DA 2026-03-09
ER

PT J
AU Watanabe, A
   Choe, S
   Chaptal, V
   Rosenberg, JM
   Wright, EM
   Grabe, M
   Abramson, J
AF Watanabe, Akira
   Choe, Seungho
   Chaptal, Vincent
   Rosenberg, John M.
   Wright, Ernest M.
   Grabe, Michael
   Abramson, Jeff
TI The mechanism of sodium and substrate release from the binding pocket of vSGLT
SO NATURE
LA English
DT Article
ID amino-acid antiporter; molecular-dynamics; crystal-structure; transporter; cotransporter; model; resolution; software; insights; homolog
AB Membrane co-transport proteins that use a five-helix inverted repeat motif have recently emerged as one of the largest structural classes of secondary active transporters(1,2). However, despite many structural advances there is no clear evidence of how ion and substrate transport are coupled. Here we report a comprehensive study of the sodium/galactose transporter from Vibrio parahaemolyticus (vSGLT), consisting of molecular dynamics simulations, biochemical characterization and a new crystal structure of the inward-open conformation at a resolution of 2.7 angstrom. Our data show that sodium exit causes a reorientation of transmembrane helix 1 that opens an inner gate required for substrate exit, and also triggers minor rigid-body movements in two sets of transmembrane helical bundles. This cascade of events, initiated by sodium release, ensures proper timing of ion and substrate release. Once set in motion, these molecular changes weaken substrate binding to the transporter and allow galactose readily to enter the intracellular space. Additionally, we identify an allosteric pathway between the sodium-binding sites, the unwound portion of transmembrane helix 1 and the substrate-binding site that is essential in the coupling of co-transport.
C1 [Watanabe, Akira; Chaptal, Vincent; Wright, Ernest M.; Abramson, Jeff] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA.
   [Choe, Seungho; Rosenberg, John M.; Grabe, Michael] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
   [Rosenberg, John M.; Grabe, Michael] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
C3 University of California System; University of California Los Angeles; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Abramson, J (corresponding author), Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA.
EM mdgrabe@pitt.edu; jabramson@mednet.ucla.edu
FU NIH [GM078844, RGY0069, DK19567]; Human Frontier Science Program
NR 39
TC 159
Z9 186
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 DEC 16
PY 2010
VL 468
IS 7326
BP 988
EP U162
DI 10.1038/nature09580
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 695BC
UT WOS:000285344600052
PM 21131949
DA 2026-03-09
ER

PT J
AU Lawler, MJ
   Fujita, K
   Lee, J
   Schmidt, AR
   Kohsaka, Y
   Kim, CK
   Eisaki, H
   Uchida, S
   Davis, JC
   Sethna, JP
   Kim, EA
AF Lawler, M. J.
   Fujita, K.
   Lee, Jhinhwan
   Schmidt, A. R.
   Kohsaka, Y.
   Kim, Chung Koo
   Eisaki, H.
   Uchida, S.
   Davis, J. C.
   Sethna, J. P.
   Kim, Eun-Ah
TI Intra-unit-cell electronic nematicity of the high-Tc copper-oxide pseudogap states
SO NATURE
LA English
DT Article
ID fluctuating stripes; magnetic order; phase; symmetry; insulator; breaking
AB In the high-transition-temperature (high-T-c) superconductors the pseudogap phase becomes predominant when the density of doped holes is reduced(1). Within this phase it has been unclear which electronic symmetries (if any) are broken, what the identity of any associated order parameter might be, and which microscopic electronic degrees of freedom are active. Here we report the determination of a quantitative order parameter representing intra-unit-cell nematicity: the breaking of rotational symmetry by the electronic structure within each CuO2 unit cell. We analyse spectroscopic-imaging scanning tunnelling microscope images of the intra-unit-cell states in underdoped Bi2Sr2CaCu2O8 + delta and, using two independent evaluation techniques, find evidence for electronic nematicity of the states close to the pseudogap energy. Moreover, we demonstrate directly that these phenomena arise from electronic differences at the two oxygen sites within each unit cell. If the characteristics of the pseudogap seen here and by other techniques all have the same microscopic origin, this phase involves weak magnetic states at the O sites that break 90 degrees-rotational symmetry within every CuO2 unit cell.
C1 [Lawler, M. J.; Fujita, K.; Lee, Jhinhwan; Schmidt, A. R.; Kim, Chung Koo; Davis, J. C.; Sethna, J. P.; Kim, Eun-Ah] Cornell Univ, Dept Phys, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
   [Lawler, M. J.] SUNY Binghamton, Dept Phys Appl Phys & Astron, Binghamton, NY 13902 USA.
   [Fujita, K.; Lee, Jhinhwan; Schmidt, A. R.; Kim, Chung Koo; Davis, J. C.] Brookhaven Natl Lab, Condensed Matter Phys & Mat Sci Dept, Upton, NY 11973 USA.
   [Fujita, K.; Uchida, S.] Univ Tokyo, Dept Phys, Bunkyo Ku, Tokyo 1130033, Japan.
   [Lee, Jhinhwan] Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea.
   [Kohsaka, Y.] RIKEN, Magnet Mat Lab, Wako, Saitama 3510198, Japan.
   [Eisaki, H.] Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki 3058568, Japan.
   [Davis, J. C.] Univ St Andrews, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
C3 Cornell University; State University of New York (SUNY) System; Binghamton University, SUNY; United States Department of Energy (DOE); Brookhaven National Laboratory; University of Tokyo; Korea Advanced Institute of Science & Technology (KAIST); RIKEN; National Institute of Advanced Industrial Science & Technology (AIST); University of St Andrews
RP Kim, EA (corresponding author), Cornell Univ, Dept Phys, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
EM eun-ah.kim@cornell.edu
FU NSF [DMR-0520404]; Center for Emergent Superconductivity; Energy Frontier Research Center; US Department of Energy [DE-2009-BNL-PM015]; Ministry of Science and Education (Japan); Japan Society for the Promotion of Science; US Army Research Office; Physics and Astronomy Department at the University of British Columbia, Vancouver, Canada; Direct For Mathematical & Physical Scien; Division Of Materials Research [1005479] Funding Source: National Science Foundation
NR 30
TC 515
Z9 583
U1 0
U2 158
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 15
PY 2010
VL 466
IS 7304
BP 347
EP 351
DI 10.1038/nature09169
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100044
PM 20631795
DA 2026-03-09
ER

PT J
AU Ciocchi, S
   Herry, C
   Grenier, F
   Wolff, SBE
   Letzkus, JJ
   Vlachos, I
   Ehrlich, I
   Sprengel, R
   Deisseroth, K
   Stadler, MB
   Müller, C
   Lüthi, A
AF Ciocchi, Stephane
   Herry, Cyril
   Grenier, Francois
   Wolff, Steffen B. E.
   Letzkus, Johannes J.
   Vlachos, Ioannis
   Ehrlich, Ingrid
   Sprengel, Rolf
   Deisseroth, Karl
   Stadler, Michael B.
   Mueller, Christian
   Luethi, Andreas
TI Encoding of conditioned fear in central amygdala inhibitory circuits
SO NATURE
LA English
DT Article
ID long-term potentiation; central nucleus; synaptic plasticity; projection neurons; rat; complex; organization; forebrain; transmission; mechanisms
AB The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour.
C1 [Ciocchi, Stephane; Herry, Cyril; Grenier, Francois; Wolff, Steffen B. E.; Letzkus, Johannes J.; Ehrlich, Ingrid; Stadler, Michael B.; Mueller, Christian; Luethi, Andreas] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
   [Vlachos, Ioannis] Bernstein Ctr Computat Neurosci, D-79104 Freiburg, Germany.
   [Sprengel, Rolf] Max Planck Inst Med Res, Dept Mol Neurobiol, D-69120 Heidelberg, Germany.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
C3 Friedrich Miescher Institute for Biomedical Research; Max Planck Society; Stanford University
RP Lüthi, A (corresponding author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM andreas.luthi@fmi.ch
FU Austrian Science Fund (FWF); Swiss National Science Foundation; Schering Foundation; European Commission [HEALTH-F2-2009-241498]; Indo Swiss Joint Research Programme; BMBF [01GQ0420]; Neurex Interreg-IV; Volkswagen Stiftung; Novartis Institutes for Biomedical Research; Novartis Research Foundation
NR 46
TC 727
Z9 842
U1 1
U2 132
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 277
EP U239
DI 10.1038/nature09559
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000045
PM 21068837
DA 2026-03-09
ER

PT J
AU Niessing, J
   Friedrich, RW
AF Niessing, Joern
   Friedrich, Rainer W.
TI Olfactory pattern classification by discrete neuronal network states
SO NATURE
LA English
DT Article
ID binary odor mixtures; antennal lobe; mitral cells; sensory information; attractor dynamics; glomerular layer; bulb; representations; zebrafish; discrimination
AB The categorial nature of sensory, cognitive and behavioural acts indicates that the brain classifies neuronal activity patterns into discrete representations. Pattern classification may be achieved by abrupt switching between discrete activity states of neuronal circuits, but few experimental studies have directly tested this. We gradually varied the concentration or molecular identity of odours and optically measured responses across output neurons of the olfactory bulb in zebrafish. Whereas population activity patterns were largely insensitive to changes in odour concentration, morphing of one odour into another resulted in abrupt transitions between odour representations. These transitions were mediated by coordinated response changes among small neuronal ensembles rather than by shifts in the global network state. The olfactory bulb therefore classifies odour-evoked input patterns into many discrete and defined output patterns, as proposed by attractor models. This computation is consistent with perceptual phenomena and may represent a general information processing strategy in the brain.
C1 [Niessing, Joern; Friedrich, Rainer W.] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research
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; Deutsche Forschungsgemeinschaft [FOR 643]; Studienstiftung des deutschen Volkes
NR 54
TC 134
Z9 149
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 47
EP U53
DI 10.1038/nature08961
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900028
PM 20393466
DA 2026-03-09
ER

PT J
AU Sansom, RS
   Gabbott, SE
   Purnell, MA
AF Sansom, Robert S.
   Gabbott, Sarah E.
   Purnell, Mark A.
TI Non-random decay of chordate characters causes bias in fossil interpretation
SO NATURE
LA English
DT Article
ID burgess shale; preservation; vertebrates; phylogeny; branchiostoma; organisms; evolution; taphonomy; biology; origin
AB Exceptional preservation of soft-bodied Cambrian chordates provides our only direct information on the origin of vertebrates(1,2). Fossil chordates from this interval offer crucial insights into how the distinctive body plan of vertebrates evolved, but reading this pre-biomineralization fossil record is fraught with difficulties, leading to controversial and contradictory interpretations(3,4). The cause of these difficulties is taphonomic: we lack data on when and how important characters change as they decompose, resulting in a lack of constraint on anatomical interpretation and a failure to distinguish phylogenetic absence of characters from loss through decay(3). Here we show, from experimental decay of amphioxus and ammocoetes, that loss of chordate characters during decay is non-random: the more phylogenetically informative are the most labile, whereas plesiomorphic characters are decay resistant. The taphonomic loss of synapomorphies and relatively higher preservation potential of chordate plesiomorphies will thus result in bias towards wrongly placing fossils on the chordate stem. Application of these data to Cathaymyrus (Cambrian period of China) and Metaspriggina (Cambrian period of Canada) highlights the difficulties: these fossils cannot be placed reliably in the chordate or vertebrate stem because they could represent the decayed remains of any non-biomineralized, total-group chordate. Preliminary data suggest that this decay filter also affects other groups of organisms and that 'stem-ward slippage' may be a widespread but currently unrecognized bias in our understanding of the early evolution of a number of phyla.
C1 [Sansom, Robert S.; Gabbott, Sarah E.; Purnell, Mark A.] Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
C3 University of Leicester
RP Purnell, MA (corresponding author), Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
EM mark.purnell@le.ac.uk
FU UK Natural Environment Research Council [NE/E015336/1]; NERC [NE/E015336/1] Funding Source: UKRI; Natural Environment Research Council [NE/E015336/1] Funding Source: researchfish
NR 30
TC 178
Z9 206
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2010
VL 463
IS 7282
BP 797
EP 800
DI 10.1038/nature08745
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300037
PM 20118914
DA 2026-03-09
ER

PT J
AU Sattler, A
   Parkin, G
AF Sattler, Aaron
   Parkin, Gerard
TI Cleaving carbon-carbon bonds by inserting tungsten into unstrained aromatic rings
SO NATURE
LA English
DT Article
ID heterocyclic nitrogen-compounds; hydrodenitrogenation catalysis; metal; chemistry; complex; coordination; isocyanides; quinoxaline; molybdenum; activation
AB The cleavage of C-H and C-C bonds by transition metal centres is of fundamental interest and plays an important role in the synthesis of complex organic molecules from petroleum feedstocks(1-6). But while there are many examples for the oxidative addition of C-H bonds to a metal centre, transformations that feature oxidative addition of C-C bonds are rare. The paucity of transformations that involve the cleavage of C-C rather than C-H bonds is usually attributed to kinetic factors arising from the greater steric hindrance and the directional nature of the sp(n) hybrids that form the C-C bond, and to thermodynamic factors arising from the fact that M-C bonds are weaker than M-H bonds(2-5). Not surprisingly, therefore, most examples of C-C bond cleavage either avoid the kinetic limitations by using metal compounds in which the C-C bond is held in close proximity to the metal centre, or avoid the thermodynamic limitations by using organic substrates in which the cleavage is accompanied by either a relief of strain energy or the formation of an aromatic system(2-5). Here, we show that a tungsten centre can be used to cleave a strong C-C bond that is a component of an unstrained 6-membered aromatic ring. The cleavage is enabled by the formation of an unusual chelating di(isocyanide) ligand, which suggests that other metal centres with suitable ancillary ligands could also accomplish the cleavage of strong C-C bonds of aromatic substrates and thereby provide new ways of functionalizing such molecules.
C1 [Sattler, Aaron; Parkin, Gerard] Columbia Univ, Dept Chem, New York, NY 10027 USA.
C3 Columbia University
RP Parkin, G (corresponding author), Columbia Univ, Dept Chem, New York, NY 10027 USA.
EM parkin@columbia.edu
FU US Department of Energy, Office of Basic Energy Sciences [DE-FG02-93ER14339]; National Science Foundation [CHE-0619638]
NR 30
TC 162
Z9 172
U1 1
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 523
EP 526
DI 10.1038/nature08730
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100047
PM 20110998
DA 2026-03-09
ER

PT J
AU Vörösmarty, CJ
   McIntyre, PB
   Gessner, MO
   Dudgeon, D
   Prusevich, A
   Green, P
   Glidden, S
   Bunn, SE
   Sullivan, CA
   Liermann, CR
   Davies, PM
AF Voeroesmarty, C. J.
   McIntyre, P. B.
   Gessner, M. O.
   Dudgeon, D.
   Prusevich, A.
   Green, P.
   Glidden, S.
   Bunn, S. E.
   Sullivan, C. A.
   Liermann, C. Reidy
   Davies, P. M.
TI Global threats to human water security and river biodiversity
SO NATURE
LA English
DT Article
ID american fresh-water; marine; vulnerability; indicators; resources; map
AB Protecting the world's freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world's population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.
C1 [Voeroesmarty, C. J.; Green, P.] CUNY City Coll, Environm CrossRd Initiat, New York, NY 10035 USA.
   [McIntyre, P. B.] Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA.
   [Gessner, M. O.] Swiss Fed Inst Technol, Eawag Swiss Fed Inst Aquat Sci & Technol, Dept Aquat Ecol, CH-8600 Dubendorf, Switzerland.
   [Gessner, M. O.] Swiss Fed Inst Technol, Inst Integrat Biol IBZ, CH-8600 Dubendorf, Switzerland.
   [Gessner, M. O.] Leibniz Inst Freshwater Ecol & Inland Fisheries I, D-16775 Stechlin, Germany.
   [Dudgeon, D.] Univ Hong Kong, Sch Biol Sci, Div Ecol & Biodivers, Hong Kong, Hong Kong, Peoples R China.
   [Prusevich, A.; Glidden, S.] Univ New Hampshire, Water Syst Anal Grp, Durham, NH 03824 USA.
   [Bunn, S. E.] Griffith Univ, Australian Rivers Inst, Nathan, Qld 4111, Australia.
   [Sullivan, C. A.] So Cross Univ, Sch Environm Sci & Management, Lismore, NSW 2480, Australia.
   [Liermann, C. Reidy] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
   [Davies, P. M.] Univ Western Australia, Ctr Excellence Nat Resource Management, Albany 6330, Australia.
C3 City University of New York (CUNY) System; City College of New York (CUNY); University of Michigan System; University of Michigan; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Swiss Federal Institutes of Technology Domain; ETH Zurich; Leibniz Association; Leibniz Institut fur Gewasserokologie und Binnenfischerei (IGB); University of Hong Kong; University System Of New Hampshire; University of New Hampshire; Griffith University; Southern Cross University; University of Washington; University of Washington Seattle; University of Western Australia
RP Vörösmarty, CJ (corresponding author), CUNY City Coll, Environm CrossRd Initiat, New York, NY 10035 USA.
EM contact@riverthreat.net
FU NASA [NNX07AF28G]; NSF Division of Earth Sciences [0854957]; Global Environment Facility [UPI 00345306]; D.H. Smith Fellowship; Directorate For Geosciences; Division Of Earth Sciences [0854957] Funding Source: National Science Foundation
NR 50
TC 5440
Z9 6365
U1 96
U2 3350
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 2010
VL 467
IS 7315
BP 555
EP 561
DI 10.1038/nature09440
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 655TT
UT WOS:000282273100031
PM 20882010
DA 2026-03-09
ER

PT J
AU Ding, BS
   Nolan, DJ
   Butler, JM
   James, D
   Babazadeh, AO
   Rosenwaks, Z
   Mittal, V
   Kobayashi, H
   Shido, K
   Lyden, D
   Sato, TN
   Rabbany, SY
   Rafii, S
AF Ding, Bi-Sen
   Nolan, Daniel J.
   Butler, Jason M.
   James, Daylon
   Babazadeh, Alexander O.
   Rosenwaks, Zev
   Mittal, Vivek
   Kobayashi, Hideki
   Shido, Koji
   Lyden, David
   Sato, Thomas N.
   Rabbany, Sina Y.
   Rafii, Shahin
TI Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
SO NATURE
LA English
DT Article
ID cells; angiogenesis; growth; vegf; differentiation; expression; id1
AB During embryogenesis, endothelial cells induce organogenesis before the development of circulation(1-4). These findings suggest that endothelial cells not only form passive conduits to deliver nutrients and oxygen, but also establish an instructive vascular niche, which through elaboration of paracrine trophogens stimulates organ regeneration, in a manner similar to endothelial-cell-derived angiocrine factors that support haematopoiesis(5-7). However, the precise mechanism by which tissue-specific subsets of endothelial cells promote organogenesis in adults is unknown. Here we demonstrate that liver sinusoidal endothelial cells (LSECs) constitute a unique population of phenotypically and functionally defined VEGFR3(+)CD34(-)VEGFR2(+)VE-cadherin(+)FactorVIII(+)CD452(-) endothelial cells, which through the release of angiocrine trophogens initiate and sustain liver regeneration induced by 70% partial hepatectomy. After partial hepatectomy, residual liver vasculature remains intact without experiencing hypoxia or structural damage, which allows study of physiological liver regeneration. Using this model, we show that inducible genetic ablation of vascular endothelial growth factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst of hepatocyte proliferation (days 1-3 after partial hepatectomy) and subsequent reconstitution of the hepatovascular mass (days 4-8 after partial hepatectomy) by inhibiting upregulation of the endothelial-cell-specific transcription factor Id1. Accordingly, Id1-deficient mice also manifest defects throughout liver regeneration, owing to diminished expression of LSEC-derived angiocrine factors, including hepatocyte growth factor (HGF) and Wnt2. Notably, in in vitro co-cultures, VEGFR2-Id1 activation in LSECs stimulates hepatocyte proliferation. Indeed, intrasplenic transplantation of Id1(+/+) or Id1(-/-) LSECs transduced with Wnt2 and HGF (Id1(-/-)Wnt2(+)HGF(+) LSECs) re-establishes an inductive vascular niche in the liver sinusoids of the Id1(-/-) mice, initiating and restoring hepatovascular regeneration. Therefore, in the early phases of physiological liver regeneration, VEGFR2-Id1-mediated inductive angiogenesis in LSECs through release of angiocrine factors Wnt2 and HGF provokes hepatic proliferation. Subsequently, VEGFR2-Id1-dependent proliferative angiogenesis reconstitutes liver mass. Therapeutic co-transplantation of inductive VEGFR2(+)Id1(+)Wnt2(+)HGF(+) LSECs with hepatocytes provides an effective strategy to achieve durable liver regeneration.
C1 [Ding, Bi-Sen; Nolan, Daniel J.; Butler, Jason M.; James, Daylon; Babazadeh, Alexander O.; Kobayashi, Hideki; Shido, Koji; Rabbany, Sina Y.; Rafii, Shahin] Weill Cornell Med Coll, Ansary Stem Cell Inst, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Ding, Bi-Sen; Nolan, Daniel J.; Butler, Jason M.; James, Daylon; Babazadeh, Alexander O.; Kobayashi, Hideki; Shido, Koji; Rabbany, Sina Y.; Rafii, Shahin] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA.
   [Rosenwaks, Zev] Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10065 USA.
   [Mittal, Vivek] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
   [Lyden, David] Weill Cornell Med Coll, Dept Pediat, New York, NY 10065 USA.
   [Sato, Thomas N.] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara, Japan.
   [Rabbany, Sina Y.] Hofstra Univ, Bioengn Program, Hempstead, NY 11549 USA.
C3 Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Nara Institute of Science & Technology; Hofstra University
RP Rafii, S (corresponding author), Weill Cornell Med Coll, Ansary Stem Cell Inst, Howard Hughes Med Inst, New York, NY 10065 USA.
EM srafii@med.cornell.edu
FU Howard Hughes Medical Institute; Ansary Stem Cell Institute; National Institutes of Health [HL097797, U01 HL-66592-03, RC1 AI080309]; Qatar National Priorities Research Program; Anbinder and Newmans Own Foundations; Empire State Stem Cell Board; New York State Department of Health [NYS C024180]; MEXT; Takeda Science Foundation; Uehara Memorial Life Science Foundation
NR 36
TC 663
Z9 787
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 NOV 11
PY 2010
VL 468
IS 7321
BP 310
EP U240
DI 10.1038/nature09493
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000052
PM 21068842
DA 2026-03-09
ER

PT J
AU Qin, JJ
   Li, RQ
   Raes, J
   Arumugam, M
   Burgdorf, KS
   Manichanh, C
   Nielsen, T
   Pons, N
   Levenez, F
   Yamada, T
   Mende, DR
   Li, JH
   Xu, JM
   Li, SC
   Li, DF
   Cao, JJ
   Wang, B
   Liang, HQ
   Zheng, HS
   Xie, YL
   Tap, J
   Lepage, P
   Bertalan, M
   Batto, JM
   Hansen, T
   Le Paslier, D
   Linneberg, A
   Nielsen, HB
   Pelletier, E
   Renault, P
   Sicheritz-Ponten, T
   Turner, K
   Zhu, HM
   Yu, C
   Li, ST
   Jian, M
   Zhou, Y
   Li, YR
   Zhang, XQ
   Li, SG
   Qin, N
   Yang, HM
   Wang, J
   Brunak, S
   Dore, J
   Guarner, F
   Kristiansen, K
   Pedersen, O
   Parkhill, J
   Weissenbach, J
   Bork, P
   Ehrlich, SD
   Wang, J
AF Qin, Junjie
   Li, Ruiqiang
   Raes, Jeroen
   Arumugam, Manimozhiyan
   Burgdorf, Kristoffer Solvsten
   Manichanh, Chaysavanh
   Nielsen, Trine
   Pons, Nicolas
   Levenez, Florence
   Yamada, Takuji
   Mende, Daniel R.
   Li, Junhua
   Xu, Junming
   Li, Shaochuan
   Li, Dongfang
   Cao, Jianjun
   Wang, Bo
   Liang, Huiqing
   Zheng, Huisong
   Xie, Yinlong
   Tap, Julien
   Lepage, Patricia
   Bertalan, Marcelo
   Batto, Jean-Michel
   Hansen, Torben
   Le Paslier, Denis
   Linneberg, Allan
   Nielsen, H. Bjorn
   Pelletier, Eric
   Renault, Pierre
   Sicheritz-Ponten, Thomas
   Turner, Keith
   Zhu, Hongmei
   Yu, Chang
   Li, Shengting
   Jian, Min
   Zhou, Yan
   Li, Yingrui
   Zhang, Xiuqing
   Li, Songgang
   Qin, Nan
   Yang, Huanming
   Wang, Jian
   Brunak, Soren
   Dore, Joel
   Guarner, Francisco
   Kristiansen, Karsten
   Pedersen, Oluf
   Parkhill, Julian
   Weissenbach, Jean
   Bork, Peer
   Ehrlich, S. Dusko
   Wang, Jun
TI A human gut microbial gene catalogue established by metagenomic sequencing
SO NATURE
LA English
DT Article
ID 16s ribosomal-rna; intestinal microbiota; community; host; diversity; obesity; fermentation; environment; alignment; networks
AB To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, similar to 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
C1 [Qin, Junjie; Li, Ruiqiang; Li, Junhua; Xu, Junming; Li, Shaochuan; Li, Dongfang; Cao, Jianjun; Wang, Bo; Liang, Huiqing; Zheng, Huisong; Xie, Yinlong; Zhu, Hongmei; Yu, Chang; Li, Shengting; Jian, Min; Zhou, Yan; Li, Yingrui; Zhang, Xiuqing; Li, Songgang; Qin, Nan; Yang, Huanming; Wang, Jian; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Raes, Jeroen; Arumugam, Manimozhiyan; Yamada, Takuji; Mende, Daniel R.; Bork, Peer] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Raes, Jeroen] Vrije Univ Brussel VIB, B-1050 Brussels, Belgium.
   [Burgdorf, Kristoffer Solvsten; Nielsen, Trine; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, DK-2820 Copenhagen, Denmark.
   [Manichanh, Chaysavanh; Guarner, Francisco] Hosp Univ Val dHebron, Barcelona 08035, Spain.
   [Pons, Nicolas; Levenez, Florence; Tap, Julien; Lepage, Patricia; Batto, Jean-Michel; Renault, Pierre; Dore, Joel; Ehrlich, S. Dusko] INRA, F-78350 Jouy En Josas, France.
   [Li, Junhua; Xie, Yinlong] S China Univ Technol, Sch Software Engn, Guangzhou 510641, Peoples R China.
   [Li, Dongfang] Shenzhen Univ, Sch Med, Genome Res Inst, Shenzhen 518000, Peoples R China.
   [Bertalan, Marcelo; Nielsen, H. Bjorn; Sicheritz-Ponten, Thomas; Brunak, Soren] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Le Paslier, Denis; Pelletier, Eric; Weissenbach, Jean] CEA, F-91000 Evry, France.
   [Linneberg, Allan] Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.
   [Turner, Keith; Parkhill, Julian] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Kristiansen, Karsten; Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark.
   [Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, DK-8000 Aarhus, Denmark.
C3 Beijing Genomics Institute (BGI); European Molecular Biology Laboratory (EMBL); Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); Novo Nordisk; Hagedorn Research Institute; Universite Paris Saclay; INRAE; South China University of Technology; Shenzhen University; Technical University of Denmark; CEA; Wellcome Trust Sanger Institute; University of Copenhagen; Aarhus University; University of Copenhagen
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM dusko.ehrlich@jouy.inra.fr; wangj@genomics.org.cn
FU European Community [HEALTH-F4-2007-201052]; Danish Natural Science Research Council; Solexa project [272-07-0196]; Shenzhen Municipal Government of China; National Natural Science Foundation of China [30725008]; International Science and Technology Cooperation, China [CXB200903110066A, ZYC200903240076A]; Danish Strategic Research Council [2106-07-0021]; Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care; Instituto de Salud Carlos III (Spain)
NR 44
TC 8565
Z9 10698
U1 66
U2 2639
PU 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 4
PY 2010
VL 464
IS 7285
BP 59
EP U70
DI 10.1038/nature08821
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563GZ
UT WOS:000275117500033
PM 20203603
DA 2026-03-09
ER

PT J
AU Ko, H
   Takei, K
   Kapadia, R
   Chuang, S
   Fang, H
   Leu, PW
   Ganapathi, K
   Plis, E
   Kim, HS
   Chen, SY
   Madsen, M
   Ford, AC
   Chueh, YL
   Krishna, S
   Salahuddin, S
   Javey, A
AF Ko, Hyunhyub
   Takei, Kuniharu
   Kapadia, Rehan
   Chuang, Steven
   Fang, Hui
   Leu, Paul W.
   Ganapathi, Kartik
   Plis, Elena
   Kim, Ha Sul
   Chen, Szu-Ying
   Madsen, Morten
   Ford, Alexandra C.
   Chueh, Yu-Lun
   Krishna, Sanjay
   Salahuddin, Sayeef
   Javey, Ali
TI Ultrathin compound semiconductor on insulator layers for high-performance nanoscale transistors
SO NATURE
LA English
DT Article
ID silicon; density; devices; inas
AB Over the past several years, the inherent scaling limitations of silicon (Si) electron devices have fuelled the exploration of alternative semiconductors, with high carrier mobility, to further enhance device performance(1-8). In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied(7,9,10): such devices combine the high mobility of III-V semiconductors and the well established, low-cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored(9,11-13)-but besides complexity, high defect densities and junction leakage currents present limitations in this approach. Motivated by this challenge, here we use an epitaxial transfer method for the integration of ultrathin layers of single-crystal InAs on Si/SiO2 substrates. As a parallel with silicon-on-insulator (SOI) technology(14), we use 'XOI' to represent our compound semiconductoron-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high-quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsOx layer (similar to 1 nm thick). The fabricated field-effect transistors exhibit a peak transconductance of similar to 1.6 mS mu m(-1) at a drain-source voltage of 0.5 V, with an on/off current ratio of greater than 10,000.
C1 [Ko, Hyunhyub; Takei, Kuniharu; Kapadia, Rehan; Chuang, Steven; Fang, Hui; Leu, Paul W.; Madsen, Morten; Ford, Alexandra C.; Javey, Ali] Univ Calif Berkeley, Berkeley Sensor & Actuator Ctr, Berkeley, CA 94720 USA.
   [Ko, Hyunhyub; Takei, Kuniharu; Kapadia, Rehan; Chuang, Steven; Fang, Hui; Leu, Paul W.; Madsen, Morten; Ford, Alexandra C.; Javey, Ali] Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Chen, Szu-Ying; Chueh, Yu-Lun] Natl Tsing Hua Univ, Hsinchu 30013, Taiwan.
   [Plis, Elena; Kim, Ha Sul; Krishna, Sanjay] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87106 USA.
   [Plis, Elena; Kim, Ha Sul; Krishna, Sanjay] Univ New Mexico, Ctr High Technol Mat, Albuquerque, NM 87106 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; National Tsing Hua University; University of New Mexico; University of New Mexico
RP Javey, A (corresponding author), Univ Calif Berkeley, Berkeley Sensor & Actuator Ctr, Berkeley, CA 94720 USA.
EM ajavey@eecs.berkeley.edu
FU MARCO/MSD Focus Center; Intel Corporation; BSAC; LDRD from Lawrence Berkeley National Laboratory; Sloan research fellowship; NSF; Sunchon National University; Danish Research Council for Technology and Production Sciences; AFOSR [FA9550-10-1-0113]; National Science Council, Taiwan [NSC 98-2112-M-007-025-MY3]
NR 29
TC 378
Z9 437
U1 2
U2 233
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 286
EP 289
DI 10.1038/nature09541
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000047
PM 21068839
DA 2026-03-09
ER

PT J
AU Warren, WC
   Clayton, DF
   Ellegren, H
   Arnold, AP
   Hillier, LW
   Künstner, A
   Searle, S
   White, S
   Vilella, AJ
   Fairley, S
   Heger, A
   Kong, LS
   Ponting, CP
   Jarvis, ED
   Mello, CV
   Minx, P
   Lovell, P
   Velho, TAF
   Ferris, M
   Balakrishnan, CN
   Sinha, S
   Blatti, C
   London, SE
   Li, Y
   Lin, YC
   George, J
   Sweedler, J
   Southey, B
   Gunaratne, P
   Watson, M
   Nam, K
   Backström, N
   Smeds, L
   Nabholz, B
   Itoh, Y
   Whitney, O
   Pfenning, AR
   Howard, J
   Voelker, M
   Skinner, BM
   Griffin, DK
   Ye, L
   McLaren, WM
   Flicek, P
   Quesada, V
   Velasco, G
   Lopez-Otin, C
   Puente, XS
   Olender, T
   Lancet, D
   Smit, AFA
   Hubley, R
   Konkel, MK
   Walker, JA
   Batzer, MA
   Gu, WJ
   Pollock, DD
   Chen, L
   Cheng, Z
   Eichler, EE
   Stapley, J
   Slate, J
   Ekblom, R
   Birkhead, T
   Burke, T
   Burt, D
   Scharff, C
   Adam, I
   Richard, H
   Sultan, M
   Soldatov, A
   Lehrach, H
   Edwards, SV
   Yang, SP
   Li, XC
   Graves, T
   Fulton, L
   Nelson, J
   Chinwalla, A
   Hou, SF
   Mardis, ER
   Wilson, RK
AF Warren, Wesley C.
   Clayton, David F.
   Ellegren, Hans
   Arnold, Arthur P.
   Hillier, LaDeana W.
   Kuenstner, Axel
   Searle, Steve
   White, Simon
   Vilella, Albert J.
   Fairley, Susan
   Heger, Andreas
   Kong, Lesheng
   Ponting, Chris P.
   Jarvis, Erich D.
   Mello, Claudio V.
   Minx, Pat
   Lovell, Peter
   Velho, Tarciso A. F.
   Ferris, Margaret
   Balakrishnan, Christopher N.
   Sinha, Saurabh
   Blatti, Charles
   London, Sarah E.
   Li, Yun
   Lin, Ya-Chi
   George, Julia
   Sweedler, Jonathan
   Southey, Bruce
   Gunaratne, Preethi
   Watson, Michael
   Nam, Kiwoong
   Backstroem, Niclas
   Smeds, Linnea
   Nabholz, Benoit
   Itoh, Yuichiro
   Whitney, Osceola
   Pfenning, Andreas R.
   Howard, Jason
   Voelker, Martin
   Skinner, Bejamin M.
   Griffin, Darren K.
   Ye, Liang
   McLaren, William M.
   Flicek, Paul
   Quesada, Victor
   Velasco, Gloria
   Lopez-Otin, Carlos
   Puente, Xose S.
   Olender, Tsviya
   Lancet, Doron
   Smit, Arian F. A.
   Hubley, Robert
   Konkel, Miriam K.
   Walker, Jerilyn A.
   Batzer, Mark A.
   Gu, Wanjun
   Pollock, David D.
   Chen, Lin
   Cheng, Ze
   Eichler, Evan E.
   Stapley, Jessica
   Slate, Jon
   Ekblom, Robert
   Birkhead, Tim
   Burke, Terry
   Burt, David
   Scharff, Constance
   Adam, Iris
   Richard, Hugues
   Sultan, Marc
   Soldatov, Alexey
   Lehrach, Hans
   Edwards, Scott V.
   Yang, Shiaw-Pyng
   Li, XiaoChing
   Graves, Tina
   Fulton, Lucinda
   Nelson, Joanne
   Chinwalla, Asif
   Hou, Shunfeng
   Mardis, Elaine R.
   Wilson, Richard K.
TI The genome of a songbird
SO NATURE
LA English
DT Article
ID gene-expression; dosage compensation; learned birdsong; brain; evolution; nucleus; chicken; mechanisms; reveals; rna
AB The zebra finch is an important model organism in several fields(1,2) with unique relevance to human neuroscience(3,4). Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken(5)-the only bird with a sequenced genome until now(6). Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes(7). We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
C1 [Warren, Wesley C.; Hillier, LaDeana W.; Minx, Pat; Ye, Liang; Graves, Tina; Fulton, Lucinda; Nelson, Joanne; Chinwalla, Asif; Hou, Shunfeng; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Ctr, Sch Med, St Louis, MO 63108 USA.
   [Clayton, David F.; Ferris, Margaret; Balakrishnan, Christopher N.; Sinha, Saurabh; Blatti, Charles; London, Sarah E.; Li, Yun; Lin, Ya-Chi; George, Julia; Sweedler, Jonathan; Southey, Bruce] Univ Illinois, Urbana, IL 61801 USA.
   [Ellegren, Hans; Kuenstner, Axel; Nam, Kiwoong; Backstroem, Niclas; Smeds, Linnea; Nabholz, Benoit] Uppsala Univ, Inst Evolut & Genet Syst, S-75236 Uppsala, Sweden.
   [Arnold, Arthur P.; Itoh, Yuichiro] Univ Calif Los Angeles, Los Angeles, CA 90056 USA.
   [Searle, Steve; White, Simon; Fairley, Susan] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Vilella, Albert J.; McLaren, William M.] EMBL EBI, Cambridge CB10 1SD, England.
   [Heger, Andreas; Kong, Lesheng; Ponting, Chris P.] Univ Oxford, Funct Genom Unit, MRC, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Jarvis, Erich D.; Whitney, Osceola; Pfenning, Andreas R.; Howard, Jason] Duke Univ, Med Ctr, Dept Neurobiol, Howard Hughes Med Inst, Durham, NC 27710 USA.
   [Mello, Claudio V.; Lovell, Peter; Velho, Tarciso A. F.; Flicek, Paul] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
   [Gunaratne, Preethi] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
   [Watson, Michael; Voelker, Martin] Inst Anim Hlth, Dept Bioinformat, Compton RG20 7NN, Berks, England.
   [Skinner, Bejamin M.; Griffin, Darren K.] Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England.
   [Quesada, Victor; Velasco, Gloria; Lopez-Otin, Carlos; Puente, Xose S.] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, E-33006 Oviedo, Spain.
   [Olender, Tsviya; Lancet, Doron] Weizmann Inst Sci, Dept Mol Genet, Crown Human Genome Ctr, IL-76100 Rehovot, Israel.
   [Smit, Arian F. A.; Hubley, Robert] Inst Syst Biol, Seattle, WA 98103 USA.
   [Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Gu, Wanjun; Pollock, David D.] Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
   [Chen, Lin; Cheng, Ze; Eichler, Evan E.; Stapley, Jessica] Univ Washington, Seattle, WA 98195 USA.
   [Slate, Jon; Ekblom, Robert; Birkhead, Tim; Burke, Terry] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Scharff, Constance; Adam, Iris] Free Univ Berlin, Inst Biol, D-14195 Berlin, Germany.
   [Burt, David] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9OS, Midlothian, Scotland.
   [Burt, David] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9OS, Midlothian, Scotland.
   [Richard, Hugues; Sultan, Marc; Soldatov, Alexey; Lehrach, Hans] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany.
   [Edwards, Scott V.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Yang, Shiaw-Pyng] Monsanto Co, St Louis, MO 63167 USA.
   [Li, XiaoChing] Louisiana State Univ, Hlth Sci Ctr, Ctr Neurosci, New Orleans, LA 70112 USA.
C3 Washington University (WUSTL); University of Illinois System; University of Illinois Urbana-Champaign; Uppsala University; University of California System; University of California Los Angeles; Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Oxford; Duke University; Howard Hughes Medical Institute; Oregon Health & Science University; University of Houston System; University of Houston; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Pirbright Institute; University of Kent; University of Oviedo; Instituto Universitario de Oncologia de Asturias; Weizmann Institute of Science; Institute for Systems Biology (ISB); Louisiana State University System; Louisiana State University; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Washington; University of Washington Seattle; University of Sheffield; Free University of Berlin; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; Max Planck Society; Harvard University; Monsanto; Louisiana State University System; Louisiana State University Health Sciences Center New Orleans
RP Warren, WC (corresponding author), Washington Univ, Genome Ctr, Sch Med, Campus Box 8501,4444 Forest Pk Ave, St Louis, MO 63108 USA.
EM wwarren@watson.wustl.edu; dclayton@illinois.edu; hans.ellegren@ebc.uu.se; arnold@ucla.edu
FU National Human Genome Research Institute (NHGRI); NIH [RO1 NS045264, RO1 NS051820, R01 DC007218, RO1 GM59290]; Swedish Research Council; Knut and Alice Wallenberg Foundation; Biotechnology and Biological Sciences Research Council [BBE0175091]; BBSRC [BB/F007590/1, BB/E017509/1, BB/D013704/2, BB/E010652/1, BBS/E/I/00001425, BB/D013704/1] Funding Source: UKRI; MRC [MC_U137761446] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D013704/1, BB/F007590/1, BB/E010652/1, BBS/E/I/00001425, BB/E017509/1, BB/D013704/2] Funding Source: researchfish; Medical Research Council [MC_U137761446] Funding Source: researchfish; National Human Genome Research Institute [R01HG002939] Funding Source: NIH RePORTER; National Institute on Drug Abuse [P30DA018310] Funding Source: NIH RePORTER
NR 35
TC 661
Z9 969
U1 3
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 APR 1
PY 2010
VL 464
IS 7289
BP 757
EP 762
DI 10.1038/nature08819
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 577EO
UT WOS:000276205000045
PM 20360741
DA 2026-03-09
ER

PT J
AU Barash, Y
   Calarco, JA
   Gao, WJ
   Pan, Q
   Wang, XC
   Shai, O
   Blencowe, BJ
   Frey, BJ
AF Barash, Yoseph
   Calarco, John A.
   Gao, Weijun
   Pan, Qun
   Wang, Xinchen
   Shai, Ofer
   Blencowe, Benjamin J.
   Frey, Brendan J.
TI Deciphering the splicing code
SO NATURE
LA English
DT Article
ID tract binding-protein; regulatory elements; exportin 4; rna; exons; identification; expression; exclusion; insights; pathway
AB Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a 'splicing code', which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations of features, the establishment of low exon inclusion levels that are overcome by features in specific tissues, the appearance of features deeper into introns than previously appreciated, and the modulation of splice variant levels by transcript structure characteristics. The code detected a class of exons whose inclusion silences expression in adult tissues by activating nonsense-mediated messenger RNA decay, but whose exclusion promotes expression during embryogenesis. The code facilitates the discovery and detailed characterization of regulated alternative splicing events on a genome-wide scale.
C1 [Barash, Yoseph; Gao, Weijun; Wang, Xinchen; Shai, Ofer; Frey, Brendan J.] Univ Toronto, Dept Elect & Comp Engn, Toronto, ON M5S 3G4, Canada.
   [Barash, Yoseph; Calarco, John A.; Pan, Qun; Wang, Xinchen; Blencowe, Benjamin J.; Frey, Brendan J.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Barash, Yoseph; Calarco, John A.; Pan, Qun; Wang, Xinchen; Blencowe, Benjamin J.; Frey, Brendan J.] Univ Toronto, Donnelly Ctr, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
   [Frey, Brendan J.] Microsoft Res, Cambridge, England.
C3 University of Toronto; University of Toronto; University of Toronto; Microsoft; Microsoft United Kingdom
RP Frey, BJ (corresponding author), Univ Toronto, Dept Elect & Comp Engn, 10 Kings Coll Rd, Toronto, ON M5S 3G4, Canada.
EM b.blencowe@utoronto.ca; frey@psi.toronto.edu
FU Genome Canada through the OGI; NSERC/CFI/OIT CRC; CIHR; NCIC; NSERC EWR Steacie; Canadian Institute for Advanced Research
NR 50
TC 655
Z9 842
U1 2
U2 127
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 6
PY 2010
VL 465
IS 7294
BP 53
EP 59
DI 10.1038/nature09000
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 591OW
UT WOS:000277311900029
PM 20445623
DA 2026-03-09
ER

PT J
AU Mayer, L
   Kazantzidis, S
   Escala, A
   Callegari, S
AF Mayer, L.
   Kazantzidis, S.
   Escala, A.
   Callegari, S.
TI Direct formation of supermassive black holes via multi-scale gas inflows in galaxy mergers
SO NATURE
LA English
DT Article
ID accretion; evolution; growth; collapse; quasars; spin
AB Observations of distant quasars indicate that supermassive black holes of billions of solar masses already existed less than a billion years after the Big Bang(1). Models in which the 'seeds' of such black holes form by the collapse of primordial metal-free stars(2,3) cannot explain the rapid appearance of these supermassive black holes because gas accretion is not sufficiently efficient(4-6). Alternatively, these black holes may form by direct collapse of gas within isolated protogalaxies(7,8), but current models require idealized conditions, such as metal-free gas, to prevent cooling and star formation from consuming the gas reservoir(9-11). Here we report simulations showing that mergers between massive protogalaxies naturally produce the conditions for direct collapse into a supermassive black hole with no need to suppress cooling and star formation. Merger-driven gas inflows give rise to an unstable, massive nuclear gas disk of a few billion solar masses, which funnels more than 10(8) solar masses of gas to a sub-parsec-scale gas cloud in only 100,000 years. The cloud undergoes gravitational collapse, which eventually leads to the formation of a massive black hole. The black hole can subsequently grow to a billion solar masses on timescales of about 10(8) years by accreting gas from the surrounding disk.
C1 [Mayer, L.; Callegari, S.] Univ Zurich, Inst Theoret Phys, CH-8057 Zurich, Switzerland.
   [Kazantzidis, S.] Ohio State Univ, Ctr Cosmol & Astroparticle Phys, Columbus, OH 43210 USA.
   [Kazantzidis, S.] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Kazantzidis, S.] Ohio State Univ, Dept Astron, Columbus, OH 43210 USA.
   [Escala, A.] Univ Chile, Dept Astron, Santiago 7550000, Chile.
   [Escala, A.] Stanford Univ, KIPAC, Menlo Pk, CA 94025 USA.
C3 University of Zurich; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Universidad de Chile; Stanford University
RP Mayer, L (corresponding author), Univ Zurich, Inst Theoret Phys, 190 Winterthurestr, CH-8057 Zurich, Switzerland.
EM lmayer@physik.unizh.ch
FU Swiss National Science Foundation (SNF); Center for Cosmology and Astro Particle Physics (CCAPP) at Ohio State University; Kavli Institute for Particle Astrophysics (KIPAC) at Stanford University
NR 30
TC 200
Z9 217
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 26
PY 2010
VL 466
IS 7310
BP 1082
EP 1084
DI 10.1038/nature09294
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600034
PM 20740009
DA 2026-03-09
ER

PT J
AU Lehnert, MD
   Nesvadba, NPH
   Cuby, JG
   Swinbank, AM
   Morris, S
   Clément, B
   Evans, CJ
   Bremer, MN
   Basa, S
AF Lehnert, M. D.
   Nesvadba, N. P. H.
   Cuby, J. -G.
   Swinbank, A. M.
   Morris, S.
   Clement, B.
   Evans, C. J.
   Bremer, M. N.
   Basa, S.
TI Spectroscopic confirmation of a galaxy at redshift z=8.6
SO NATURE
LA English
DT Article
ID lyman-break galaxy; ly-alpha emitters; ultra-deep-field; ionized bubbles; reionization; evolution; continuum; z-similar-to-3; universe; quasars
AB Galaxies had their most significant impact on the Universe when they assembled their first generations of stars. Energetic photons emitted by young, massive stars in primeval galaxies ionized the intergalactic medium surrounding their host galaxies, cleared sight-lines along which the light of the young galaxies could escape, and fundamentally altered the physical state of the intergalactic gas in the Universe continuously until the present day(1,2). Observations of the cosmic microwave background(3), and of galaxies and quasars at the highest redshifts(4), suggest that the Universe was reionized through a complex process that was completed about a billion years after the Big Bang, by redshift z approximate to 6. Detecting ionizing Lyman-alpha photons from increasingly distant galaxies places important constraints on the timing, location and nature of the sources responsible for reionization. Here we report the detection of Ly alpha photons emitted less than 600 million years after the Big Bang. UDFy-38135539 (ref. 5) is at a redshift of z = 8.5549 +/- 0.0002, which is greater than those of the previously known most distant objects, at z = 8.2 (refs 6 and 7) and z = 6.96 (ref. 8). We find that this single source is unlikely to provide enough photons to ionize the volume necessary for the emission line to escape, requiring a significant contribution from other, probably fainter galaxies nearby(9).
C1 [Lehnert, M. D.] Univ Paris Diderot, CNRS, Observ Paris, GEPI, F-92190 Meudon, France.
   [Nesvadba, N. P. H.] Univ Paris 11, CNRS, Inst Astrophys Spatiale, UMR 8617, F-91405 Orsay, France.
   [Cuby, J. -G.; Clement, B.; Basa, S.] Univ Aix Marseille, Lab Astrophys Marseille, OAMP, F-13388 Marseille 13, France.
   [Cuby, J. -G.; Clement, B.; Basa, S.] CNRS, F-13388 Marseille 13, France.
   [Swinbank, A. M.] Univ Durham, Dept Phys, Inst Computat Cosmol, Durham DH1 3LE, England.
   [Morris, S.] Univ Durham, Dept Phys, Durham DH1 3AJ, England.
   [Evans, C. J.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Bremer, M. N.] Univ Bristol, HH Wills Phys Lab, Dept Phys, Bristol BS8 1TL, Avon, England.
C3 Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Durham University; Durham University; University of Edinburgh; University of Bristol
RP Lehnert, MD (corresponding author), Univ Paris Diderot, CNRS, Observ Paris, GEPI, 5 Pl Jules Janssen, F-92190 Meudon, France.
EM matthew.lehnert@obspm.fr; nicole.nesvadba@ias.u-psud.fr
FU Science and Technology Facilities Council [ST/H005234/1, ST/F002742/1, ST/F002963/1, PP/E001181/1] Funding Source: researchfish; STFC [ST/F002742/1, ST/F002963/1, ST/H005234/1] Funding Source: UKRI
NR 29
TC 98
Z9 104
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 OCT 21
PY 2010
VL 467
IS 7318
BP 940
EP 942
DI 10.1038/nature09462
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700032
PM 20962840
DA 2026-03-09
ER

PT J
AU Long, MA
   Jin, DZZ
   Fee, MS
AF Long, Michael A.
   Jin, Dezhe Z.
   Fee, Michale S.
TI Support for a synaptic chain model of neuronal sequence generation
SO NATURE
LA English
DT Article
ID hippocampal pyramidal neurons; identified hvc neurons; whole-cell recordings; zebra finch; terminal dendrites; neural activity; vocal control; nucleus hvc; in-vitro; songbird
AB In songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC. To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing zebra finches (Taeniopygia guttata). We found that the subthreshold membrane potential is characterized by a large, rapid depolarization 5-10 ms before burst onset, consistent with a synaptically connected chain of neurons in HVC. We found no evidence for the slow membrane potential modulation predicted by models in which burst timing is controlled by subthreshold dynamics. Furthermore, bursts ride on an underlying depolarization of similar to 10-ms duration, probably the result of a regenerative calcium spike within HVC neurons that could facilitate the propagation of activity through a chain network with high temporal precision. Our results provide insight into the fundamental mechanisms by which neural circuits can generate complex sequential behaviours.
C1 [Long, Michael A.; Fee, Michale S.] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Jin, Dezhe Z.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
C3 Massachusetts Institute of Technology (MIT); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Fee, MS (corresponding author), MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM fee@mit.edu
FU National Institutes of Health [MH067105, DC009280]; Alfred P. Sloan Research Fellowship; National Science Foundation [IOS-0827731]
NR 46
TC 283
Z9 369
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 394
EP 399
DI 10.1038/nature09514
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100034
PM 20972420
DA 2026-03-09
ER

PT J
AU Maertens, GN
   Hare, S
   Cherepanov, P
AF Maertens, Goedele N.
   Hare, Stephen
   Cherepanov, Peter
TI The mechanism of retroviral integration from X-ray structures of its key intermediates
SO NATURE
LA English
DT Article
ID virus integrase; dna integration; amino-acid; sites; transposition; intasome; complex; hiv-1
AB To establish productive infection, a retrovirus must insert a DNA replica of its genome into host cell chromosomal DNA(1,2). This process is operated by the intasome, a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the viral DNA ends(3,4). The intasome engages chromosomal DNA within a target capture complex to carry out strand transfer, irreversibly joining the viral and cellular DNA molecules. Although several intasome/transpososome structures from the DDE(D) recombinase superfamily have been reported(4-6), the mechanics of target DNA capture and strand transfer by these enzymes remained unclear. Here we report crystal structures of the intasome from prototype foamy virus in complex with target DNA, elucidating the pre-integration target DNA capture and post-catalytic strand transfer intermediates of the retroviral integration process. The cleft between IN dimers within the intasome accommodates chromosomal DNA in a severely bent conformation, allowing widely spaced IN active sites to access the scissile phosphodiester bonds. Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences.
C1 [Maertens, Goedele N.; Hare, Stephen; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England.
C3 Imperial College London
RP Cherepanov, P (corresponding author), Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, St Marys Campus,Norfolk Pl, London W2 1PG, England.
EM p.cherepanov@imperial.ac.uk
FU UK Medical Research Council; Medical Research Council [G1000917, G0900116] Funding Source: researchfish; MRC [G0900116] Funding Source: UKRI
NR 26
TC 256
Z9 290
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 NOV 11
PY 2010
VL 468
IS 7321
BP 326
EP U217
DI 10.1038/nature09517
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000055
PM 21068843
DA 2026-03-09
ER

PT J
AU Schindler, DE
   Hilborn, R
   Chasco, B
   Boatright, CP
   Quinn, TP
   Rogers, LA
   Webster, MS
AF Schindler, Daniel E.
   Hilborn, Ray
   Chasco, Brandon
   Boatright, Christopher P.
   Quinn, Thomas P.
   Rogers, Lauren A.
   Webster, Michael S.
TI Population diversity and the portfolio effect in an exploited species
SO NATURE
LA English
DT Article
ID pacific salmon; fresh-water; biodiversity; fishery; biocomplexity; management; nutrients; dynamics
AB One of the most pervasive themes in ecology is that biological diversity stabilizes ecosystem processes and the services they provide to society(1-4), a concept that has become a common argument for biodiversity conservation(5). Species-rich communities are thought to produce more temporally stable ecosystem services because of the complementary or independent dynamics among species that perform similar ecosystem functions(6). Such variance dampening within communities is referred to as a portfolio effect(7) and is analogous to the effects of asset diversity on the stability of financial portfolios(8). In ecology, these arguments have focused on the effects of species diversity on ecosystem stability but have not considered the importance of biologically relevant diversity within individual species(9). Current rates of population extirpation are probably at least three orders of magnitude higher than species extinction rates(10), so there is a pressing need to clarify how population and life history diversity affect the performance of individual species in providing important ecosystem services. Here we use five decades of data from Oncorhynchus nerka (sockeye salmon) in Bristol Bay, Alaska, to provide the first quantification of portfolio effects that derive from population and life history diversity in an important and heavily exploited species. Variability in annual Bristol Bay salmon returns is 2.2 times lower than it would be if the system consisted of a single homogenous population rather than the several hundred discrete populations it currently consists of. Furthermore, if it were a single homogeneous population, such increased variability would lead to ten times more frequent fisheries closures. Portfolio effects are also evident in watershed food webs, where they stabilize and extend predator access to salmon resources. Our results demonstrate the critical importance of maintaining population diversity for stabilizing ecosystem services and securing the economies and livelihoods that depend on them. The reliability of ecosystem services will erode faster than indicated by species loss alone.
C1 [Schindler, Daniel E.; Hilborn, Ray; Chasco, Brandon; Boatright, Christopher P.; Quinn, Thomas P.; Rogers, Lauren A.] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
   [Webster, Michael S.] Gordon & Betty Moore Fdn, Palo Alto, CA 94304 USA.
C3 University of Washington; University of Washington Seattle
RP Schindler, DE (corresponding author), Univ Washington, Sch Aquat & Fishery Sci, Box 355020, Seattle, WA 98195 USA.
EM deschind@u.washington.edu
FU Gordon and Betty Moore Foundation; US National Science Foundation; University of Washington; Alaska salmon processing industry; H. Mason Keeler Professorship
NR 31
TC 1282
Z9 1505
U1 16
U2 732
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 3
PY 2010
VL 465
IS 7298
BP 609
EP 612
DI 10.1038/nature09060
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 604AF
UT WOS:000278249000040
PM 20520713
DA 2026-03-09
ER

PT J
AU Wolf, B
   Zheng, XH
   Brueggemann, N
   Chen, WW
   Dannenmann, M
   Han, XG
   Sutton, MA
   Wu, HH
   Yao, ZS
   Butterbach-Bahl, K
AF Wolf, Benjamin
   Zheng, Xunhua
   Brueggemann, Nicolas
   Chen, Weiwei
   Dannenmann, Michael
   Han, Xingguo
   Sutton, Mark A.
   Wu, Honghui
   Yao, Zhisheng
   Butterbach-Bahl, Klaus
TI Grazing-induced reduction of natural nitrous oxide release from continental steppe
SO NATURE
LA English
DT Article
ID carbon-dioxide; soil-water; n2o; emissions; fluxes; methane; grassland
AB Atmospheric concentrations of the greenhouse gas nitrous oxide (N2O) have increased significantly since pre-industrial times owing to anthropogenic perturbation of the global nitrogen cycle(1,2), with animal production being one of the main contributors(3). Grasslands cover about 20 per cent of the temperate land surface of the Earth and are widely used as pasture. It has been suggested that high animal stocking rates and the resulting elevated nitrogen input increase N2O emissions(4-7). Internationally agreed methods to upscale the effect of increased livestock numbers on N2O emissions are based directly on per capita nitrogen inputs(8). However, measurements of grassland N2O fluxes are often performed over short time periods(9), with low time resolution and mostly during the growing season. In consequence, our understanding of the daily and seasonal dynamics of grassland N2O fluxes remains limited. Here we report year-round N2O flux measurements with high and low temporal resolution at ten steppe grassland sites in Inner Mongolia, China. We show that short-lived pulses of N2O emission during spring thaw dominate the annual N2O budget at our study sites. The N2O emission pulses are highest in ungrazed steppe and decrease with increasing stocking rate, suggesting that grazing decreases rather than increases N2O emissions. Our results show that the stimulatory effect of higher stocking rates on nitrogen cycling(4,7) and, hence, on N2O emission is more than offset by the effects of a parallel reduction in microbial biomass, inorganic nitrogen production and wintertime water retention. By neglecting these freeze-thaw interactions, existing approaches may have systematically overestimated N2O emissions over the last century for semi-arid, cool temperate grasslands by up to 72 per cent.
C1 [Wolf, Benjamin; Brueggemann, Nicolas; Dannenmann, Michael; Butterbach-Bahl, Klaus] Karlsruhe Inst Technol, Inst Meteorol & Climate Res, D-82467 Garmisch Partenkirchen, Germany.
   [Zheng, Xunhua; Chen, Weiwei; Yao, Zhisheng] Chinese Acad Sci, Inst Atmospher Phys, State Key Lab Atmospher Boundary Layer Phys & Atm, Beijing 100029, Peoples R China.
   [Han, Xingguo; Wu, Honghui] Chinese Acad Sci, Inst Bot, State Key Lab Vegetat & Environm Change, Beijing 100093, Peoples R China.
   [Sutton, Mark A.] Ctr Ecol & Hydrol, Penicuik EH26 0QB, Midlothian, Scotland.
C3 Helmholtz Association; Karlsruhe Institute of Technology; Chinese Academy of Sciences; Institute of Atmospheric Physics, CAS; Chinese Academy of Sciences; Institute of Botany, CAS; UK Centre for Ecology & Hydrology (UKCEH)
RP Butterbach-Bahl, K (corresponding author), Karlsruhe Inst Technol, Inst Meteorol & Climate Res, Kreuzeckbahnstr 19, D-82467 Garmisch Partenkirchen, Germany.
EM klaus.butterbach-bahl@kit.edu
FU German Research Foundation (DFG) [536]; National Natural Science Foundation of China [40805061]; European Commission
NR 28
TC 260
Z9 297
U1 13
U2 579
PU NATURE PUBLISHING 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 8
PY 2010
VL 464
IS 7290
BP 881
EP 884
DI 10.1038/nature08931
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300035
PM 20376147
DA 2026-03-09
ER

PT J
AU Parnell, J
   Boyce, AJ
   Mark, D
   Bowden, S
   Spinks, S
AF Parnell, John
   Boyce, Adrian J.
   Mark, Darren
   Bowden, Stephen
   Spinks, Sam
TI Early oxygenation of the terrestrial environment during the Mesoproterozoic
SO NATURE
LA English
DT Article
ID microbial sulfate reduction; sulfur-isotope; atmospheric oxygen; northwest scotland; proterozoic ocean; evolution; age; fractionation; combustion; biosphere
AB Geochemical data from ancient sedimentary successions provide evidence for the progressive evolution of Earth's atmosphere and oceans(1-7). Key stages in increasing oxygenation are postulated for the Palaeoproterozoic era (similar to 2.3 billion years ago, Gyr ago) and the late Proterozoic eon (about 0.8 Gyr ago), with the latter implicated in the subsequent metazoan evolutionary expansion(8). In support of this rise in oxygen concentrations, a large database(1-3,9) shows a marked change in the bacterially mediated fractionation of seawater sulphate to sulphide of Delta (34)S, 25 parts per thousand before 1 Gyr to >= 50 parts per thousand after 0.64 Gyr. This change in Delta (34)S has been interpreted to represent the evolution from single-step bacterial sulphate reduction to a combination of bacterial sulphate reduction and sulphide oxidation, largely bacterially mediated(3,7,9). This evolution is seen as marking the rise in atmospheric oxygen concentrations and the evolution of non-photosynthetic sulphide-oxidizing bacteria(3,7,10). Here we report Delta (34)S values exceeding 50 parts per thousand from a terrestrial Mesoproterozoic (1.18 Gyr old) succession in Scotland, a time period that is at present poorly characterized. This level of fractionation implies disproportionation in the sulphur cycle, probably involving sulphide-oxidizing bacteria, that is not evident from Delta (34)S data in the marine record(1-3,9). Disproportionation in both red beds and lacustrine black shales at our study site suggests that the Mesoproterozoic terrestrial environment was sufficiently oxygenated to support a biota that was adapted to an oxygen-rich atmosphere, but had also penetrated into subsurface sediment.
C1 [Parnell, John; Bowden, Stephen; Spinks, Sam] Univ Aberdeen, Sch Geosci, Aberdeen AB24 3UE, Scotland.
   [Boyce, Adrian J.; Mark, Darren] Scottish Univ Environm Res Ctr, Glasgow G75 0QF, Lanark, Scotland.
C3 University of Aberdeen; Scottish Universities Research & Reactor Center
RP Parnell, J (corresponding author), Univ Aberdeen, Sch Geosci, Aberdeen AB24 3UE, Scotland.
EM j.parnell@abdn.ac.uk
FU University of Aberdeen; NERC; Scottish Universities Consortium; Natural Environment Research Council [aif10001] Funding Source: researchfish; NERC [icsf010001, aif10001] Funding Source: UKRI
NR 30
TC 82
Z9 93
U1 3
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 290
EP 293
DI 10.1038/nature09538
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000048
PM 21068840
DA 2026-03-09
ER

PT J
AU Tacconi, LJ
   Genzel, R
   Neri, R
   Cox, P
   Cooper, MC
   Shapiro, K
   Bolatto, A
   Bouché, N
   Bournaud, F
   Burkert, A
   Combes, F
   Comerford, J
   Davis, M
   Schreiber, NMF
   Garcia-Burillo, S
   Gracia-Carpio, J
   Lutz, D
   Naab, T
   Omont, A
   Shapley, A
   Sternberg, A
   Weiner, B
AF Tacconi, L. J.
   Genzel, R.
   Neri, R.
   Cox, P.
   Cooper, M. C.
   Shapiro, K.
   Bolatto, A.
   Bouche, N.
   Bournaud, F.
   Burkert, A.
   Combes, F.
   Comerford, J.
   Davis, M.
   Schreiber, N. M. Foerster
   Garcia-Burillo, S.
   Gracia-Carpio, J.
   Lutz, D.
   Naab, T.
   Omont, A.
   Shapley, A.
   Sternberg, A.
   Weiner, B.
TI High molecular gas fractions in normal massive star-forming galaxies in the young Universe
SO NATURE
LA English
DT Article
ID lyman break galaxy; submillimeter galaxy; disk galaxy; z-similar-to-2; co; clouds; sample; haloes; m51
AB Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly(1,2). Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars(3-5), and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts, < z > of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today's massive spiral galaxies(6). The slow decrease between z approximate to 2 and z approximate to 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.
C1 [Tacconi, L. J.; Genzel, R.; Bouche, N.; Schreiber, N. M. Foerster; Gracia-Carpio, J.; Lutz, D.] Max Planck Inst Extraterr Phys MPE, D-85748 Garching, Germany.
   [Genzel, R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Neri, R.; Cox, P.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, Grenoble, France.
   [Cooper, M. C.; Weiner, B.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Shapiro, K.; Comerford, J.; Davis, M.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Bolatto, A.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Bournaud, F.] CEA Saclay, DAPNIA, Serv Astrophys, F-91191 Gif Sur Yvette, France.
   [Burkert, A.; Naab, T.] Univ Munich, Univ Sternwarte, D-81679 Munich, Germany.
   [Combes, F.] Observ Paris, LERMA, F-75014 Paris, France.
   [Garcia-Burillo, S.] OAN, Alcala De Henares 28800, Spain.
   [Omont, A.] Univ Paris 06, F-75014 Paris, France.
   [Omont, A.] CNRS, Inst Astrophys, F-75014 Paris, France.
   [Shapley, A.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Sternberg, A.] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
C3 Max Planck Society; University of California System; University of California Berkeley; University of Arizona; University of California System; University of California Berkeley; University System of Maryland; University of Maryland College Park; Universite Paris Saclay; CEA; University of Munich; Universite PSL; Observatoire de Paris; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; University of California System; University of California Los Angeles; Tel Aviv University
RP Tacconi, LJ (corresponding author), Max Planck Inst Extraterr Phys MPE, Giessenbachstr 1, D-85748 Garching, Germany.
EM linda@mpe.mpg.de
FU INSU/CNRS (France); MPG (Germany); IGN (Spain); Cluster of Excellence "Origin and Structure of the Universe"
NR 31
TC 858
Z9 934
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 FEB 11
PY 2010
VL 463
IS 7282
BP 781
EP 784
DI 10.1038/nature08773
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 553VG
UT WOS:000274394300033
PM 20148033
DA 2026-03-09
ER

PT J
AU Pleasance, ED
   Cheetham, RK
   Stephens, PJ
   McBride, DJ
   Humphray, SJ
   Greenman, CD
   Varela, I
   Lin, ML
   Ordóñez, GR
   Bignell, GR
   Ye, K
   Alipaz, J
   Bauer, MJ
   Beare, D
   Butler, A
   Carter, RJ
   Chen, LN
   Cox, AJ
   Edkins, S
   Kokko-Gonzales, PI
   Gormley, NA
   Grocock, RJ
   Haudenschild, CD
   Hims, MM
   James, T
   Jia, MM
   Kingsbury, Z
   Leroy, C
   Marshall, J
   Menzies, A
   Mudie, LJ
   Ning, ZM
   Royce, T
   Schulz-Trieglaff, OB
   Spiridou, A
   Stebbings, LA
   Szajkowski, L
   Teague, J
   Williamson, D
   Chin, L
   Ross, MT
   Campbell, PJ
   Bentley, DR
   Futreal, PA
   Stratton, MR
AF Pleasance, Erin D.
   Cheetham, R. Keira
   Stephens, Philip J.
   McBride, David J.
   Humphray, Sean J.
   Greenman, Chris D.
   Varela, Ignacio
   Lin, Meng-Lay
   Ordonez, Gonzalo R.
   Bignell, Graham R.
   Ye, Kai
   Alipaz, Julie
   Bauer, Markus J.
   Beare, David
   Butler, Adam
   Carter, Richard J.
   Chen, Lina
   Cox, Anthony J.
   Edkins, Sarah
   Kokko-Gonzales, Paula I.
   Gormley, Niall A.
   Grocock, Russell J.
   Haudenschild, Christian D.
   Hims, Matthew M.
   James, Terena
   Jia, Mingming
   Kingsbury, Zoya
   Leroy, Catherine
   Marshall, John
   Menzies, Andrew
   Mudie, Laura J.
   Ning, Zemin
   Royce, Tom
   Schulz-Trieglaff, Ole B.
   Spiridou, Anastassia
   Stebbings, Lucy A.
   Szajkowski, Lukasz
   Teague, Jon
   Williamson, David
   Chin, Lynda
   Ross, Mark T.
   Campbell, Peter J.
   Bentley, David R.
   Futreal, P. Andrew
   Stratton, Michael R.
TI A comprehensive catalogue of somatic mutations from a human cancer genome
SO NATURE
LA English
DT Article
ID nucleotide excision-repair; ets transcription factor; carcinogenesis; epidemiology; mechanisms; pathways; receptor; breast
AB All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
C1 [Pleasance, Erin D.; Stephens, Philip J.; McBride, David J.; Greenman, Chris D.; Varela, Ignacio; Lin, Meng-Lay; Ordonez, Gonzalo R.; Bignell, Graham R.; Beare, David; Butler, Adam; Chen, Lina; Edkins, Sarah; Jia, Mingming; Leroy, Catherine; Marshall, John; Menzies, Andrew; Mudie, Laura J.; Ning, Zemin; Stebbings, Lucy A.; Teague, Jon; Campbell, Peter J.; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Cheetham, R. Keira; Humphray, Sean J.; Bauer, Markus J.; Carter, Richard J.; Cox, Anthony J.; Kokko-Gonzales, Paula I.; Gormley, Niall A.; Grocock, Russell J.; Hims, Matthew M.; James, Terena; Kingsbury, Zoya; Schulz-Trieglaff, Ole B.; Spiridou, Anastassia; Szajkowski, Lukasz; Ross, Mark T.; Bentley, David R.] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
   [Ye, Kai] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands.
   [Ye, Kai] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, NL-2333 ZC Leiden, Netherlands.
   [Alipaz, Julie; Royce, Tom] Illumina Inc, Corp Headquarters, San Diego, CA 92121 USA.
   [Haudenschild, Christian D.; Williamson, David] Illumina Hayward, Hayward, CA 94545 USA.
   [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
C3 Wellcome Trust Sanger Institute; Illumina; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Illumina; Illumina; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of London; Institute of Cancer Research - UK
RP Stratton, MR (corresponding author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
EM paf@sanger.ac.uk; mrs@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]
NR 41
TC 1289
Z9 1607
U1 0
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 191
EP U73
DI 10.1038/nature08658
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700027
PM 20016485
DA 2026-03-09
ER

PT J
AU Elden, AC
   Kim, HJ
   Hart, MP
   Chen-Plotkin, AS
   Johnson, BS
   Fang, XD
   Armakola, M
   Geser, F
   Greene, R
   Lu, MM
   Padmanabhan, A
   Clay-Falcone, D
   McCluskey, L
   Elman, L
   Juhr, D
   Gruber, PJ
   Rüb, U
   Auburger, G
   Trojanowski, JQ
   Lee, VMY
   Van Deerlin, VM
   Bonini, NM
   Gitler, AD
AF Elden, Andrew C.
   Kim, Hyung-Jun
   Hart, Michael P.
   Chen-Plotkin, Alice S.
   Johnson, Brian S.
   Fang, Xiaodong
   Armakola, Maria
   Geser, Felix
   Greene, Robert
   Lu, Min Min
   Padmanabhan, Arun
   Clay-Falcone, Dana
   McCluskey, Leo
   Elman, Lauren
   Juhr, Denise
   Gruber, Peter J.
   Rueb, Udo
   Auburger, Georg
   Trojanowski, John Q.
   Lee, Virginia M. -Y.
   Van Deerlin, Vivianna M.
   Bonini, Nancy M.
   Gitler, Aaron D.
TI Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS
SO NATURE
LA English
DT Article
ID amyotrophic-lateral-sclerosis; spinocerebellar ataxia; alpha-synuclein; saccharomyces-cerevisiae; trinucleotide repeat; stress granules; p-body; tdp-43; toxicity; aggregation
AB The causes of amyotrophic lateral sclerosis (ALS), a devastating human neurodegenerative disease, are poorly understood, although the protein TDP-43 has been suggested to have a critical role in disease pathogenesis. Here we show that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. ATXN2 and TDP-43 associate in a complex that depends on RNA. In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that intermediate-length polyQ expansions (27-33 glutamines) in ATXN2 were significantly associated with ALS. These data establish ATXN2 as a relatively common ALS susceptibility gene. Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.
C1 [Elden, Andrew C.; Hart, Michael P.; Johnson, Brian S.; Fang, Xiaodong; Armakola, Maria; Lu, Min Min; Padmanabhan, Arun; Gitler, Aaron D.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
   [Kim, Hyung-Jun; Bonini, Nancy M.] Univ Penn, Howard Hughes Med Inst, Dept Biol, Philadelphia, PA 19104 USA.
   [Chen-Plotkin, Alice S.; Geser, Felix; Greene, Robert; Clay-Falcone, Dana; Trojanowski, John Q.; Lee, Virginia M. -Y.; Van Deerlin, Vivianna M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Chen-Plotkin, Alice S.; Geser, Felix; Greene, Robert; Clay-Falcone, Dana; Trojanowski, John Q.; Lee, Virginia M. -Y.; Van Deerlin, Vivianna M.] Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
   [Chen-Plotkin, Alice S.; McCluskey, Leo; Elman, Lauren] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
   [Juhr, Denise; Gruber, Peter J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Rueb, Udo] Goethe Univ Frankfurt, Inst Clin Neuroanat, D-60590 Frankfurt, Germany.
   [Auburger, Georg] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany.
C3 University of Pennsylvania; University of Pennsylvania; Howard Hughes Medical Institute; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Goethe University Frankfurt; Goethe University Frankfurt
RP Gitler, AD (corresponding author), Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
EM nbonini@sas.upenn.edu; gitler@mail.med.upenn.edu
FU University of Pennsylvania Institute on Aging; NIH [1DP2OD004417-01, 1R01NS065317-01, P01 AG-09215, AG-10124, AG-17586, K08 AG-033101-01]; Pew Charitable Trusts; Burroughs Wellcome Fund; Howard Hughes Medical Institute; Deutsche Heredo-Ataxie Gesellschaft (DHAG); Autosomal Dominant Cerebellar Ataxia (ADCA) Vereniging Nederland; Spinocerebellar Ataxias (EuroSCA); Deutsche Forschungsgemeinschaft (DFG) [AU96/11-1]
NR 33
TC 1066
Z9 1272
U1 4
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1069
EP U77
DI 10.1038/nature09320
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600032
PM 20740007
DA 2026-03-09
ER

PT J
AU Ulijasz, AT
   Cornilescu, G
   Cornilescu, CC
   Zhang, JR
   Rivera, M
   Markley, JL
   Vierstra, RD
AF Ulijasz, Andrew T.
   Cornilescu, Gabriel
   Cornilescu, Claudia C.
   Zhang, Junrui
   Rivera, Mario
   Markley, John L.
   Vierstra, Richard D.
TI Structural basis for the photoconversion of a phytochrome to the activated Pfr form
SO NATURE
LA English
DT Article
ID chromophore-binding domain; pseudomonas-aeruginosa bacteriophytochrome; induced proton release; tetrapyrrole chromophore; signal-transduction; dipolar couplings; crystal-structure; ground-state; gaf domain; cyanobacterial
AB Phytochromes are a collection of bilin-containing photoreceptors that regulate numerous photoresponses in plants and microorganisms through their ability to photointerconvert between a red-light-absorbing, ground state (Pr) and a far-red-light-absorbing, photoactivated state (Pfr)(1,2). Although the structures of several phytochromes as Pr have been determined(3-7), little is known about the structure of Pfr and how it initiates signalling. Here we describe the three-dimensional solution structure of the bilin-binding domain as Pfr, using the cyanobacterial phytochrome from Synechococcus OSB'. Contrary to predictions, light-induced rotation of the A pyrrole ring but not the D ring is the primary motion of the chromophore during photoconversion. Subsequent rearrangements within the protein then affect intradomain and interdomain contact sites within the phytochrome dimer. On the basis of our models, we propose that phytochromes act by propagating reversible light-driven conformational changes in the bilin to altered contacts between the adjacent output domains, which in most phytochromes direct differential phosphotransfer.
C1 [Ulijasz, Andrew T.; Zhang, Junrui; Vierstra, Richard D.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA.
   [Cornilescu, Gabriel; Cornilescu, Claudia C.; Markley, John L.] Univ Wisconsin, Natl Magnet Resonance Facil Madison, Madison, WI 53706 USA.
   [Rivera, Mario] Univ Kansas, Lawrence, KS 66057 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Kansas
RP Vierstra, RD (corresponding author), Univ Wisconsin, Dept Genet, Madison, WI 53706 USA.
EM vierstra@wisc.edu
FU US National Science Foundation; American Heart Association; U. S. National Institutes of Health; US National Institute of Health; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1022010] Funding Source: National Science Foundation
NR 43
TC 118
Z9 143
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 JAN 14
PY 2010
VL 463
IS 7278
BP 250
EP U143
DI 10.1038/nature08671
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700040
PM 20075921
DA 2026-03-09
ER

PT J
AU Ganin, AY
   Takabayashi, Y
   Jeglic, P
   Arcon, D
   Potocnik, A
   Baker, PJ
   Ohishi, Y
   McDonald, MT
   Tzirakis, MD
   McLennan, A
   Darling, GR
   Takata, M
   Rosseinsky, MJ
   Prassides, K
AF Ganin, Alexey Y.
   Takabayashi, Yasuhiro
   Jeglic, Peter
   Arcon, Denis
   Potocnik, Anton
   Baker, Peter J.
   Ohishi, Yasuo
   McDonald, Martin T.
   Tzirakis, Manolis D.
   McLennan, Alec
   Darling, George R.
   Takata, Masaki
   Rosseinsky, Matthew J.
   Prassides, Kosmas
TI Polymorphism control of superconductivity and magnetism in Cs3C60 close to the Mott transition
SO NATURE
LA English
DT Article
ID doped c-60; fullerides; rb3c60
AB The crystal structure of a solid controls the interactions between the electronically active units and thus its electronic properties. In the high-temperature superconducting copper oxides, only one spatial arrangement of the electronically active Cu2+ units-a two-dimensional square lattice-is available to study the competition between the cooperative electronic states of magnetic order and superconductivity(1). Crystals of the spherical molecular C-60(3-) anion support both superconductivity and magnetism but can consist of fundamentally distinct three-dimensional arrangements of the anions. Superconductivity in the A(3)C(60) (A = alkali metal) fullerides has been exclusively associated with face-centred cubic (f.c.c.) packing of C-60(3-) (refs 2, 3), but recently the most expanded (and thus having the highest superconducting transition temperature, T-o ref. 4) composition Cs3C60 has been isolated as a body-centred cubic (b.c.c.) packing, which supports both superconductivity and magnetic order(5,6). Here we isolate the f.c.c. polymorph of Cs3C60 to show how the spatial arrangement of the electronically active units controls the competing superconducting and magnetic electronic ground states. Unlike all the other f.c.c. A(3)C(60) fullerides, f.c.c. Cs3C60 is not a superconductor but a magnetic insulator at ambient pressure, and becomes superconducting under pressure. The magnetic ordering occurs at an order of magnitude lower temperature in the geometrically frustrated f.c.c. polymorph (Neel temperature T-N = 2.2 K) than in the b.c.c.-based packing (T-N = 46 K). The different lattice packings of C-60(3-) change T-c from 38 K in b.c.c. Cs3C60 to 35 K in f.c.c. Cs3C60 (the highest found in the f.c.c. A(3)C(60) family). The existence of two superconducting packings of the same electronically active unit reveals that T-c scales universally in a structure-independent dome-like relationship with proximity to the Mott metal-insulator transition, which is governed by the role of electron correlations characteristic of high-temperature superconducting materials other than fullerides.
C1 [Ganin, Alexey Y.; McLennan, Alec; Darling, George R.; Rosseinsky, Matthew J.] Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Merseyside, England.
   [Takabayashi, Yasuhiro; McDonald, Martin T.; Tzirakis, Manolis D.; Prassides, Kosmas] Univ Durham, Dept Chem, Durham DH1 3LE, England.
   [Jeglic, Peter; Arcon, Denis; Potocnik, Anton] Jozef Stefan Inst, Ljubljana 1000, Slovenia.
   [Arcon, Denis] Univ Ljubljana, Fac Math & Phys, Ljubljana 1000, Slovenia.
   [Baker, Peter J.] STFC Rutherford Appleton Lab, ISIS Pulsed Neutron & Muon Source, Didcot OX11 0QX, Oxon, England.
   [Ohishi, Yasuo; Takata, Masaki] Japan Synchrotron Radiat Res Inst, SPring 8, Hyogo 6795198, Japan.
   [Takata, Masaki] RIKEN, Ctr SPring 8, Mikazuki, Hyogo 6795148, Japan.
C3 University of Liverpool; Durham University; Slovenian Academy of Sciences & Arts (SASA); Jozef Stefan Institute; University of Ljubljana; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; RIKEN
RP Rosseinsky, MJ (corresponding author), Univ Liverpool, Dept Chem, Liverpool L69 7ZD, Merseyside, England.
EM M.J.Rosseinsky@liverpool.ac.uk; K.Prassides@durham.ac.uk
FU EPSRC [EP/G037132, EP/G037949]; EPSRC [EP/G037949/1, EP/G037132/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G037132/1, EP/G037949/1] Funding Source: researchfish
NR 20
TC 205
Z9 215
U1 2
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 8
PY 2010
VL 466
IS 7303
BP 221
EP U93
DI 10.1038/nature09120
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 621LR
UT WOS:000279580800033
PM 20485340
DA 2026-03-09
ER

PT J
AU Lund, K
   Manzo, AJ
   Dabby, N
   Michelotti, N
   Johnson-Buck, A
   Nangreave, J
   Taylor, S
   Pei, RJ
   Stojanovic, MN
   Walter, NG
   Winfree, E
   Yan, H
AF Lund, Kyle
   Manzo, Anthony J.
   Dabby, Nadine
   Michelotti, Nicole
   Johnson-Buck, Alexander
   Nangreave, Jeanette
   Taylor, Steven
   Pei, Renjun
   Stojanovic, Milan N.
   Walter, Nils G.
   Winfree, Erik
   Yan, Hao
TI Molecular robots guided by prescriptive landscapes
SO NATURE
LA English
DT Article
ID dna; enzyme; deoxyribozyme; computation; devices; motors
AB Traditional robots(1) rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment(2-4). A first step in this direction was the development of DNA walkers(5), which have developed from being non-autonomous(6,7) to being capable of directed but brief motion on one-dimensional tracks(8-11). Here we demonstrate that previously developed random walkers(12)-so-called molecular spiders that comprise a streptavidin molecule as an inert 'body' and three deoxyribozymes as catalytic 'legs'-show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape(13). When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as 'start', 'follow', 'turn' and 'stop'. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour(14,15); another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour(2,16,17).
C1 [Taylor, Steven; Pei, Renjun; Stojanovic, Milan N.] Columbia Univ, Dept Med, Div Expt Therapeut, New York, NY 10032 USA.
   [Lund, Kyle; Nangreave, Jeanette; Yan, Hao] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Lund, Kyle; Nangreave, Jeanette; Yan, Hao] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA.
   [Manzo, Anthony J.; Michelotti, Nicole; Johnson-Buck, Alexander; Walter, Nils G.] Univ Michigan, Dept Chem, Single Mol Anal Grp, Ann Arbor, MI 48109 USA.
   [Dabby, Nadine; Winfree, Erik] CALTECH, Pasadena, CA 91125 USA.
   [Michelotti, Nicole] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
   [Stojanovic, Milan N.] Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA.
C3 Columbia University; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; University of Michigan System; University of Michigan; California Institute of Technology; University of Michigan System; University of Michigan; Columbia University
RP Stojanovic, MN (corresponding author), Columbia Univ, Dept Med, Div Expt Therapeut, New York, NY 10032 USA.
EM mns18@columbia.edu; nwalter@umich.edu; winfree@caltech.edu; hao.yan@asu.edu
FU US National Science Foundation (NSF) EMT; US National Science Foundation (NSF) CBC; Kinship Foundation (Searle); Leukemia & Lymphoma Society; Juvenile Diabetes Research Foundation; NSF ITR; US Army Research Office; NSF; US Office of Naval Research; US National Institutes of Health; US Department of Energy; Sloan Research Fellowship; NIH; Direct For Computer & Info Scie & Enginr [0829579] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [0832824, 0829685] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [0829744, 0829805] Funding Source: National Science Foundation; Division of Computing and Communication Foundations [0829579] Funding Source: National Science Foundation
NR 30
TC 774
Z9 916
U1 9
U2 744
PU 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 13
PY 2010
VL 465
IS 7295
BP 206
EP 210
DI 10.1038/nature09012
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 594SS
UT WOS:000277558500032
PM 20463735
DA 2026-03-09
ER

PT J
AU de Calignon, A
   Fox, LM
   Pitstick, R
   Carlson, GA
   Bacskai, BJ
   Spires-Jones, TL
   Hyman, BT
AF de Calignon, Alix
   Fox, Leora M.
   Pitstick, Rose
   Carlson, George A.
   Bacskai, Brian J.
   Spires-Jones, Tara L.
   Hyman, Bradley T.
TI Caspase activation precedes and leads to tangles
SO NATURE
LA English
DT Article
ID mouse model; neurofibrillary tangles; neuronal loss; tau-phosphorylation; congo red; cleavage; aggregation; truncation; dissociation; expression
AB Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death(1,2), severe cytological abnormalities(3), and markers of caspase activation and apoptosis(4-6), leading to the idea that tangles cause neurodegeneration in Alzheimer's disease and tau-related frontotemporal dementia. However, using in vivo multiphoton imaging to observe tangles and activation of executioner caspases in living tau transgenic mice (Tg4510 strain), we find the opposite: caspase activation occurs first, and precedes tangle formation by hours to days. New tangles form within a day. After a new tangle forms, the neuron remains alive and caspase activity seems to be suppressed. Similarly, introduction of wild-type 4-repeat tau (tau-4R) into wild-type animals triggered caspase activation, tau truncation and tau aggregation. Adeno-associated virus-mediated expression of a construct mimicking caspase-cleaved tau into wild-type mice led to the appearance of intracellular aggregates, tangle-related conformational-and phospho-epitopes, and the recruitment of full-length endogenous tau to the aggregates. On the basis of these data, we propose a new model in which caspase activation cleaves tau to initiate tangle formation, then truncated tau recruits normal tau to misfold and form tangles. Because tangle-bearing neurons are long-lived, we suggest that tangles are 'off pathway' to acute neuronal death. Soluble tau species, rather than fibrillar tau, may be the critical toxic moiety underlying neurodegeneration.
C1 [de Calignon, Alix; Fox, Leora M.; Bacskai, Brian J.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Alzheimers Dis Res Lab, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol,Med S, Charlestown, MA 02129 USA.
   [de Calignon, Alix] Univ Paris 06, F-75005 Paris, France.
   [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT 59401 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Sorbonne Universite; McLaughlin Research Institute for Biomedical Sciences, Inc.
RP Hyman, BT (corresponding author), Harvard Univ, Alzheimers Dis Res Lab, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol,Med S, Charlestown, MA 02129 USA.
EM bhyman@partners.org
FU Alzheimer's disease Drug Discovery Foundation; Harvard Medical School Shore Award;  [AG08487];  [AG 026249];  [K99 AG033670-01A1]
NR 30
TC 432
Z9 522
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 APR 22
PY 2010
VL 464
IS 7292
BP 1201
EP U123
DI 10.1038/nature08890
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 586FR
UT WOS:000276891100039
PM 20357768
DA 2026-03-09
ER

PT J
AU Song, H
   Hu, JX
   Chen, W
   Elliott, G
   Andre, P
   Gao, B
   Yang, YZ
AF Song, Hai
   Hu, Jianxin
   Chen, Wen
   Elliott, Gene
   Andre, Philipp
   Gao, Bo
   Yang, Yingzi
TI Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning
SO NATURE
LA English
DT Article
ID left-right asymmetry; nodal expression; gene-expression; situs-inversus; leftward flow; pathways; mouse; establishment; polarization; regulator
AB Defining the three body axes is a central event of vertebrate morphogenesis. Establishment of left-right (L-R) asymmetry in development follows the determination of dorsal-ventral and anterior-posterior (A-P) body axes 1,2, although the molecular mechanism underlying precise L-R symmetry breaking in reference to the other two axes is still poorly understood. Here, by removing both Vangl1 and Vangl2, the two mouse homologues of a Drosophila core planar cell polarity (PCP) gene Van Gogh (Vang), we reveal a previously unrecognized function of PCP in the initial breaking of lateral symmetry. The leftward nodal flow across the posterior notochord (PNC) has been identified as the earliest event in the de novo formation of L-R asymmetry(3,4). We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry. In the absence of Vangl1 and Vangl2, cilia are positioned randomly around the centre of the PNC cells and nodal flow is turbulent, which results in disrupted L-R asymmetry. PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells. Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.
C1 [Song, Hai; Hu, Jianxin; Chen, Wen; Andre, Philipp; Gao, Bo; Yang, Yingzi] NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Yang, YZ (corresponding author), NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
FU National Human Genome Research Institute; National Human Genome Research Institute [ZICHG200349] Funding Source: NIH RePORTER
NR 32
TC 238
Z9 293
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 JUL 15
PY 2010
VL 466
IS 7304
BP 378
EP U130
DI 10.1038/nature09129
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 625BP
UT WOS:000279867100051
PM 20562861
DA 2026-03-09
ER

PT J
AU Armulik, A
   Genové, G
   Mäe, M
   Nisancioglu, MH
   Wallgard, E
   Niaudet, C
   He, LQ
   Norlin, J
   Lindblom, P
   Strittmatter, K
   Johansson, BR
   Betsholtz, C
AF Armulik, Annika
   Genove, Guillem
   Mae, Maarja
   Nisancioglu, Maya H.
   Wallgard, Elisabet
   Niaudet, Colin
   He, Liqun
   Norlin, Jenny
   Lindblom, Per
   Strittmatter, Karin
   Johansson, Bengt R.
   Betsholtz, Christer
TI Pericytes regulate the blood-brain barrier
SO NATURE
LA English
DT Article
ID endothelial-cells; up-regulation; mutant mice; expression; induction; leads; abnormality; transcripts; astrocytes; activation
AB The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS)(1). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport(2). Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes(3), but the relative contribution of these different components to the BBB remains largely unknown(1,3). Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.
C1 [Armulik, Annika; Genove, Guillem; Mae, Maarja; Nisancioglu, Maya H.; Wallgard, Elisabet; Niaudet, Colin; He, Liqun; Norlin, Jenny; Strittmatter, Karin; Betsholtz, Christer] Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden.
   [Lindblom, Per] AstraZeneca AB, Clin Dev, SE-43183 Molndal, Sweden.
   [Johansson, Bengt R.] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Electron Microscopy Unit, SE-40530 Gothenburg, Sweden.
C3 Karolinska Institutet; AstraZeneca; University of Gothenburg
RP Betsholtz, C (corresponding author), Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Scheelesvag 2, SE-17177 Stockholm, Sweden.
EM annika.armulik@ki.se; christer.betsholtz@ki.se
FU Leducq Foundation; Swedish Governmental Agency for Innovation Systems (Vinnova); EU; Swedish Cancer Society and Research Council; Knut and Alice Wallenberg, Inga-Britt and Arne Lundberg, and Torsten and Ragnar Soderberg Foundations
NR 33
TC 2233
Z9 2673
U1 6
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 NOV 25
PY 2010
VL 468
IS 7323
BP 557
EP U231
DI 10.1038/nature09522
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 684WA
UT WOS:000284584200041
PM 20944627
DA 2026-03-09
ER

PT J
AU Gupta, RA
   Shah, N
   Wang, KC
   Kim, J
   Horlings, HM
   Wong, DJ
   Tsai, MC
   Hung, T
   Argani, P
   Rinn, JL
   Wang, YL
   Brzoska, P
   Kong, B
   Li, R
   West, RB
   van de Vijver, MJ
   Sukumar, S
   Chang, HY
AF Gupta, Rajnish A.
   Shah, Nilay
   Wang, Kevin C.
   Kim, Jeewon
   Horlings, Hugo M.
   Wong, David J.
   Tsai, Miao-Chih
   Hung, Tiffany
   Argani, Pedram
   Rinn, John L.
   Wang, Yulei
   Brzoska, Pius
   Kong, Benjamin
   Li, Rui
   West, Robert B.
   van de Vijver, Marc J.
   Sukumar, Saraswati
   Chang, Howard Y.
TI Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
SO NATURE
LA English
DT Article
ID aggressive breast-cancer; epithelial-cells; gene-expression; carcinoma; invasion; genome; signature; patterns; survival; growth
AB Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome(1-3) yet their potential involvement in human disease is not well understood(4,5). Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities(6-8). Here we show that lincRNAs in the HOX loci become systematically dys-regulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
C1 [Gupta, Rajnish A.; Wang, Kevin C.; Wong, David J.; Tsai, Miao-Chih; Hung, Tiffany; Chang, Howard Y.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Gupta, Rajnish A.; Wang, Kevin C.; Wong, David J.; Tsai, Miao-Chih; Hung, Tiffany; Chang, Howard Y.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Kim, Jeewon] Stanford Univ, Sch Med, Stanford Canc Ctr, Stanford, CA 94305 USA.
   [Kim, Jeewon] Stanford Univ, Sch Med, Transgenic Mouse Res Ctr, Stanford, CA 94305 USA.
   [Li, Rui; West, Robert B.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Shah, Nilay; Sukumar, Saraswati] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Argani, Pedram] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
   [Horlings, Hugo M.; van de Vijver, Marc J.] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands.
   [Rinn, John L.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
   [Rinn, John L.] MIT, Cambridge, MA 02142 USA.
   [Wang, Yulei; Brzoska, Pius; Kong, Benjamin] Appl Biosyst Inc, Foster City, CA 94404 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University; Stanford University; Stanford Medicine; Stanford Cancer Institute; Stanford University; Stanford University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Vrije Universiteit Amsterdam; University of Amsterdam; Academic Medical Center Amsterdam; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Thermo Fisher Scientific; Applied Biosystems
RP Chang, HY (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM howchang@stanford.edu
FU National Institutes of Health (NIH); Emerald Foundation; American Cancer Society; Dermatology Foundation; Susan Komen Foundation; NSF; Department of Defense BCRP; Howard Hughes Medical Institute
NR 30
TC 4475
Z9 5179
U1 2
U2 804
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 15
PY 2010
VL 464
IS 7291
BP 1071
EP U148
DI 10.1038/nature08975
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 582XW
UT WOS:000276635000045
PM 20393566
DA 2026-03-09
ER

PT J
AU Sen, GL
   Reuter, JA
   Webster, DE
   Zhu, L
   Khavari, PA
AF Sen, George L.
   Reuter, Jason A.
   Webster, Daniel E.
   Zhu, Lilly
   Khavari, Paul A.
TI DNMT1 maintains progenitor function in self-renewing somatic tissue
SO NATURE
LA English
DT Article
ID dna methylation; stem-cells; gene-expression; differentiation; methyltransferase; genome; demethylation; proliferation; keratinocytes; patterns
AB Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation(1,2). DNA methylation(3-5) provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)(6,7) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance(8), the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A(11,12) and B-13, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.
C1 [Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.] Stanford Univ, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA.
   [Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.] Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Khavari, Paul A.] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA.
C3 Stanford University; Stanford University; Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System
RP Khavari, PA (corresponding author), Stanford Univ, Program Epithelial Biol, Stanford, CA 94305 USA.
EM khavari@stanford.edu
FU USVA Office of Research and Development; NIH/NIAMS [AR45192]; LVMH Recherche; NIH [AR055849]; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR045192, R01AR049737] Funding Source: NIH RePORTER
NR 38
TC 370
Z9 445
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 563
EP U189
DI 10.1038/nature08683
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100056
PM 20081831
DA 2026-03-09
ER

PT J
AU Mangan, SA
   Schnitzer, SA
   Herre, EA
   Mack, KML
   Valencia, MC
   Sanchez, EI
   Bever, JD
AF Mangan, Scott A.
   Schnitzer, Stefan A.
   Herre, Edward A.
   Mack, Keenan M. L.
   Valencia, Mariana C.
   Sanchez, Evelyn I.
   Bever, James D.
TI Negative plant-soil feedback predicts tree-species relative abundance in a tropical forest
SO NATURE
LA English
DT Article
ID local neighborhood; density-dependence; seedling mortality; maintain diversity; spatial-patterns; pathogens; community; growth; recruitment; coexistence
AB The accumulation of species-specific enemies around adults is hypothesized to maintain plant diversity by limiting the recruitment of conspecific seedlings relative to heterospecific seedlings(1-6). Although previous studies in forested ecosystems have documented patterns consistent with the process of negative feedback(7-16), these studies are unable to address which classes of enemies (for example, pathogens, invertebrates, mammals) exhibit species-specific effects strong enough to generate negative feedback(17), and whether negative feedback at the level of the individual tree is sufficient to influence community-wide forest composition. Here we use fully reciprocal shade-house and field experiments to test whether the performance of conspecific tree seedlings (relative to heterospecific seedlings) is reduced when grown in the presence of enemies associated with adult trees. Both experiments provide strong evidence for negative plant-soil feedback mediated by soil biota. In contrast, above-ground enemies (mammals, foliar herbivores and foliar pathogens) contributed little to negative feedback observed in the field. In both experiments, we found that tree species that showed stronger negative feedback were less common as adults in the forest community, indicating that susceptibility to soil biota may determine species relative abundance in these tropical forests. Finally, our simulation models confirm that the strength of local negative feedback that we measured is sufficient to produce the observed community-wide patterns in tree-species relative abundance. Our findings indicate that plant-soil feedback is an important mechanism that can maintain species diversity and explain patterns of tree-species relative abundance in tropical forests.
C1 [Mangan, Scott A.; Schnitzer, Stefan A.] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA.
   [Mangan, Scott A.; Schnitzer, Stefan A.; Herre, Edward A.; Sanchez, Evelyn I.] Smithsonian Trop Res Inst, MRC 0580 06, Dpo, AA 34002 USA.
   [Mack, Keenan M. L.; Bever, James D.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Valencia, Mariana C.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA.
C3 University of Wisconsin System; University of Wisconsin Milwaukee; Smithsonian Institution; Smithsonian Tropical Research Institute; Indiana University System; Indiana University Bloomington; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Mangan, SA (corresponding author), Univ Wisconsin, Dept Biol Sci, POB 413, Milwaukee, WI 53201 USA.
EM smangan37@gmail.com
FU Smithsonian Tropical Research Institute (STRI); University of Wisconsin-Milwaukee (UWM) Research Growth Initiative; UWM Research Foundation; National Science Foundation; STRI Soil Initiative; Direct For Biological Sciences; Division Of Environmental Biology [1019436] Funding Source: National Science Foundation
NR 30
TC 857
Z9 1007
U1 22
U2 834
PU NATURE PUBLISHING 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 5
PY 2010
VL 466
IS 7307
BP 752
EP U10
DI 10.1038/nature09273
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500038
PM 20581819
DA 2026-03-09
ER

PT J
AU Ghoreschi, K
   Laurence, A
   Yang, XP
   Tato, CM
   McGeachy, MJ
   Konkel, JE
   Ramos, HL
   Wei, L
   Davidson, TS
   Bouladoux, N
   Grainger, JR
   Chen, QA
   Kanno, Y
   Watford, WT
   Sun, HW
   Eberl, G
   Shevach, E
   Belkaid, Y
   Cua, DJ
   Chen, WJ
   O'Shea, JJ
AF Ghoreschi, Kamran
   Laurence, Arian
   Yang, Xiang-Ping
   Tato, Cristina M.
   McGeachy, Mandy J.
   Konkel, Joanne E.
   Ramos, Haydee L.
   Wei, Lai
   Davidson, Todd S.
   Bouladoux, Nicolas
   Grainger, John R.
   Chen, Qian
   Kanno, Yuka
   Watford, Wendy T.
   Sun, Hong-Wei
   Eberl, GerRard
   Shevach, EthanM.
   Belkaid, Yasmine
   Cua, Daniel J.
   Chen, WanJun
   O'Shea, John J.
TI Generation of pathogenic TH17 cells in the absence of TGF-β signalling
SO NATURE
LA English
DT Article
ID regulatory t-cells; growth-factor-beta; helper-cells; autoimmune encephalomyelitis; proinflammatory il-17(+); th17 cells; in-vivo; differentiation; lineage; inflammation
AB CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity(1-4). Although crucial for T(H)17 cells in vivo(5,6), IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-beta 1 have been proposed to be the factors responsible for initiating specification(7-10). Here we show that T(H)17 differentiation can occur in the absence of TGF-beta signalling. Neither IL-6 nor IL-23 alone efficiently generated T(H)17 cells; however, these cytokines in combination with IL-1 beta effectively induced IL-17 production in naive precursors, independently of TGF-beta. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-beta 1, allowing the generation of cells that co-expressed ROR gamma t (encoded by Rorc) and T-bet. T-bet(+)ROR gamma t(+) T(H)17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred T(H)17 cells generated with IL-23 without TGF-beta 1 were pathogenic in this disease model. These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications.
C1 [Ghoreschi, Kamran; Laurence, Arian; Yang, Xiang-Ping; Ramos, Haydee L.; Wei, Lai; Kanno, Yuka; Watford, Wendy T.; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
   [Tato, Cristina M.; McGeachy, Mandy J.; Cua, Daniel J.] Merck Res Labs, Palo Alto, CA 94304 USA.
   [Konkel, Joanne E.; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
   [Davidson, Todd S.; Chen, Qian; Shevach, EthanM.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Bouladoux, Nicolas; Grainger, John R.; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Sun, Hong-Wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
   [Eberl, GerRard] Inst Pasteur, Lymphoid Tissue Dev Unit, F-75724 Paris, France.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); Merck & Company; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); 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 Arthritis & Musculoskeletal & Skin Diseases (NIAMS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
RP Ghoreschi, K (corresponding author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM ghoreschik@mail.nih.gov; osheajo@mail.nih.gov
FU NIAMS; NIDCR; NIAID; National Institute of Allergy and Infectious Diseases [ZIAAI001132, ZIAAI000224] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIHAR041173, ZIAAR041159] Funding Source: NIH RePORTER; National Institute of Dental and Craniofacial Research [ZIADE000101] Funding Source: NIH RePORTER
NR 34
TC 1202
Z9 1426
U1 0
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 21
PY 2010
VL 467
IS 7318
BP 967
EP U144
DI 10.1038/nature09447
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 668FT
UT WOS:000283254700039
PM 20962846
DA 2026-03-09
ER

PT J
AU Vastenhouw, NL
   Zhang, Y
   Woods, IG
   Imam, F
   Regev, A
   Liu, XS
   Rinn, J
   Schier, AF
AF Vastenhouw, Nadine L.
   Zhang, Yong
   Woods, Ian G.
   Imam, Farhad
   Regev, Aviv
   Liu, X. Shirley
   Rinn, John
   Schier, Alexander F.
TI Chromatin signature of embryonic pluripotency is established during genome activation
SO NATURE
LA English
DT Article
ID rna-polymerase; zygotic transition; genes; polycomb
AB After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition(1-3). This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal-zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed(4-8). Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal-zygotic transition.
C1 [Zhang, Yong; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
   [Vastenhouw, Nadine L.; Woods, Ian G.; Imam, Farhad; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
   [Regev, Aviv; Rinn, John; Schier, Alexander F.] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Regev, Aviv; Rinn, John; Schier, Alexander F.] Harvard Univ, Cambridge, MA 02142 USA.
   [Rinn, John] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
   [Schier, Alexander F.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Schier, Alexander F.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard T.H. Chan School of Public Health; Harvard University; Tongji University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University
RP Liu, XS (corresponding author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM xsliu@jimmy.harvard.edu; schier@fas.harvard.edu
FU NIH [1R01 HG004069, 5R01 GM56211]; EMBO [LT-00090/2007]; HFSP [LT-00090/2007]
NR 35
TC 305
Z9 387
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 8
PY 2010
VL 464
IS 7290
BP 922
EP U143
DI 10.1038/nature08866
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 579TM
UT WOS:000276397300044
PM 20336069
DA 2026-03-09
ER

PT J
AU Mayack, SR
   Shadrach, JL
   Kim, FS
   Wagers, AJ
AF Mayack, Shane R.
   Shadrach, Jennifer L.
   Kim, Francis S.
   Wagers, Amy J.
TI RETRACTED: Systemic signals regulate ageing and rejuvenation of blood stem cell niches (Retracted article. See vol. 467, pg. 872, 2010)
SO NATURE
LA English
DT Article; Retracted Publication
ID hematopoietic-stem; igf-i; progenitor cells; skeletal-muscle; growth; osteoblasts; pathways; bone; identification; regeneration
AB Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.
C1 [Mayack, Shane R.; Shadrach, Jennifer L.; Kim, Francis S.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Howard Hughes Medical Institute
RP Wagers, AJ (corresponding author), Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA.
EM amy.wagers@joslin.harvard.edu
FU Burroughs-Welcome Fund; WM Keck Foundation; Glenn Foundation; National Institutes of Health (NIH) [1 DP2 OD004345-01, T32DK07260-29]; Iacocca Foundation; Joslin Diabetes Center DERC [P30DK036836]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK036836, T32DK007260] Funding Source: NIH RePORTER
NR 37
TC 111
Z9 132
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 JAN 28
PY 2010
VL 463
IS 7280
BP 495
EP U109
DI 10.1038/nature08749
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100041
PM 20110993
DA 2026-03-09
ER

PT J
AU Zhang, FC
   Kearns, SL
   Orr, PJ
   Benton, MJ
   Zhou, ZH
   Johnson, D
   Xu, X
   Wang, XL
AF Zhang, Fucheng
   Kearns, Stuart L.
   Orr, Patrick J.
   Benton, Michael J.
   Zhou, Zhonghe
   Johnson, Diane
   Xu, Xing
   Wang, Xiaolin
TI Fossilized melanosomes and the colour of Cretaceous dinosaurs and birds
SO NATURE
LA English
DT Article
ID integumentary structures; feathered dinosaurs; theropod dinosaur; yixian formation; collagen-fibers; china; evolution; origin; protofeathers
AB Spectacular fossils from the Early Cretaceous Jehol Group(1,2) of northeastern China have greatly expanded our knowledge of the diversity and palaeobiology of dinosaurs and early birds, and contributed to our understanding of the origin of birds, of flight, and of feathers. Pennaceous (vaned) feathers and integumentary filaments are preserved in birds(3-5) and non-avian theropod dinosaurs(6-12), but little is known of their microstructure. Here we report that melanosomes (colour-bearing organelles) are not only preserved in the pennaceous feathers of early birds, but also in an identical manner in integumentary filaments of non-avian dinosaurs, thus refuting recent claims(13-16) that the filaments are partially decayed dermal collagen fibres. Examples of both eumelanosomes and phaeomelanosomes have been identified, and they are often preserved in life position within the structure of partially degraded feathers and filaments. Furthermore, the data here provide empirical evidence for reconstructing the colours and colour patterning of these extinct birds and theropod dinosaurs: for example, the dark-coloured stripes on the tail of the theropod dinosaur Sinosauropteryx can reasonably be inferred to have exhibited chestnut to reddish-brown tones.
C1 [Kearns, Stuart L.; Benton, Michael J.] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Zhang, Fucheng; Zhou, Zhonghe; Xu, Xing; Wang, Xiaolin] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Orr, Patrick J.] Univ Coll Dublin, Sch Geol Sci, Dublin 4, Ireland.
   [Johnson, Diane] Open Univ, Planetary & Space Sci Res Inst, Milton Keynes MK7 6AA, Bucks, England.
C3 University of Bristol; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University College Dublin; Open University - UK
RP Benton, MJ (corresponding author), Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
EM mike.benton@bristol.ac.uk; zhonghe@yeah.net
FU NERC; MST of China; National Natural Science Foundation of China; NERC [NE/E011055/1] Funding Source: UKRI; Natural Environment Research Council [NE/E011055/1] Funding Source: researchfish
NR 30
TC 219
Z9 253
U1 4
U2 208
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 25
PY 2010
VL 463
IS 7284
BP 1075
EP 1078
DI 10.1038/nature08740
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563DR
UT WOS:000275108400035
PM 20107440
DA 2026-03-09
ER

PT J
AU Solomatin, SV
   Greenfeld, M
   Chu, S
   Herschlag, D
AF Solomatin, Sergey V.
   Greenfeld, Max
   Chu, Steven
   Herschlag, Daniel
TI Multiple native states reveal persistent ruggedness of an RNA folding landscape
SO NATURE
LA English
DT Article
ID tetrahymena ribozyme; energy landscape; single-molecule; substrate; binding; pathways; dynamics; intermediate; catalysis
AB According to the 'thermodynamic hypothesis', the sequence of a biological macromolecule defines its folded, active (or 'native') structure as a global energy minimum in the folding landscape(1,2). However, the enormous complexity of folding landscapes of large macromolecules raises the question of whether there is in fact a unique global minimum corresponding to a unique native conformation or whether there are deep local minima corresponding to alternative active conformations(3). The folding of many proteins is well described by two-state models, leading to highly simplified representations of protein folding landscapes with a single native conformation(4,5). Nevertheless, accumulating experimental evidence suggests a more complex topology of folding landscapes with multiple active conformations that can take seconds or longer to interconvert(6-8). Here we demonstrate, using single-molecule experiments, that an RNA enzyme folds into multiple distinct native states that interconvert on a timescale much longer than that of catalysis. These data demonstrate that severe ruggedness of RNA folding landscapes extends into conformational space occupied by native conformations.
C1 [Solomatin, Sergey V.; Herschlag, Daniel] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA.
   [Greenfeld, Max] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
   [Chu, Steven] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
   [Chu, Steven] Univ Calif Berkeley, Dept Phys & Mol & Cell Biol, Berkeley, CA 94720 USA.
C3 Stanford University; Stanford University; 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 Herschlag, D (corresponding author), Stanford Univ, Dept Biochem, Stanford, CA 94305 USA.
EM herschla@stanford.edu
FU US National Institutes of Health (NIH) [P01-GM-66275, GM49243]; Stanford Bio-X Program
NR 30
TC 171
Z9 222
U1 2
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2010
VL 463
IS 7281
BP 681
EP U117
DI 10.1038/nature08717
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551GB
UT WOS:000274193900040
PM 20130651
DA 2026-03-09
ER

PT J
AU Yuan, HY
   Romanowicz, B
AF Yuan, Huaiyu
   Romanowicz, Barbara
TI Lithospheric layering in the North American craton
SO NATURE
LA English
DT Article
ID azimuthal anisotropy; seismic anisotropy; upper-mantle; petrological constraints; continental tectosphere; asthenosphere boundary; shear velocity; united-states; global view; wave
AB How cratons-extremely stable continental areas of the Earth's crust-formed and remained largely unchanged for more than 2,500 million years is much debated. Recent studies of seismic-wave receiver function data have detected a structural boundary under continental cratons at depths too shallow to be consistent with the lithosphere-asthenosphere boundary, as inferred from seismic tomography and other geophysical studies. Here we show that changes in the direction of azimuthal anisotropy with depth reveal the presence of two distinct lithospheric layers throughout the stable part of the North American continent. The top layer is thick (similar to 150 km) under the Archaean core and tapers out on the surrounding Palaeozoic borders. Its thickness variations follow those of a highly depleted layer inferred from thermo-barometric analysis of xenoliths. The lithosphere-asthenosphere boundary is relatively flat (ranging from 180 to 240 km in depth), in agreement with the presence of a thermal conductive root that subsequently formed around the depleted chemical layer. Our findings tie together seismological, geochemical and geodynamical studies of the cratonic lithosphere in North America. They also suggest that the horizon detected in receiver function studies probably corresponds to the sharp mid-lithospheric boundary rather than to the more gradual lithosphere-asthenosphere boundary.
C1 [Yuan, Huaiyu; Romanowicz, Barbara] Berkeley Seismol Lab, Berkeley, CA 94720 USA.
RP Romanowicz, B (corresponding author), Berkeley Seismol Lab, 209 McCone Hall, Berkeley, CA 94720 USA.
EM barbara.romanowicz@gmail.com
FU National Science Foundation
NR 58
TC 445
Z9 517
U1 3
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 26
PY 2010
VL 466
IS 7310
BP 1063
EP U68
DI 10.1038/nature09332
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600031
PM 20740006
DA 2026-03-09
ER

PT J
AU Mariappan, M
   Li, XZ
   Stefanovic, S
   Sharma, A
   Mateja, A
   Keenan, RJ
   Hegde, RS
AF Mariappan, Malaiyalam
   Li, Xingzhe
   Stefanovic, Sandra
   Sharma, Ajay
   Mateja, Agnieszka
   Keenan, Robert J.
   Hegde, Ramanujan S.
TI A ribosome-associating factor chaperones tail-anchored membrane proteins
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; er membrane; insertion; get3; complex; recognition; binding; identification; translation; termination
AB Hundreds of proteins are inserted post-translationally into the endoplasmic reticulum (ER) membrane by a single carboxyterminal transmembrane domain (TMD)(1). During targeting through the cytosol, the hydrophobic TMD of these tail-anchored (TA) proteins requires constant chaperoning to prevent aggregation or inappropriate interactions. A central component of this targeting system is TRC40, a conserved cytosolic factor that recognizes the TMD of TA proteins and delivers them to the ER for insertion(2-4). The mechanism that permits TRC40 to find and capture its TA protein cargos effectively in a highly crowded cytosol is unknown. Here we identify a conserved three-protein complex composed of Bat3, TRC35 and Ubl4A that facilitates TA protein capture by TRC40. This Bat3 complex is recruited to ribosomes synthesizing membrane proteins, interacts with the TMDs of newly released TA proteins, and transfers them to TRC40 for targeting. Depletion of the Bat3 complex allows non-TRC40 factors to compete for TA proteins, explaining their mislocalization in the analogous yeast deletion strains(5-7). Thus, the Bat3 complex acts as a TMD-selective chaperone that effectively channels TA proteins to the TRC40 insertion pathway.
C1 [Mariappan, Malaiyalam; Li, Xingzhe; Stefanovic, Sandra; Sharma, Ajay; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
   [Li, Xingzhe] Peking Univ, Sch Basic Med Sci, Beijing 100191, Peoples R China.
   [Mateja, Agnieszka; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Peking University; University of Chicago
RP Hegde, RS (corresponding author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM hegder@mail.nih.gov
FU National Institutes of Health; Edward Mallinckrodt Jr Foundation
NR 30
TC 231
Z9 280
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1120
EP U138
DI 10.1038/nature09296
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600043
PM 20676083
DA 2026-03-09
ER

PT J
AU Branch, TA
   Watson, R
   Fulton, EA
   Jennings, S
   McGilliard, CR
   Pablico, GT
   Ricard, D
   Tracey, SR
AF Branch, Trevor A.
   Watson, Reg
   Fulton, Elizabeth A.
   Jennings, Simon
   McGilliard, Carey R.
   Pablico, Grace T.
   Ricard, Daniel
   Tracey, Sean R.
TI The trophic fingerprint of marine fisheries
SO NATURE
LA English
DT Article
ID food webs; ecological indicators; global fishery; world fishery; gulf; biodiversity; perspective; aquaculture; ecosystems; impacts
AB Biodiversity indicators provide a vital window on the state of the planet, guiding policy development and management(1,2). The most widely adopted marine indicator is mean trophic level (MTL) from catches, intended to detect shifts from high-trophic-level predators to low-trophic-level invertebrates and plankton-feeders(3-5). This indicator underpins reported trends in human impacts, declining when predators collapse ("fishing down marine food webs'')(3) and when low-trophic-level fisheries expand ("fishing through marine food webs'')(6). The assumption is that catch MTL measures changes in ecosystem MTL and biodiversity(2,5). Here we combine model predictions with global assessments of MTL from catches, trawl surveys and fisheries stock assessments(7) and find that catch MTL does not reliably predict changes in marine ecosystems. Instead, catch MTL trends often diverge from ecosystem MTL trends obtained from surveys and assessments. In contrast to previous findings of rapid declines in catch MTL3, we observe recent increases in catch, survey and assessment MTL. However, catches from most trophic levels are rising, which can intensify fishery collapses even when MTL trends are stable or increasing. To detect fishing impacts on marine biodiversity, we recommend greater efforts to measure true abundance trends for marine species, especially those most vulnerable to fishing.
C1 [Branch, Trevor A.; McGilliard, Carey R.] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
   [Watson, Reg; Pablico, Grace T.] Univ British Columbia, Fisheries Ctr, Sea Around Us Project, Vancouver, BC V6T 1Z4, Canada.
   [Fulton, Elizabeth A.] CSIRO Wealth Oceans, Hobart, Tas 7001, Australia.
   [Jennings, Simon] Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 0HT, Suffolk, England.
   [Jennings, Simon] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Ricard, Daniel] Dalhousie Univ, Dept Biol, Halifax, NS B3H 4J1, Canada.
   [Tracey, Sean R.] Univ Tasmania, Tasmanian Aquaculture & Fisheries Inst, Marine Res Labs, Hobart, Tas 7001, Australia.
C3 University of Washington; University of Washington Seattle; University of British Columbia; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Centre for Environment Fisheries & Aquaculture Science; University of East Anglia; Dalhousie University; University of Tasmania
RP Branch, TA (corresponding author), Univ Washington, Sch Aquat & Fishery Sci, Box 355020, Seattle, WA 98195 USA.
EM tbranch@uw.edu
FU University of California Santa Barbara; US National Science Foundation (NSF); Moore Foundation; School of Aquatic and Fishery Sciences, University of Washington; Canadian Natural Sciences and Engineering Research Council; Canadian Foundation for Innovation; Pew Charitable Trusts; Directorate For Geosciences; Division Of Ocean Sciences [1041570] Funding Source: National Science Foundation
NR 29
TC 304
Z9 352
U1 4
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 NOV 18
PY 2010
VL 468
IS 7322
BP 431
EP 435
DI 10.1038/nature09528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100041
PM 21085178
DA 2026-03-09
ER

PT J
AU Guang, SH
   Bochner, AF
   Burkhart, KB
   Burton, N
   Pavelec, DM
   Kennedy, S
AF Guang, Shouhong
   Bochner, Aaron F.
   Burkhart, Kirk B.
   Burton, Nick
   Pavelec, Derek M.
   Kennedy, Scott
TI Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription
SO NATURE
LA English
DT Article
ID pre-messenger-rna; caenorhabditis-elegans; c-elegans; genetic interference; mediated pathways; reveals; nucleus; target; lin-15
AB Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that regulate heterochromatin formation, developmental timing, defence against parasitic nucleic acids and genome rearrangement. Many small regulatory RNAs are thought to function in nuclei(1,2). For instance, in plants and fungi, short interfering RNA (siRNAs) associate with nascent transcripts and direct chromatin and/or DNA modifications(1,2). To understand further the biological roles of small regulatory RNAs, we conducted a genetic screen to identify factors required for RNA interference (RNAi) in Caenorhabditis elegans nuclei(3). Here we show that the gene nuclear RNAi defective-2 (nrde-2) encodes an evolutionarily conserved protein that is required for siRNA-mediated silencing in nuclei. NRDE-2 associates with the Argonaute protein NRDE-3 within nuclei and is recruited by NRDE-3/siRNA complexes to nascent transcripts that have been targeted by RNAi. We find that nuclear-localized siRNAs direct an NRDE-2-dependent silencing of pre-messenger RNAs (pre-mRNAs) 3' to sites of RNAi, an NRDE-2-dependent accumulation of RNA polymerase (RNAP) II at genomic loci targeted by RNAi, and NRDE-2-dependent decreases in RNAP II occupancy and RNAP II transcriptional activity 39 to sites of RNAi. These results define NRDE-2 as a component of the nuclear RNAi machinery and demonstrate that metazoan siRNAs can silence nuclear-localized RNAs co-transcriptionally. In addition, these results establish a novel mode of RNAP II regulation: siRNA-directed recruitment of NRDE factors that inhibit RNAP II during the elongation phase of transcription.
C1 [Guang, Shouhong; Bochner, Aaron F.; Burkhart, Kirk B.; Burton, Nick; Kennedy, Scott] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
   [Pavelec, Derek M.; Kennedy, Scott] Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Kennedy, S (corresponding author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
EM sgkennedy@wisc.edu
FU Pew and Shaw scholars programmes; National Institutes of Health; American Heart Association; National Institute of General Medical Sciences [R01GM088289] Funding Source: NIH RePORTER
NR 20
TC 234
Z9 311
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 JUN 24
PY 2010
VL 465
IS 7301
BP 1097
EP U165
DI 10.1038/nature09095
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900057
PM 20543824
DA 2026-03-09
ER

PT J
AU Janssen, BJC
   Robinson, RA
   Pérez-Brangulí, F
   Bell, CH
   Mitchell, KJ
   Siebold, C
   Jones, EY
AF Janssen, Bert J. C.
   Robinson, Ross A.
   Perez-Branguli, Francesc
   Bell, Christian H.
   Mitchell, Kevin J.
   Siebold, Christian
   Jones, E. Yvonne
TI Structural basis of semaphorin-plexin signalling
SO NATURE
LA English
DT Article
ID crystal-structure; receptor; binding; model; transmembrane; family; ligand; met; glycosylation; dimerization
AB Cell-cell signalling of semaphorin ligands through interaction with plexin receptors is important for the homeostasis and morphogenesis of many tissues and is widely studied for its role in neural connectivity, cancer, cell migration and immune responses(1). SEMA4D and Sema6A exemplify two diverse vertebrate, membrane-spanning semaphorin classes (4 and 6) that are capable of direct signalling through members of the two largest plexin classes, B and A, respectively(2,3). In the absence of any structural information on the plexin ectodomain or its interaction with semaphorins the extracellular specificity and mechanism controlling plexin signalling has remained unresolved. Here we present crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wild-type and mutant proteins, reveal that semaphorin dimers independently bind two plexin molecules and that signalling is critically dependent on the avidity of the resulting bivalent 2: 2 complex (monomeric semaphorin binds plexin but fails to trigger signalling). In combination, our data favour a cell-cell signalling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal seven-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggests that a common mode of interaction triggers all semaphorin-plexin based signalling, while distinct insertions within or between blades of the sema domains determine binding specificity.
C1 [Janssen, Bert J. C.; Robinson, Ross A.; Bell, Christian H.; Siebold, Christian; Jones, E. Yvonne] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England.
   [Perez-Branguli, Francesc; Mitchell, Kevin J.] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland.
   [Perez-Branguli, Francesc; Mitchell, Kevin J.] Trinity Coll Dublin, Inst Neurosci, Dublin 2, Ireland.
C3 University of Oxford; Wellcome Centre for Human Genetics; Trinity College Dublin; Trinity College Dublin
RP Jones, EY (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England.
EM yvonne@strubi.ox.ac.uk
FU Human Frontier Science Program; Science Foundation Ireland; Wellcome Trust; Cancer Research UK; MRC [G9900061, G0900084, G0700232] Funding Source: UKRI; Cancer Research UK [10976] Funding Source: researchfish; Medical Research Council [G9900061, G0700232, G0900084] Funding Source: researchfish
NR 54
TC 193
Z9 246
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 OCT 28
PY 2010
VL 467
IS 7319
BP 1118
EP U132
DI 10.1038/nature09468
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 671XW
UT WOS:000283548600050
PM 20877282
DA 2026-03-09
ER

PT J
AU Roberts, TF
   Tschida, KA
   Klein, ME
   Mooney, R
AF Roberts, Todd F.
   Tschida, Katherine A.
   Klein, Marguerita E.
   Mooney, Richard
TI Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning
SO NATURE
LA English
DT Article
ID long-term potentiation; dendritic spines; in-vivo; zebra finch; song; neurons; cortex; plasticity; deprivation; integration
AB Behavioural learning depends on the brain's capacity to respond to instructive experience and is often enhanced during a juvenile sensitive period. How instructive experience acts on the juvenile brain to trigger behavioural learning remains unknown. In vitro studies show that forms of synaptic strengthening thought to underlie learning are accompanied by an increase in the stability, number and size of dendritic spines, which are the major sites of excitatory synaptic transmission in the vertebrate brain(1-7). In vivo imaging studies in sensory cortical regions reveal that these structural features can be affected by disrupting sensory experience and that spine turnover increases during sensitive periods for sensory map formation(8-12). These observations support two hypotheses: first, the increased capacity for behavioural learning during a sensitive period is associated with enhanced spine dynamics on sensorimotor neurons important for the learned behaviour; second, instructive experience rapidly stabilizes and strengthens these dynamic spines. Here we report a test of these hypotheses using two-photon in vivo imaging to measure spine dynamics in zebra finches, which learn to sing by imitating a tutor song during a juvenile sensitive period(13,14). Spine dynamics were measured in the forebrain nucleus HVC, the proximal site where auditory information merges with an explicit song motor representation(15-19), immediately before and after juvenile finches first experienced tutor song(20). Higher levels of spine turnover before tutoring correlated with a greater capacity for subsequent song imitation. In juveniles with high levels of spine turnover, hearing a tutor song led to the rapid (similar to 24-h) stabilization, accumulation and enlargement of dendritic spines in HVC. Moreover, in vivo intracellular recordings made immediately before and after the first day of tutoring revealed robust enhancement of synaptic activity in HVC. These findings suggest that behavioural learning results when instructive experience is able to rapidly stabilize and strengthen synapses on sensorimotor neurons important for the control of the learned behaviour.
C1 [Roberts, Todd F.; Tschida, Katherine A.; Klein, Marguerita E.; Mooney, Richard] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
C3 Duke University
RP Mooney, R (corresponding author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
EM mooney@neuro.duke.edu
FU US National Science Foundation (NSF); US National Institutes of Health (NIH); Howard Hughes Medical Institute; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0821914] Funding Source: National Science Foundation
NR 29
TC 231
Z9 291
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 18
PY 2010
VL 463
IS 7283
BP 948
EP U123
DI 10.1038/nature08759
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 556HZ
UT WOS:000274582700046
PM 20164928
DA 2026-03-09
ER

